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At least 775 records · Page 43Linked to original sources
PubMed2001

High-performance liquid chromatography/tandem mass spectrometry for the quantitative analysis of a novel taxane derivative (BAY59-8862) in biological samples and characterisation of its metabolic profile in rat bile samples.

A sensitive, specific, accurate and reproducible high-performance liquid chromatography (HPLC) analytical method was developed and validated for the quantification of the novel oral taxane analogue BAY59-8862 in mouse plasma and tissue samples. A fully automated solid-phase extraction procedure was applied to the plasma after internal standard (IS) addition, with only 0.2 mL volume of the sample loaded on a CN-Sep-pak cartridge. In the case of the tissues a very simple acetonitrile extraction was used to recover BAY59-8862 and its internal standard from liver. The procedure for the quantification of BAY59-8862 and its IS (IDN5127) is based on high-performance liquid chromatography/ion spray-tandem mass spectrometry, operating in selected ion monitoring mode. The retention times of BAY and IS were 7.21 and 10.36 min, respectively. In both plasma and tissue specimens the assay was linear in the range 50-5000 ng/mL (ng/g). The overall precision and accuracy were assessed on three different days. The results for plasma were within 6.1% (precision) and between 99 and 112% (accuracy), and for the liver samples within 7.3% and between 104 and 118%, respectively. The LOD was 5 ng/mL and 20 ng/g in the plasma and liver, respectively. In addition, the biliary excretion of the compound in rats was studied. The study showed that an oxidative chemical reaction was the preferred metabolic pathway for biliary excretion, and two sets of mono- and dihydroxylated metabolites were detected by LC/ISP-MS/MS experiments. With this method, BAY59-8862 pharmacokinetic was determined in mice. The combined results demonstrate that the methodology can be considered a valid approach to conduct pharmacokinetic and metabolic studies during preclinical and clinical investigations.

Animals↗
PubMed2002

An empirical comparison of substance and alcohol dependence patterns in the homeless in Madrid (Spain) and Los Angeles (CA, USA).

BACKGROUND: Alcohol and drug use continue to figure heavily in the experience of the contemporary homeless population. The comparison among pattern of use plays a central role in the cross-cultural view of this topic. This article shows the results of comparing the data concerning alcohol and other drug abuse and dependence among the homeless population of Madrid (Spain) and Los Angeles (USA). METHODS: Data come from two studies carried out independently in each city. Both studies used a comparable methodology which included the same inclusion and diagnostics criteria, representative sampling methods and similar diagnostic structured interviews. In the present study, the data from these two studies are combined in a unique database which allows global and item-to-item comparison between the two studies. RESULTS: The results show different sociodemographic profiles for each city. Once controlled for the sociodemographic differences (age, education, current employment status and marital status), the life and 12-month prevalence rates of alcohol and other drug disorders (DSM-III-R) are also different. There are also significant differences in social, emotional and health problems associated with the consumption of alcohol and other drugs. The Madrid and LA samples also present differences in the time patterns of the beginning of the homelessness situation and the onset of alcohol- and drug-related disorders. CONCLUSIONS: The pattern of results is discussed in the light of the differences in both socioeconomic and cultural among Madrid and Los Angeles which might explain, in turn, differences in the homelessness situation as well as in the alcohol and other drug use patterns.

Adolescent↗
PubMed2005

Substrate hydroxylation in methane monooxygenase: quantitative modeling via mixed quantum mechanics/molecular mechanics techniques.

Using broken-symmetry unrestricted density functional theory quantum mechanical (QM) methods in concert with mixed quantum mechanics/molecular mechanics (QM/MM) methods, the hydroxylation of methane and substituted methanes by intermediate Q in methane monooxygenase hydroxylase (MMOH) has been quantitatively modeled. This protocol allows the protein environment to be included throughout the calculations and its effects (electrostatic, van der Waals, strain) upon the reaction to be accurately evaluated. With the current results, recent kinetic data for CH3X (X = H, CH3, OH, CN, NO2) substrate hydroxylation in MMOH (Ambundo, E. A.; Friesner, R. A.; Lippard, S. J. J. Am. Chem. Soc. 2002, 124, 8770-8771) can be rationalized. Results for methane, which provide a quantitative test of the protocol, including a substantial kinetic isotope effect (KIE), are in reasonable agreement with experiment. Specific features of the interaction of each of the substrates with MMO are illuminated by the QM/MM modeling, and the resulting effects upon substrate binding are quantitatively incorporated into the calculations. The results as a whole point to the success of the QM/MM methodology and enhance our understanding of MMOH catalytic chemistry. We also identify systematic errors in the evaluation of the free energy of binding of the Michaelis complexes of the substrates, which most likely arise from inadequate sampling and/or the use of harmonic approximations to evaluate the entropy of the complex. More sophisticated sampling methods will be required to achieve greater accuracy in this aspect of the calculation.

