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Results for “knowledge accumulation”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

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At least 415 records · Page 23Linked to original sources
PubMed1986

Infection of the intervertebral space following conventional and microsurgical operation on the herniated lumbar intervertebral disc. A controlled clinical trial.

Review of the literature reveals that considerable knowledge has accumulated on intervertebral space infection following lumbar disc surgery. This is based on more than 400 observations. There are, however, no unifying concepts regarding the pathogenesis of the condition. While the reported incidence has seemed to increase in the last three decades, we noticed a significant reduction in frequency of this important complication of lumbar disc surgery after introducing microsurgical techniques. The significance of this finding is discussed with respect to pathogenesis.

Adult↗
PubMed1995

Molecular evolution of viruses: an interim summary.

The origin and molecular evolution of viruses in this issue is dealt with at two levels: (1) tracing the past evolutionary pathways of viruses belonging to RNA virus families, retroviruses, and small and large DNA viruses; (2) tracing current changes in the RNA and DNA viral genomes that lead to the evolution of new virus mutants. In this interim summary, a time scale for the evolutionary processes is given, based on the accumulated published knowledge concerning the postulated origins of life on planet Earth, and the hypothesis that living cells with RNA genomes may have emerged (the "RNA world hypothesis") that then developed into cells with DNA genomes in eukaryotic and prokaryotic cells (1-3). The ideas about the evolution of RNA and DNA viruses from ancient cellular RNA and DNA molecules over a period of 3.5 billion years are discussed. It may be possible that by studying virus genes and molecular processes in virus-infected cells, and their involvement in the shaping of the genomes of bacteria, yeast, plants, insects, mammals, and humans, it will be possible to understand the importance of viruses in past evolution and to predict their possible impact on current and future evolutionary trends in biology.

DNA, Viral↗
PubMedDate not supplied

Looking around: 35 years of oculomotor modeling.

Eye movements have attracted an unusually large number of researchers from many disparate fields, especially over the past 35 years. The lure of this system stemmed from its apparent simplicity of description, measurement, and analysis, as well as the promise of providing a "window in the mind." Investigators in areas ranging from biological control systems and neurological diagnosis to applications in advertising and flight simulation expected eye movements to provide clear indicators of what the sensory-motor system was accomplishing and what the brain found to be of interest. The parallels between compensatory eye movements and perception of spatial orientation have been a subject for active study in visual-vestibular interaction, where substantial knowledge has accumulated through experiments largely guided by the challenge of proving or disproving model predictions. Even though oculomotor control has arguably benefited more from systems theory than any other branch of motor control, many of the original goals remain largely unfulfilled. This paper considers some of the promising potential benefits of eye movement research and compares accomplishments with anticipated results. Four topics are considered in greater detail: (i) the definition of oculomotor system input and output, (ii) optimization of the eye movement system, (iii) the relationship between compensatory eye movements and spatial orientation through the "internal model," and (iv) the significance of eye movements as measured in (outer) space.

Aerospace Medicine↗
PubMedDate not supplied

Historical evolution of circuit models for the electrode-electrolyte interface.

Electrodes are widely used to measure bioelectric events and to stimulate excitable tissues. In one form or another, electrodes have been around for nearly two centuries; yet our ability to predict their properties is extremely limited, despite considerable research, especially during the last century. This paper chronicles the accumulation of knowledge about the electrode-electrolyte interface as a circuit element. Our understanding of this interface starts with the Helmholtz double layer of charge and progresses through the Warburg and Fricke low-current-density models, which demonstrated that the resistive and capacitive components are polarization elements, the values of which depend on frequency. The discovery by Schwan, showing that the components of the Warburg-Fricke model are current-density dependent, is recounted, along with the discovery of the rectifying properties of the electrode-electrolyte interface and how it was put to practical use. The very high current-density operation of the interface is discussed in terms of gas evolution, arching, and shock-wave production. Finally the evolution of recording electrodes is traced. Because electrodes can be operated over a very wide range of current density, it is unlikely that a single model can be created for the electrode-electrolyte interface, although over a restricted current-density range such a model may be possible.

Biosensing Techniques↗
PubMed1998

Evolution of myoglobin.

The distribution, physiological function, amino acid sequence and gene structure of myoglobin and myoglobin-like proteins from various taxa are summarized, and their evolution is discussed. Although it has long been thought that all haemoglobins and myoglobins have evolved from a common ancestral gene, the knowledge presently accumulated about the structures of these proteins suggests that there may be three distinct origins: a 'universal globin', a 'compact globin' and an 'IDO-like globin'.

Amino Acid Sequence↗
PubMed2005

Biostatistical methods for demonstrating efficacy in the regulatory setting. An epistemological approach to adaptive designs.

