New 4-Amino-7,8-dimethoxy-5h-pyrimido[5,4-b]indole Derivatives: Synthesis and Studies as Inhibitors of Phosphodiesterases

A series of 4-amino-7,8-dimethoxy-5h-pyrimido[5,4-b]indole derivatives has been synthesized. These compounds resemble carbazeram and other pyridazino compounds with activity in the cardiovascular system. Some of these new compounds possess inotropic activity (Table 2), with a complementary effect on the inhibition of different CGI-PDE (Table 3). The most active compounds 5, 6d , and 7 also possess activity as vasodilators (Table 4). Some of these new compounds inhibit blood platelet aggregation induced by ADP and AA and are active as inhibitors of human platelet PDEs (Tables 5 and 6).     

Effects of incorrect computer-aided detection (CAD) output on human decision-making in mammography

RATIONALE AND OBJECTIVES: To investigate the effects of incorrect computer output on the reliability of the decisions of human users. This work followed an independent UK clinical trial that evaluated the impact of computer-aided detection(CAD) in breast screening. The aim was to use data from this trial to feed into probabilistic models (similar to those used in "reliability engineering") which would detect and assess possible ways of improving the human-CAD interaction. Some analyses required extra data; therefore, two supplementary studies were conducted. Study 1 was designed to elucidate the effects of computer failure on human performance. Study 2 was conducted to clarify unexpected findings from Study 1. MATERIALS AND METHODS: In Study 1, 20 film readers viewed 60 sets of mammograms (30 of which contained cancer) and provided "recall/no recall" decisions for each case. Computer output for each case was available to the participants. The test set was designed to contain an unusually large proportion (50%) of cancers for which CAD had generated incorrect output. In Study 2, 19 different readers viewed the same set of cases in similar conditions except that computer output was not available. RESULTS: The average sensitivity of readers in Study 1 (with CAD) was significantly lower than the average sensitivity of read-ers in Study 2 (without CAD). The difference was most marked for cancers for which CAD failed to provide correct prompting. CONCLUSION: Possible automation bias effects in CAD use deserve further study because they may degrade human decision-making for some categories of cases under certain conditions. This possibility should be taken into account in the assessment and design of CAD tools.     

Higher professional education as a means for development in nursing

The author reflects on how higher training contributes to development in Nursing, understanding by this term the discipline but also the set of professionals which exercise it. Therefore, the author analyzes those elements which are part of professional development; be this intrinsic, professional discourse, excellent professional exercise, market dominance, syndical capacity or representation. The author ends her article with a very simple proposal: make a world full of care, with a recognition of successes, a correction of errors and a deepening of attitudes.     

A model for forecasting emergency hospital admissions: effect of environmental variables

This study modeled patterns and trends in emergency hospital admissions at a hospital in Madrid, Spain. The purpose was to quantify qualitative associations that have been detected between such admissions and a number of environmental variables. The following data were used: unscheduled daily emergency hospital admissions, Madrid air pollution data, and meteorological data. Time-series analysis was performed, with Box-Jenkins modeling. A multivariate model was constructed, incorporating the different causes of admissions and the respective environmental variables. Statistically significant associations were found between hospital admissions and other variables, indicating relationships with temperature, relative humidity, and mean daily tropospheric ozone concentrations. Whereas the effect of heat on admissions was short term, that of cold was in evidence from the second week. The association with ozone showed a seven-day lag and basically manifested itself as an influence on admissions for circulatory disease.     

Heat waves in Madrid 1986–1997: effects on the health of the elderly

OBJECTIVE: The objective of this paper is to analyse and quantify the effects exerted on summer mortality by extremes of heat, particularly among persons aged 65-74 and 75 years and over, groups in which mortality is higher. METHODS: The study included the period from 1 January 1986 to 31 December 1997, for all people aged over 65 years resident in Madrid, based on mortality due to all causes except accidents (ICD-9 codes 1-799), and circulatory (390-459) and respiratory (460-487) causes. Meteorological variables analysed were: daily maximum temperature, daily minimum temperature and relative humidity. To control the effect of air pollution on mortality we considered the daily mean values of sulphur dioxide (SO2), total suspended particulate (TSP), nitric oxides (NOx), nitrogen dioxide (NO2) and tropospheric ozone (O3). Univariate and multivariate ARIMA models were used. Box-Jenkins pre-whitening was performed. RESULTS: The results yielded by this study indicate a mortality increase up to 28.4% for every degree the temperature rises above 36.5 degrees C, with particular effect in women over the age of 75 years and circulatory-cause mortality. The first heat wave that leads to the greatest effects on mortality, due to the higher number of susceptible people and the duration of the heat wave, show an exponential growth in mortality. Furthermore, low relative humidity enhances the effects of high temperature, linking dryness to air pollutants, ozone in particular. CONCLUSIONS: Since a warmer climate is predicted in the future, the incidence of heat wave should increase, and more comprehensive measures, both medical and social, should be adopted to prevent the effects of extreme heat on the population, particularly the elderly.     

Field evidence that roe deer (Capreolus capreolus) are a natural host for Ehrlichia phagocytophila

Samples of blood, spleen and legs from 112 culled roe deer (Capreolus capreolus) were collected from nine sites widespread in the United Kingdom. The prevalence of infection with Ehrlichia phagocytophila was determined by serology and polymerase chain reaction. Means of 58% of 102 plasma or serum samples were seroreactive by IFA, 38% of 84 blood samples and 29% of 82 spleen samples were positive by PCR. Ticks on legs of 71 roe deer were Ixodes ricinus larvae, nymphs and adults and 83% of legs were infested. Numbers of ticks corresponded positively to the percentage of samples positive for E. phagocytophila by serology and PCR for different sampling sites. Ixodes ricinus nymphs collected from the vegetation at one site with infected deer were analysed for infection with E. phagocytophila by examination of Feulgen stained salivary glands. Of 135 nymphs 5% were infected. These results confirm that roe deer are commonly parasitized by both E. phagocytophila and its vector tick in such a way that it is likely to be an important natural mammalian reservoir of E. phagocytophila.     

Identification of a novel mutation (Leu282Arg) of the human presenilin 1 gene in Alzheimer''s disease

Many different mutations, causative of Alzheimer's disease, have been found in the presenilin-1 gene (PS-1). We have developed a screening method based on denaturing gradient gel electrophoresis (DGGE), which allows the mutational analysis of the whole exon 9 of PS-1. Upon the screening of a Spanish sample of early onset familial Alzheimer disease cases, we have found a novel mutation in the PS-1 gene. The mutation (a T to G transition) results in a change of the amino acid at position 282 of the presenilin protein from leucine to arginine. This mutation is located in the hydrophobic domain number 7 (exon 9) close to the site of physiological cleavage processing. The average of onset of the affected members of this family is 43±5 years, and the average age of exitus of affected members is 56±3 years. The possibility to determine the specific pathologic mechanisms of this mutation is now open.