Over the counter drugs. Telematics will be useful in providing information.
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Communication↗
Biomedical subjects
F Sanz
Publications and source records attributed to F Sanz.
Cytotoxicity and mutagenicity of 6-aminonicotinamide in Chinese hamster ovary cells.
A strong teratogen-6-aminonicotinamide (6-AN)-was tested for its ability to induce cytotoxicity and mutagenicity in Chinese hamster ovary (CHO) cells. Tests were performed in the presence and absence of a metabolic activation system (S-9 mix). Cytotoxicity was evaluated in CHO cells by the total protein content. The two single-gene mutation systems in CHO cells have been investigated. Both involve evaluating the response of the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus and specific inhibitors of the cellular (Na2+K+)-ATPase using 6-thioguanine and ouabain as selective agents, respectively. From our results, 6-AN showed a higher cytotoxic effect at concentrations over 1 x 10(-1) mg/ml. Cytotoxicity was significantly different with and without S-9 mix. 6-AN was cytotoxic per se, however, when 6-AN was biotransformed, in the presence of S-9 mix no biological activity (cytotoxic) was detected. Non-significant mutagenic activity was detected with 6-AN in the presence and in the absence of the metabolic activation system.
6-Aminonicotinamide↗
Toxicity of potential irritants in mammalian cells in vitro.
Four bioactive materials were tested for their ability to produce toxicity in vitro in two cell lines: rabbit corneal cells (SIRC) and human fibroblasts. These compounds are widely used by industries, causing toxic effects to ecosystems and particularly having an impact on human health. Different chemicals were chosen which were structurally unrelated: triethanolamine, zinc pyrithione, sodium lauryl sulfate, and oleamine. Cytotoxicity was evaluated measuring the total protein content (inhibition of cell growth). Results indicated that zinc pyrithione produced the highest inhibition of cell growth when two cell lines were treated in the two doses tested. The lowest cytotoxic effect was observed with oleamine. Triethanolamine and sodium lauryl sulfate produced a similar cytotoxic effect in Fe cells, although sodium lauryl sulfate revealed higher inhibition of cell growth than triethanolamine on SIRC cells. From these results, it can be concluded that some products as triethanolamine and zinc pyrithione should be observed in future special toxicological studies.
Amines↗
Acute toxicity of several organophosphorous insecticides and protection by cholinergic antagonists and 2-PAM on Artemia salina larvae.
The acute toxicity of chlorpyrifos, methylchlorpyrifos, parathion and methylparathion to three age classes of Artemia salina was determined. In general, A. salina 24-h old was less sensitive to these organophosphorous insecticides (OPI) than A. salina 48-h old and A. salina 48-h old was significantly more tolerant than A. salina 72-h old, in contrast, chlorpyrifos was equally toxic to A. salina 48- and 72-h old. There were some differences among the three age classes of A. salina in the relative order of toxicity of OPI tested. The rank order of toxicity to A. salina 48-h old was methylparathion < parathion < methyl-chlorpyrifos < chlorpyrifos, while to A. salina 24- and 72-h old it was methylparathion = parathion < methyl-chlorpyrifos < chlorpyrifos. The protective effect of the cholinergic antagonists atropine, hexamethonium, pirenzepine and 11-(2-((diethyl-amino)methyl)-1-piperidinylacetyl)-5, 11-dihydro-6H-pyrido(2,3-b)-(1,4)-benzodiazepine-6-one (AF-DX 116) and a cholinesterase-reactivating oxime 2-pyridine aldoxime methochloride (2-PAM) on the mortality due to four selected OPI in Artemia salina 24-h old was investigated. The lethal action of OPI tested was completely prevented by pretreatment of Artemia salina 24-h old with 2-PAM (10(-5) M) and atropine (10(-4 )M). However no concentration of hexamethonium, pirenzepine or AF-DX 116 protected 100% of the animals poisoned by LC84 of the OPI selected, maximum protection obtained was 71 to 88%. In contrast, the maximum inhibition of mortality obtained with AF-DX 116 pretreatment was about 55% because this compound was used at concentrations which were non toxic to control Artemia salina. Atropine, hexamethonium, pirenzepine, AF-DX 116 and 2-PAM afforded 50 % protection (IC50) of Artemia salina against mortality by LC84 of the OPI selected at concentrations in the range of 6.62x10(-7)-1.6x10(-6) M, 2. 38x10(-4)-2.05x10(-3)M, 8.91x10(-7)-1.24x10(-6) M, 9.66x10(-8)-1. 34x10(-7 )M, and 1.95x10(-8)-2.73x10(-8 )M, respectively. Pretreatment of atropine plus 2-PAM to determine whether this combination afforded greater inhibition of the lethality induced by four OPI tested than pretreatment with either atropine or 2-PAM alone was investigated. Atropine (10(-5) M) in combination with 2-PAM (10(-7 )M) inhibited completely the acute toxicity of all OPI tested, while the pretreatment with atropine (10(-6) M) plus 2-PAM at the same concentration gave a inhibition of mortality (about 62%) significantly greater than each antagonist alone (about 14 and 46%, respectively).