Adaptive designs are one of the most promising developments in statistics with applications to clinical trials. Obviously the knowledge at the beginning of a clinical trial will always be limited. In consequence it may be considered necessary that the knowledge from accumulating information should be used to optimize the design of the trial. This paper discusses conditions under which this may be possible in phase III clinical trials where the principle aim is confirmation of hypotheses that have been developed in earlier stages of drug development.

Biometry↗
PubMed1998

Lessons from transplantation and future perspectives.

Organ transplantation is now a routine treatment for a number of chronic kidney, heart, lung, and liver diseases. We have accumulated much knowledge about these treatments in the respective disciplines, and it seems appropriate to reflect on some general "across-the-border" lessons that may be important for medicine as a whole. The natural history of several diseases has been extended; however, we have also learned much about temporary organ replacement, with the possibility of treating and, perhaps, also preventing some diseases in ways that were not possible in the past. This study explores the phenomenon of temporary organ replacement, whereby organs that are in danger in losing their function may recover in quiescence. It raises the question of whether there might be a common, underlying mechanism-such as apoptosis-for some very different diseases. Pharmacological interventions designed to modulate apoptosis are being developed that will hopefully reduce the amount of time needed for organs to recover their function. We have learned some lessons, but are there more possibilities that need to be explored?

Apoptosis↗
PubMed2001

A landscape ecological approach to address scaling problems in conservation management and monitoring.

Management of many African game reserves is today often still an art based on experience and intuition, rather than a science. Decision-making is based on an informal integration of accumulated individual knowledge and keen field observations. Data are generally poorly captured and curated. Until fairly recently, denominators of biological parameters (such as the unit of land or unit of plant production used as measurement) have generally been treated as being homogenous. The patchiness of landscapes and the issue of ecological scaling were ignored, often because of a lack of appropriate technical tools. The ecological data available on the 49,000-ha Songimvelo Game Reserve (SGR) result from a number of discrete survey and monitoring projects undertaken by different researchers, with different objectives, at different spatial and temporal scales. A landscape ecological approach towards research and monitoring is appropriate for an area of the size and diversity of the SGR. A combination of a database approach and spatial representation was used to consolidate and integrate data across temporal and spatial scales. Herbivore spatial and temporal distribution patterns were explored across three spatial scales. An understanding was achieved of the importance of landscape patchiness in controlling resource availability for herbivores. This insight is important in guiding management and monitoring of the SGR by placing perceived patch overutilization in its proper landscape context. The landscape ecological approach bridges the traditional scale-independent view to a more contemporary scale-related understanding of ecosystem diversity and functioning.

Africa↗
PubMed2003

Contribution of radiotherapy to function preservation and cancer outcome in primary treatment of nasopharyngeal carcinoma.

Development of primary treatment for nasopharyngeal carcinoma is summarized and the contribution of radiotherapy (RT) is reviewed. Accumulation of knowledge, together with technological advances, has led to significant improvement both for tumor control and organ preservation. With contemporary RT, it is possible to achieve a 10-year disease-specific survival of 47% with a severe late complication rate of 5%. Presenting stage is one of the most important prognostic factors, but unfortunately late presentation and delayed diagnosis remains a common problem. The average local control rate is 80% for tumor confined within the nasopharynx, but only 50% for those associated with erosion of the base of the skull or cranial nerve involvement. Nodal deposits from nasopharyngeal carcinoma are much more radiosensitive than those from other head and neck cancers. An average control rate of 75% can be achieved with RT alone, even in patients with nodes > 6 cm in diameter. Successful locoregional control is important, not only because it is crucial for survival but also because it is associated with a lower incidence of distant failure (29% versus 41%). Distant failure remains a sinister problem, especially for patients presenting with advanced T or N-stage cancers. Randomized trials exploring the value of additional chemotherapy are reviewed. The significant improvement in 3-year overall survival achieved by the addition of concurrent and adjuvant chemotherapy (78% versus 47%) recently reported is encouraging, but remaining uncertainties are also discussed.

Brachytherapy↗
PubMed2006

Regulatory T cells in human autoimmune diseases.

