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Biomedical subjects

F Sanz

Publications and source records attributed to F Sanz.

At least 55 records · Page 3Linked to original sources

The VATAM guidelines.

Evaluation and assessment of the impact of information and communication technology in medicine is gaining interest. Unfortunately, till now there were no agreed upon approaches. The objective of the VATAM project is to develop guidelines that will assist assessors to set-up and execute studies. This paper describes the background of the VATAM project and provides an account of the current state of the guidelines. It concludes with an indication of the developments that will take place in the short term to further elaborate the guidelines and some considerations for consolidation of VATAM's results.

Databases, Factual↗

Inventory of validation approaches in selected health telematics projects.

This paper presents the results from an inventory of validation approaches and methodologies which have been used in selected health telematics projects. The inventory was performed in the VATAM Validation of Telematic Applications in Medicine project, HC1115HC. The purpose of the inventory was to analyse the methodologies and their application assumptions in order to identify possibilities for harmonization and consolidation. The inventory was performed using five validation dimensions: IT-development; quality; user; technology assessment and marketing. The inventory results show that possibilities exist to synthesise methodologies and to provide practical guidance and support for projects that are developing health telematics applications. All stakeholders in health telematics projects, i.e. users, health care decision-makers, developers, suppliers and IT-industries, can benefit from practical validation guidelines and support for validation when guidelines are represented in a usable, easy to access and informative way.

Humans↗

Detection of mitomycin C-induced genetic damage in fish cells by use of RAPD.

Concern about genetic alterations in fish populations arising from anthropogenic activities has led to the adaptation and/or development of new tests and techniques that shed light on these alterations. The high number and the reduced size of chromosomes and the long cell cycle associated with most fish species preclude the use of most accepted genotoxicity assays. The purpose of this work was to study the capability of the randomly amplified polymorphic DNA technique to show genotoxic effects induced by chemicals in fish cells. To do that we studied the effect of 0.5 microg/ml mitomycin C (MMC) on an established rainbow trout cell line (RTG-2). To increase the sensitivity of detecting altered copies of DNA and to avoid the presence of false positives and a lack of reproducibility, the amounts of DNA template and primer present in amplification reactions were studied and optimized after comparison between the control and exposed fingerprints for 4, 6 and 8 h. Results show that 5 ng of DNA template and 4 pM chosen primer were optimum to show differences between control and exposed cells and to obtain reproducible results. The results obtained, after optimum conditions were established, show that this system could be useful for the assessment of DNA alterations in in vitro genotoxicity studies.

Animals↗

Telematics applications to support the role of the community pharmacists as self-medication advisors. TESEMED Consortium.

One of the applications developed within the EU-funded projects TESEMED and TESEMED-II is a program for the information and continuous training of community pharmacists, with the aim to empower them as advisors of the citizens about self-medication topics. Several programs are being developed on the basis of ad-hoc developed protocols about minor ailments (currently, cold and flu, haemorrhoids, constipation and cough). Each program includes three modules: a hypertextual version of the protocol, an interactive scheme of it, and an educational tool called Encounter Simulator, that trains the pharmacist about the protocol by means of simulated pharmacist-customer interactions. The testing of these applications with 84 community pharmacists offers positive results in terms of expectations, program characteristics and perceived usefulness.

Common Cold↗

[Smoking initiation in students: cross-sectional and longitudinal study of predictive factors].

BACKGROUND: This study examines the evolution of tobacco use among schoolchildren in sixth and seventh grades in Barcelona (11-13 years) and identifies smoking risk factors through cross-sectional and follow-up analysis. POBLATION AND METHODS: The cohort consists of 1,003 students attending 13 schools who served as control units for a study assessing the effects of a school-based addictive substances prevention program. Participants answered the same questionnaire in 1990 and 1991. Risk factors for the experimentation and for regular smoking are studied through cross-sectional and prospective studies. RESULT: In a year, smokers increase from 9.7% to 18.9% and regular smokers rise from 1.1% to 5.5%. The initial cross-sectional analysis finds stronger associations than the follow-up one. Some variables loose their significance in the longitudinal analysis. Among non-smokers, the strongest predictors to emerge are intention to smoke, the belief that smoking is fun, peers, siblings and mother consumption, and being male; however girls appear to consolidate the consumption more than boys among the cohort of triers. CONCLUSIONS: Tobacco use prevalences are consistent with other studies developed in our city. Social environment emerges as an important predictor; friends, siblings and mothers tobacco use and gender are the main risk factors.

Adolescent↗

Immunodeficiency associated with anorexia nervosa is secondary and improves after refeeding.

