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[The topography and cytoarchitectonic of the diencephalon of the cow (Bos taurus var. domesticus L.). II. The internal structure of the diencephalon of the cow (Bos taurus var. domesticus L.) (author's transl)].

The five parts of the diencephalon of the cow are distinctly separated by fibrous tractuses or plates. The three main tractuses (Fornix, Tractus mamillo-thalamicus and Fasciculus retroflexus) are very strongly developed. Regarding the essential fibrous structures and the cytoarchitectonic features 62 nuclei can be differentiated in either half of the diencephalon, of which the thalamus contains 28 and the hypothalamus 23 nuclei. Epithalamus, Metathalamus and Subthalamus possess 2 big nuclei on each side. The findings are briefly compared with the data on the diencephalic structures of cow, sheep goat, pig and dromedar given in literature.

Animals↗

A model of complete random molecular evolution by recurrent mutation.

A model for random molecular evolution based on recurrent mutation is proposed. Recurrent mutation replaces completely any original base in a nucleotidic site. This occurs if more than four times the number of reproductive cycles equal to the reciprocal of the mutation rate happen; no matter the population size, the number of nucleotides a genome has, or the taxa at which it belongs. The main results are: i) the expected distribution of DNA bases in a site is an isotetranomial distribution, where Adenine (A), Guanine (G), Cytosine (C) and Thymine (T) occur with probability equal to 0.25; ii) the distribution of bases in a site is independent from the distribution of bases in other sites. Several expected consequences that can be contrasted with actual data are generated. Species or operational taxonomic units (OTUs) that evolved in big populations should present distances equal to zero and similarities equal to one. OTUs evolving in small populations should present distances equal to 3/4 and similarities equal to 1/4. Thus, random molecular evolution by recurrent mutation cannot yield a tree at all. The only possible tree is that produced by random fluctuations of distances according to their variances (stochastic tree). Some consequences of the model on the expected primary structure of proteins are also analyzed. There are sufficient generations for any DNA segment evolving apart during the last four hundred million years, to reach those expected base distributions.

Chymotrypsinogen↗

[Development of an anticancer drug in Japan based on a new clinical trial system].

According to the revision of Pharmaceutical Affairs Law in 1996, the GCP has been enacted into the law. Next year the new GCP was established based on the ICH-GCP and it has been active since April, 1997. Though the new GCP makes it possible for the regulatory authorities (Japan, the United States and European Union) to accept clinical trial data mutually, the circumstances of clinical trial in Japan have been required big changes. But considerable investigators/institutions in Japan which carry out clinical trials seem to have not still adapted their usual clinical trial system to a new one yet. At the first time, in this article are described the process of both the revision of Japanese pharmaceutical law and the establishment of the new Japanese GCP. The second, the characteristics of the new Japanese GCP especially about the roles and responsibilities of investigators are discussed. Furthermore approaches of the US FDA for new anticancer drugs development are also described.

Antineoplastic Agents↗

Analysis of cell proliferation data.

When estimating the labeling index is of interest, the design of experiments raises a number of methodological questions: How many cells should be scored? How big a difference in labeling index is likely to be detectable? What is the potential effect of low growth fraction on detecting a treatment effect? What are appropriate ways of expressing treatment effects on labeling index? Data from two labeling index experiments are used to shed light on these questions. The answers to all questions depend on the level of labeling index under consideration: a low frequency of labeling makes it important to count more cells, but this should not be done at the expense of using fewer animals. Detecting differences between treated and control groups when labeling index is low or when growth fraction is low is difficult, and caution must be used when expressing treatment effect as fold increase when labeling index is small.

Analysis of Variance↗

Environmental monitoring of heavy metals in Bulgarian Black Sea green algae.

Fe, Mn, Cu, Pb and Cd concentration distribution in six green macroalgae species from the Bulgarian Black Sea coast were determined. The measurement of these metals was carried out during six seasons from 1996 to 2002 using atomic absorption spectrometry (AAS). Samples were collected from eight different sites-Shabla, Kaliakra, Tuzlata, Ravda, Ahtopol and Sinemoretz. The obtained heavy metal (HM) data (mean values microg/g) for all algae are: 650 +/- 100 for Fe, 184 +/- 15 for Mn, 5.6 +/- 0.5 for Cu, 3.3 +/- 0.3 for Pb and 1.1 +/- 0.2 for Cd. The obtained HM contents indicate that different species demonstrate various degree of metal accumulation and the obtained higher values in the northern sector of the studied zone can be attributed to the discharge influence of the big rivers, entering the Black Sea-Danube, Dnyepr, Dnester and local pollutant emissions. All data show that there is no serious contamination in green macroalgae with heavy and toxic metals along the whole Bulgarian Black Sea coast.

