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Sample records for human clinical study

  1. Human reporter genes: potential use in clinical studies

    Energy Technology Data Exchange (ETDEWEB)

    Serganova, Inna [Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021 (United States); Ponomarev, Vladimir [Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021 (United States); Blasberg, Ronald [Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021 (United States); Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021 (United States)], E-mail: blasberg@neuro1.mskcc.org

    2007-10-15

    The clinical application of positron-emission-tomography-based reporter gene imaging will expand over the next several years. The translation of reporter gene imaging technology into clinical applications is the focus of this review, with emphasis on the development and use of human reporter genes. Human reporter genes will play an increasingly more important role in this development, and it is likely that one or more reporter systems (human gene and complimentary radiopharmaceutical) will take leading roles. Three classes of human reporter genes are discussed and compared: receptors, transporters and enzymes. Examples of highly expressed cell membrane receptors include specific membrane somatostatin receptors (hSSTrs). The transporter group includes the sodium iodide symporter (hNIS) and the norepinephrine transporter (hNET). The endogenous enzyme classification includes human mitochondrial thymidine kinase 2 (hTK2). In addition, we also discuss the nonhuman dopamine 2 receptor and two viral reporter genes, the wild-type herpes simplex virus 1 thymidine kinase (HSV1-tk) gene and the HSV1-tk mutant (HSV1-sr39tk). Initial applications of reporter gene imaging in patients will be developed within two different clinical disciplines: (a) gene therapy and (b) adoptive cell-based therapies. These studies will benefit from the availability of efficient human reporter systems that can provide critical monitoring information for adenoviral-based, retroviral-based and lenteviral-based gene therapies, oncolytic bacterial and viral therapies, and adoptive cell-based therapies. Translational applications of noninvasive in vivo reporter gene imaging are likely to include: (a) quantitative monitoring of gene therapy vectors for targeting and transduction efficacy in clinical protocols by imaging the location, extent and duration of transgene expression; (b) monitoring of cell trafficking, targeting, replication and activation in adoptive T-cell and stem/progenitor cell therapies

  2. Human reporter genes: potential use in clinical studies

    International Nuclear Information System (INIS)

    Serganova, Inna; Ponomarev, Vladimir; Blasberg, Ronald

    2007-01-01

    The clinical application of positron-emission-tomography-based reporter gene imaging will expand over the next several years. The translation of reporter gene imaging technology into clinical applications is the focus of this review, with emphasis on the development and use of human reporter genes. Human reporter genes will play an increasingly more important role in this development, and it is likely that one or more reporter systems (human gene and complimentary radiopharmaceutical) will take leading roles. Three classes of human reporter genes are discussed and compared: receptors, transporters and enzymes. Examples of highly expressed cell membrane receptors include specific membrane somatostatin receptors (hSSTrs). The transporter group includes the sodium iodide symporter (hNIS) and the norepinephrine transporter (hNET). The endogenous enzyme classification includes human mitochondrial thymidine kinase 2 (hTK2). In addition, we also discuss the nonhuman dopamine 2 receptor and two viral reporter genes, the wild-type herpes simplex virus 1 thymidine kinase (HSV1-tk) gene and the HSV1-tk mutant (HSV1-sr39tk). Initial applications of reporter gene imaging in patients will be developed within two different clinical disciplines: (a) gene therapy and (b) adoptive cell-based therapies. These studies will benefit from the availability of efficient human reporter systems that can provide critical monitoring information for adenoviral-based, retroviral-based and lenteviral-based gene therapies, oncolytic bacterial and viral therapies, and adoptive cell-based therapies. Translational applications of noninvasive in vivo reporter gene imaging are likely to include: (a) quantitative monitoring of gene therapy vectors for targeting and transduction efficacy in clinical protocols by imaging the location, extent and duration of transgene expression; (b) monitoring of cell trafficking, targeting, replication and activation in adoptive T-cell and stem/progenitor cell therapies

  3. Functional MRI studies of human vision on a clinical imager

    International Nuclear Information System (INIS)

    George, J.S.; Lewine, J.D.; Aine, C.J.; van Hulsteyn, D.; Wood, C.C.; Sanders, J.; Maclin, E.; Belliveau, J.W.; Caprihan, A.

    1992-01-01

    During the past decade, Magnetic Resonance Imaging (MRI) has become the method of choice for imaging the anatomy of the human brain. Recently, Belliveau and colleagues have reported the use of echo planar magnetic resonance imaging (EPI) to image patterns of neural activity. Here, we report functional MR imaging in response to visual stimulation without the use of contrast agents, and without the extensive hardware modifications required for EPI. Regions of activity were observed near the expected locations of V1, V2 and possibly V3 and another active region was observed near the parietal-occipital sulcus on the superior surface of the cerebrum. These locations are consistent with sources observed in neuromagnetic studies of the human visual response

  4. Functional MRI in human motor control studies and clinical applications

    International Nuclear Information System (INIS)

    Toma, Keiichiro

    2002-01-01

    Functional magnetic resonance imaging (fMRI) has been a useful tool for the noninvasive mapping of brain function associated with various motor and cognitive tasks. Because fMRI is based on the blood oxygenation level dependent (BOLD) effect, it does not directly record neural activity. With the fMRI technique, distinguishing BOLD signals creased by cortical projection neurons from those created by intracortical neurons appears to be difficult. Two major experimental designs are used in fMRI studies: block designs and event-related designs. Block-designed fMRI presupposes the steady state of regional cerebral blood flow and has been applied to examinations of brain activation caused by tasks requiring sustained or repetitive movements. By contrast, the more recently developed event-related fMRI with time resolution of a few seconds allows the mapping of brain activation associated with a single movement according to the transient aspects of the hemodynamic response. Increasing evidence suggests that multiple motor areas are engaged in a networked manner to execute various motor acts. In order to understand functional brain maps, it is important that one understands sequential and parallel organizations of anatomical connections between multiple motor areas. In fMRI studies of complex motor tasks, elementary parameters such as movement length, force, velocity, acceleration and frequency should be controlled, because inconsistency in those parameters may alter the extent and intensity of motor cortical activation, confounding interpretation of the findings obtained. In addition to initiation of movements, termination of movements plays an important role in the successful achievement of complex movements. Brain areas exclusively related to the termination of movements have been, for the first time, uncovered with an event-related fMRI technique. We propose the application of fMRI to the elucidation of the pathophysiology of movement disorders, particularly dystonia

  5. Functional MRI in human motor control studies and clinical applications

    Energy Technology Data Exchange (ETDEWEB)

    Toma, Keiichiro [Kyoto Univ. (Japan). Graduate School of Medicine; Nakai, Toshiharu [Inst. of Biomedical Research and Innovation, Kobe (Japan)

    2002-07-01

    Functional magnetic resonance imaging (fMRI) has been a useful tool for the noninvasive mapping of brain function associated with various motor and cognitive tasks. Because fMRI is based on the blood oxygenation level dependent (BOLD) effect, it does not directly record neural activity. With the fMRI technique, distinguishing BOLD signals creased by cortical projection neurons from those created by intracortical neurons appears to be difficult. Two major experimental designs are used in fMRI studies: block designs and event-related designs. Block-designed fMRI presupposes the steady state of regional cerebral blood flow and has been applied to examinations of brain activation caused by tasks requiring sustained or repetitive movements. By contrast, the more recently developed event-related fMRI with time resolution of a few seconds allows the mapping of brain activation associated with a single movement according to the transient aspects of the hemodynamic response. Increasing evidence suggests that multiple motor areas are engaged in a networked manner to execute various motor acts. In order to understand functional brain maps, it is important that one understands sequential and parallel organizations of anatomical connections between multiple motor areas. In fMRI studies of complex motor tasks, elementary parameters such as movement length, force, velocity, acceleration and frequency should be controlled, because inconsistency in those parameters may alter the extent and intensity of motor cortical activation, confounding interpretation of the findings obtained. In addition to initiation of movements, termination of movements plays an important role in the successful achievement of complex movements. Brain areas exclusively related to the termination of movements have been, for the first time, uncovered with an event-related fMRI technique. We propose the application of fMRI to the elucidation of the pathophysiology of movement disorders, particularly dystonia

  6. A tool to facilitate clinical biomarker studies - a tissue dictionary based on the Human Protein Atlas

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    Kampf Caroline

    2012-09-01

    Full Text Available Abstract The complexity of tissue and the alterations that distinguish normal from cancer remain a challenge for translating results from tumor biological studies into clinical medicine. This has generated an unmet need to exploit the findings from studies based on cell lines and model organisms to develop, validate and clinically apply novel diagnostic, prognostic and treatment predictive markers. As one step to meet this challenge, the Human Protein Atlas project has been set up to produce antibodies towards human protein targets corresponding to all human protein coding genes and to map protein expression in normal human tissues, cancer and cells. Here, we present a dictionary based on microscopy images created as an amendment to the Human Protein Atlas. The aim of the dictionary is to facilitate the interpretation and use of the image-based data available in the Human Protein Atlas, but also to serve as a tool for training and understanding tissue histology, pathology and cell biology. The dictionary contains three main parts, normal tissues, cancer tissues and cells, and is based on high-resolution images at different magnifications of full tissue sections stained with H & E. The cell atlas is centered on immunofluorescence and confocal microscopy images, using different color channels to highlight the organelle structure of a cell. Here, we explain how this dictionary can be used as a tool to aid clinicians and scientists in understanding the use of tissue histology and cancer pathology in diagnostics and biomarker studies.

  7. Ozone exposure and pulmonary effects in panel and human clinical studies: Considerations for design and interpretation.

    Science.gov (United States)

    Rohr, Annette C

    2018-04-01

    A wealth of literature exists regarding the pulmonary effects of ozone, a photochemical pollutant produced by the reaction of nitrogen oxide and volatile organic precursors in the presence of sunlight. This paper focuses on epidemiological panel studies and human clinical studies of ozone exposure, and discusses issues specific to this pollutant that may influence study design and interpretation as well as other, broader considerations relevant to ozone-health research. The issues are discussed using examples drawn from the wider literature. The recent panel and clinical literature is also reviewed. Health outcomes considered include lung function, symptoms, and pulmonary inflammation. Issues discussed include adversity, reversibility, adaptation, variability in ozone exposure metric used and health outcomes evaluated, co-pollutants in panel studies, influence of temperature in panel studies, and multiple comparisons. Improvements in and standardization of panel study approaches are recommended to facilitate comparisons between studies as well as meta-analyses. Additional clinical studies at or near the current National Ambient Air Quality Standard (NAAQS) of 70 ppb are recommended, as are clinical studies in sensitive subpopulations such as asthmatics. The pulmonary health impacts of ozone exposure have been well documented using both epidemiological and chamber study designs. However, there are a number of specific methodological and related issues that should be considered when interpreting the results of these studies and planning additional research, including the standardization of exposure and health metrics to facilitate comparisons among studies.

  8. Quantitative imaging of the human upper airway: instrument design and clinical studies

    Science.gov (United States)

    Leigh, M. S.; Armstrong, J. J.; Paduch, A.; Sampson, D. D.; Walsh, J. H.; Hillman, D. R.; Eastwood, P. R.

    2006-08-01

    Imaging of the human upper airway is widely used in medicine, in both clinical practice and research. Common imaging modalities include video endoscopy, X-ray CT, and MRI. However, no current modality is both quantitative and safe to use for extended periods of time. Such a capability would be particularly valuable for sleep research, which is inherently reliant on long observation sessions. We have developed an instrument capable of quantitative imaging of the human upper airway, based on endoscopic optical coherence tomography. There are no dose limits for optical techniques, and the minimally invasive imaging probe is safe for use in overnight studies. We report on the design of the instrument and its use in preliminary clinical studies, and we present results from a range of initial experiments. The experiments show that the instrument is capable of imaging during sleep, and that it can record dynamic changes in airway size and shape. This information is useful for research into sleep disorders, and potentially for clinical diagnosis and therapies.

