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At least 199 records · Page 11Linked to original sources
PubMedDate not supplied

A new approach to phenotyping disseminated tumor cells: methodological advances and clinical implications.

At the time of primary therapy (surgery, systemic chemotherapy and/or radiation), disseminated tumor cells in the bone marrow can be found in almost one-third of patients with cancer of the breast, ovary, esophagus, stomach, colon, and other solid tumors. Whereas the prognostic impact of the mere presence of these cells is still a matter of debate, it has been shown that expression of tumor-associated antigens in disseminated tumor cells is linked to more aggressive disease. Therefore, further characterization of disseminated tumor cells at the protein and gene level has become increasingly important. To date, the most common detection method for disseminated tumor cells in the bone marrow is an immunocytochemical approach using cytokeratin-directed antibodies for detection of epithelial cells and the APAAP system for their visualization. We have established a new double immunofluorescence technique enabling simultaneous detection, phenotyping, and antigen quantification of disseminated tumor cells. Mononuclear cells from bone marrow are enriched by Ficoll gradient centrifugation and cytospins are prepared. Double immunofluorescence is performed using antibodies against cytokeratins 8/18/19 (mAb A45B/B3) and the uPA receptor CD87 (pAb HU277). CD87 expression is recorded by confocal laser scanning microscopy (CLSM) using fluorescence labeled latex beads as the reference; staining intensities of all the scans are then summed and quantified (extended focus). This protocol, originally designed for disseminated tumor cells in bone marrow, can also be applied to disseminated tumor cells in blood, to leukapheresis cells or to cells present in malignant ascites or other malignant effusions. The tumor cells detected may be used for gene and mRNA analyses. Furthermore, disseminated tumor cells also represent interesting targets for clinical studies on patient prognosis or prediction of therapy response as well as for specific tumor-biological therapies.

Biomarkers, Tumor↗
PubMed1987

The therapeutic efficacy of critical care units from two perspectives: a traditional cohort approach vs a new case-control methodology.

The therapeutic efficacy of critical care units-whether they do more good than harm and for whom--has not been established, except for patients who are admitted for life-sustaining interventions, such as mechanical support of ventilation. However, most patients are admitted for observation, and to facilitate intervention if deterioration occurs or complications develop. The objective of this study was to determine whether direct admission to critical care units reduced mortality rates. The population under study consisted of all 604 patients admitted to the medical service during a one month period. At the time of admission, the responsible residents rated patients as to how sick and stable they were. These ratings of illness severity and stability have been shown to be the most significant predictors of in-hospital mortality and morbidity, respectively; they were employed to stratify the patients prognostically. The first analysis utilized the entire cohort of 604 patients. After patients who would have been ineligible for entry into a trial were removed, direct admission to the unit was associated with a reduced mortality in only one group of patients: the unstable, moderately ill (p less than 0.05). "Unstable, severely ill" patients had high mortality rates when admitted to the floor or units, and stable patients (mildly or moderately ill) did equally well when admitted to either location. A further analysis revealed a possible explanation for these findings. Among the unstable, moderately ill patients, the rate of deterioration of pre-existing problems was significantly lower among patients directly admitted to the unit (p less than 0.05), whereas the rate of new complications did not differ.(ABSTRACT TRUNCATED AT 250 WORDS)

Critical Care↗
PubMed1989

Methodological approach and diagnostic usefulness of a new assay for anti-thyroid peroxidase autoantibodies.

Although thyroid microsomal antibodies (anti-MAb) have been recently proven to be directly to thyroid peroxidase (TPO), current methods for MAb detection still employ unpurified microsomal fractions. The authors have therefore developed and evaluated a specific radioimmunoassay (RIA) for autoantibodies to TPO (anti-TPO Ab) based on competitive inhibition of 125I-TPO to an anti-TPO monoclonal antibody coated on plastic microtiter wells (RIA-1) or tubes (RIA-2). Preliminary experiments showed that both assays were able to specifically detect anti-TPO Ab, while negative results were obtained with normal sera and with sera containing other organ- and non-organ-specific autoantibodies including anti-thyroglobulin antibodies (anti-TgAb). No significant difference in sensitivity, specificity and reproducibility was found between RIA-1 and RIA-2, and the results obtained with the two techniques were therefore pooled together. Anti-TPO Ab were then assayed in 110 normal controls and in 441 patients with different autoimmune (AITD) or non-autoimmune (N-AITD) thyroid diseases and compared to anti-M Ab as assessed by passive hemagglutination (PH). Positive anti-TPO Ab were observed in 4/110 (3.6 p. cent) normal controls, 88/117 (80 p. cent) patients with Graves' disease, 122/123 with Hashimoto's thyroiditis or idiopathic myxedema and 21/201 (10.4 p. cent) with miscellaneous N-AITD. A highly significant positive correlation (r = 0.91, p less than 0.0001) was found between anti-MAb by PH and anti-TPO Ab by RIA ;discrepant results were limited to sera with negative or low (1/100-1/400) anti-M Ab titers.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoantibodies↗
PubMed1994

Methodological issues in studies of the treatment, diagnosis, and etiology of prostate cancer.