In the most simplistic terms, immune tolerance can be envisioned as a balance with autoreactive cells that arise naturally in all individuals on one side and regulatory mechanisms designed to counter those autoreactive processes on the other. A tilt of the balance toward the autoreactive side, either by increasing the number or function of autoreactive cells or by diminishing regulatory mechanisms, is manifested as autoimmunity. In contrast, tilting of the balance toward increased regulation could conceivably cause immunodeficiency. Regulatory T cells (T(REG)), and particularly the naturally arising CD4(+)CD25(+) subset of T(REG) cells, provide a substantial component of the autoimmune counterbalance. The identification of forkhead box P3 (FOXP3) as a critical determinant of CD4(+)CD25(+) T(REG) development and function has provided new opportunities and generated expanded interest in studying the delicate balance between autoimmunity and regulatory mechanisms in human autoimmune diseases. Identification of both human and mouse syndromes in which FOXP3 is mutated, and consequently CD4(+)CD25(+) T(REG) cells are absent, has led to a rapid accumulation of knowledge regarding T(REG) development and function over the past 5 years. The recent development of antibody reagents to specifically identify CD4(+)CD25(+) T(REG) cells by their FOXP3 expression has provided new tools to identify these elusive cells and investigate their role in human disease. This review will focus on the current state of knowledge regarding the role of T(REG) in human autoimmune diseases and on specific human immunodeficiencies that provide interesting models of autoimmunity.

Animals↗
PubMed1998

Clinical research in surgery: questions but few answers.

BACKGROUND: Surgeons must be prepared to be questioned about their understanding, activities, and achievements in basic and clinical research in terms of structural, organizational, and financial support of surgical research. RESULTS: Clinical research today comprises basic research related to accumulation of knowledge about biological systems, disease-related research including experimental research with animals, and in vitro research with biological material and clinical studies with the strongest empirical basis in data derived from controlled clinical trials. Most clinical methods related to diagnosis and treatment have been introduced into the practice of everyday medicine even in university hospitals without passing a prospective evaluation protocol. To test the efficacy of a new drug or a newly developed surgical technique, the controlled prospective clinical trial is the best method; however, fewer than 50% of clinical questions can be answered by controlled clinical studies. In Germany the frequency of controlled clinical trials for answering clinical questions is presently low; this is particularly true for surgery, in comparison with other countries. The concept of evidence-based medicine is based on the principles of data generation from controlled trials and meta-analyses of those studies. Best-evidence synthesis means a reasonable synthesis of evident knowledge, experience and intuition. The challenge of professionalization of clinical research in surgery is linked to the establishment of full time positions for basic scientists and clinical researchers and the establishment of clinical research teams and of research professorships including basic scientists in surgical departments. CONCLUSION: Clinical research can be effective only if there is good cooperation between clinicians and basic scientists, if high grade scientific methods are established in clinical research institutions, if there is sufficient financial and personal supply, and if there are enough laboratories and animal operating facilities. There is an urgent need for structures integrating basic scientists in clinical research groups, for more interdisciplinary research projects and more multidisciplinary research, independent of clinical care in terms of manpower.

Clinical Medicine↗
PubMed1997

Cellular immune reactions directed against Toxoplasma gondii with special emphasis on the central nervous system.

Toxoplasma gondii is an obligate intracellular parasite which, after primary infection of humans, is maintained in a dormant state by the host cellular immune system. In the event of an acquired immunosuppression, those parasites surviving as dormant cysts in the host may undergo a change in status, proliferate and cause a life-threatening toxoplasmic encephalitis. Over the last decade much knowledge has accumulated concerning the immune response against T. gondii. This review focuses attention particularly on the anti-parasitic effector mechanisms and the cellular immune reactions in the central nervous system during the course of reactivated toxoplasmic encephalitis.

Astrocytes↗
PubMed2005

[Drug therapy and pharmacogenomics--hopes and facts].

Recent achievements in molecular genetics, in particular the characterization of a large number of non-synonymous single-nucleotide polymorphisms (ns-SNPs) have led to a substantial accumulation of knowledge about the mechanisms of interindividual variability in drug response. The concept of elucidating drug reactions by genetic analysis is termed "pharmacogenomics". Pharmacogenomics is set to provide a relevant contribution to our understanding of adverse drug reactions and non-responsiveness to drug therapy and may help realize the vision of providing individualized therapies. The greatest challenges for the field of pharmacogenomics relate to the issues of genotype-phenotype- and genotype-environment- interactions, optimal selection of study designs, predictivity and ethical aspects. Although its current impact on the routine of medicine is minimal, it is likely that pharmacogenomics will provide important contributions to the practice of drug therapy. Pharmacogenetic concepts may prove important for approximately 20% of therapeutic drugs.

Adult↗
PubMed2001

Gene therapy: future therapy for erectile dysfunction.

Advances in molecular biological techniques, completion of the Human Genome Project, and the ensuing age of molecular medicine, in conjuction with the sum of a decades-long accumulation of knowledge of the physiology of erection and the pathophysiology of erectile dysfunction have converged to make gene therapy for erectile dysfunction a distinct possibility. In short, both the intrinsic complexities of mechanisms responsible for ensuring normal erection and the multifactorial nature of erectile dysfunction ensure that there is a relatively vast number of physiologically relevant molecular targets for gene therapy. As such, perhaps it is not surprising that virtually every preclinical gene therapy strategy/target examined thus far has been largely successful in ameliorating conditions associated with compromised erectile function in vivo and/or in vitro. This report highlights the goals and strategies of gene therapy for erectile dysfunction and reviews the strategies that initially have been employed. In short, the preclinical data, while still quite preliminary in many regards, are nonetheless quite impressive and encouraging. If similar success is obtained in clinical trials, gene therapy for erectile dysfunction may provide the first concrete "proof of concept" for using gene therapy in the treatment of human smooth muscle disorders.