  9. Clinical Studies

    DEFF Research Database (Denmark)

    Pallesen, Ulla

    universities and practicing dentists restore millions of teeth throughout the World with composite resin materials. Do we know enough about the clinical performance of these restorations over time? Numerous in vitro studies are being published on resin materials and adhesion, some of them attempting to imitate...... in vivo conditions. But real life is different and in vitro studies cannot include all variables. Only clinical studies can provide valid information on the clinical performance of restorations over time. What do we know about longevity of posterior resin restorations? What are the reasons for replacement...... and results from own up to 30-year prospective clinical university studies and practice based studies from Public Dental Health Service on the clinical performance of posterior composite resin restorations....

  10. 3D virtual human atria: A computational platform for studying clinical atrial fibrillation.

    Science.gov (United States)

    Aslanidi, Oleg V; Colman, Michael A; Stott, Jonathan; Dobrzynski, Halina; Boyett, Mark R; Holden, Arun V; Zhang, Henggui

    2011-10-01

    Despite a vast amount of experimental and clinical data on the underlying ionic, cellular and tissue substrates, the mechanisms of common atrial arrhythmias (such as atrial fibrillation, AF) arising from the functional interactions at the whole atria level remain unclear. Computational modelling provides a quantitative framework for integrating such multi-scale data and understanding the arrhythmogenic behaviour that emerges from the collective spatio-temporal dynamics in all parts of the heart. In this study, we have developed a multi-scale hierarchy of biophysically detailed computational models for the human atria--the 3D virtual human atria. Primarily, diffusion tensor MRI reconstruction of the tissue geometry and fibre orientation in the human sinoatrial node (SAN) and surrounding atrial muscle was integrated into the 3D model of the whole atria dissected from the Visible Human dataset. The anatomical models were combined with the heterogeneous atrial action potential (AP) models, and used to simulate the AP conduction in the human atria under various conditions: SAN pacemaking and atrial activation in the normal rhythm, break-down of regular AP wave-fronts during rapid atrial pacing, and the genesis of multiple re-entrant wavelets characteristic of AF. Contributions of different properties of the tissue to mechanisms of the normal rhythm and arrhythmogenesis were investigated. Primarily, the simulations showed that tissue heterogeneity caused the break-down of the normal AP wave-fronts at rapid pacing rates, which initiated a pair of re-entrant spiral waves; and tissue anisotropy resulted in a further break-down of the spiral waves into multiple meandering wavelets characteristic of AF. The 3D virtual atria model itself was incorporated into the torso model to simulate the body surface ECG patterns in the normal and arrhythmic conditions. Therefore, a state-of-the-art computational platform has been developed, which can be used for studying multi

  11. Clinical PET of Neuroendocrine Tumors Using 64Cu-DOTATATE: First-in-Humans Study

    DEFF Research Database (Denmark)

    Pfeifer, Andreas Klaus; Knigge, Ulrich Peter; Mortensen, Jann

    2012-01-01

    MBq of 64Cu-DOTATATE, with the liver being the organ with the highest absorbed radiation dose (0.16 mGy/MBq). Conclusion: This first-in-humans study supports the clinical use of 64Cu-DOTATATE for SRI with excellent imaging quality, reduced radiation burden, and increased lesion detection rate when...... administration. Tissue radioactivity concentrations for normal organs and lesions were quantified, and standardized uptake values were calculated for the early (1 h) and delayed (3 h) scans. Using the data for 5 patients, we assessed the radiation dose with OLINDA/EXM software. Furthermore, the clinical...... performance of 64Cu-DOTATATE with respect to lesion detection was compared with conventional SRI. Results: SRI with 64Cu-DOTATATE produced images of excellent quality and high spatial resolution. Images were characterized by high and stable tumor-to-background ratios over an imaging time window of at least 3...

  12. Resveratrol and Clinical Trials: The Crossroad from In Vitro Studies to Human Evidence

    Science.gov (United States)

    Tomé-Carneiro, Joao; Larrosa, Mar; González-Sarrías, Antonio; Tomás-Barberán, Francisco A.; García-Conesa, María Teresa; Espín, Juan Carlos

    2013-01-01

    Resveratrol (3,5,4’-trihydroxy-trans-stilbene) is a non-flavonoid polyphenol that may be present in a limited number of food-stuffs such as grapes and red wine. Resveratrol has been reported to exert a plethora of health benefits through many different mechanisms of action. This versatility and presence in the human diet have drawn the worldwide attention of many research groups over the past twenty years, which has resulted in a huge output of in vitro and animal (preclinical) studies. In line with this expectation, many resveratrol-based nutraceuticals are consumed all over the world with questionable clinical/scientific support. In fact, the confirmation of these benefits in humans through randomized clinical trials is still very limited. The vast majority of preclinical studies have been performed using assay conditions with a questionable extrapolation to humans, i.e. too high concentrations with potential safety concerns (adverse effects and drug interactions), short-term exposures, in vitro tests carried out with non-physiological metabolites and/or concentrations, etc. Unfortunately, all these hypothesis-generating studies have contributed to increased the number of ‘potential’ benefits and mechanisms of resveratrol but confirmation in humans is very limited. Therefore, there are many issues that should be addressed to avoid an apparent endless loop in resveratrol research. The so-called ‘Resveratrol Paradox’, i.e., low bioavailability but high bioactivity, is a conundrum not yet solved in which the final responsible actor (if any) for the exerted effects has not yet been unequivocally identified. It is becoming evident that resveratrol exerts cardioprotective benefits through the improvement of inflammatory markers, atherogenic profile, glucose metabolism and endothelial function. However, safety concerns remain unsolved regarding chronic consumption of high RES doses, specially in medicated people. This review will focus on the currently

  13. Teaching medical students to discern ethical problems in human clinical research studies.

    Science.gov (United States)

    Roberts, Laura Weiss; Warner, Teddy D; Green Hammond, Katherine A; Brody, Janet L; Kaminsky, Alexis; Roberts, Brian B

    2005-10-01

    Investigators and institutional review boards are entrusted with ensuring the conduct of ethically sound human studies. Assessing ethical aspects of research protocols is a key skill in fulfilling this duty, yet no empirically validated method exists for preparing professionals to attain this skill. The authors performed a randomized controlled educational intervention, comparing a criteria-based learning method, a clinical-research- and experience-based learning method, and a control group. All 300 medical students enrolled at the University of New Mexico School of Medicine in 2001 were invited to participate. After a single half-hour educational session, a written posttest of ability to detect ethical problems in hypothetical protocol vignettes was administered. The authors analyzed responses to ten protocol vignettes that had been evaluated independently by experts. For each vignette, a global assessment of the perceived significance of ethical problems and the identification of specific ethical problems were evaluated. Eighty-three medical students (27%) volunteered: 50 (60%) were women and 55 (66%) were first- and second-year students. On global assessments, the criteria-focused group perceived ethical problems as more significant than did the other two groups (p evaluation skills. This work supports the potential value of empirically derived methods for preparing professionals to discern ethical aspects of human studies.

  14. Mechanoreceptors of the Achilles tendon: a histomorphological study in pigs with clinical significance for humans.

    Science.gov (United States)

    Kapetanakis, Stylianos; Gkasdaris, Grigorios; Daneva, Eleni; Givissis, Panagiotis; Papathanasiou, Jannis; Xanthos, Theodoros

    2017-01-01

    Tendons contain neurosensory elements called mechanoreceptors which contribute to the neuromuscular system as sources of reflex signals. The literature is lacking in histological assessment of mechanoreceptors of the Achilles tendon in piglets and our aim was to indicate their types, location and quantity. The study was performed using histological tissue samples from the Achilles tendon of ten healthy pigs, five left, five right, six males, four females. The samples were taken up to 12 hours after death. Immediately after removal, the tendons were placed in the laboratory where sections were taken and examined microscopically. The tendons were stained with the gold chloride method. The results showed that Golgi tendon organs, free nerve endings and Pacinian-like corpuscles were found in the Achilles tendon of pigs. Most structures were near the osteotendinous and myotendinous junctions, away from the middle portion of the tendon. As shown in other studies and similarly in ours, mechanoreceptors tend to be close to the distant thirds and not in the middle third of the tendon. This study could have clinical application on human Achilles tendon and its repair after damage. IV.

  15. Clinical studies of pigmented lesions in human skin by using a multiphoton tomograph

    Science.gov (United States)

    Balu, Mihaela; Kelly, Kristen M.; Zachary, Christopher B.; Harris, Ronald M.; Krasieva, Tatiana B.; König, Karsten; Tromberg, Bruce J.

    2013-02-01

    In vivo imaging of pigmented lesions in human skin was performed with a clinical multiphoton microscopy (MPM)-based tomograph (MPTflex, JenLab, Germany). Two-photon excited fluorescence was used for visualizing endogenous fluorophores such as NADH/FAD, keratin, melanin in the epidermal cells and elastin fibers in the dermis. Collagen fibers were imaged by second harmonic generation. Our study involved in vivo imaging of benign melanocytic nevi, atypical nevi and melanoma. The goal of this preliminary study was to identify in vivo the characteristic features and their frequency in pigmented lesions at different stages (benign, atypical and malignant) and to evaluate the ability of in vivo MPM to distinguish atypical nevi from melanoma. Comparison with histopathology was performed for the biopsied lesions. Benign melanocytic nevi were characterized by the presence of nevus cell nests at the epidermal-dermal junction. In atypical nevi, features such as lentiginous hyperplasia, acanthosis and architectural disorder were imaged. Cytological atypia was present in all the melanoma lesions imaged, showing the strongest correlation with malignancy. The MPM images demonstrated very good correlation with corresponding histological images, suggesting that MPM could be a promising tool for in vivo non-invasive pigmented lesion diagnosis, particularly distinguishing atypical nevi from melanoma.

  16. Stereomicroscopic study of the human tooth caries: clinical and morphological correlations

    Science.gov (United States)

    Oancea, Roxana; Vasile, Liliana; Marchese, Cristian; Sava-Rosianu, Ruxandra

    2012-06-01

    loss that is very useful in grading the progression of the carious lesion. Conclusions: The stereomicroscopic study correlated with clinical and morphological data allowed to appreciate the extent of tissue involved in the carious process, but also the understanding of the enamel, dentine and cement matrix demineralization process, in proximity with the morpho-embryological markings of the human tooth structure.

  17. Nutrition studies with human volunteers, designs and compliance to good clinical practice

    NARCIS (Netherlands)

    Schaafsma, G.