Chlorophyta↗

Effects of prostaglandin E1, dobutamine and placebo on hemodynamic, renal and neurohumoral variables in patients with advanced heart failure.

Excessive neurohumoral activity remains a major burden to the circulation of patients with advanced heart failure. Prostaglandin E1 (PGE1), a balanced i.v. vasodilator, was shown to elicit favorable hemodynamic and clinical effects in this cohort. A prospective randomized parallel group trial was performed to evaluate acute, intermediate and chronic changes in hemodynamic, neurohumoral and renal variables in response to PGE1, dobutamine and placebo. Thirty patients with class III and IV heart failure and low cardiac index (mean 1.9 l/min/m2) two hours after oral drugs including high dose enalapril were included. A 7-day-infusion of PGE1 (16.5 +/- 5 ng/kg/min, range 10 to 20 ng/kg/min, group A n = 10), dobutamine (4.5 +/- 1 micrograms/kg/min, range 2.5 to 5 micrograms/kg/min, group B n = 10) or placebo (saline, group C n = 10) was administered via a central venous access line after stepwise titration until intolerable side effects developed with PGE1 or a 20% increase in cardiac index occurred with dobutamine, which was continued on this dose throughout while PGE1 was maintained on 50% peak dose. Hemodynamic data were collected at baseline, at peak dosages, after 12 hours and after 7 days. Of neurohumoral variables plasma norepinephrine, big endothelin (Big ET) and atrial natriuretic peptide (ANP) were simultaneously evaluated using RIA methods. Renal plasma flow (by paraaminohippurate clearance) and glomerular filtration rate (by iothalamate clearance) was measured prior to and during the infusions (after 12 hours and after 7 days). At peak dose and at 12 hours significant drops from baseline of mean pulmonary artery pressure, pulmonary capillary wedge pressure and systemic vascular resistance were observed which were accompanied by a rise in cardiac output with both PGE1 and dobutamine. These changes were maintained through 7 days when pulmonary vascular resistance levels also fell with both active drugs. Blood pressure did not change throughout, but PGE1 increased heart rate slightly at 12 hrs. Both PGE1 and dobutamine enhanced renal plasma flow after 7 days, but only PGE1 decreased glomerular filtration fraction significantly. Glomerular filtration rate did not change with either drug. PGE1 decreased ANP levels at 12 hrs, and dobutamine increased big ET levels at peak, but decreased big ET at 7 days. Norepinephrine levels were unaffected throughout. Except a slight decrease in right atrial pressure after 7 days placebo did not change any measured variable significantly. Taken together, these data suggest that treatment with PGE1 is as efficacious as low-dose dobutamine in improving cardiac performance and renal perfusion in advanced heart failure. Of importance, no deleterious neurohumoral counterregulation was observed with PGE1.

Alprostadil↗

The big five factors of personality and their relationship to personality disorders.

Articles examining the relationship between the Big Five factors of personality and personality disorders (PDs) are reviewed. A survey of these studies indicates that there is some agreement regarding the relationship between the Big Five and PDs. However, the level of agreement varies and may be a function of instrumentation, the method of report, or how data have been analyzed. Future research should consider the role of peer-ratings, examine the relationship between PDs and the first-order factors of the Big Five, consider dimensions over and above the Big Five as predictors of PDs.

Humans↗

Gender differences in depression: the role of personality factors.

The goal of the study was to determine the association between gender and the Big Five personality factors, and to identify the role of personality factors in the association between gender and depression among adults in the United States. Data were drawn from the Midlife Development in the United States Survey (N=3032). Multivariate analysis of variance (MANOVA) was used to examine gender differences on the Big Five personality factors (i.e. agreeableness, neuroticism, openness to experience, extraversion, and conscientiousness). Multivariate logistic regression analyses were conducted to examine the relation between gender and depression, and to test whether this association is moderated by neuroticism. Levels of neuroticism, agreeableness, extraversion, and conscientiousness were significantly higher among females than among males; in contrast, level of openness to experience was significantly higher among males. Female gender was associated with increased odds of experiencing depression. Results showed that neuroticism played a significant contributory role in the relationship between being female and major depression, though the role of gender remained statistically significant after adjustment. These data suggest that gender differences in personality factors, specifically neuroticism, may play a key role in the well-documented gender difference in depression. Our findings indicate that neuroticism may moderate the association between female gender and increased risk of depression among adults. These findings require replication using longitudinal data.

Adult↗

[Standardizing terminology in pediatric oncology--the basic data set].

BACKGROUND: In the context of more than 20 therapy optimizing clinical trials in pediatric oncology an extensive documentation with a big number of case report forms was developed in the last 20 to 25 years. Across these trials same information is partially captured in different terminological ways, by which documentation about patients in the clinics is made more difficult. METHOD: Terminology of therapy optimizing clinical trials of German Society for Pediatric Oncology and Hematology (GPOH) is standardized by a central "standards committee". RESULT: As a first result the basic data set of GPOH could be revised and made available in internet via http://www.dospo.uni-hd.de. CONCLUSION: A basis of a unique documentation language in pediatric oncology is available for German speaking regions.

Child↗

Neural network in hematopoietic malignancies.

BACKGROUND: In the last 30 years, the automatization of the hematology laboratory has led to a high increase in the number of full blood counts (FBC) performed daily as well as a very high degree in the quality assessment in terms of accuracy and precision. Moreover, the produced data are so many that their full interpretation needs an expert; often these new parameters are not exploited. The new challenge of the hematology laboratory consists in the translation of numerical data and new parameters into clinical meaningful information also offering, when possible, a pre-diagnostic guideline, maintaining similar high quality level also in these new aspects. METHODS: Since the first development of automated cytochemistry for leukocyte differential count, a new efficient pre-microscopic approach to leukemia diagnosis and classification, was made possible at the time of the automated blood cell count. This original method, used by the Bayer hematological H* series and ADVIA120 analyzers, is based on a light assessment of basic cell properties: volume and peroxidase activity (P) in the Perox channel, which is used to differentiate the main leukocyte types according to the different enzyme content and Nuclear density (ND) in the basophil channel, which is used to count basophils and blast cells according the chromatin pattern and to flag the presence of abnormal or immature cells. The simple observation of P and ND two-dimensional cytograms can be used to include any single case in a separate and distinct diagnostic category correlated to FAB and WHO classifications of hematological malignancies. Moreover, on the RBC map, it is possible to obtain some information about the pathological cluster. The simultaneous observation of these three cytograms and the introduction of a simple and quick score provide objective informations on blast lineage, level of myeloid differentiation, chronic versus acute leukemias. Using a simple visual score system, we have reached in a previous study a pre-diagnostic efficiency in 91% of the analyzed samples. ADVIA120 provides cytogram cell distribution at the end of the analytical processes that include the evaluation of 492 signals, the so-called raw data. The working hypothesis is to create a knowledge-based system, an Artificial Neural Network able to directly handle these raw-data for producing classes of diagnostic probability with a high level of efficiency. The Bayer R&D team in Tarrytown has created an ANN software for connecting a set of input data to output through weighted "hidden layers" (i) assessing the 84 ADVIA120 parameter sets to be used, (ii) defining the interim analysis tool for fitting to standard "normal archetypes", (iii) finding a discriminant function normal vs. pathological. We have collected from 22 Italian hematological centers data from peripheral blood of 1000 patients having mainly hematopoietic disorders at diagnosis. RESULTS AND CONCLUSIONS: The ANN has been trained with labeled samples. Same analysis has been performed for constructing the "pathological archetypes". Finally, we have tested the ANN model with a small selected set of the collected pathological samples. The preliminary encouraging results show the high capability of this ANN of clustering signals according to the pre-defined normal as well as pathological archetypes. The next big step is to create an application for discriminating different types of anemia, simply using data from patient's peripheral blood.

Hematologic Neoplasms↗

In vitro release and biosynthesis of tumor ACTH in ectopic ACTH producing tumors.