Acetonitriles↗
PubMedDate not supplied

Explaining the utilisation of dental care. Experiences from the Finnish dental market.

In this paper a model based on the theory of demand for health and of supplier inducement is developed to explain the utilisation of dental care. Of special interest are the effects of money price and various forms of inducement. It is also explored how the results are affected if different model specifications and estimation techniques are applied and what is the most appropriate one, when utilisation is measured by dental expenditure. The data come from a sample of 1779 employees, whose dental expenditure is refunded from 0 to 99.75%. Other things being equal, the methodological choices make a clear difference in parameter estimates. Only a log-linear two-part model and two-part tobit with selectivity were suitable for explaining expenditure and produced quite similar results. Money price elasticity was small, but significant (-0.069). General and personal inducement appear to have a considerable effect on utilisation, but did not have any systematic connection with dentist/population ratio.

Adult↗
PubMed2002

X-ray absorption spectroscopy to watch catalysis by metalloenzymes: status and perspectives discussed for the water-splitting manganese complex of photosynthesis.

Understanding structure-function relations is one of the main interests in the molecular biosciences. X-ray absorption spectroscopy of biological samples (BioXAS) has gained the status of a useful tool for characterization of the structure of protein-bound metal centers with respect to the electronic structure (oxidation states, orbital occupancies) and atomic structure (arrangement of ligand atoms). Owing to progress in the performance characteristics of synchrotron radiation sources and of experimental stations dedicated to the study of (ultra-dilute) biological samples, it is now possible to carry out new types of BioXAS experiments, which have been impracticable in the past. Of particular interest are approaches to follow biological catalysis at metal sites by characterization of functionally relevant structural changes. In this Article, the first steps towards the use of BioXAS to 'watch' biological catalysis are reviewed for the water-splitting reactions occurring at the manganese complex of photosynthesis. The following aspects are considered: the role of BioXAS in life sciences; methodological aspects of BioXAS; catalysis at the Mn complex of photosynthesis; combination of EXAFS and crystallographic information; the freeze-quench technique to capture semi-stable states; time-resolved BioXAS using a freeze-quench approach; room-temperature experiments and 'real-time' BioXAS; tasks and perspectives.

Absorptiometry, Photon↗
PubMedDate not supplied

Examining bowel preparation before flexible sigmoidoscopy.

AIM: To investigate bowel preparation for a flexible sigmoidoscopy, particularly the procedure for the administration of a phosphate enema and patient expectation to 'wait as long as they can' before the urge to rush to the toilet. METHOD: A survey approach was used with a questionnaire recording the time to toilet after the enema and level of bowel clearance. RESULTS: Over half of participants (24 of 40) chose to use the toilet immediately. Bowel clearance was reported as good in 32 of the 40 participants and side-effects were reduced. CONCLUSION: Giving patients choice when to visit the toilet after an enema improved their experience and achieved good bowel clearance for the procedures. Further research should be undertaken due to the small size of the study.

Adult↗
PubMed1988

NIOSH epidemiologic studies of pregnancy outcomes.

The conduct of pregnancy outcome studies among occupationally exposed populations is a relatively new research area with many methodologic and pragmatic difficulties. This paper reviews the experience of conducting reproductive epidemiologic research at the National Institute for Occupational Safety and Health (NIOSH). The advantages and disadvantages of the three epidemiologic study types most often conducted at NIOSH are discussed: 1) surveillance studies, 2) descriptive studies, and 3) industrywide studies. Some of the problems inherent in the conduct of industrywide investigations are illustrated in a discussion of a reproductive outcome study of video display operators currently underway. These problems include sample size, referent availability, exposure and outcome validation, tracing, analytic methods, and cost.

Cluster Analysis↗
PubMed2004

Methodology study on evaluation of radon flux from soil in China.

Radon flux rate from soil is one of the most important factors for the evaluation of environmental radon levels. The objective of our study is to make a rough estimation of the nationwide radon flux rate from soil in China. Considering the applicability to the large area and complex distribution of soil types in China, a simple model was established. To test the model, field measurements on radon flux rate totally in 47 points from different areas were carried out from spring to summer in 2003. Laboratory experiments of each soil sample on related soil properties, such as radium contents, water contents, soil dry bulk density and soil texture were performed simultaneously. Approximately 30% of the samples had very consistent calculated values with their measured values, their relative errors were less than 0.25. In spite of the large uncertainties in the model which is influenced by so many factors, the considerable validation of the model can be shown. Based on the discussion of distribution of the errors as well as the reasons causing the errors, a trial modification of the model was made. A modification function looked necessary when soil water content was <10%.