    2002-01-01

    In vitro experiments with cell cultures, studies with the TNO gastrointestinal model, animal experiments, and studies with human volunteers are used in nutrition research on the assessment of efficacy and safety of ingredients that can be used as bio actives in functional foods, functional drinks

  18. Mathematical modeling of human glioma growth based on brain topological structures: study of two clinical cases.

    Directory of Open Access Journals (Sweden)

    Cecilia Suarez

    Full Text Available Gliomas are the most common primary brain tumors and yet almost incurable due mainly to their great invasion capability. This represents a challenge to present clinical oncology. Here, we introduce a mathematical model aiming to improve tumor spreading capability definition. The model consists in a time dependent reaction-diffusion equation in a three-dimensional spatial domain that distinguishes between different brain topological structures. The model uses a series of digitized images from brain slices covering the whole human brain. The Talairach atlas included in the model describes brain structures at different levels. Also, the inclusion of the Brodmann areas allows prediction of the brain functions affected during tumor evolution and the estimation of correlated symptoms. The model is solved numerically using patient-specific parametrization and finite differences. Simulations consider an initial state with cellular proliferation alone (benign tumor, and an advanced state when infiltration starts (malign tumor. Survival time is estimated on the basis of tumor size and location. The model is used to predict tumor evolution in two clinical cases. In the first case, predictions show that real infiltrative areas are underestimated by current diagnostic imaging. In the second case, tumor spreading predictions were shown to be more accurate than those derived from previous models in the literature. Our results suggest that the inclusion of differential migration in glioma growth models constitutes another step towards a better prediction of tumor infiltration at the moment of surgical or radiosurgical target definition. Also, the addition of physiological/psychological considerations to classical anatomical models will provide a better and integral understanding of the patient disease at the moment of deciding therapeutic options, taking into account not only survival but also life quality.

  19. Nutraceuticals for Skin Care: A Comprehensive Review of Human Clinical Studies.

    Science.gov (United States)

    Pérez-Sánchez, Almudena; Barrajón-Catalán, Enrique; Herranz-López, María; Micol, Vicente

    2018-03-24

    The skin is the body's largest organ, it participates in sensitivity and offers protection against microorganisms, chemicals and ultraviolet (UV) radiation. Consequently, the skin may suffer alterations such as photo-ageing, immune dysfunction and inflammation which may significantly affect human health. Nutraceuticals represent a promising strategy for preventing, delaying, or minimising premature ageing of the skin and also to alleviate certain skin disorders. Among them, bioactive peptides and oligosaccharides, plant polyphenols, carotenoids, vitamins and polyunsaturated fatty acids are the most widely used ingredients. Supplementation with these products has shown evidence of having an effect on the signs of ageing and protection against UV radiation ageing in several human trials. In this review, the most relevant human studies on skin nutraceuticals are evaluated and the statistical resolution, biological relevance of their results, and, the trial protocols are discussed. In conclusion, quality and rigorousness of the trials must be improved to build credible scientific evidence for skin nutraceuticals and to establish a cause-effect relationship between the ingredients the beneficial effects for the skin.

  20. Nutraceuticals for Skin Care: A Comprehensive Review of Human Clinical Studies

    Directory of Open Access Journals (Sweden)

    Almudena Pérez-Sánchez

    2018-03-01

    Full Text Available The skin is the body’s largest organ, it participates in sensitivity and offers protection against microorganisms, chemicals and ultraviolet (UV radiation. Consequently, the skin may suffer alterations such as photo-ageing, immune dysfunction and inflammation which may significantly affect human health. Nutraceuticals represent a promising strategy for preventing, delaying, or minimising premature ageing of the skin and also to alleviate certain skin disorders. Among them, bioactive peptides and oligosaccharides, plant polyphenols, carotenoids, vitamins and polyunsaturated fatty acids are the most widely used ingredients. Supplementation with these products has shown evidence of having an effect on the signs of ageing and protection against UV radiation ageing in several human trials. In this review, the most relevant human studies on skin nutraceuticals are evaluated and the statistical resolution, biological relevance of their results, and, the trial protocols are discussed. In conclusion, quality and rigorousness of the trials must be improved to build credible scientific evidence for skin nutraceuticals and to establish a cause-effect relationship between the ingredients the beneficial effects for the skin.

  1. Nutraceuticals for Skin Care: A Comprehensive Review of Human Clinical Studies

    Science.gov (United States)

    Pérez-Sánchez, Almudena; Micol, Vicente

    2018-01-01

    The skin is the body’s largest organ, it participates in sensitivity and offers protection against microorganisms, chemicals and ultraviolet (UV) radiation. Consequently, the skin may suffer alterations such as photo-ageing, immune dysfunction and inflammation which may significantly affect human health. Nutraceuticals represent a promising strategy for preventing, delaying, or minimising premature ageing of the skin and also to alleviate certain skin disorders. Among them, bioactive peptides and oligosaccharides, plant polyphenols, carotenoids, vitamins and polyunsaturated fatty acids are the most widely used ingredients. Supplementation with these products has shown evidence of having an effect on the signs of ageing and protection against UV radiation ageing in several human trials. In this review, the most relevant human studies on skin nutraceuticals are evaluated and the statistical resolution, biological relevance of their results, and, the trial protocols are discussed. In conclusion, quality and rigorousness of the trials must be improved to build credible scientific evidence for skin nutraceuticals and to establish a cause-effect relationship between the ingredients the beneficial effects for the skin. PMID:29587342

  2. Fundamental and clinical study of direct immunoradiometric assay in human renin concentration

    International Nuclear Information System (INIS)

    Kurimoto, Fumihiko; Horiuchi, Junko; Sakurai, Hyoichiro; Suzuki, Hiromichi; Takita, Takashi; Saruta, Takao.

    1988-01-01

    'Renin RIA Pasteur' kit for directly measuring renin concentration in human plasma (PRC) was fundamentally and clinically evaluated. A standard curve for PRC was linear in the range of 10 - 640 pg/ml. Reproducibility, recovery, and stability were satisfactory. There was a significantly positive correlation between direct PRC and conventional plasma renin activity (PRA) and indirect PRC. PRC was directly measured in 119 healthy volunteers and 15 patients with primary aldosteronism (4), Cushing's syndrome (6), or non-functioning tumor (5). The basal PRC was 32.4 +- 18.8 pg/ml for men and 37.9 +- 22.6 pg/ml for women. PRC for primary aldosteronism was below detectable levels, and remained unchanged even after the administratin of ACTH. In the case of Cushing's syndrome, mean PRC and PRA were 19 pg/ml and 1.2 ng/ml/hr, and did not respond to ACTH. Although the administration of ATCH was significantly associated with a decreased PRC, there was only tendency toward the decreased PRA in the case of non-functioning tumors. The results indicate the usefulness of the present kit in terms of its ability to directly measure PRC without any complicated procedures. (Namekawa, K.)

  3. Oncogenic human papillomavirus genital infection in southern Iranian women: population-based study versus clinic-based data

    Directory of Open Access Journals (Sweden)

    Eghbali Seyed

    2012-09-01

    Full Text Available Abstract Background Epidemiological studies on genital human papilloma viruses infection (HPVs in general population are crucial for the implementation of health policy guidelines for developing the strategies to prevent the primary and secondary cervical cancer. In different parts of Iran, there is a lack of population-based studies to determine the prevalence of HPV in the general population. The aim of this population-based study is to compare the prevalence rate of genital HPV infection among reproductive women with our previous clinic-based data, which showed a prevalence rate of 5% in women in southern Iran. Results Using general primers for all genotypes of HPV, of 799 randomly selected women, five (0.63%, 95% CI 0.23-1.55% tested positive for HPV DNA. Overall, seven different HPV genotypes were detected: six types (16, 18, 31, 33, 51 and 56 were carcinogenic, or “high risk genotypes” and one genotype (HPV-66 was “probably carcinogenic.” Conclusions In a population-based study, the prevalence of HPV infection among southern Iranian women was lower than that observed worldwide. However, our gynaecological clinic-based study on the prevalence of HPV infection showed results comparable with other studies in the Middle East and Persian Gulf countries. Since gynaecological clinic-based data may generally overestimate HPV prevalence, estimates of prevalence according to clinic-based data should be adjusted downward by the population-based survey estimates.

  4. A learning activity to introduce undergraduate students to bioethics in human clinical research: a case study.

    Science.gov (United States)

    Segarra, Ignacio; Gomez, Manuel

    2014-12-01

    We developed a pharmacology practicum assignment to introduce students to the research ethics and steps involved in a clinical trial. The assignment included literature review, critical analysis of bioethical situations, writing a study protocol and presenting it before a simulated ethics committee, a practice interview with a faculty member to obtain informed consent, and a student reflective assessment and self-evaluation. Students were assessed at various steps in the practicum; the learning efficiency of the activity was evaluated using an independent survey as well as students' reflective feedback. Most of the domains of Bloom's and Fink's taxonomies of learning were itemized and covered in the practicum. Students highly valued the translatability of theoretical concepts into practice as well as the approach to mimic professional practice. This activity was within a pharmacy program, but may be easily transferable to other medical or health sciences courses. © The Author(s) 2014.

  5. Study on human chondrocyte culture viability for autologous transplantation in clinical application

    Directory of Open Access Journals (Sweden)

    Christiane Lombello

    2003-06-01

    Full Text Available Objective: The limited regenerative capacity of the cartilage tissuemakes the treatment of chondral lesions difficult. The techniquescurrently available to treat cartilage lesions may relieve symptoms,but do not regenerate the injured tissue. Autologous chondrocytetransplantation uses cell biology and cell culture techniques toregenerate the hyaline cartilage. Methods: In this study, we analyzechondrocyte biopsy collection and culture for autologoustransplantation. Ultrastructural analyses of hyaline cartilage biopsieswere performed 0, 6, 24 and 48 hours after collection. The tissue evenafter 48 hours. Eleven cell culture assays were performed to evaluateisolation, viability, morphology, proliferation and absence ofcontaminants. Results: The cell culture techniques used allowedchondrocyte proliferation. Rates on cell viability were maintained abovethe acceptable patterns (above 90. Control of cell culture laboratoryconditions showed absence of contaminants, assuring safety of theprocess. The chondrocytes obtained presented the morphology typicalof cultured cell monolayers. Conclusion: The results indicate viabilityof chondrocyte culture technique for clinical application in autologoustransplantation.

  6. The Fibularis (Peroneus Tertius Muscle in Humans: A Meta-Analysis of Anatomical Studies with Clinical and Evolutionary Implications

    Directory of Open Access Journals (Sweden)

    Kaissar Yammine

    2017-01-01

    Full Text Available Being considered an exclusive human structure for a long time, fibularis tertius (FT is believed to have a secondary function of foot dorsiflexion and eversion. This study is an attempt to approach the issue from an anatomical perspective. A systematic literature search identified 35 studies (7601 legs which met the inclusion criteria. The weighted results of FT presence were as follows: an “adult cadaveric” frequency of 93.2% and a clinical frequency of 80%. The most common FT origin and insertion sites were the distal half of fibula and the base of the 5th metatarsal, respectively. In 95% of cases, an accessory fibular muscle was detected when FT was lacking. We demonstrated that the discrepancy found between the adult cadaveric and clinical frequency values would point out a probable bias in interpreting previous kinesiological results. On an evolutionary level, comparative anatomy demonstrated a very low FT prevalence among monkeys while reaching a frequency of 30% in gorillas, the only non-human apes having an almost exclusive terrestrial locomotion. The consistent prevalence among humans and the presence of similar functional muscles when it is missing would support an essential role of FT during the phylogenetic development of the erect bipedal posture and probably during gait.

  7. First-in-human study and clinical case reports of the alveolar bone regeneration with the secretome from human mesenchymal stem cells.