Erectile Dysfunction↗
PubMed1992

Metabolic regulations and biological functions of phospholipids in Escherichia coli.

Extensive genetic and biochemical studies in the last two decades have elucidated almost completely the framework of synthesis and turnover of quantitatively major phospholipids in E. coli. The knowledge thus accumulated has allowed to formulate a novel working model that assumes sophisticated regulatory mechanisms in E. coli to achieve the optimal phospholipid composition and content in the membranes. E. coli also appears to possess the ability to adapt phospholipid synthesis to various cellular conditions. Understanding of the functional aspects of E. coli phospholipids is now advancing significantly and it will soon be able to explain many of the hitherto unclear cell's activities on the molecular basis. Phosphatidylglycerol is believed to play the central role both in metabolism and functions of phospholipids in E. coli. The results obtained with E. coli should undoubtedly be helpful in the study of more complicated phospholipid metabolism and functions in higher organisms.

Animals↗
PubMed1995

Isolation of mature olfactory neurones using retrograde labelling and flow cytometry.

Currently we can observe an increasing interest for epithelial olfactory neurones. Several laboratories are involved in elucidation of the odorant-molecule recognition process and transduction cascade which brings information to the olfactory bulb. Others use this model, unique in mammals, to accumulate new knowledge on the neurogenesis phenomenon. Here we describe a simple and efficient method to purify mature olfactory neurone populations extracted from the nasal cavity. The approach relies on retrograde axonal tracing followed by flow cytometry sorting. For this purpose we inject a fluorescent dye (Fast Blue or diI C18(3)) in the olfactory bulb of adult rats. Seven days later, we extract the nasal turbinates and separate the mucosa from the subjacent lamina propria. The tissue is enzymatically dissociated and the labelled cells are sorted with a flow cytometer. Purification of the mature olfactory neurones varies from 80 to 99%.

Amidines↗
PubMed1983

The relevance of traditional medical cultures to modern primary health care.

This paper attempts to identify forms of traditional medicine which have the greatest potential for advancing primary health care goals. It begins by differentiating traditional medical systems into types, according to the kinds of medical knowledge which they depend on for preventing, diagnosing, and treating sickness. Emphasis is given to the facts that some traditional systems concentrate on producing varieties of pathophysiological knowledge, while others focus on forms of etiological knowledge; and that some traditional systems accumulate the medical knowledge which they produce, while others diffuse and fragment it. These differences give clues to a medical tradition's abstract potential for achieving three distinct, and only sometimes linked, ends: curing disease, healing illness, and enhancing the productivity of official primary health care programs. To make these clues concrete, it is also necessary to know something about the different ways in which traditional medical beliefs and practices are embedded, together with modern (cosmopolitan) medicine, in actual patterns of resort. The remainder of the paper assesses the relevance, for advancing primary health care goals, of particular classes of traditional healers--e.g. herbalists, midwives, bonesetters--and technologies within different types of medical systems. Four possibilities are described; integration, complementarity, rivalry and intercalation.

Diagnosis↗
PubMed2005

A new cancer diagnostic system based on a CDK profiling technology.

A series of molecular pathological investigations of the molecules that stimulate the cyclin dependent kinases (CDK1, 2, 4, and 6) have led to enormous accumulation of knowledge of the clinical significance of these molecules for cancer diagnosis. However, the molecules have yet to be applied to clinical cancer diagnosis, as there is no available technology for application of the knowledge in a clinical setting. We hypothesized that the direct measurement of CDK activities and expressions (CDK profiling) might produce clinically relevant values for the diagnosis. This study investigated the clinical relevance of CDK profiling in gastrointestinal carcinoma tissues by using originally developed expression and activity analysis methods. We have established novel methods and an apparatus for analyzing the expression and activities of the CDK molecules in lysate of tumor tissue in a clinical setting, and examined 30 surgically dissected gastrointestinal carcinomas and corresponding normal mucosal specimens. We demonstrate here that remarkably elevated CDK2 activity is evident in more than 70% of carcinoma tissues. Moreover, a G1-CDK activity profiling accurately mirrored the differences in proliferation between tumor and normal colonic tissues. Our results suggest that CDK profiling is a potent molecular-clinical approach to complement the conventional pathological diagnosis, and to further assist in the individualized medications.

Adult↗