Algorithms↗
PubMed2003

Parameter scanning ultrafiltration: rapid optimisation of protein separation.

High-resolution fractionation of proteins using ultrafiltration is feasible only at highly optimised conditions. Conventional process optimisation methodology demands both time and material. Pulsed sample injection ultrafiltration has been suggested as a rapid process optimisation technique. In the present work the scope of this technique is further extended by "parameter scanning ultrafiltration," which involves continuous change of a process parameter (e.g., pH, salt concentration). The time and material consumption are thus further reduced. The technique was validated using different proteins and membranes. Sieving coefficients at different pH and salt concentration were compared to those obtained in fixed parameter ultrafiltration experiments. As fractionation case studies the separation of monoclonal antibody from bovine serum albumin and separation of human IgG from human serum albumin were examined.

Alemtuzumab↗
PubMed1991

Origins of childhood fears: an evaluation of Rachman's theory of fear acquisition.

This study explored Rachman's (1977) theory of fear acquisition in a large sample of Australian and American children and adolescents. Participants completed a questionnaire that addressed different pathways of fear acquisition for 10 highly prevalent fears. The majority of children attributed the onset of their fears to vicarious and instructional factors, although these indirect sources of fear were often combined with direct conditioning experiences. Also examined were effects for gender, age, and nationality. Boys and preadolescents were found to report more direct and vicarious experiences than girls or adolescents. Effects due to nationality were minimal. Methodological limitations attendant to self-reports were acknowledged.

Adolescent↗
PubMed1985

ELISA for the detection of the lymphokine soluble immune response suppressor.

Murine soluble immune response suppressor (SIRS) is a product of Ly 2+ suppressor T cells which is activated to SIRSox by peroxide produced by macrophages. SIRSox inhibits cell division by normal and transformed cell lines and antibody secretion by B lymphocytes. Rat monoclonal anti-SIRS antibodies were developed to determine if ELISA methodology could replace bioassays for quantitation of SIRS in biological samples. Purified SIRS, applied to nitrocellulose, was detected with an avidin-biotin-horseradish peroxidase system. This ELISA was capable of detecting pg quantities of SIRS and detected SIRS after fractionation by high performance liquid chromatography. However, SIRS in crude supernatant fluids was undetectable by this method, presumably due to the small percentage of SIRS protein in relation to total protein in these samples. Thus, a competitive ELISA was adopted which, in initial experiments, detected SIRS in impure sources. This competitive ELISA may be useful in evaluating the presence or absence of SIRS in various biological samples.

Animals↗
PubMed2005

A unified framework for unraveling the functional interaction structure of a biomolecular network based on stimulus-response experimental data.

We propose a unified framework for the identification of functional interaction structures of biomolecular networks in a way that leads to a new experimental design procedure. In developing our approach, we have built upon previous work. Thus we begin by pointing out some of the restrictions associated with existing structure identification methods and point out how these restrictions may be eased. In particular, existing methods use specific forms of experimental algebraic equations with which to identify the functional interaction structure of a biomolecular network. In our work, we employ an extended form of these experimental algebraic equations which, while retaining their merits, also overcome some of their disadvantages. Experimental data are required in order to estimate the coefficients of the experimental algebraic equation set associated with the structure identification task. However, experimentalists are rarely provided with guidance on which parameters to perturb, and to what extent, to perturb them. When a model of network dynamics is required then there is also the vexed question of sample rate and sample time selection to be resolved. Supplying some answers to these questions is the main motivation of this paper. The approach is based on stationary and/or temporal data obtained from parameter perturbations, and unifies the previous approaches of Kholodenko et al. (PNAS 99 (2002) 12841-12846) and Sontag et al. (Bioinformatics 20 (2004) 1877-1886). By way of demonstration, we apply our unified approach to a network model which cannot be properly identified by existing methods. Finally, we propose an experiment design methodology, which is not limited by the amount of parameter perturbations, and illustrate its use with an in numero example.

Computational Biology↗
PubMed2004

Evaluation of patient satisfaction with nursing care: quantitative or qualitative approach?

The purpose of this study was to assess the results, along with the feasibility, applicability and relative merits of paradigm triangulation in the field of nursing care quality by conducting, concurrently, a quantitative and a qualitative study of patient satisfaction. The sample consisted of 200 randomly selected in-patients from two large Greek metropolitan hospitals. Highest ratings were assigned to the technical aspects of care, whilst information delivery items were associated with the lowest ratings. Qualitative analysis revealed a perception of nurses as weak against organisational limitations as the core theme underlying all categories of patients' complaints with nursing care. Seven more common themes were identified. The interpersonal aspect of care was central to patients' experience. The combination of qualitative and quantitative methodology appeared to contribute to the completeness of description and understanding of the phenomenon.