    Science.gov (United States)

    Katagiri, Wataru; Osugi, Masashi; Kawai, Takamasa; Hibi, Hideharu

    2016-01-15

    Secreted growth factors and cytokines in the conditioned medium from bone marrow-derived mesenchymal stem cells (MSC-CM) have several effects on cell behavior. Our previous studies revealed that MSC-CM enhances bone regeneration by increasing cell mobilization, angiogenesis, and osteogenesis in vitro and in vivo. This clinical study was undertaken to evaluate the safety and use of MSC-CM for alveolar bone regeneration in eight patients who were diagnosed as needing bone augmentation prior to dental implant placement. The protocol of this clinical study was approved by the ethics committee of Nagoya University Hospital. MSC-CM was prepared from conditioned medium from commercially available human bone marrow-derived MSCs. Patients were treated with beta-tricalcium phosphate (β-TCP) or an atelocollagen sponge soaked with MSC-CM. Clinical and radiographic assessments were performed during the follow-up period. Histological assessments were also performed in some cases. Clinical and histological data from patients who underwent the SFE procedure without MSC-CM were also used retrospectively as reference controls. MSC-CM contained several cytokines such as insulin-like growth factor-1, vascular endothelial growth factor, transforming growth factor-β1, and hepatocyte growth factor in relatively low amounts. No systemic or local complications were reported throughout the study. Radiographic evaluation revealed early bone formation in all cases. Histological evaluation also supported the radiographic findings. Furthermore, infiltration of inflammatory cells was scarce throughout the specimens. MSC-CM was used safely and with less inflammatory signs and appears to have great osteogenic potential for regenerative medicine of bone. This is the first in-human clinical study of alveolar bone regeneration using MSC-CM.

  8. Clinical study of 67Ga labelled human fibrinogen for detection of thrombi

    International Nuclear Information System (INIS)

    Katsuura, Yutaka

    1988-01-01

    The usefulness to detect thrombi by Ga-67 labelled human fibrinogen (Ga-F) was investigated in 22 patients with various diseases who had thrombi or were suspected to have thrombi. In 5 of 9 patients with aortic aneurysm, images of thrombi were obtained by Ga-F. In 1 of 2 patients with myocardial infarction, left ventricular thrombi were detected. In 1 of 5 patients with mitral stenosis, left atrial thrombus was recognized. Of these patients, in 2 patients who have no evidence of thrombi confirmed at another methods, thrombi were detected by Ga-F. In 6 out of 8 patients with thrombi confirmed at echocardiography or computed tomography, thrombi were detected by Ga-F. In these patients, 2 patients with negative images were treated by antithromboticdrugs. In 7 patients, both Ga-F and In-111 labelled platelets (In-P) were comparatively studied simultaniuosly. No difference in the sensitivity of the detection of thrombi were recognized between two groups. The images of thrombi by both Ga-F and In-P were detected positively in 3 patients and were not found in 4 patients. However, the handling of Ga-F method was much easier than that of In-P method. In conclusion, Ga-F could be useful for the detection of thrombi in various thrombotic diseases. Fibrinogen kinetic studies using Ga-F were performed. Fibrinogen turnover rates (FTR) in the cases with positive image by Ga-F were higher than those in the cases with Ga-F negative image. (positive : 24.3 ± 9.5 mg/kg/day, negative : 19.7 ± 8.5 mg/kg/day) The results of kinetic studies by Ga-F were similar to those by 1 - 125 fibrinogen. (author)

  9. Cultivation and grafting of human keratinocytes on a poly(hydroxyethyl methacrylate) support to the wound bed: a clinical study.

    Science.gov (United States)

    Dvoránková, B; Smetana, K; Königová, R; Singerová, H; Vacík, J; Jelínková, M; Kapounková, Z; Zahradník, M

    1998-01-01

    Cultured epithelial sheets on a textile support are used for the treatment of seriously burned patients. In this study we demonstrate a new procedure for the grafting of keratinocytes directly on a polymer cultivation support. This procedure is much easier in comparison with classical techniques, and encouraging results of clinical trials demonstrate the improved healing of the wound bed after the use of this procedure. There is no difference in the cytokeratine pattern (LP-34, cytokeratin-10) of the reconstructed epidermis and normal human skin.

  10. Implementing human factors in clinical practice

    Science.gov (United States)

    Timmons, Stephen; Baxendale, Bryn; Buttery, Andrew; Miles, Giulia; Roe, Bridget; Browes, Simon

    2015-01-01

    Objectives To understand whether aviation-derived human factors training is acceptable and useful to healthcare professionals. To understand whether and how healthcare professionals have been able to implement human factors approaches to patient safety in their own area of clinical practice. Methods Qualitative, longitudinal study using semi-structured interviews and focus groups, of a multiprofessional group of UK NHS staff (from the emergency department and operating theatres) who have received aviation-derived human factors training. Results The human factors training was evaluated positively, and thought to be both acceptable and relevant to practice. However, the staff found it harder to implement what they had learned in their own clinical areas, and this was principally attributed to features of the informal organisational cultures. Conclusions In order to successfully apply human factors approaches in hospital, careful consideration needs to be given to the local context and informal culture of clinical practice. PMID:24631959

  11. Stem cell-based treatments against stroke: observations from human proof-of-concept studies and considerations regarding clinical applicability

    Directory of Open Access Journals (Sweden)

    Thorsten Roland Doeppner

    2014-10-01

    Full Text Available Ischemic stroke remains a heavy burden for industrialized countries. The only causal therapy is the recanalization of occluded vessels via thrombolysis, which due to a narrow time window still can be offered only to a minority of patients. Since the majority of patients continues to exhibit neurological deficits even following successful thrombolysis, restorative therapies are urgently needed that promote brain remodeling and repair once stroke injury has occurred. Due to their unique properties of action, stem cell-based strategies gained increasing interest during recent years. Using various stroke models in both rodents and primates, the transplantation of stem cells, namely of bone marrow derived mesenchymal stem cells (MSCs or neural progenitor cells (NPCs, has been shown to promote neurological recovery most likely via indirect bystander actions. In view of promising observations, clinical proof-of-concept studies are currently under way, in which effects of stem and precursor cells are evaluated in human stroke patients. In this review we summarize already published studies, which due to the broad experience in other medical contexts mostly employed bone marrow-derived MSCs by means of intravenous transplantation. With the overall number of clinical trials limited in number, only a fraction of these studies used non-treated control groups, and only single studies were adequately blinded. Despite these limitations, first promising results justify the need for more elaborate clinical trials in order to make stem cell transplantation a success for stroke treatment in the future.

  12. 78 FR 12664 - Human Subject Protection; Acceptance of Data From Clinical Studies for Medical Devices

    Science.gov (United States)

    2013-02-25

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Parts 807, 812, and... this document) identifying ethical and other principles that provide assurance of the quality and... communities as ``a standard for the design, conduct, performance, monitoring, auditing, recording, analyses...

  13. In vitro study of RRS HA injectable mesotherapy/biorevitalization product on human skin fibroblasts and its clinical utilization.

    Science.gov (United States)

    Deglesne, Pierre-Antoine; Arroyo, Rodrigo; Ranneva, Evgeniya; Deprez, Philippe

    2016-01-01

    Mesotherapy/biorevitalization with hyaluronic acid (HA) is a treatment approach currently used for skin rejuvenation. Various products with a wide range of polycomponent formulations are available on the market. Most of these formulations contain noncross-linked HA in combination with a biorevitalization cocktail, formed by various amounts of vitamins, minerals, amino acids, nucleotides, coenzymes, and antioxidants. Although ingredients are very similar among the different products, in vitro and clinical effects may vary substantially. There is a real need for better characterization of these products in terms of their action on human skin or in vitro skin models. In this study, we analyzed the effect of the RRS(®) (Repairs, Refills, Stimulates) HA injectable medical device on human skin fibroblasts in vitro. Skin fibroblast viability and its capacity to induce the production of key extracellular matrix were evaluated in the presence of different concentrations of RRS HA injectable. Viability was evaluated through colorimetric MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay, and key extracellular matrix genes, type I collagen and elastin, were quantified by quantitative polymerase chain reaction. Results demonstrated that RRS HA injectable could promote human skin fibroblast viability (+15%) and increase fibroblast gene expression of type I collagen and elastin by 9.7-fold and 14-fold in vitro, respectively. These results demonstrate that mesotherapy/biorevitalization products can, at least in vitro, effectively modulate human skin fibroblasts.

  14. Clinical Trials: A Crucial Key to Human Health Research

    Science.gov (United States)

    ... Past Issues Clinical Trials: A Crucial Key to Human Health Research Past Issues / Summer 2006 Table of Contents ... Javascript on. Photo: PhotoDisc At the forefront of human health research today are clinical trials—studies that use ...

  15. Clinical and histological evaluation of thermal injury thresholds in human teeth: a preliminary study.

    Science.gov (United States)

    Baldissara, P; Catapano, S; Scotti, R

    1997-11-01

    The effect on healthy dental pulp of thermal increases ranging from 8.9 to 14.7 degrees C was evaluated. These temperature increases correspond approximately to those caused by certain restorative procedures, such as tooth preparation with high-speed instruments and the fabrication of direct provisional crowns. Two criteria of evaluation have been used in conjunction, a clinical (symptomatic) and a histological one, to assert with greater precision potential damage to the pulp. The results suggest a low susceptibility of cells to heat, which does not appear to be a major factor of injury, at least in the short term. The main cause of postoperative inflammation or necrosis of the pulp is probably the injury of the dentine, a tissue in direct functional and physiological connection with the pulp.

  16. Human Fitting Studies of Cleveland Clinic Continuous-Flow Total Artificial Heart

    Science.gov (United States)

    Karimov, Jamshid H.; Steffen, Robert J.; Byram, Nicole; Sunagawa, Gengo; Horvath, David; Cruz, Vincent; Golding, Leonard A.R.; Fukamachi, Kiyotaka; Moazami, Nader

    2015-01-01

    Implantation of mechanical circulatory support devices is challenging, especially in patients with a small chest cavity. We evaluated how well the Cleveland Clinic continuous-flow total artificial heart (CFTAH) fit the anatomy of patients about to receive a heart transplant. A mock pump model of the CFTAH was rapid-prototyped using biocompatible materials. The model was brought to the operative table, and the direction, length, and angulation of the inflow/outflow ports and outflow conduits were evaluated after the recipient's ventricles had been resected. Thoracic cavity measurements were based on preoperative computed tomographic data. The CFTAH fit well in all five patients (height, 170 ± 9 cm; weight, 75 ± 24 kg). Body surface area was 1.9 ± 0.3 m2 (range, 1.6-2.1 m2). The required inflow and outflow port orientation of both the left and right housings appeared consistent with the current version of the CFTAH implanted in calves. The left outflow conduit remained straight, but the right outflow direction necessitated a 73 ± 22 degree angulation to prevent potential kinking when crossing over the connected left outflow. These data support the fact that our design achieves the proper anatomical relationship of the CFTAH to a patient's native vessels. PMID:25806613

  17. In vitro study of RRS HA injectable mesotherapy/biorevitalization product on human skin fibroblasts and its clinical utilization

    Directory of Open Access Journals (Sweden)

    Deglesne PA

    2016-02-01

    Full Text Available Pierre-Antoine Deglesne,* Rodrigo Arroyo,* Evgeniya Ranneva, Philippe Deprez Research and Development, SKIN TECH PHARMA GROUP, Castelló d'Empúries, Spain  *These authors contributed equally to this work Abstract: Mesotherapy/biorevitalization with hyaluronic acid (HA is a treatment approach currently used for skin rejuvenation. Various products with a wide range of polycomponent formulations are available on the market. Most of these formulations contain noncross-linked HA in combination with a biorevitalization cocktail, formed by various amounts of vitamins, minerals, amino acids, nucleotides, coenzymes, and antioxidants. Although ingredients are very similar among the different products, in vitro and clinical effects may vary substantially. There is a real need for better characterization of these products in terms of their action on human skin or in vitro skin models. In this study, we analyzed the effect of the RRS® (Repairs, Refills, Stimulates HA injectable medical device on human skin fibroblasts in vitro. Skin fibroblast viability and its capacity to induce the production of key extracellular matrix were evaluated in the presence of different concentrations of RRS HA injectable. Viability was evaluated through colorimetric MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay, and key extracellular matrix genes, type I collagen and elastin, were quantified by quantitative polymerase chain reaction. Results demonstrated that RRS HA injectable could promote human skin fibroblast viability (+15% and increase fibroblast gene expression of type I collagen and elastin by 9.7-fold and 14-fold in vitro, respectively. These results demonstrate that mesotherapy/biorevitalization products can, at least in vitro, effectively modulate human skin fibroblasts.Keywords: mesotherapy, medical device, RRS, collagen, elastin, extracellular matrix

  18. Ultrastructural study of the mycelial phase of clinical isolates of Sporothrix schenckii obtained from feline, canine and human cases of sporotrichosis

    Directory of Open Access Journals (Sweden)

    Isabel Martins Madrid

    2011-09-01

    Full Text Available Using transmission electron microscopy, we studied the presence of melanin and cell wall thickness of clinical isolates of Sporothrix schenckii obtained from cats, dogs and humans as compared to reference strains. We detected differences regarding presence of the melanin among the clinical isolates of S. schenckii and a correlation between presence of melanin and cell wall thickness.