Several studies have addressed the question of starvation effects on immune function by means of changes in lymphocyte subsets, cytokine induction or lymphocyte activation. Anorexia nervosa (AN) patients are severely malnourished and contradictory results have been obtained regarding the accompanying immunodeficiency, including its assignation as a part of the primary nervous disorder. In the present work, an extensive immunological function examination was carried out on 40 AN patients who were compared with a control group of 14 healthy girls. The AN patients were also classified according to their nutritional status (by the Body Mass Index: BMI), this being critical for a better understanding of these secondary immunodeficiency bases. Moreover, another immune system study was performed on five patients after refeeding. Lymphocyte subsets and function, cytokine induction and peripheral blood concentrations, and innate as well as humoral immunity were evaluated. Deregulation in the cytokine network, owing to the interaction of the central nervous (CNS) and immune systems, seems to be the initial immune alteration in AN immunodeficiency but it has not been disproved that the immunodeficiency is a direct consequence of the original psychiatric perturbation. Spontaneous high levels of circulating interleukin-1beta (IL-1beta) and tumour necrosis factor-alpha (TNF-alpha) have been observed; this is probably one of the causes of the anomalies found in the T-cell subpopulations (mainly the naive CD4+CD45RA+ reduction and the cytotoxic CD8+ increase) and T-cell activation status (mainly the down-regulation of the CD2 and CD69 activation pathways). This finally leads to an impairment, not only in T-cell function but also in T-cell to B-cell co-operation. The AN specificity of these results is confirmed by the fact that these immune alterations improve after refeeding and when nutritional status becomes less critical, which also suggests that AN immunodeficiency is indeed secondary to malnutrition.

Adolescent↗

Role of UEV-1, an inactive variant of the E2 ubiquitin-conjugating enzymes, in in vitro differentiation and cell cycle behavior of HT-29-M6 intestinal mucosecretory cells.

By means of differential RNA display, we have isolated a cDNA corresponding to transcripts that are down-regulated upon differentiation of the goblet cell-like HT-29-M6 human colon carcinoma cell line. These transcripts encode proteins originally identified as CROC-1 on the basis of their capacity to activate transcription of c-fos. We show that these proteins are similar in sequence, and in predicted secondary and tertiary structure, to the ubiquitin-conjugating enzymes, also known as E2. Despite the similarities, these proteins lack a critical cysteine residue essential for the catalytic activity of E2 enzymes and, in vitro, they do not conjugate or transfer ubiquitin to protein substrates. These proteins constitute a distinct subfamily within the E2 protein family and are highly conserved in phylogeny from yeasts to mammals. Therefore, we have designated them UEV (ubiquitin-conjugating E2 enzyme variant) proteins, defined as proteins similar in sequence and structure to the E2 ubiquitin-conjugating enzymes but lacking their enzymatic activity (HW/GDB-approved gene symbol, UBE2V). At least two human genes code for UEV proteins, and one of them, located on chromosome 20q13.2, is expressed as at least four isoforms, generated by alternative splicing. All human cell types analyzed expressed at least one of these isoforms. Constitutive expression of exogenous human UEV in HT-29-M6 cells inhibited their capacity to differentiate upon confluence and caused both the entry of a larger proportion of cells in the division cycle and an accumulation in G2-M. This was accompanied with a profound inhibition of the mitotic kinase, cdk1. These results suggest that UEV proteins are involved in the control of differentiation and could exert their effects by altering cell cycle distribution.

Amino Acid Sequence↗

IMASIS. A multicenter hospital information system--experience in Barcelona.

The present study aimed to analyse physicians' attitudes towards IMASIS, and their potential influence on IMASIS medical record project. IMAS (Institut Municipal d'Assistència Sanitària) is the health care organisation of the City Council of Barcelona. IMAS hospital information system (IMASIS), which first applications were designed and implemented in 1984, is currently facing a new phase, focused on clinical information management. Our approach included a personal interview with representatives of every hospital unit, and a self-administered questionnaire distributed to every clinician. Both provided a worthy insight into the cultural patterns to be considered in the HIS implementation process. Moreover, the results helped to define the subsequent steps of IMASIS evolution. Our experience is proposed as a tool to assess clinical informations systems from a user point of view.

Adult↗

Three-dimensional modelling of human cytochrome P450 1A2 and its interaction with caffeine and MeIQ.

The three-dimensional modelling of proteins is a useful tool to fill the gap between the number of sequenced proteins and the number of experimentally known 3D structures. However, when the degree of homology between the protein and the available 3D templates is low, model building becomes a difficult task and the reliability of the results depends critically on the correctness of the sequence alignment. For this reason, we have undertaken the modelling of human cytochrome P450 1A2 starting by a careful analysis of several sequence alignment strategies (multiple sequence alignments and the TOPITS threading technique). The best results were obtained using TOPITS followed by a manual refinement to avoid unlikely gaps. Because TOPITS uses secondary structure predictions, several methods that are available for this purpose (Levin, Gibrat, DPM, NnPredict, PHD, SOPM and NNSP) have also been evaluated on cytochromes P450 with known 3D structures. More reliable predictions on alpha-helices have been obtained with PHD, which is the method implemented in TOPITS. Thus, a 3D model for human cytochrome P450 1A2 has been built using the known crystal coordinates of P450 BM3 as the template. The model was refined using molecular mechanics computations. The model obtained shows a consistent location of the substrate recognition segments previously postulated for the CYP2 family members. The interaction of caffeine and a carcinogenic aromatic amine (MeIQ), which are characteristic P450 1A2 substrates, has been investigated. The substrates were solvated taking into account their molecular electrostatic potential distributions. The docking of the solvated substrates in the active site of the model was explored with the AUTODOCK programme, followed by molecular mechanics optimisation of the most interesting complexes. Stable complexes were obtained that could explain the oxidation of the considered substrates by cytochrome P450 1A2 and could offer an insight into the role played by water molecules.