Clinical and epidemiological research on prostate cancer is faced with some unusual methodological challenges. The very high prevalence of latent cancer, much of which never becomes clinically manifest, complicates the approach to screening and the conduct of epidemiological studies. Cost-effectiveness issues are especially relevant regarding screening policies, and these trade-offs are complicated by the absence of definitive results on the effectiveness of the various treatment options. The presentation of advanced disease is also unusual, in that the vast majority of patients do not have measurable disease suitable for traditional studies of new chemotherapy agents. These problems necessitate creative approaches to the design and analysis of research studies in this disease: cost-effectiveness analysis is crucial to the evaluation of screening policies; opportunistic designs will be essential to the valid study of cancer etiology, eg, the use of cystoprostatectomy series for studies of epidemiologic risk factors; and posttreatment changes in PSA levels may be valuable as a criterion for screening new agents in advanced disease. Regardless of these new methods, traditional methodological approaches are essential to the valid study of prostate cancer. Randomization is required for valid comparison of treatments and screening strategies. Statistical analysis should observe the intent-to-treat principle whereby patient groups are analyzed with respect to the planned, rather than the delivered therapy, and studies should have sufficiently large sample sizes to reliably distinguish the true effects of the interventions from random statistical fluctuation. Recently, meta-analysis has become popular as a tool for synthesizing the information from available studies on a specific clinical problem. Its most conspicuous success has been in showing the efficacy of adjuvant therapy in breast cancer, for which many individual studies appeared to give conflicting results.64 In this setting there was a large number of published randomized trials, many of which had large sample sizes and long follow-up, and so the meta-analysis was able to show convincingly a small but clinically meaningful treatment effect on long-term disease recurrence and survival. This is similar to the situation in localized prostate cancer in all respects except for the availability of randomized trials. Unfortunately there is no free lunch. This technique can only be applied if the high quality data are available. One must be similarly cautious in applying decision analytic techniques (and also cost-effectiveness analysis) to try to resolve clinical dilemmas.(ABSTRACT TRUNCATED AT 400 WORDS)

Clinical Trials as Topic↗
PubMed1988

[New developments in bone density measurement by quantitative computer tomography].

The standard procedure in bone mineral measurements of the lumbar spine with QCT is presented in detail and analyzed with respect to the steps that may influence the accuracy and precision of the measurement. As new technical and methodological approaches, we present an improved implementation of dual energy CT and algorithms for automated determination of the CT slice and the evaluation region of interest. Dual energy methods provide greater accuracy; the automated algorithms relieve the operator of a tedious task and ensure greater precision. With respect to the clinical requirement to determine changes in bone mineral density as reliably and as early as possible, the precision increasing measures are considered more important. They also constitute a new methodological concept in radiology. Dual energy CT is only recommended for basic studies at this time.

Adult↗
PubMedDate not supplied

[Methodological approaches to evaluating the sensitizing properties of new drug preparations in preclinical trials].

For testing allergenic activity of 18 drugs with various pharmacological properties the reaction of specific leukocyte agglomeration, specific leukocyte lysis reaction, determination of Mg2+ blood serum content and epicutaneous drug application were used. An attempt was made to establish the relationship between the development of immunological response and the time and duration of allergization, the dosage and routes of allergen administration and also to determine the optimal experimental conditions for appearance of the most pronounced response.

Allergens↗
PubMed2002

Rapid appraisal methodology for 'health for all' policy formulation analysis.