  19. [Epidemiological and clinical characteristics of infants admitted to hospital due to human parechovirus infections: A prospective study in Spain].

    Science.gov (United States)

    Martín Del Valle, Fernando; Calvo, Cristina; Martinez-Rienda, Inés; Cilla, Amaia; Romero, María P; Menasalvas, Ana Isabel; Reis-Iglesias, Leticia; Roda, Diana; Pena, María J; Rabella, Nuria; Portugués de la Red, María Del Mar; Megías, Gregoria; Moreno-Docón, Antonio; Otero, Almudena; Cabrerizo, María

    2018-02-01

    Human parechovirus (HPeV) is one of the recently described picornaviridae viruses that have been associated with fever of unknown origin (FUO), clinical sepsis, gastroenteritis, meningitis, or encephalitis in very young infants. The aim of this study is to describe the epidemiology and clinical features of these viruses. A prospective multicentre 3-year study was conducted in 12 hospitals in Spain. Out of 850 specimens examined, 47 were positive (5.52%), with HPeV-3 being the most frequent (29 cases). Infections occurred throughout the year, but mainly in May and July, and a biennial distribution was observed. More than half (57%) were neonates, and only 2 children were older than 3 months. Fever was present in all children, with irritability in 45%, rash in 18.6%, and diarrhoea in 14%. The results of biochemical tests were all in normal range. The most common final diagnosis was FUO (61%), followed by clinical sepsis (29%). Up to 29% of infants were admitted to the intensive care unit, but only one patient had sequelae. Out of 850 specimens examined, 47 were positive (5.52%) for HPeV, with HPeV-3 being the most frequent (29 cases). Infections occurred throughout the year, but mainly in May and July, and a biennial distribution was observed. More than half (57%) were neonates, and only 2 children were older than 3 months. Fever was present in all children, with irritability in 45%, rash in 18.6%, and diarrhoea in 14%. The results of biochemical tests were all in normal range. The most common final diagnosis was FUO (61%), followed by clinical sepsis (29%). Up to 29% of infants were admitted to the intensive care unit, but only one patient had sequelae CONCLUSIONS: HPeV circulates in our country, mainly during spring and summer, and affects young infants with a FUO and clinical sepsis. Molecular diagnostic techniques in all hospitals could help in improving the management of patients with these infections. Copyright © 2016 Asociación Española de Pediatr

  20. ROC [Receiver Operating Characteristics] study of maximum likelihood estimator human brain image reconstructions in PET [Positron Emission Tomography] clinical practice

    International Nuclear Information System (INIS)

    Llacer, J.; Veklerov, E.; Nolan, D.; Grafton, S.T.; Mazziotta, J.C.; Hawkins, R.A.; Hoh, C.K.; Hoffman, E.J.

    1990-10-01

    This paper will report on the progress to date in carrying out Receiver Operating Characteristics (ROC) studies comparing Maximum Likelihood Estimator (MLE) and Filtered Backprojection (FBP) reconstructions of normal and abnormal human brain PET data in a clinical setting. A previous statistical study of reconstructions of the Hoffman brain phantom with real data indicated that the pixel-to-pixel standard deviation in feasible MLE images is approximately proportional to the square root of the number of counts in a region, as opposed to a standard deviation which is high and largely independent of the number of counts in FBP. A preliminary ROC study carried out with 10 non-medical observers performing a relatively simple detectability task indicates that, for the majority of observers, lower standard deviation translates itself into a statistically significant detectability advantage in MLE reconstructions. The initial results of ongoing tests with four experienced neurologists/nuclear medicine physicians are presented. Normal cases of 18 F -- fluorodeoxyglucose (FDG) cerebral metabolism studies and abnormal cases in which a variety of lesions have been introduced into normal data sets have been evaluated. We report on the results of reading the reconstructions of 90 data sets, each corresponding to a single brain slice. It has become apparent that the design of the study based on reading single brain slices is too insensitive and we propose a variation based on reading three consecutive slices at a time, rating only the center slice. 9 refs., 2 figs., 1 tab

  1. Implementing human factors in clinical practice.

    Science.gov (United States)

    Timmons, Stephen; Baxendale, Bryn; Buttery, Andrew; Miles, Giulia; Roe, Bridget; Browes, Simon

    2015-05-01

    To understand whether aviation-derived human factors training is acceptable and useful to healthcare professionals. To understand whether and how healthcare professionals have been able to implement human factors approaches to patient safety in their own area of clinical practice. Qualitative, longitudinal study using semi-structured interviews and focus groups, of a multiprofessional group of UK NHS staff (from the emergency department and operating theatres) who have received aviation-derived human factors training. The human factors training was evaluated positively, and thought to be both acceptable and relevant to practice. However, the staff found it harder to implement what they had learned in their own clinical areas, and this was principally attributed to features of the informal organisational cultures. In order to successfully apply human factors approaches in hospital, careful consideration needs to be given to the local context and informal culture of clinical practice. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  2. International Conference on Harmonisation; Guidance on M3(R2) Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals; availability. Notice.

    Science.gov (United States)

    2010-01-21

    The Food and Drug Administration (FDA) is announcing the availability of a guidance entitled "M3(R2) Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals.'' The guidance was prepared under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The guidance, which is a revision of an existing guidance, discusses the types of nonclinical studies, their scope and duration, and their relation to the conduct of human clinical trials and marketing authorization for pharmaceuticals. The guidance is intended to facilitate the timely conduct of clinical trials and reduce the unnecessary use of animals and other drug development resources.

  3. [Human papillomavirus infection and its correlates with clinically relevant gynecological and obstetric conditions: A cross-sectional study].

    Science.gov (United States)

    López-Hernández, Daniel; Beltrán-Lagunes, Luis; Brito-Aranda, Leticia; López-Hernández, Maria de la Luz

    2016-08-05

    To analyze the prevalence of human papillomavirus (HPV) infection and the possible epidemiological association with conditions of clinical relevance in women. A cross-sectional study from Mexico City was conducted from January 2012 to December 2014. HPV molecular detection was performed on cervical samples. Data were analyzed with appropriated statistic tests. A total of 1,604 females (median 47, interquartile range 38-54) were analyzed. Global prevalence of infection for any HPV is 9.91% (95% CI 8.6-11.3). An association between infection with 16-HPV and number of abortions (NA) (OR=1.427; 95% CI 1.091-1.866), by univariate regression model (UVRM) was estimated. Moreover, menarche (OR=1.566; 95% CI 1.079-2.272), NA (OR=1.570; 95% CI 1.106-2.227) and number of pregnancies (NP) (OR=0.461; 95% CI 0.260-0.818) have a direct and inverse association with infection by genotype 18 of HPV, respectively. Also, infection with HR-HPV genotypes has an inverse association with NP (OR=0.791; 95% CI 0.707-0.884) by normal labor (OR=0.867; 95% CI 0.767-0.979) and NA (OR=0.715; 95% CI 0.534-0.959) (UVRM), and a direct association with number of sexual partners (OR=1.082; 95% CI 1.015-1.154). Onset of sexual activity has an inverse association with infection by genotype 16- (UVRM: OR=0.814; 95% CI 0.715-0.926; multinomial regression model (MNRM): OR=0.803; 95% CI 0.702-0.918) and HR-HPV (UVRM: OR=0.933; 95% CI 0.889-0.980, and MNRM: OR=0.912; 95% CI 0.867-0.959), all P values were lower than .03. Prevalence of HPV cervical infection is different according to age and it is associated with several medical conditions of clinical relevance in women. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  4. Evaluation of the Potential Risk of Drugs to Induce Hepatotoxicity in Human?Relationships between Hepatic Steatosis Observed in Non-Clinical Toxicity Study and Hepatotoxicity in Humans-

    OpenAIRE

    Goda, Keisuke; Kobayashi, Akio; Takahashi, Akemi; Takahashi, Tadakazu; Saito, Kosuke; Maekawa, Keiko; Saito, Yoshiro; Sugai, Shoichiro

    2017-01-01

    In the development of drugs, we sometimes encounter fatty change of the hepatocytes (steatosis) which is not accompanied by degenerative change in the liver in non-clinical toxicity studies. In this study, we investigated the relationships between fatty change of the hepatocytes noted in non-clinical toxicity studies of compound X, a candidate compound in drug development, and mitochondrial dysfunction in order to estimate the potential risk of the compound to induce drug-induced liver injury...

  5. Clinical phenotype-based gene prioritization: an initial study using semantic similarity and the human phenotype ontology.

    Science.gov (United States)

    Masino, Aaron J; Dechene, Elizabeth T; Dulik, Matthew C; Wilkens, Alisha; Spinner, Nancy B; Krantz, Ian D; Pennington, Jeffrey W; Robinson, Peter N; White, Peter S

    2014-07-21

    Exome sequencing is a promising method for diagnosing patients with a complex phenotype. However, variant interpretation relative to patient phenotype can be challenging in some scenarios, particularly clinical assessment of rare complex phenotypes. Each patient's sequence reveals many possibly damaging variants that must be individually assessed to establish clear association with patient phenotype. To assist interpretation, we implemented an algorithm that ranks a given set of genes relative to patient phenotype. The algorithm orders genes by the semantic similarity computed between phenotypic descriptors associated with each gene and those describing the patient. Phenotypic descriptor terms are taken from the Human Phenotype Ontology (HPO) and semantic similarity is derived from each term's information content. Model validation was performed via simulation and with clinical data. We simulated 33 Mendelian diseases with 100 patients per disease. We modeled clinical conditions by adding noise and imprecision, i.e. phenotypic terms unrelated to the disease and terms less specific than the actual disease terms. We ranked the causative gene against all 2488 HPO annotated genes. The median causative gene rank was 1 for the optimal and noise cases, 12 for the imprecision case, and 60 for the imprecision with noise case. Additionally, we examined a clinical cohort of subjects with hearing impairment. The disease gene median rank was 22. However, when also considering the patient's exome data and filtering non-exomic and common variants, the median rank improved to 3. Semantic similarity can rank a causative gene highly within a gene list relative to patient phenotype characteristics, provided that imprecision is mitigated. The clinical case results suggest that phenotype rank combined with variant analysis provides significant improvement over the individual approaches. We expect that this combined prioritization approach may increase accuracy and decrease effort for

  6. Correlation of contrast-detail analysis and clinical image quality assessment in chest radiography with a human cadaver study.