Animals↗
Differential effects of 2'-deoxyguanosine on peripheral blood mononuclear cell proliferation in healthy donors and Hashimoto's thyroiditis patients.
The aim of this study was to determine possible differences in peripheral blood mononuclear cells (PBMC) proliferation of healthy donors and Hashimoto's thyroiditis patients and whether a statistical approach to cell proliferation analysis might be used to discern the differences. The effect of a wide range of 2'-deoxyguanosine (dGuo) concentrations (0-1250 microM) on the mitogen-induced proliferation of PBMC was studied in healthy donors and Hashimoto's thyroiditis patients. Activity levels of purine nucleoside phosphorylase (PNP) and adenosine deaminase (ADA) in PBMC were also measured. For the first time in a study of these models of dGuo toxicity in vitro, the analysis of polynomial trends of orders from 1 to 7 was applied to evaluate cell proliferation. A dose-dependent inhibition of mitogen-induced PBMC proliferation was observed in both groups. Data for linear trend established that PBMC from Hashimoto's thyroiditis patients were more sensitive to dGuo toxicity than PBMC from healthy donors. A positive quadratic trend at low dGuo doses was found in the cell proliferation of Hashimoto's thyroiditis patients. A decrease in PNP activity (P < 0.025) and an increase in ADA activity (P < 0.005) was observed in PBMC of Hashimoto's thyroiditis group. The differences in PBMC proliferation subjected to dGuo toxicity between the two groups could be related with the distinct pattern of purine salvage enzymes observed.
Adenosine Deaminase↗
[Informatics in medical schools and postgraduate education centers for health professionals. Survey on the situation in Spain].
BACKGROUND: Informatics is acquiring an increasing relevance in the medical profession. METHODS: During the year 1993, a survey was carried out at the medical schools (MS) and postgraduate education centres (PEC) in Epidemiology, Public Health and Health Administration of Spain, on the available computer infrastructure and the teaching activities. The percentages of respondents were 81 at the MS and 100 at the PEC. RESULTS: 81% of the MS and 100% of the PEC had a computer laboratory, mainly equipped with personal computers with MS-DOS operating system. The use of general purpose applications was predominant. The number of students using the computer laboratory was very variable (5-300 per day). 48% of the MS organized courses on microcomputer applications. 66% of the MS included subjects related with informatics in the new curricula. CONCLUSIONS: Use of computers in the Spanish MS is heterogeneous. Compared with the Nord-American MS, they do not usually use applications of computer-assisted-instruction. The use of the computers at the PEC is much more generalized.
Curriculum↗
[Evaluation of the use of statistical techniques in original articles published in the Medicina Clínica during 3 decades (1962-1992)].