BACKGROUND: Although in the last 20 years, the WHO 'Health for All' principles have been widely used in national, regional and local health policy documents, there is still a gap in the literature regarding how to appraise or compare them, which weakens the social accountability process. METHODOLOGY: A new, rapid approach to analyse the formulation of health policies is proposed. It is based on the selection of a small number of tracers and the development of a gold standard to be completed with input from a review of the literature, and opinions of expert panel members. This methodology has been empirically applied to the health strategies of two Spanish regions (Catalonia and Valencia). RESULTS: A framework for analysis was produced containing three dimensions: timing (early or late policy options), action level (individuals or social focus) and equity (social class, gender and ethnic groups). The health problems selected as tracers were HIV/AIDS, traffic injuries and ageing-related disabilities. In the two regions studied, the policies formulated for HIV/AIDS and age-related disabilities provide interventions late in the evolution of the health problem. The strategy established in the region of Valencia is more community-oriented than in Catalonia. Neither region had implemented specific policies regarding social class, gender or ethnic groups. INTERPRETATION: The methodology proposed here makes it possible to map the formulation of Health Strategies, compare different geographical areas and even forecast the policies' usefulness. The simplicity of the method, together with the fact that citizens and politicians alike can easily understand its results are major advantages. For the framework to be fully useful, it will be necessary to build evidence-based policy databases.

Accidents, Traffic↗
PubMed1989

[Methods and instruments for measuring and evaluating quality of life].

The measurement of quality of life is a new and methodologically difficult approach for assessing the outcome of an operation. It is not a degenerated slogan of a superficial "recreation society". It must be determined by a team of surgeons and professionals using psychometry and social sciences. If possible, only validated test procedures should be employed in clinical trials. The quick development of new procedures should be avoided. The quality of life is today generally a more sensitive criterion for the success of an operation than perioperative mortality.

Activities of Daily Living↗
PubMed2004

Non-linear analysis using continuous chaotic modeling.

Recent research in nanotechnology is opening exciting new avenues not only for understanding the human body but also for creating devices that can effectively interact with it to alleviate the effects of disease. These new developments present both challenges and opportunities for adaptation of existing methodologies to create new approaches for analysis and modeling of nanotechnology-based systems. The concept of continuous chaotic modeling presents an avenue for a paradigm shift away from traditional digital computing to take advantage of analog models that are more compatible with biological systems. The theoretical basis of continuous chaotic modeling is summarized, followed by illustrations of applications of this methodology.

Diagnosis↗
PubMed1996

Optimisation of metric matrix embedding by genetic algorithms.

To improve the convergence properties of 'embedding' distance geometry, a new approach was developed by combining the distance-geometry methodology with a genetic algorithm. This new approach is called DG-OMEGA (DG omega, optimised metric matrix embedding by genetic algorithms). The genetic algorithm was used to combine well-defined parts of individual structures generated by the distance-geometry program, and to identify new lower and upper distance bounds within the original experimental restraints in order to restrict the sampling of the metrisation algorithm to promising regions of the conformational space. The algorithm was tested on cyclosporin A, which is notorious for its intrinsic difficult sampling properties. A set of 58 distance restraints was employed. It was shown that DG omega resulted in an improvement of convergence behaviour as well as sampling properties with respect to the standard distance-geometry protocol.

Algorithms↗
PubMed2003

2,3-Anhydro sugars in glycoside bond synthesis. Highly stereoselective syntheses of oligosaccharides containing alpha- and beta-arabinofuranosyl linkages.

The ever-increasing discovery of biologically important events mediated by carbohydrates has generated great interest in the synthesis of oligosaccharides and the development of new methods for glycosidic bond formation. In this paper, we report that 2,3-anhydrofuranose thioglycosides (1, 5) and glycosyl sulfoxides (2, 6), in which the hydroxyl groups C-2 and C-3 are "protected" as an epoxide, glycosylate alcohols with an exceptionally high degree of stereocontrol. The predominant or exclusive product of reactions with this fundamentally new class of glycosylating agent is that in which the newly formed glycosidic bond is cis to the epoxide moiety. We further demonstrate that subsequent nucleophilic opening of the epoxide moiety proceeds under basic conditions to give products in high yield and with good to excellent regioselectivity. The major ring-opened products possess the arabino stereochemistry, and thus this methodology constitutes a new approach for the synthesis of arabinofuranosides. In the epoxide opening reactions of glycosides with the 2,3-anhydro-beta-D-lyxo stereochemistry (e.g., 73), the addition of (-)-sparteine (78) to the reaction mixture dramatically enhanced the regioselectivity in favor of the arabino product. This represents the first example of the use of 78 to influence the regioselectivity of an epoxide ring opening reaction with a non-carbon nucleophile. We have demonstrated the utility of this methodology through the efficient synthesis of an arabinofuranosyl hexasaccharide, 7, which is a key structural motif in two mycobacterial cell wall polysaccharides.

Arabinose↗
PubMed2000

Current millennium biotechniques for biomedical research on parasites and host-parasite interactions.

The development of biotechnology in the last three decades has generated the feeling that the newest scientific achievements will deliver high standard quality of life through abundance of food and means for successfully combating diseases. Where the new biotechnologies give access to genetic information, there is a common belief that physiological and pathological processes result from subtle modifications of gene expression. Trustfully, modern genetics has produced genetic maps, physical maps and complete nucleotide sequences from 141 viruses, 51 organelles, two eubacteria, one archeon and one eukaryote (Saccharomices cerevisiae). In addition, during the Centennial Commemoration of the Oswaldo Cruz Institute the nearly complete human genome map was proudly announced, whereas the latest Brazilian key stone contribution to science was the publication of the Shillela fastidiosa genomic sequence highlythed on a Nature cover issue. There exists a belief among the populace that further scientific accomplishments will rapidly lead to new drugs and methodological approaches to cure genetic diseases and other incurable ailments. Yet, much evidence has been accumulated, showing that a large information gap exists between the knowledge of genome sequence and our knowledge of genome function. Now that many genome maps are available, people wish to know what are we going to do with them. Certainly, all these scientific accomplishments will shed light on many more secrets of life. Nevertheless, parsimony in the weekly announcements of promising scientific achievements is necessary. We also need many more creative experimental biologists to discover new, as yet un-envisaged biotechnological approaches, and the basic resource needed for carrying out mile stone research necessary for leading us to that "promised land" often proclaimed by the mass media.

Animals↗
PubMed2000

Microbial biofilms: from ecology to molecular genetics.

Biofilms are complex communities of microorganisms attached to surfaces or associated with interfaces. Despite the focus of modern microbiology research on pure culture, planktonic (free-swimming) bacteria, it is now widely recognized that most bacteria found in natural, clinical, and industrial settings persist in association with surfaces. Furthermore, these microbial communities are often composed of multiple species that interact with each other and their environment. The determination of biofilm architecture, particularly the spatial arrangement of microcolonies (clusters of cells) relative to one another, has profound implications for the function of these complex communities. Numerous new experimental approaches and methodologies have been developed in order to explore metabolic interactions, phylogenetic groupings, and competition among members of the biofilm. To complement this broad view of biofilm ecology, individual organisms have been studied using molecular genetics in order to identify the genes required for biofilm development and to dissect the regulatory pathways that control the plankton-to-biofilm transition. These molecular genetic studies have led to the emergence of the concept of biofilm formation as a novel system for the study of bacterial development. The recent explosion in the field of biofilm research has led to exciting progress in the development of new technologies for studying these communities, advanced our understanding of the ecological significance of surface-attached bacteria, and provided new insights into the molecular genetic basis of biofilm development.

Bacterial Adhesion↗
PubMedDate not supplied

[Remote teaching in surgery: problem-based learning, telementoring, and evaluation tests].

The authors propose the use of distant learning in the surgical knowledge teaching. The problem based learning methodology can support this new didactic approach. Telementoring is an interactive experimental methodology that allows young surgeons education by distant learning tutoring of an expert surgeon. The problem about assessment of efficacy and quality of computer-assisted instruction is to day under evaluation.

Education, Distance↗
PubMed2000

Hybrid cardiac imaging with MR-CAT scan: a feasibility study.

We demonstrate the feasibility of a new versatile hybrid imaging concept, the combined acquisition technique (CAT), for cardiac imaging. The cardiac CAT approach, which combines new methodology with existing technology, essentially integrates fast low-angle shot (FLASH) and echoplanar imaging (EPI) modules in a sequential fashion, whereby each acquisition module is employed with independently optimized imaging parameters. One important CAT sequence optimization feature is the ability to use different bandwidths for different acquisition modules. Twelve healthy subjects were imaged using three cardiac CAT acquisition strategies: a) CAT was used to reduce breath-hold duration times while maintaining constant spatial resolution; b) CAT was used to increase spatial resolution in a given breath-hold time; and c) single-heart beat CAT imaging was performed. The results obtained demonstrate the feasibility of cardiac imaging using the CAT approach and the potential of this technique to accelerate the imaging process with almost conserved image quality.

Coronary Vessels↗
PubMedDate not supplied

[Challenges for developing a comparative analytical model for health services].

This paper presents different models that describe health determinants, services, and systems. It highlights the important model developed by Contandriopoulos, proposing a separation between the health status and health care circuits. The article is intended as a contribution to the field of comparative analysis with a new theoretical, methodological, and evaluative approach. Problems were identified in the development of a new model. Decentralization and access are introduced as categories, suggesting that they may take part in such new model.

Health Services↗