    Science.gov (United States)

    De Crop, An; Bacher, Klaus; Van Hoof, Tom; Smeets, Peter V; Smet, Barbara S; Vergauwen, Merel; Kiendys, Urszula; Duyck, Philippe; Verstraete, Koenraad; D'Herde, Katharina; Thierens, Hubert

    2012-01-01

    To determine the correlation between the clinical and physical image quality of chest images by using cadavers embalmed with the Thiel technique and a contrast-detail phantom. The use of human cadavers fulfilled the requirements of the institutional ethics committee. Clinical image quality was assessed by using three human cadavers embalmed with the Thiel technique, which results in excellent preservation of the flexibility and plasticity of organs and tissues. As a result, lungs can be inflated during image acquisition to simulate the pulmonary anatomy seen on a chest radiograph. Both contrast-detail phantom images and chest images of the Thiel-embalmed bodies were acquired with an amorphous silicon flat-panel detector. Tube voltage (70, 81, 90, 100, 113, 125 kVp), copper filtration (0.1, 0.2, 0.3 mm Cu), and exposure settings (200, 280, 400, 560, 800 speed class) were altered to simulate different quality levels. Four experienced radiologists assessed the image quality by using a visual grading analysis (VGA) technique based on European Quality Criteria for Chest Radiology. The phantom images were scored manually and automatically with use of dedicated software, both resulting in an inverse image quality figure (IQF). Spearman rank correlations between inverse IQFs and VGA scores were calculated. A statistically significant correlation (r = 0.80, P chest radiography. © RSNA, 2011.

  7. Improving the Clinical Pharmacologic Assessment of Abuse Potential: Part 2: Optimizing the Design of Human Abuse Potential Studies.

    Science.gov (United States)

    Sellers, Edward M

    2018-04-01

    This article discusses the conduct of a human abuse potential study as outlined in the Food and Drug Administration Final Guidance to Industry on Assessment of Abuse Potential. In addition, areas where alternative approaches should be considered are proposed. The design, end points, conduct, and interpretation of the human abuse potential study were reviewed, analyzed, and placed in the context of current scientific knowledge and best practices to mitigate regulatory risk and expedite drug development. The guidance is based on regulatory needs and current scientific practices. However, the reliability and utility of such studies can be improved with better subject selection, data collection, standardization of data collection and staff training, and a better understanding of the measurement properties of the dependent measures. The guidance provides a useful framework for conduct of human abuse potential studies. However, design assumptions, poor choice of end points, failure to consider alternate approaches, and limited experience with interpretation can result in an inadequate study or one that does not fairly represent the abuse potential of a new chemical entity. Methodologic development is needed to strengthen the regulatory framework. The Food and Drug Administration or the National Institutes on Drug Abuse could take a targeted initiative to encourage this work.

  8. Nutritional adequacy of a novel human milk fortifier from donkey milk in feeding preterm infants: study protocol of a randomized controlled clinical trial.

    Science.gov (United States)

    Coscia, Alessandra; Bertino, Enrico; Tonetto, Paola; Peila, Chiara; Cresi, Francesco; Arslanoglu, Sertac; Moro, Guido E; Spada, Elena; Milani, Silvano; Giribaldi, Marzia; Antoniazzi, Sara; Conti, Amedeo; Cavallarin, Laura

    2018-01-09

    Fortification of human milk is a standard practice for feeding very low birth weight infants. However, preterm infants often still experience suboptimal growth and feeding intolerance. New fortification strategies and different commercially available fortifiers have been developed. Commercially available fortifiers are constituted by a blend of ingredients from different sources, including plant oils and bovine milk proteins, thus presenting remarkable differences in the quality of macronutrients with respect to human milk. Based on the consideration that donkey milk has been suggested as a valid alternative for children allergic to cow's milk proteins, due to its biochemical similarity to human milk, we hypothesized that donkey milk could be a suitable ingredient for developing an innovative human milk fortifier. The aim of the study is to evaluate feeding tolerance, growth and clinical short and long-term outcomes in a population of preterm infants fed with a novel multi-component fortifier and a protein concentrate derived from donkey milk, in comparison to an analogous population fed with traditional fortifier and protein supplement containing bovine milk proteins. The study has been designed as a randomized, controlled, single-blind clinical trial. Infants born milk-based multicomponent fortifier and protein supplement, or a combination of a novel multicomponent fortifier and protein supplement derived from donkey milk. The fortification protocol followed is the same for the two groups, and the two diets were designed to be isoproteic and isocaloric. Weight, length and head circumference are measured; feeding tolerance is assessed by a standardized protocol. The occurrence of sepsis, necrotizing enterocolitis and adverse effects are monitored. This is the first clinical study investigating the use of a human milk fortifier derived from donkey milk for the nutrition of preterm infants. If donkey milk derived products will be shown to improve the feeding

  9. Evaluation of the Potential Risk of Drugs to Induce Hepatotoxicity in Human—Relationships between Hepatic Steatosis Observed in Non-Clinical Toxicity Study and Hepatotoxicity in Humans-

    Science.gov (United States)

    Goda, Keisuke; Kobayashi, Akio; Takahashi, Akemi; Takahashi, Tadakazu; Saito, Kosuke; Maekawa, Keiko; Saito, Yoshiro; Sugai, Shoichiro

    2017-01-01

    In the development of drugs, we sometimes encounter fatty change of the hepatocytes (steatosis) which is not accompanied by degenerative change in the liver in non-clinical toxicity studies. In this study, we investigated the relationships between fatty change of the hepatocytes noted in non-clinical toxicity studies of compound X, a candidate compound in drug development, and mitochondrial dysfunction in order to estimate the potential risk of the compound to induce drug-induced liver injury (DILI) in humans. We conducted in vivo and in vitro exploratory studies for this purpose. In vivo lipidomics analysis was conducted to investigate the relationships between alteration of the hepatic lipids and mitochondrial dysfunction. In the liver of rats treated with compound X, triglycerides containing long-chain fatty acids, which are the main energy source of the mitochondria, accumulated. Accumulation of these triglycerides was considered to be related to the inhibition of mitochondrial respiration based on the results of in vitro mitochondria toxicity studies. In conclusion, fatty change of the hepatocytes (steatosis) in non-clinical toxicity studies of drug candidates can be regarded as a critical finding for the estimation of their potential risk to induce DILI in humans when the fatty change is induced by mitochondrial dysfunction. PMID:28417920

  10. Prolactinomas : clinical studies

    NARCIS (Netherlands)

    Kars, Marleen

    2008-01-01

    Prolactinoma are treated with dopamine agonists, which are effective in reducing prolactin and tumor size. Studies reporting clinical and radiological outcome are scarce. The study described in chapter 2, assesses long-term outcome in patients treated with dopamine agonists for macroprolactinoma. An

  11. Frequency and gravity of human envenomations caused by marine catfish (suborder siluroidei): a clinical and epidemiological study.

    Science.gov (United States)

    Haddad, Vidal; Martins, Itamar Alves

    2006-06-15

    Catfish occur in marine and freshwater environments worldwide. They have three serrated venomous bony stings in the dorsal and pectoral fins that are used for defence against predators and are refilled by glandular tissues under the epithelium. However, some catfishes do not have poisonous glands next to the sting and cause traumatic wounds without poisoning. The objective of this study was to provide data for, and comment on, the epidemiological and clinical problems caused by marine catfish. The authors have observed, followed and documented 127 injuries caused by marine catfish stings during different phases of the envenoming over a time period of 8 years at three points along the Western Atlantic Ocean coast. The patients presented intense pain during the acute phase of envenoming and complications, such as bacterial and fungi infections and retention of bony fragments, in the later phase. Immersion of the affected extremity in hot water was used in about 20% of cases with excellent results. Injuries caused by marine catfish are common (about 20% of injuries caused by marine animals in a series of more than 700 injuries recorded by the author) and cause intense pain and later complications. Immersion of the affected extremity in hot water results in improvement in the acute phase, but does not prevent the appearance of secondary infection or foreign body reactions.

  12. Biological and Clinical Study of 6-Deoxy-6-Iodo-D-Glucose: a iodinated tracer of glucose transport and of insulin-resistance in human

    International Nuclear Information System (INIS)

    Barone-Rochette, Gilles

    2013-01-01

    Insulin resistance (IR), characterized by a depressed cellular sensitivity to insulin in insulin-sensitive organs, is a central feature to obesity, the metabolic syndrome, and diabetes mellitus and leads to increase cardiovascular diseases, particularly heart failure. All these events are today serious public health problems. But actually, there is no simple tool to measure insulin resistance. The gold standard technique remains the hyperinsulinemic euglycemic clamp. However, the complexity and length of this technique render it unsuitable for routine clinical use. Many methods or index have been proposed to assess insulin resistance in human, but none have shown enough relevance to be used in clinical use. The U1039 INSERM unit previously has validated a new tracer of glucose transport, radiolabelled with 123 iodine and has developed a fast and simple imaging protocol with a small animal gamma camera, which allows the obtaining of an IR index for each organ, showing more discriminating for the heart. The project of my thesis was the human transfer of this measurement technique, perfectly validated in animal. The first part of this thesis evaluated to tolerance, in vivo kinetics, distribution and dosimetry of novel tracer of glucose transport, the [ 123 I]-6DIG. The safeties of new tracer and measurement technique were adequate. There were no adverse effects with excellent tolerance of the whole protocol. 6DIG eliminating was fast, primarily in the urine and complete within 72 h. The effective whole-body absorbed dose for a complete scan with injection of 92.5 * 2 MBq was between 3 to 4 mSv. The second part of this thesis evaluated in human feasibility and reproducibility of the measurement technique validated in animal. The third part showed techniques used to allow human transfer of this method. The study protocol was applied on 12 subjects (healthy volunteers (n=6) and type 2 diabetic patients (n=6)). With a method adapted to measure in humans, we determined an

  13. BALANOPOSTHITIS: A CLINICAL STUDY

    Directory of Open Access Journals (Sweden)

    Raju

    2015-01-01

    Full Text Available INTRODUCTION: The inflammation of the non - keratinized epithelium of the glans penis (i.e., Balanities and that of prepuce (i.e., posthitis together comprise the term Balanoposthitis. AIMS AND OBJECTIVES: To determine the aetiological and p redisposing factors for the development of Balanoposthitis, and to know its relation with venereal and non - venereal disease, local and systemic precipitatin g factors. To know the prevalence of Balanoposthitis in STD clinic. Study design - retrospective study . MATERIALS AND METHODS: The study material consists of 75 cases of balanoposthitis attending out - patient department Skin & STD clinic during a period exten din g from Feb, 1998 to Feb, 1999 . CRITERIA FOR SELECTION OF A CASE: Only those cases which have a history of redness of glans or mucous surface of prepuce, with or without genital discharge or ulcer on glans or mucosal surface of prepuce with or without discharge or growth on the penis or fissuring of fore skin were selected for the study. RESULTS: Incidence of balanoposthitis during the period from Feb. 98 to Feb.99 was – 11.53%, out of 650 new STD cases. It was observed that maximum number of pat i ents w as in the 21 - 30 age group (33.34%. The next predominant groups affected were 17 - 20 & 31 - 40 age group (20% each. The third most common age group affected was 41 - 50 (16%. In this study 69 patients (92% who presented with balanoposthitis of whatever cause were found to be uncircumcised, only 6 cases (8% were found to be circumcised. Most cases who presented with balanoposthitis gave a history of exposure to STD risk. CONCLUSIONS: Balanoposthitis is very commonly encountered condition in the STD clinics wi th a multi factorial aetiology. Infective causes dominated over the other possible causes, and 30% of the candidial infection had diabetes mellitus as a predisposing factor.