Amino Acid Sequence↗

Synthesis, affinity at 5-HT2A, 5-HT2B and 5-HT2C serotonin receptors and structure-activity relationships of a series of cyproheptadine analogues.

Cyproheptadine is a drug that shows high affinity for type 2 (5-HT2) receptors. We studied a series of compounds obtained by modification of the tricyclic system of Cyp (dibenzocycloheptadiene): 2f (thioxanthene), 2g (xanthene), 2h (dihydrodibenzocycloheptadiene), 2j (diphenyl), 2i (fluorene), and 3b (phenylmethyl). Their activities at the rat cerebral cortex 5-HT2A receptor were (pKi +/- S.E.M.): 8.80 +/- 0.11 (Cyp), 8.60 +/- 0.07 (2f), 8.40 +/- 0.02 (2g), 8.05 +/- 0.03 (2h), 7.87 +/- 0.12 (2j), 6.70 +/- 0.02 (2i) and 6.45 +/- 0.02 (3b); those at the rat stomach fundus 5-HT2B receptor (pA2 +/- S.E.M.) were: 9.14 +/- 0.25 (Cyp), 8.49 +/- 0.07 (2f), 7.58 +/- 0.58 (2g), 7.02 +/- 0.14 (2h), 6.07 +/- 0.20 (2j), and undetectable (2i, 3b): and those at the pig choroidal plexus 5-HT2C receptor (pKi +/- S.E.M.) were: 8.71 +/- 0.08 (Cyp), 8.68 +/- 0.01 (2f), 8.58 +/- 0.20 (2g), 7.95 +/- 0.05 (2h), 7.57 +/- 0.04 (2j), 6.98 +/- 0.04 (2i) and 6.63 +/- 0.20 (3b). The slopes did not differ significantly from unity. The compounds exhibited the same order of activities at every type of receptor, and the most active molecules presented certain steric (butterfly conformation of the tricyclic system) and electrostatic (proton affinity on the top of the central rings) patterns. It is concluded that the activity of cyproheptadine derivatives at 5-HT2 receptors is related to these molecular features, which make feasible a common disposition to interact with all three 5-HT2 subtypes.

Animals↗

VATAM: developing consensus in validation of health telematics applications.

VATAM (Validation of Telematics Applications in Medicine) is an EU supported project in the Health care sector of the Telematics Application Programme. Its objective is to assist other health telematics projects by providing a platform for discussion on validation, eventually resulting in 'guidelines for validation of telematics applications in medicine'. The VATAM work can be subdivided into three phases: the inventory phase (1996) in which information is collected on validation approaches in the Telematics Application Programme, previous efforts and expertise. The dissemination phase (1997) will be used to extend and adapt the framework developed in the inventory phase, through cooperation with other projects The experiences phase (1998) in which the projects are actually applying validation, will be used by VATAM to validate the VATAM methodology. VATAM has finished the inventory phase successfully and is now working on the dissemination phase by--among others--establishing contacts with other projects, and providing information on the inventory through the World Wide Web (URL: http:(/)/www-vatam.unimaas.nl). This paper discusses the approach adopted and the proposed VATAM framework to structure the large variety of validation approaches.

Computer Communication Networks↗

In vitro cytotoxicity of guanylhydrazones (MGBG and PGBG) on cultured Chinese hamster ovary cells.

Guanylhydrazones, methylglyoxal bis(guanylhydrazone) (MGBG) and a new compound, phenylglyoxal bis(guanylhydrazone) (PGBG), interfering with polyamine biosynthesis have considerable potential for the use as antiparasitic and antitumor agents. The effect of these drugs on the cellular viability of Chinese hamster ovary cells was examined by in vitro neutral red assay. The time exposure and metabolic influence was studied. These compounds have a dose- and time-dependent cytotoxicity. The IC50 values were of 597.22 micrograms/ml and 1.77 micrograms/ml for MGBG after 3 and 24 h of incubation, respectively, and 380.50 micrograms/ml for PGBG after 24 h of incubation. The PGBG treatment during 3 h had no cytotoxic effect when the concentrations were lower than 3000 micrograms/ml. With the cytotoxicity assay used, we observed that the presence of S9 in cultured medium did not influence the cytotoxicity of these compounds.

Adenosylmethionine Decarboxylase↗