BACKGROUND: The incorrect use of statistical techniques in medical articles may seriously compromise the validity of conclusions. This finding otherwise is relatively common. METHODS: A total of 84 original articles published in Medicina Clínica between 1962 and 1992 were reviewed with the aim of assessing the use and appropriateness of statistical techniques. The use of statistics, the quality of the analyses performed, and the inaccuracy of the statistical techniques used were evaluated. We also classified the statistical techniques most commonly used throughout the study period. RESULTS: There was a marked increase in the use of statistical analyses, from 8.3% in 1962 to 83.3% in 1992. It should be noted that a substantial part of this increase has been due to the use of inferential tests, which accounted up to 70% in the sample of articles published in 1992. This finding, however, was associated with an increase in the number of incorrect analyses. The most common statistical errors included assumption of normal distribution of data (with no mention of the test used to confirm this fact), mistake between standard deviation and standard error of the mean, inadequate inferences on the basis of the sample size, inappropriate use of the Student's t test, chi-square test, nonparametric tests or multivariate analyses as well as misunderstanding of linear regression and correlation. CONCLUSIONS: High standards in scientific research have been accompanied by a significant increase in the number of clinical studies with statistical analysis of data. However, this apparently favorable situation has been associated with an increase in the number of inaccurate analyses. It has been found that sophisticated statistical tests are rarely used in articles published in Medicina Clínica.
Chi-Square Distribution↗
[Errors in bibliographic references: a retrospective study in Medicina Clinica (1962-1992)].
BACKGROUND: Misspellings of transcription or the copy of references of articles published in the literature without verifying the information with the original document may be the cause of incorrect citations. The purpose of this study was to determine the accuracy of citations to journal articles in 1962 to 1992 volumes of Medicina Clínica. METHODS: A method of systematic sampling was used to choose five references for each of the 12 original articles per year selected at 5-year intervals (1962, 1967, 1972, 1977, 1982, 1987, 1992). In the final sample of 420 references, errors in the six standard bibliographic elements--authors' names, article title, journal title, year, volume number, and page numbers--were analyzed. Major errors were defined when inaccuracies prevented identification of the cited article. RESULTS: Of the total 368 references verified, 132 (35.86%) were error free and the remaining 236 (64, 13%) were inaccurate. Multiple errors were found in 45% of cases. The mean number of errors per references was 1.13. Twelve references were incorrect, 221 errors were found in the authors' name, 131 in the title of the article, 14 in the name of the journal, 5 in the year of publication, 12 in the number of the volume, and 22 in the initial or final pages of the article. Major errors were detected in 94 (22.54%) cases and minor errors in 323 (77.45%). There were no statistically significant differences in the variation of the overall percentage of errors throughout the study period. CONCLUSIONS: A high rate of citation errors has been also documented in a Spanish medical journal. The importance of reference verification should be emphasized and authors should exercise more care in preparing bibliographies of their articles.
Bibliographies as Topic↗
Influence of nutrition, thyroid hormones, and rectal temperature on in-hospital mortality of elderly patients with acute illness.
The present study was undertaken to investigate the interrelation of nutrition, core temperature, and thyroid function and their influence on survival of patients aged > or = 70 y admitted to the hospital with acute conditions. Sixty-seven patients entered the study. Nutritional state, thyroid function, rectal temperature, and the APACHE II score were recorded at admission. The patients were followed until death or hospital discharge. Patients with a serum albumin concentration < 35 g/L showed a lower triiodothyronine (T3) concentration, a higher reverse triiodothyronine (rT3) concentration, and a higher death rate. Prior weight loss (> or = 10%) did not influence thyroid status but increased the mortality rate. Eleven patients were hypothermic (< 36.5 degrees C) and had a higher mortality, lower total T3 concentration, and higher rT3 concentration than the normothermic or hyperthermic subjects. Serum albumin, body weight, and total T3 concentration were higher in survivors (n = 51) than in nonsurvivors (n = 16). Ongoing weight loss and hypoalbuminemia at admission are highly prevalent in elderly people with acute disease, and influence their clinical outcome. Mild hypothermia was a good predictor of death. Hypoalbuminemia and hypothermia were associated with low T3 and high rT3 values.
APACHE↗
IMASIS computer-based medical record project: dealing with the human factor.
The Institut Municipal d'Assistència Sanitària (IMAS) is a health care organization in Barcelona, comprising two general hospitals, a psychiatric hospital, a surgical clinic, a geriatric center, some primary care clinics, and a research institute. Since 1984, IMAS has been engaged in creating a multicenter integrated hospital information system (IMASIS). Currently, IMASIS offers the possibility to manage administrative data, laboratory results, pathology and cytology reports, radiology reports, and pharmacy inpatient orders; it also shares this information on-line among IMAS centers. IMASIS users may also work with a word processor, a spreadsheet, a database, or a statistical package and have access to MEDLINE. A second phase of IMASIS development began in December 1993 focused on clinical information management. The goal was to move towards an integrated multimedia medical record [1]. As a first step, the implementation experiences of the most advanced hospital information systems around the world were studied. Some of these experiences detected behavioral, cultural, and organizational factors [2] as the main sources of delay, or even failure, in HIS projects. A preliminary analysis to define such factors, assess their potential impact, and introduce adequate measures to deal with them seemed unavoidable before structuring of the project. In our approach to physician attitudes analysis, two survey techniques were applied. First, every hospital service head was contacted to schedule an interview, with either a service representative or a group of staff physicians and residents. The aim was to provide detailed information about project objectives and collect personal opinions, problems encountered in the current HIS, and specific needs of every medical and surgical specialty (including imaging needs). Every service head was asked to distribute a questionnaire among all clinicians, which assessed frequency of use of IMASIS current applications, user's satisfaction level, problems to be solved in utilization of the system, errors detected in the systems' database, and the personal interest in participating in the IMASIS project. The questionnaire was also intended to be a tool to monitor IMASIS evolution. Our study showed that medical staff had a lack of information about the current HIS, leading to a poor utilization of some system options. Another major characteristic, related to the above, was the feeling that the project would negatively affect the organization of work at the hospitals. A computer-based medical record was feared to degrade physician-patient relationship, introduce supplementary administrative burden in clinicians day-to-day work, unnecessarily slow history taking, and imply too-rigid patterns of work. The most frequent problems in using the current system could be classified into two groups: problems related to lack of agility and consistency in user interface design, and those derived from lack of a common patient identification number. Duplication of medical records was the most frequent error detected by physicians. Analysis of physicians' attitudes towards IMASIS revealed a lack of confidence globally. This was probably the consequence of two current features: a lack of complete information about IMASIS possibilities and problems faced when using the system. To deal with such factors, three types of measures have been planned. First, an effort is to be done to ensure that every physician is able to adequately use the current system and understands long-term benefits of the project. This task will be better accomplished by personal interaction between clinicians and a physician from the Informatics Department than through formal teaching of IMASIS. Secondly, a protocol for evaluating the HIS is being developed and will be systematically applied to detect both database errors and systemUs design pitfalls. Finally, the IMASIS project has to find a convenient point for starting, to offer short-term re
Attitude of Health Personnel↗
[Original articles published in Medicina Clínica during 30 years (1962-1992): number of authors, interval between acceptance and publication and bibliographic references].
BACKGROUND: To study different aspects of original articles published in Medicina Clínica (Barcelona) over a 30-year period (1962-1992), with special emphasis on references. METHODS: We selected 12 articles per year at 5-year intervals (1962, 1967, 1972, 1977, 1982, 1987, 1992) using a systematic sampling procedure. The following variables were assessed: number of authors, interval between acceptance of the manuscript and publication in the journal, total number of references, language, document type, and name of the journal. RESULTS: The mean (+/- standard deviation) number of authors showed a statistically significant increase (ANOVA; F = 13.666; p = 0.0001) from 1.83 +/- 0.71 in 1962 to 6.41 +/- 1.97 in 1992. The interval between acceptance and publication decreased from 315.72 +/- 20.48 days in 1982 to 206.16 +/- 89.23 in 1992 (ANOVA, F = 6.074; p = 0.0058). A total of 1816 references were found (24.2 references per article). English was the language of publication most commonly found (76.76%) followed by Spanish (12.6%). There was a statistically significant increase in the use of references corresponding to English articles over the study period (chi 2 = 314.431; p = 0.0001). A significant change was also observed in the type of document use (chi 2 = 143.996; p = 0.0001); references from journals increased from 73.51% in 1962 to 91.40% in 1992. In addition, 50.46% of the articles were published in only 7.84% of the journals. Eight journals devoted to internal medicine (1.79% of all journals) included 23.46% of the references. CONCLUSIONS: The number of authors has shown a significant increase during the study period. The time elapsed between acceptance and publication has decreased significantly. Spanish authors acquired information mostly from the English literature. Articles published in journals are also mostly used as references. A large percentage of references consisted of articles published in core general journals. These journals accumulate a remarkable percentage of the information.