  14. Clinical and epidemiologic characteristics of human bocavirus in Danish infants: results from a prospective birth cohort study

    DEFF Research Database (Denmark)

    von Linstow, Marie-Louise; Høgh, Mette; Høgh, Birthe

    2008-01-01

    BACKGROUND: Human bocavirus (HBoV) is a recently discovered parvovirus that has been detected in respiratory samples from children with acute respiratory tract infection (ARTI) and in feces from children with gastroenteritis. However, its role as a causative agent of respiratory disease is not de......BACKGROUND: Human bocavirus (HBoV) is a recently discovered parvovirus that has been detected in respiratory samples from children with acute respiratory tract infection (ARTI) and in feces from children with gastroenteritis. However, its role as a causative agent of respiratory disease...

  15. Non-clinical immuno-toxicological evaluation of HER1 cancer vaccine in non-human primates: a 12-month study.

    Science.gov (United States)

    Barro, Ana M Bada; Rivero, Arianna Iglesias; Goñi, Avelina León; Navarro, Bárbara O González; Angarica, Meilis Mesa; Ramírez, Belinda Sánchez; Bedoya, Darel Martínez; Triana, Consuelo González; Rodríguez, Axel Mancebo; Parada, Ángel Casacó

    2012-12-17

    Human epidermal growth factor receptor (HER1) constitutes a tumor associated antigen. Its overexpression in many epithelial tumors has been associated with bad prognosis and poor survival. Cancer vaccine based on the extracellular domain (ECD) of HER1 and adjuvated in very small sized proteoliposomes (VSSP) and Montanide ISA 51-VG is a new and complementary approach for the treatment of epithelial tumors. The present study deals with the immunogenicity of this vaccine in Macaca fascicularis monkeys and evaluation of its toxicity during 12 months. Twelve monkeys were randomized into two groups of 3 animals per sex: control and vaccinated. Treated monkeys received 9 doses of vaccination and were daily inspected for clinical signs. Body weight, rectal temperature, cardiac and respiratory rates were measured during the study. Humoral immune response, clinical pathology parameters and delayed type hypensensitivity were analyzed. Skin biopsy was performed at the end of the study in all animals. Animal's survival in the study was 100% (n=12). Local reactions were observed at the administration site of four treated animals (n=6), with two showing slight inflammatory cutaneous damage. Clinical pathology parameters were not affected. HER1 vaccine induced high IgG antibodies titers in the treated animals even when DTH was not observed. The induced antibodies recognized HER1+ tumor cell lines, decreased HER1 phosphorylation and showed anti-proliferative and pro-apoptotic effects in H125 cells. In general the present study showed that HER1 vaccine induced specific immune response in M. fascicularis monkeys and was well tolerated, suggesting it could be safely used in clinical studies in epithelial cancer patients. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. Ridge Preservation Comparing a Nonresorbable PTFE Membrane to a Resorbable Collagen Membrane: A Clinical and Histologic Study in Humans.

    Science.gov (United States)

    Arbab, Hussain; Greenwell, Henry; Hill, Margaret; Morton, Dean; Vidal, Ricardo; Shumway, Brian; Allan, Nicholas D

    2016-02-01

    The primary aim of this randomized, controlled, blinded clinical trial was to compare the effect of a resorbable collagen membrane (CM group) versus a nonresorbable high-density polytetrafluoroethylene membrane (PTFE group) on the clinical and histologic outcomes of a ridge preservation procedure. All 24 sites received an intrasocket cancellous allograft and a buccal overlay bovine derived xenograft. The change in horizontal crestal ridge width was -1.4 ± 1.2 mm for the CM group, whereas the PTFE group lost -2.2 ± 1.5 mm, which was not statistically significant between groups (P > 0.05). Vertical ridge height change was -1.2 ± 1.5 for the CM group, whereas the PTFE group lost -0.5 ± 1.6, which was not significantly different between groups (P > 0.05). The percent vital bone was similar and not significantly different between groups. Primary closure was not obtained and the exposed membrane portion over the socket opening healed with keratinized tissue. The choice of a resorbable versus a nonresorbable barrier membrane did not affect the clinical or the histologic outcome of ridge preservation treatment.

  17. Immunology in the clinic review series; focus on type 1 diabetes and viruses: the enterovirus link to type 1 diabetes: critical review of human studies

    Science.gov (United States)

    Stene, L C; Rewers, M

    2012-01-01

    OTHER THEMES PUBLISHED IN THIS IMMUNOLOGY IN THE CLINIC REVIEW SERIES Metabolic diseases, host responses, cancer, autoinflammatory diseases, allergy. The hypothesis that under some circumstances enteroviral infections can lead to type 1 diabetes (T1D) was proposed several decades ago, based initially on evidence from animal studies and sero-epidemiology. Subsequently, enterovirus RNA has been detected more frequently in serum of patients than in control subjects, but such studies are susceptible to selection bias and reverse causality. Here, we review critically recent evidence from human studies, focusing on longitudinal studies with potential to demonstrate temporal association. Among seven longitudinal birth cohort studies, the evidence that enterovirus infections predict islet autoimmunity is quite inconsistent in our interpretation, due partially, perhaps, to heterogeneity in study design and a limited number of subjects studied. An association between enterovirus and rapid progression from autoimmunity to T1D was reported by one longitudinal study, but although consistent with evidence from animal models, this novel observation awaits replication. It is possible that a potential association with initiation and/or progression of islet autoimmunity can be ascribed to a subgroup of the many enterovirus serotypes, but this has still not been investigated properly. There is a need for larger studies with frequent sample intervals and collection of specimens of sufficient quality and quantity for detailed characterization of enterovirus. More research into the molecular epidemiology of enteroviruses and enterovirus immunity in human populations is also warranted. Ultimately, this knowledge may be used to devise strategies to reduce the risk of T1D in humans. PMID:22385232

  18. In vivo imaging of twist drill drainage for subdural hematoma: a clinical feasibility study on electrical impedance tomography for measuring intracranial bleeding in humans.

    Science.gov (United States)

    Dai, Meng; Li, Bing; Hu, Shijie; Xu, Canhua; Yang, Bin; Li, Jianbo; Fu, Feng; Fei, Zhou; Dong, Xiuzhen

    2013-01-01

    Intracranial bleeding is one of the most severe medical emergencies in neurosurgery. Early detection or diagnosis would largely reduce the rate of disability and mortality, and improve the prognosis of the patients. Electrical Impedance Tomography (EIT) can non-invasively image the internal resistivity distribution within a human body using a ring of external electrodes, and is thus a promising technique to promptly detect the occurrence of intracranial bleedings because blood differs from other brain tissues in resistivity. However, so far there is no experimental study that has determined whether the intracranial resistivity changes in humans could be repeatedly detected and imaged by EIT. Hence, we for the first time attempt to clinically validate this by in vivo imaging the influx and efflux of irrigating fluid (5% dextrose in water, D5W) during the twist-drill drainage operation for the patients with subdural hematoma (SDH). In this study, six patients (four male, two female) with subacute or chronic SDH received the surgical operation in order to evacuate the hematoma around subdural region, and EIT measurements were performed simultaneously on each patient's head. The results showed that the resistivity significantly increased on the corresponding position of EIT images during the influx of D5W and gradually decreased back to baseline during the efflux. In the quantitative analysis, the average resistivity values demonstrated the similar results and had highly linear correlation (R(2) = 0.93 ± 0.06) with the injected D5W volumes, as well as the area of the resistivity gain(R(2) = 0.94 ± 0.05). In conclusion, it was clinically validated that intracranial resistivity changes in humans were detectable and quantifiable by the EIT method. After further technical improvements, EIT has the great potential of being a routine neuroimaging tool for early detection of intracranial bleedings.

  19. In vivo imaging of twist drill drainage for subdural hematoma: a clinical feasibility study on electrical impedance tomography for measuring intracranial bleeding in humans.

    Directory of Open Access Journals (Sweden)

    Meng Dai

    Full Text Available Intracranial bleeding is one of the most severe medical emergencies in neurosurgery. Early detection or diagnosis would largely reduce the rate of disability and mortality, and improve the prognosis of the patients. Electrical Impedance Tomography (EIT can non-invasively image the internal resistivity distribution within a human body using a ring of external electrodes, and is thus a promising technique to promptly detect the occurrence of intracranial bleedings because blood differs from other brain tissues in resistivity. However, so far there is no experimental study that has determined whether the intracranial resistivity changes in humans could be repeatedly detected and imaged by EIT. Hence, we for the first time attempt to clinically validate this by in vivo imaging the influx and efflux of irrigating fluid (5% dextrose in water, D5W during the twist-drill drainage operation for the patients with subdural hematoma (SDH. In this study, six patients (four male, two female with subacute or chronic SDH received the surgical operation in order to evacuate the hematoma around subdural region, and EIT measurements were performed simultaneously on each patient's head. The results showed that the resistivity significantly increased on the corresponding position of EIT images during the influx of D5W and gradually decreased back to baseline during the efflux. In the quantitative analysis, the average resistivity values demonstrated the similar results and had highly linear correlation (R(2 = 0.93 ± 0.06 with the injected D5W volumes, as well as the area of the resistivity gain(R(2 = 0.94 ± 0.05. In conclusion, it was clinically validated that intracranial resistivity changes in humans were detectable and quantifiable by the EIT method. After further technical improvements, EIT has the great potential of being a routine neuroimaging tool for early detection of intracranial bleedings.

  20. In vitro radiation studies on Ewing's sarcoma cell lines and human bone marrow: application to the clinical use of total body irradiation (TBI)

    International Nuclear Information System (INIS)

    Kinsella, T.J.; Mitchell, J.B.; McPherson, S.; Miser, J.; Triche, T.; Glatstein, E.

    1984-01-01

    Patients with Ewing's sarcoma who present with a central axis or proximal extremity primary and/or with metastatic disease have a poor prognosis despite aggressive combination chemotherapy and local irradiation. In this high risk group of patients, total body irradiation (TBI) has been proposed as a systemic adjuvant. To aid in the design of a clinical TBI protocol, the authors have studied in the in vitro radiation response of two established cell lines of Ewing's sarcoma and human bone marrow CFUc. The Ewing's lines showed a larger D 0 and anti-n compared to the bone marrow CFU. No repair of potentially lethal radiation damage (PLDR) was found after 4.5 Gy in plateau phase Ewing's sarcoma cells. A theoretical split dose survival curve for both the Ewing's sarcoma lines and human bone marrow CFUc using this TBI schedule shows a significantly lower surviving fraction (10 -4 -10 -5 ) for the bone marrow CFUc. Based on these in vitro results, two 4.0 Gy fractions separated by 24 hours is proposed as the TBI regimen. Because of the potentially irreversible damage to bone marrow, autologous bone marrow transplantation following the TBI is felt to be necessary. The details of this clinical protocol in high risk Ewing's sarcoma patients are outlined

  1. Translational research into species differences of endocrine toxicity via steroidogenesis inhibition by SMP-028 — For human safety in clinical study

    International Nuclear Information System (INIS)

    Nishizato, Yohei; Imai, Satoki; Okahashi, Noriko; Yabunaka, Atsushi; Kunimatsu, Takeshi; Kikuchi, Kaoru; Yabuki, Masashi