Adult↗
PubMed2003

SMART amplification maintains representation of relative gene expression: quantitative validation by real time PCR and application to studies of alcoholic liver disease in primates.

The small quantities of tissue available for most studies of human disease are a significant limitation for meaningful gene expression profiling. The Atlas Switch Mechanism At the 5' end of Reverse Transcript (SMART) probe amplification kit uses as little as 50 ng of total RNA to generate complex cDNA probes for DNA array and other analyses. However, the extent to which this attractive methodology maintains representation of relative gene expression has not been quantified. In this study, we demonstrate using real-time quantitative PCR analysis that the relative expression levels of a range of low- to high-abundance mRNAs are retained after SMART amplification independent of transcript abundance and full-length transcript, coding region and PCR product size. Using this technology, a mean amplification of 3800-fold was achieved in human liver samples, greatly enhancing the ability to perform replicate DNA array experiments. Probes generated with the SMART amplification method were used to detect increased expression of genes involved with inflammation, fibrosis, xenobiotic metabolism, immune function, oxidant stress and endothelium in liver from the baboon model of alcoholic liver disease.

DNA, Complementary↗
PubMed1987

Validity and reliability of the Experience-Sampling Method.

To understand the dynamics of mental health, it is essential to develop measures for the frequency and the patterning of mental processes in every-day-life situations. The Experience-Sampling Method (ESM) is an attempt to provide a valid instrument to describe variations in self-reports of mental processes. It can be used to obtain empirical data on the following types of variables: a) frequency and patterning of daily activity, social interaction, and changes in location; b) frequency, intensity, and patterning of psychological states, i.e., emotional, cognitive, and conative dimensions of experience; c) frequency and patterning of thoughts, including quality and intensity of thought disturbance. The article reviews practical and methodological issues of the ESM and presents evidence for its short- and long-term reliability when used as an instrument for assessing the variables outlined above. It also presents evidence for validity by showing correlation between ESM measures on the one hand and physiological measures, one-time psychological tests, and behavioral indices on the other. A number of studies with normal and clinical populations that have used the ESM are reviewed to demonstrate the range of issues to which the technique can be usefully applied.

Activities of Daily Living↗
PubMed1982

A case report of data monitoring experience: the nocturnal oxygen therapy trial.

The monitoring of accumulating data in a clinical trial is a challenging endeavor, yet one that must be undertaken to fulfill the ethical responsibility to the participating subject. This paper, using the Nocturnal Oxygen Therapy Trial as an example, discusses three issues often faced by data monitoring committees. These are (1) the multiplicity of outcomes, (2) decisions about extension of the patient recruitment period in order to achieve specified sample size goals, and (3) problems in monitoring survival data with a lag in the reporting of events. The decision process can be quite complex and existing statistical methodology can at best serve as a guide in this decision process.

Clinical Trials as Topic↗
PubMed2003

Fine-needle aspiration cytology vs. core biopsy in the diagnosis of breast lesions.

Fine-needle aspiration cytology (FNAC) is an established, highly accurate method for diagnosing breast lesions. However, in recent years there has been increased use of core biopsy (CB) in this setting. The aim of this study was to evaluate the accuracy of FNAC and compare the quality assessment parameters of FNAC and CB in palpable and nonpalpable breast lesions. Data regarding FNAC, CB, and excision biopsy (EB) diagnoses were retrieved from the archives of our department. A total of 4,367 FNAC samples from the years 1999-2001 was reviewed. Of these, corresponding histology results were available for 1,275 lesions, of which 1,248 were primary breast epithelial lesions (788 EB, 199 CB, 261 EB+CB). All cases were analyzed for sensitivity and specificity of FNAC. Cases with both FNAC and CB were compared and quality assessment parameters were calculated using the methodology detailed in the National Health Service Breast Screening Program guidelines. High specificity and sensitivity, as calculated for satisfactory specimens, were achieved with the use of both FNAC and CB. False-positive and false-negative diagnoses were seen in 7/404 (1.7%) and 45/635 (7.1%) of biopsy-proven specimens sampled by FNAC. The corresponding values for CB were 0% and 5.7%, respectively. Inadequate sampling (15.1%) with use of FNAC was particularly seen in collagenous lesions and in submitted specimens sampled by physicians lacking experience with the FNAC procedure. FNAC is a valuable method, although moderately less sensitive than CB. CB is the preferred method for preoperative diagnosis when sampling FNAC provides scarce material and suspicion of a fibrotic and collagenous lesion such as lobular carcinoma and radial scar arises. FNAC is most accurate when experienced cytologists are available and when immediate assessment by professionals is performed for evaluation of material adequacy, so that additional aspirations can be done when needed.

Adenocarcinoma↗