Authorship↗
Synthesis and atypical antipsychotic profile of some 2-(2-piperidinoethyl)benzocycloalkanones as analogues of butyrophenone.
Four new 2-(2-piperidinoethyl)benzocycloalkanone derivatives, 20-23, were prepared and evaluated as potential antipsychotic agents in receptor binding assays for dopamine (DA) and 5-HT2A receptors and in functional and behavioral screens. Their affinities for D2 receptors (Ki's in the nanomolar range: 46.7-70.7) and D1 receptors (Ki's in the micromolar range: 1.09-2.81) were slightly lower than that showed by haloperidol (Ki's in the nanomolar range: 5.01 and 97.72 for D2 and for D1 receptors, respectively). The ratio of pKi's values D1/D2 showed that the new molecules are more D2-selective than haloperidol. In contrast, in the [3H]-ketanserin binding assays the new compounds had greater affinity for 5-HT2A receptors (pKi's 7.89-8.60) than haloperidol (pKi 7.70) and in functional studies, endothelium-stripped aorta rings, the pA2 values (6.75-8.12) were slightly lower than that of ketanserin (8.87) in suppressing serotonin-induced contractions. The pKi's for D2 binding (and to a lesser extent pKi's for D1 binding) tend to be greater among typical (classical) than among atypical antipsychotics, while these two classes of antipsychotics exhibit no difference with regard to pKi's for 5-HT2A receptors. The ratios of pKi's for 5-HT2A/D2 receptors may be useful for rapid screening of new compounds, and its potential induction of extrapyramidal symptoms (ratio values > 1.12 were predictive of an atypical antipsychotic profile). The new molecules had a ratio value in the range 1.08-1.20, while haloperidol showed a ratio of 0.93. In the behavioral screening tests, the new molecules showed antagonist activity of amphetamine-inducing hyperactivity and apomorphine-induced climbing (predictive tests for antipsychotic activity). In the catalepsy test (predictive test for induction of extrapyramidal symptoms), the values obtained were in accordance with an atypical antipsychotic drugs profile.
Amphetamine↗
Validation of the medical expert system RENOIR.
RENOIR is an expert system developed to assist the diagnosis of 37 diseases of connective tissue and inflammatory arthropathies. Precise diagnosis of rheumatic diseases implies great uncertainty and there is no gold standard with which to compare the expert system output. To overcome this problem a set of clinical cases was submitted to RENOIR and its diagnoses were compared with those of clinicians. Medical records of 81 patients with rheumatic diseases were interpreted by RENOIR and by 12 clinicians at three different expertise levels in rheumatology. Distances between the likelihoods of the 37 considered diseases provided by clinicians and RENOIR were computed as a disagreement measure. Mahalanobis distance was used to correct the collinearity between the possibilities of each pair of diseases. Using the resulting matrices of distances between experts, cluster analyses were carried out to classify RENOIR among human experts. Greater differences between RENOIR and clinicians than among clinicians themselves were not found.
Cluster Analysis↗
Antiserotoninergic activity of 2-aminoethylbenzocyclanones in rat aorta: structure-activity relationships.
The antiserotoninergic activity at the serotonin receptor subtype 2 (5-HT2) of seven new 2-aminoethylbenzocyclanones was determined with respect to serotonin-induced contractions in rat aorta and compared with that of ketanserine (pA2 = 8.87). Competitive antagonism was observed in six compounds (6.72 < or = pA2 < or = 8.12). Three-dimensional structures and molecular electrostatic potential distributions of ketanserine and 2-aminoethylbenzocyclanones were analyzed. Several molecular features correlated with the rank of antiserotoninergic activity. In the case of the cyclanone fragment, the rank of activity was associated with the degree of planarity of the bicyclic system. The steric and electrostatic effects due to the loss of planarity were analyzed. In the case of the amino moiety, activity was associated with a particular spatial pattern defined by the amino nitrogen, the aromatic system, and molecular electrostatic potential minima generated by the oxygen atom.
Animals↗
Cyproheptadine analogues: synthesis, antiserotoninergic activity, and structure-activity relationships.
A series of cyproheptadine related compounds was synthesized and tested pharmacologically. In comparison with cyproheptadine, these compounds do not have a central ring and some contain groups other than N-methyl. Synthesis was carried out with low-valent titanium to generate the exocyclic double bond. The serotoninergic activity of the compounds was determined by standard determination of pA2 (-log of the motor concentration of antagonist required to maintain a constant response when concentration of agonist is doubled) for the inhibition of serotonin-induced contractions in rat stomach fundus. Two of the nitrogen-containing compounds were active, but their activities were lower than that of cyproheptadine. Structure-activity relationships were studied by Mulliken net charges, molecular electrostatic potentials, and conformational analysis; activities are better correlated with electrostatic potentials than with net charges. The decrease in potency of the open cyproheptadine analogues may be due to "dilution" of the active conformer as the result of their conformational flexibility.
Animals↗
MEPSIM: a computational package for analysis and comparison of molecular electrostatic potentials.
MEPSIM is a computational system which allows an integrated computation, analysis, and comparison of molecular electrostatic potential (MEP) distributions. It includes several modules. Module MEPPLA supplies MEP values for the points of a grid defined on a plane which is specified by a set of three points. The results of this program can easily be converted into MEP maps using third-parties graphical software. Module MEPMIN allows to find automatically the MEP minima of a molecular system. It supplies the cartesian coordinates of these minima, their values, and all the geometrical relationships between them (distances, angles, and dihedral angles). Module MEPCOMP computes a similarity coefficient between the MEP distributions of two molecules and finds their relative position that maximizes the similarity. Module MEPCONF performs the same process as MEPCOMP, considering not only the relative position of both molecules but also a conformational degree of freedom of one of them. The most recently developed module, MEPPAR, is another modification of MEPCOMP in order to compute the MEP similarity between two molecules, but only taking into account a particular plane. The latter module is particularly useful to compare MEP distributions generated by pi systems of aromatic rings. MEPSIM can use several wavefunction computation approaches to obtain MEP distributions. MEPSIM has a menu type interface to simplify the following tasks: creation of input files from output files of external programs (GAUSSIAN and AMPAC/MOPAC), setting the parameters for the current computation, and submitting jobs to the batch queues of the computer. MEPSIM has been coded in FORTRAN and its current version runs on VMS/VAX computers.
Drug Design↗
Introducing medical students to medical informatics.
Medical informatics (MI) has been introduced to medical students in several countries. Before outlining a course plan it was necessary to conduct a survey on students' computer literacy. A questionnaire was designed for students, focusing on knowledge and previous computer experience. The questions reproduced a similar questionnaire submitted to medical students from North Carolina University in Chapel Hill (NCU). From the results it is clear that although almost 80% of students used computers, less than 30% used general purpose applications, and utilization of computer-aided search of databases or use in the laboratory was exceptional. Men reported more computer experience than women in each area investigated by our questionnaire but this did not appear to be related to academic performance, age or course. Our main objectives when planning an MI course were to give students a general overview of the medical applications of computers and instruct them in the use of computers in future medical practice. As our medical school uses both Apple Macintosh and IBM compatibles, we decided to provide students with basic knowledge of both. The programme was structured with a mix of theoretico-practical lectures and personalized practical sessions in the computer laboratory. As well as providing a basic overview of medical informatics, the course and computer laboratory were intended to encourage other areas of medicine to incorporate the computer into their teaching programmes.
Computer Literacy↗
[Discovery of a mycelial fungus in a blood culture (Bactec NR-860) from a patient with an implantable reservoir].
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Adult↗