    2014-01-01

    SMP-028 is a drug candidate developed for the treatment of asthma. In a 13-week repeated dose toxicity study of SMP-028 in rats and monkeys, differences of endocrine toxicological events between rats and monkeys were observed. In rats, these toxicological events mainly consisted of pathological changes in the adrenal, testis, ovary, and the other endocrine-related organs. On the other hand, in monkeys, no toxicological events were observed. The goal of this study is to try to understand the reason why only rats, but not monkeys, showed toxicological events following treatment with SMP-028 and to eventually predict the possible toxicological effect of this compound on human endocrine organs. Our results show that SMP-028 inhibits neutral cholesterol esterase more strongly than other steroidogenic enzymes in rats. Although SMP-028 also inhibits monkeys and human neutral cholesterol esterase, this inhibition is much weaker than that of rat neutral cholesterol esterase. These results indicate (1) that the difference in endocrine toxicological events between rats and monkeys is mainly due to inhibition of steroidogenesis by SMP-028 in rats, not in monkeys, and (2) that SMP-028 may not affect steroidogenesis in humans and therefore might cause no endocrine toxicological events in clinical studies. - Highlights: • SMP-028 inhibits neutral CEase more strongly than other steroidogenic enzymes in rats. • Inhibition of neutral CEase in rats by SMP-028 suppresses steroidogenesis in vivo. • SMP-028 does not inhibit neutral CEase in monkeys in vivo. • Steroidogenesis pathway in monkeys treated with SMP-028 was not suppressed. • SMP-028 may not inhibit LIPE in humans in vivo

  2. Translational research into species differences of endocrine toxicity via steroidogenesis inhibition by SMP-028 — For human safety in clinical study

    Energy Technology Data Exchange (ETDEWEB)

    Nishizato, Yohei, E-mail: yohei-nishizato@ds-pharma.co.jp [Preclinical Research Laboratories, Dainippon Sumitomo Pharma Co., Ltd., 33-94, Enoki-cho, Suita, Osaka 564-0053 (Japan); Imai, Satoki [Preclinical Research Laboratories, Dainippon Sumitomo Pharma Co., Ltd., 33-94, Enoki-cho, Suita, Osaka 564-0053 (Japan); Okahashi, Noriko [Research Planning and Intelligence, Dainippon Sumitomo Pharma Co., Ltd., 33-94, Enoki-cho, Suita, Osaka 564-0053 (Japan); Yabunaka, Atsushi; Kunimatsu, Takeshi [Preclinical Research Laboratories, Dainippon Sumitomo Pharma Co., Ltd., 33-94, Enoki-cho, Suita, Osaka 564-0053 (Japan); Kikuchi, Kaoru [Innovative Drug Discovery Laboratories, Dainippon Sumitomo Pharma Co., Ltd., 33-94, Enoki-cho, Suita, Osaka 564-0053 (Japan); Yabuki, Masashi [Preclinical Research Laboratories, Dainippon Sumitomo Pharma Co., Ltd., 33-94, Enoki-cho, Suita, Osaka 564-0053 (Japan)

    2014-05-01

    SMP-028 is a drug candidate developed for the treatment of asthma. In a 13-week repeated dose toxicity study of SMP-028 in rats and monkeys, differences of endocrine toxicological events between rats and monkeys were observed. In rats, these toxicological events mainly consisted of pathological changes in the adrenal, testis, ovary, and the other endocrine-related organs. On the other hand, in monkeys, no toxicological events were observed. The goal of this study is to try to understand the reason why only rats, but not monkeys, showed toxicological events following treatment with SMP-028 and to eventually predict the possible toxicological effect of this compound on human endocrine organs. Our results show that SMP-028 inhibits neutral cholesterol esterase more strongly than other steroidogenic enzymes in rats. Although SMP-028 also inhibits monkeys and human neutral cholesterol esterase, this inhibition is much weaker than that of rat neutral cholesterol esterase. These results indicate (1) that the difference in endocrine toxicological events between rats and monkeys is mainly due to inhibition of steroidogenesis by SMP-028 in rats, not in monkeys, and (2) that SMP-028 may not affect steroidogenesis in humans and therefore might cause no endocrine toxicological events in clinical studies. - Highlights: • SMP-028 inhibits neutral CEase more strongly than other steroidogenic enzymes in rats. • Inhibition of neutral CEase in rats by SMP-028 suppresses steroidogenesis in vivo. • SMP-028 does not inhibit neutral CEase in monkeys in vivo. • Steroidogenesis pathway in monkeys treated with SMP-028 was not suppressed. • SMP-028 may not inhibit LIPE in humans in vivo.

  3. Human Polymorphisms as Clinical Predictors in Leprosy

    Directory of Open Access Journals (Sweden)

    Ernesto Prado Montes de Oca

    2011-01-01

    Full Text Available Genetic and serum markers in human host can predict leprosy susceptibility per se as well as be useful in classification and/or prediction of clinical variants and immunological responses in leprosy. Adequate and timely assessment of potential risks associated with these 38 host leprosy genes could diminish epidemiological burden and improve life quality of patients with this still prevalent mycobacterial disease.

  4. [Clinical studies on regulatory system of thyroid hormone secretion and serum triiodothyronine. Part. I. Solid-state radioimmunoassy for human serum TSH and its clinical application (author's transl)].

    Science.gov (United States)

    Takeda, Y

    1975-01-20

    A solid-state RIA method using a plastic microtiter plate for human TSH was developed: 1) The choice of carrier protein for standard TSH was critical in this method and pooled sera from untreated Graves patients was found to be suitable for this purpose. The mean lowest detectable TSH level was 0.2 muU/assay, which was almost equal to those reported by other methods. This method is superior in simple assay procedure, especially in the separation of bound and free TSH and in the shorter incubation time required in the double antibody method. 2) Serum TSH concentration in 22 normal subjects, 17 patients with Graves' disease, 35 Hashimoto's thyroiditis, 18 primary hypothyrodism, 16 simple goiter, 4 nodular goiter and 7 secondary hypothyroidism was estimated as 4.7 +/- 2.0 muU/ml (mean +/- s.d.), 2.1 +/- 0.2 mu/U/ml, 14.1 +/- 26.5 muU/ml, 211 +/- 177 muU/ml, 3.6 +/- 2.4 muU/ml, 3.2 +/- 2.4 muU/ml and 2.6 +/- 1.0 muU/ml, respectively. 3) A statistically significant and hyperbolic inverse correlation (r= --0.37, N=90) was found between TSH and T4 levels. Some cases with normal T4 level were found to be high in TSH levels. It was also noted that 36 of 65 euthyroid cases (55.4%) who had been treated with 131I for Graves' disease showed elevated TSH levels. 4) After intravenous injection of 500 mug TRH, TSH level reached its peak value of 8 to 32 muU/ml at 15 to 45 minutes in normal subjects. Low to no response was found in patients with Graves' disease. An exaggerated response in patients with primary hypothyroidism to TRH was observed and an inhibitory process in TSH production at the pituitary level was suggested in patients with Cushing syndrome. Hypothyroid patients with pituitary lesion showed low or no response, on the other hand some hypothyroid patients with lesions around the pituitary and hypothalamus showed high basal TSH and exaggerated response to TRH.

  5. ABDOMINAL TRAUMA- CLINICAL STUDY

    Directory of Open Access Journals (Sweden)

    Vanaja Ratnakumari Billa

    2017-08-01

    Full Text Available BACKGROUND In the recent times there has been increased incidence of abdominal trauma cases due to several causes. Quick and prompt intervention is needed to decrease the mortality of the patients. So we conducted a study to assess the cause and the management of abdominal trauma cases in our institution. The aim of this study was to know the incidence of blunt and penetrating injuries and their causes, age and sex incidence, importance of various investigations, mode of treatment offered and post-operative complications. To study the cause of death and evolve better management. MATERIALS AND METHODS The present study comprises of patients admitted to and operated in various surgical units in the Department of Surgery at Government General Hospital, attached to Guntur Medical College Guntur, from August 2014 to October 2016. RESULTS Increase incidence seen in age group 20-29 years (30%. Male predominance 77.5%. Mechanism of injury–road traffic accidents 65%. Isolated organ injury–colon and rectum 40%. Other associated injuries–chest injuries with rib fractures 7.5%. Complications–wound infection 17.5%. Duration of hospital stay 8–14 days. Bowel injury management–closure of perforation 84.6%. Resection anastomosis 15.38%. CONCLUSION Thorough clinical examination, diagnostic paracentesis, plain X-ray erect abdomen and ultrasound proved to be very helpful in the diagnosis of intra-abdominal injuries. Spleen is the commonest organ involved in blunt trauma and colon is the commonly injured organ in penetrating abdominal trauma, many patients have associated extremity and axial skeleton injuries. With advances in diagnosis and intensive care technologies, most patients of solid visceral injuries with hemodynamic stability can be managed conservatively. Surgical site infection is the most common complication following surgery. The mortality is high; reason might be patient reaching the hospital late, high incidence of postoperative septic

  6. Study of association and molecular analysis of human papillomavirus in breast cancer of Indian patients: Clinical and prognostic implication.

    Directory of Open Access Journals (Sweden)

    Saimul Islam

    Full Text Available Human papillomavirus (HPV causes tumors primarily Cervical cancer. Recently, inconsistent reports came up in Breast cancer (BC too. In India, despite treatment 70,218 BC patients die each year. So, we explored the association of HPV, if any, with BC prognosis in Indian pre-therapeutic (PT and Neo-adjuvant chemotherapy (NACT patients with subsequent analysis of HPV profile.HPV prevalence was checked and analysis of physical status, copy number, genome variation, promoter methylation and expression (mRNA and protein of the prevalent subtype was done.High prevalence of HPV was observed in both PT (64.0% and NACT (71.0% cases with significant association with younger (20-45 yrs PT patients. Interestingly, HPV infection was significantly increased from adjacent normal breast (9.5%, 2/21, fibro adenomas (30%, 3/10 to tumors (64.8%, 203/313 samples. In both PT and NACT cases, HPV16 was the most prevalent subtype (69.0% followed by HPV18 and HPV33. Survival analysis illustrated hrHPV infected PT patients had worst prognosis. So, detailed analysis of HPV16 profile was done which showed Europian-G350 as the most frequent HPV16 variant along with high rate of integration. Moreover, low copy number and hyper-methylation of P97 early promoter were concordant with low HPV16 E6 and E7 mRNA and protein expression. Notably, four novel variations (KT020838, KT020840, KT020841 and KT020839 in the LCR region and two (KT020836 and KT020837 in the E6 region were identified for the first time along with two novel E6^E7*I (KU199314 and E6^E7*II (KU199315 fusion transcript variants.Thus, significant association of hrHPV with prognosis of Indian BC patients led to additional investigation of HPV16 profile. Outcomes indicated a plausible role of HPV in Indian BC patients.

  7. Prognostic significance of equivocal human epidermal growth factor receptor 2 results and clinical utility of alternative chromosome 17 genes in patients with invasive breast cancer: A cohort study.

    Science.gov (United States)

    Sneige, Nour; Hess, Kenneth R; Multani, Asha S; Gong, Yun; Ibrahim, Nuhad K

    2017-04-01

    The 2013 testing guidelines for determining the human epidermal growth factor receptor 2 (HER2) status include new cutoff points for the HER2/chromosome enumeration probe 17 (CEP17) ratio and the average HER2 copy number per cell, and they recommend using a reflex test with alternative chromosome 17 probes (Ch17Ps) to resolve equivocal HER2 results. This study sought to determine the clinical utility of alternative Ch17Ps in equivocal cases and the effects of equivocal results and/or a change in the HER2 status on patients' outcomes. The University of Texas MD Anderson Cancer Center database of HER2 dual-probe fluorescence in situ hybridization results from 2000 to 2010 was searched for cases of invasive breast cancer with HER2/CEP17 ratios Cancer 2017;123:1115-1123. © 2016 American Cancer Society. © 2016 American Cancer Society.

  8. Dietary Supplementation with a Combination of Lactoferrin, Fish Oil, and Enterococcus faecium WB2000 for Treating Dry Eye: A Rat Model and Human Clinical Study.

    Science.gov (United States)

    Kawashima, Motoko; Nakamura, Shigeru; Izuta, Yusuke; