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Clinical pharmacology of selective COX-2 inhibitors.

The discovery of cyclooxygenase (COX)-2 has provided the rationale for the development of a new class of nonsteroidal antiinflammatory drugs (NSAIDs), the selective COX-2 inhibitors (denominated coxibs), with the aim of reducing the gastrointestinal (GI) toxicity associated with the administration of NSAIDs by virtue of COX-1 sparing. Rofecoxib and celecoxib are the first selective COX-2 inhibitors approved by the FDA and EMEA for the treatment of rheumatoid arthritis (RA), osteoarthritis (OA) and for relief of acute pain. Rofecoxib has been shown to spare COX-1 activity ex vivo, in platelets and gastric mucosa, when administered at therapeutic doses or above. In a large clinical trial, COX-2 inhibitors have been demonstrated to halve the incidence of serious upper GI events vs a nonselective NSAID. Recently, other selective COX-2 inhibitors with different COX-1/COX-2 selectivity and pharmacokinetic features have been developed, i.e. valdecoxib, parecoxib, etoricoxib and lumiracoxib. The improved biochemical selectivity of valdecoxib vs celecoxib in vitro (COX-1/COX-2 ratio: 60 vs 30, respectively) may be clinically relevant leading to an improved GI safety. Interestingly, parecoxib, a pro-drug of valdecoxib, is the only injectable coxib. Etoricoxib, showing only a slightly higher COX-2 selectivity than rofecoxib in vitro (COX-1/COX-2 ratio: 344 vs 272, respectively), has been reported to cause a similar specific COX-2 inhibition ex vivo that should translate into comparable GI safety. Lumiracoxib, the most selective COX-2 inhibitor in vitro (COX-1/COX-2 ratio: 400), is the only acidic coxib. It has been hypothesized that this pecular chemical feature may lead to an enhanced concentration in inflammatory sites that may translate into an improved clinical efficacy. The results of clinical trials have shown that coxibs have a comparable clinical efficacy and renal toxicity and an improved GI safety vs nonselective NSAIDs. Whether the different pharmacodynamic and pharmacokinetics features of the various coxibs will produce detectable differences in efficacy and toxicity remains to be evaluated in appropriate comparative randomized clinical studies.

Animals↗

The facilitation of selective attention in preschoolers.

Allocation of attention was examined on a selective attention task in which some items were relevant (i.e., their locations should be remembered) and some were irrelevant. 100 4- and 5-year-olds formed 4 experimental conditions and 1 control group. 3 experimental groups had 1 added feature to aid selectivity (fewer stimuli, increased perceptual salience of the difference between relevant and irrelevant stimuli, or extra reminders of the locations of relevant and irrelevant stimuli). The fourth experimental condition included all features. A story and explicit instructions identified which objects were relevant. During study times, children opened doors (marked with cages or houses) of a box to reveal animals or household objects. Selectivity (opening mainly relevant doors) was high, compared to previous studies using no story with 6-year-olds, even in the control condition. Selectivity increased significantly beyond the level in the control condition only when all facilitative features were combined. Selectivity was not significantly related to recall. This outcome, in conjunction with previous research, suggests a lag between the production of a strategy and its facilitative effect on recall.

Attention↗

A comprehensive approach to percutaneous injury prevention during phlebotomy: results of a multicenter study, 1993-1995.

OBJECTIVE: To examine a comprehensive approach for preventing percutaneous injuries associated with phlebotomy procedures. DESIGN AND SETTING: From 1993 through 1995, personnel at 10 university-affiliated hospitals enhanced surveillance and assessed underreporting of percutaneous injuries; selected, implemented, and evaluated the efficacy of phlebotomy devices with safety features (ie, engineered sharps injury prevention devices [ESIPDs]); and assessed healthcare worker satisfaction with ESIPDs. Investigators also evaluated the preventability of a subset of percutaneous injuries and conducted an audit of sharps disposal containers to quantify activation rates for devices with safety features. RESULTS: The three selected phlebotomy devices with safety features reduced percutaneous injury rates compared with conventional devices. Activation rates varied according to ease of use, healthcare worker preference for ESIPDs, perceived "patient adverse events," and device-specific training. CONCLUSIONS: Device-specific features and healthcare worker training and involvement in the selection of ESIPDs affect the activation rates for ESIPDs and therefore their efficacy. The implementation of ESIPDs is a useful measure in a comprehensive program to reduce percutaneous injuries associated with phlebotomy procedures.

Attitude of Health Personnel↗

Neuronal bases of categorization in starling song.

Previous studies on starling song had shown that different categories of songs are produced and discriminated. In the present study, both playback experiments in the field and electrophysiological recordings of single cells in field L (main central auditory area) were used in order to understand the perceptual bases of category recognition. In both cases, synthesized variants were used where different parameters could be changed. A method of backward correlation was used in order to visualize and determine the precise elements in song towards which the neurons responded. A high proportion of neurons was found that responded selectively to particular features in the species-specific songs. Series of neurons with similar or complementary selectivities were found. We did not find any 'category-detector' as such but key elements appeared both in neuronal selectivity and in behavioural discriminations. The data favour the propositions of the pattern recognition theory, with a multiple feature model.

Acoustic Stimulation↗

Altered acoustic cue discrimination in Broca's and conduction aphasics.

The present investigation explored the acoustic cue discrimination abilities of eight Broca's and four conduction aphasic patients and nine normal controls. A word-discrimination test was used to assess the subjects' ability to discriminate selected acoustic cues for distinctive features of phonemes. The words differed from one another by a selected minimal feature, such as stop-gap duration, duration of fricative noise, direction and extent of final format transition, or relative location of friction noise in the spectrum. Results indicated that performance for normal and aphasic subjects was poorer for altered temporal subtest items than for altered spectral subtest items. Within the spectral subtest, fewer Broca's aphasics than conduction aphasics passed the items, while 90% of the normals passed. Within the temporal subtest, fewer conduction aphasics than Broca's aphasics passed the items, while 75% of the normal subjects passed this subtest. The results support previous research suggesting that deficiencies in auditory processing of selected acoustic cues are not limited to Wernicke's aphasic individuals but may be found to a varying degree in several aphasic groups.

Adult↗

Proliferative lesions of prostate: a multivariate approach to differential diagnosis.

Prostatic needle biopsies from 142 patients were studied: 61 cases were "benign", 19 atypical small acinar proliferation, 31 high-grade prostatic intraepithelial neoplasia, and 31 adenocarcinoma. Using univariate analysis of 46 previously described morphological features, 16 variables were selected, which were followed by multivariate discriminant analysis. Of these parameters, seven (glandular fusion, crystalloids, nucleolomegaly, papillary architecture, visibility of basal cell layer, areas of normal luminal cell nucleus/cytoplasm ratio and areas of high luminal cell nucleus/cytoplasm ratio) remained significant in discriminating the groups. Multivariate analysis selected a small panel of histological features as those most helpful in the differential diagnosis of proliferative lesions in prostate biopsies.

Adenocarcinoma↗

Pharmacotherapy for major depression with melancholic features: relative efficacy of tricyclic versus selective serotonin reuptake inhibitor antidepressants.

The effectiveness of tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) were contrasted in endogenous/melancholic depression. By reviewing Hamilton Depression Rating data from controlled trials, the data indicate that TCAs are consistently more effective than the SSRIs. Despite the wide use of SSRIs in the treatment of depression, it seems reasonable that clinicians subtype their depressed patients and treat melancholic patients first with a course of TCAs. For melancholic patients who have not responded to a SSRI, pharmacotherapeutic alternatives include (1) a TCA alone; (2) TCA augmentation of the SSRI, or (3) lithium augmentation of the SSRI.

Antidepressive Agents, Tricyclic↗

Optimal selection of wavelet-packet-based features using genetic algorithm in pathological assessment of patients' speech signal with unilateral vocal fold paralysis.

Unilateral vocal fold paralysis (UVFP) is one of the most severe types of neurogenic laryngeal disorder in which the patients, due to their vocal cords malfunction, are confronted by some serious problems. As the effect of such pathologies would be significantly evident in the reduced quality and feature variation of dysphonic voices, this study is designed to scrutinize the piecewise variation of some specific types of these features, known as energy and entropy, all over the frequency range of pathological speech signals. In order to do so, the wavelet-packet coefficients, in five consecutive levels of decomposition, are used to extract the energy and entropy measures at different spectral sub-bands. As the decomposition procedure leads to a set of high-dimensional feature vectors, genetic algorithm is invoked to search for a group of optimal sub-band indexes for which the extracted features result in the highest recognition rate for pathological and normal subjects' classification. The results of our simulations, using support vector machine classifier, show that the highest recognition rate, for both optimized energy and entropy measures, is achieved at the fifth level of wavelet-packet decomposition. It is also found that entropy feature, with the highest recognition rate of 100% vs. 93.62% for energy, is more prominent in discriminating patients with UVFP from normal subjects. Therefore, entropy feature, in comparison with energy, demonstrates a more efficient description of such pathological voices and provides us a valuable tool for clinical diagnosis of unilateral laryngeal paralysis.

Adolescent↗

Attention-sensitive visual event-related potentials elicited by kinetic forms.

Previous event-related potential (ERP) studies have shown that selectively attending to a relevant stimulus feature was associated with selection negativity (SN) components. The present study aimed at investigating the ERP indices of attentional selection based on forms defined by motion (kinetic forms). ERPs were recorded from subjects who attended selectively to sequentially presented kinetic forms of bars in one visual field and detected occasional tilted bar targets. Two kinds of kinetic forms were used as the visual stimuli in separate experiments. The main findings were that spatial attention enhanced the amplitude of early ERP components 1 and N1 as well as the late component N2. Topographic maps of voltage and low resolution electromagnetic tomography (LORETA) of the dN2 wave (difference waveform between N2 under attended condition and N2 under unattended condition) suggested an origin in the right occipitotemporal cortex. According to its timing and morphology, the dN2 wave was considered to be an endogenous ERP (like the SN) and was interpreted as reflecting attentional facilitation of the processing of forms defined by motion primarily involving the right occipitotemporal areas.

Adult↗

Selection and fusion of color models for image feature detection.

The choice of a color model is of great importance for many computer vision algorithms (e.g., feature detection, object recognition, and tracking) as the chosen color model induces the equivalence classes to the actual algorithms. As there are many color models available, the inherent difficulty is how to automatically select a single color model or, alternatively, a weighted subset of color models producing the best result for a particular task. The subsequent hurdle is how to obtain a proper fusion scheme for the algorithms so that the results are combined in an optimal setting. To achieve proper color model selection and fusion of feature detection algorithms, in this paper, we propose a method that exploits nonperfect correlation between color models or feature detection algorithms derived from the principles of diversification. As a consequence, a proper balance is obtained between repeatability and distinctiveness. The result is a weighting scheme which yields maximal feature discrimination. The method is verified experimentally for three different image feature detectors. The experimental results show that the fusion method provides feature detection results having a higher discriminative power than the standard weighting scheme. Further, it is experimentally shown that the color model selection scheme provides a proper balance between color invariance (repeatability) and discriminative power (distinctiveness).

Algorithms↗

Selective tuning of cortical sound-feature processing by language experience.

In 'quantity-languages', such as Japanese or Finnish, sound duration is linguistically relevant. We showed that quantity-language speakers were superior to speakers of a non-quantity language in discriminating the duration of even non-speech sounds. In contrast, there was no group difference in the discrimination of sound frequency. This result, obtained both by behavioural and neural indices at attentive and automatic levels of processing, indicates precise feature-specific tuning of the auditory-cortex functions by the mother tongue.

Acoustic Stimulation↗

Selection of retroviral reverse transcription primer is coordinated with tRNA biogenesis.

Initiation of retrovirus reverse transcription requires the selection of a tRNA primer from the intracellular milieu. To investigate the features of primer selection, a human immunodeficiency virus type 1 (HIV-1) and a murine leukemia virus (MuLV) were created that require yeast tRNA(Phe) to be supplied in trans for infectivity. Wild-type yeast tRNA(Phe) expressed in mammalian cells was transported to the cytoplasm and aminoacylated. In contrast, tRNA(Phe) without the D loop (tRNA(Phe)D(-)) was retained within the nucleus and did not complement infectivity of either HIV-1 or MuLV; however, infectivity was restored when tRNA(Phe)D(-) was directly transfected into the cytoplasm of cells. A tRNA(Phe) mutant (tRNA(Phe)UUA) that did not have the capacity to be aminoacylated was transported to the cytoplasm and did complement infectivity of both HIV-1 and MuLV, albeit at a level less than that with wild-type tRNA(Phe). Collectively, our results demonstrate that the tRNA primer captured by HIV-1 and MuLV occurs after nuclear export of tRNA and supports a model in which primer selection for retroviruses is coordinated with tRNA biogenesis at the intracellular site of protein synthesis.

Base Sequence↗

[Structural features of the brains of rats selected for their thresholds of neuromuscular excitability].

As a result of selection of rats possessing a high threshold of neuro-muscular exitability in comparison with rats possessing a low threshold of neuro-muscular exitability, certain changes take place in the structures that are connected with the learning process: the visual cortex is wider, volumes of the pyramidal cells in the fields CA1 and CA3 of the hippocampus are increased, density of the glial elements in the fornix is essentially increased and that of neurons in the septal nucleus is decreased.

Animals↗

[Analysis of the effects of selected polymers on morpho-dynamic features of rat hepatocytes].

The thesis shows the results of the research on the influence of the film-form polymers on the hepatocytes in rats. The polymers were composed of polyethylene (PE), polyvinyl chlorides (P-25, P-47), polyesters (A, B, E) and irradiated L7 collagen. The aim of the research was to establish whether the changes in the specific morpho-dynamic characteristics-which prove the changes in the hepatocyte metabolic activity in rats-could be used to assess the usability of the above mentioned polymers for medicine. The evaluation of the research findings was analysed on the basic of the stereometric methods and factor analysis. On the basic of the obtained results, polyvinyl chlorides P-25 and P-47 have been evaluated most favourably as far as their possible application in medicine is concerned, whereas polyester E shows the most negative characteristics for such an application.

Animals↗

Relevant information for decision support systems: application in cardiology.

In the paper we show information theory tools for extracting relevant information for decision support systems from medical databases. Each proposed algorithm for selecting a set of relevant features has a specific score function defined by means of information-theoretical characteristics. Then algorithms are classified according to the primary criterion, that can lead to influence-preferring algorithms or weight-preferring algorithms. Other type of classification can be based on the way of selecting of features as forward, backward or combined algorithms. The software package called CORE (COnstitution and REduction) that supports the process of selection of features relevant for a decision making problem is described. Application on data about 1417 middle age men collected in the twenty years lasting interventional study of cardiovascular risk factors in middle aged men and for decision support in primary care are shown. However, the methodology presented is applicable for any decision making problem where extracting relevant information from data is required.

Adult↗

[Selection of Penicillium chrysogenum--producer of penicillin with several valuable technologic features].

The efficiency of the routine methods for improvement of P. chrysogenum providing specific selection by several features with testing one of them was studied. A new highly potent strain of P. chrysogenum producing phenoxymethylpenicillin was isolated. The strain is characterized by a shorter fermentation cycle, lower viscosity of the fermentation broth and capacity for synthesizing 32,600 units/ml of phenoxymethylpenicillin under industrial conditions (in a lactose medium) by the 97th hour of the cultivation in fermenters with energy consumption of 1.3 kW. The increased amylolytic activity of the strain and the decreased viscosity of the fermentation broth provided using of the fermentation media containing 3.5 per cent of corn meal.

Anti-Bacterial Agents↗