Tumor tissues obtained from 4 patients with the ectopic ACTH syndrome were studied for release and synthesis of tumor ACTH, using an in vitro incubation system. The effect of various agents on release of tumor ACTH was evaluated in three cases; beta-MSH released and adenosine 3',5'-monophosphate (cyclic AMP) formed in the tissue were determined in one. Biosynthetic experiments using labeled amino acid incorporation were performed in two cases. Secretion of tumor ACTH was significantly stimulated in all cases by crude rat median eminence extract which was also effective in stimulating beta-MSH secretion associated with elevated tissue cyclic AMP levels in one. Addition of cyclic AMP and dibutyryl cyclic AMP caused a significant increase in release of both tumor ACTH and beta-MSH in one. Biogenic amines (norepinephrine and serotonin) markedly elevated tussie cyclic AMP levels without a corresponding increase of hormone release in one. Incorporation experiments revealed that 3H- or 14C-phenylalanine was incorporated into immunoreactive ACTH of a larger molecular size (big ACTH) in both cases by chromatographic procedures. However, biological activity of big ACTH was found to be undetectable by an in vivo steroidogenic assay. A mild tryptic digestion of the big forms resulted in the appearance of little ACTH to which the major radioactive peak shifted. These data suggest that the mechanism of release of tumor ACTH and beta-MSH is very similar to that of the pituitary, and that intracellular cyclic AMP may in part play some role in release of both hormones. It is also suggested that some ectopic ACTH producing tumors predominantly synthesize big ACTH, a possible precursor of ACTH, with less bioactivity.

Adrenocorticotropic Hormone↗

A comparison of statistical methods for clustered data analysis with Gaussian error.

We investigate by simulation the properties of four different estimation procedures under a linear model for correlated data with Gaussian error: maximum likelihood based on the normal mixed linear model; generalized estimating equations; a four-stage method, and a bootstrap method that resamples clusters rather than individuals. We pay special attention to the group randomized trials where the number of independent clusters is small, cluster sizes are big, and the correlation within the cluster is weak. We show that for balanced and near balanced data when the number of independent clusters is small (< or = 10), the bootstrap is superior if analysts do not want to impose strong distribution and covariance structure assumptions. Otherwise, ML and four-stage methods are slightly better. All four methods perform well when the number of independent clusters reaches 50.

Bias↗

Putting the five-factor model into context: evidence linking big five traits to narrative identity.

The study examined relationships between the Big Five personality traits and thematic content extracted from self-reports of life history data. One hundred and five "mature age" university students (M=30.1 years) completed the NEO PI-R trait measure, and the Personality Web Protocol. The protocol examines constituents of identity by asking participants to describe 24 key "attachments" from their life histories (significant events, people, places, objects, and possessions). Participants sorted these attachments into clusters and provided a self-descriptive label for each cluster (e.g., "adventurous self"). It was predicted that the thematic content of these cluster labels would be systematically related to Big Five trait scores (e.g., that labels referring to strength or positive emotions would be linked to Extraversion). The hypothesized links were obtained for each of the Big Five trait domains except Conscientiousness. Results are discussed with a view to broadening our understanding of the Five-Factor Model in relation to units of personality other than traits.

Adult↗

Patient safety with blood products administration using wireless and bar-code technology.

Supported by a grant from the Agency for Healthcare Research and Quality, a University of Iowa Hospitals and Clinics interdisciplinary research team created an online data-capture-response tool utilizing wireless mobile devices and bar code technology to track and improve blood products administration process. The tool captures 1) sample collection, 2) sample arrival in the blood bank, 3) blood product dispense from blood bank, and 4) administration. At each step, the scanned patient wristband ID bar code is automatically compared to scanned identification barcode on requisition, sample, and/or product, and the system presents either a confirmation or an error message to the user. Following an eight-month, 5 unit, staged pilot, a 'big bang,' hospital-wide implementation occurred on February 7, 2005. Preliminary results from pilot data indicate that the new barcode process captures errors 3 to 10 times better than the old manual process.

Blood Banks↗

Plasma levels of endothelin-1, big endothelin-1 and thromboxane following acute pulmonary air embolism.

Acute pulmonary air embolism (APAE) was induced in nine piglets by repeated intravenous bolus injection of room air into a large bore central venous catheter at time=0 min so that the mean pulmonary artery pressure (MPAP) was maintained at two times the baseline value for 4 h. Another five animals served as controls. At time=0, 30, 60, 120, 240 min, circulating arterial plasma levels of endothelin-1 (ET-1), its precursor big ET-1, and thromboxane (Tx), were measured by RIA and EIA, respectively, along with hemodynamics and blood gases. The data showed that following APAE, there was a rapid increase in MPAP and a persistent decrease in Pa(O(2)), while the mean arterial blood pressure and cardiac output remained comparable. Plasma levels of ET-1, big ET-1 and Tx were also increased steadily in these first 4 h. These results showed that during APAE, the resulted changes in the pulmonary vascular and airway tones mediated by these potent mediators could explain the observed pulmonary hypertension and the deterioration of gas exchange.

Acute Disease↗

An evaluation of elongation factor 1 alpha as a phylogenetic marker for eukaryotes.

Elongation factor 1 alpha (EF-1 alpha) is a highly conserved ubiquitous protein involved in translation that has been suggested to have desirable properties for phylogenetic inference. To examine the utility of EF-1 alpha as a phylogenetic marker for eukaryotes, we studied three properties of EF-1 alpha trees: congruency with other phyogenetic markers, the impact of species sampling, and the degree of substitutional saturation occurring between taxa. Our analyses indicate that the EF-1 alpha tree is congruent with some other molecular phylogenies in identifying both the deepest branches and some recent relationships in the eukaryotic line of descent. However, the topology of the intermediate portion of the EF-1 alpha tree, occupied by most of the protist lineages, differs for different phylogenetic methods, and bootstrap values for branches are low. Most problematic in this region is the failure of all phylogenetic methods to resolve the monophyly of two higher-order protistan taxa, the Ciliophora and the Alveolata. JACKMONO analyses indicated that the impact of species sampling on bootstrap support for most internal nodes of the eukaryotic EF-1 alpha tree is extreme. Furthermore, a comparison of observed versus inferred numbers of substitutions indicates that multiple overlapping substitutions have occurred, especially on the branch separating the Eukaryota from the Archaebacteria, suggesting that the rooting of the eukaryotic tree on the diplomonad lineage should be treated with caution. Overall, these results suggest that the phylogenies obtained from EF-1 alpha are congruent with other molecular phylogenies in recovering the monophyly of groups such as the Metazoa, Fungi, Magnoliophyta, and Euglenozoa. However, the interrelationships between these and other protist lineages are not well resolved. This lack of resolution may result from the combined effects of poor taxonomic sampling, relatively few informative positions, large numbers of overlapping substitutions that obscure phylogenetic signal, and lineage-specific rate increases in the EF-1 alpha data set. It is also consistent with the nearly simultaneous diversification of major eukaryotic lineages implied by the "big-bang" hypothesis of eukaryote evolution.

Algorithms↗

[Maternal diabetes--normalized perinatal mortality, but still high fetal growth].

Studies suggest that maternal diabetes can cause both placental insufficiency and exaggerated foetal growth. Pregnant mothers with diabetes have suffered high risk of losing their child. Data from the Medical Birth Registry of Norway show a decrease in the still birth rate from 16th week of gestation from 115.7 per 1,000 in 1967-75 to 12.8 in 1986-92 in the diabetes groups. The relative risks were 7.8 and 1.4 respectively for the two time periods. The early neonatal mortality rate decreased correspondingly. The proportion of Caesarean sections in mothers with diabetes, and the proportion of children with low birth weight or born prematurely also increased in the diabetes group. However, children in the diabetes group were on average still as big at gestational age in the most recent period as in the first period. Our data suggest that the improved metabolic control of maternal diabetes has reduced the occurrence and degree of placental insufficiency, with inherent decreases in mortality and risk of complications, but without reducing the foetal growth-stimulating effect of maternal diabetes.

Birth Weight↗

Questions abound as start-up nears for physician data bank.

The start-up of the National Practitioner Data Bank is only weeks away, but hospitals and physicians still are raising questions about the system's pros and cons. While most laud the data bank's original mission--to prevent practitioners from concealing a history of incompetence--many physicians claim the scope of the system has grown too big and fear abuse of the information.

Attitude of Health Personnel↗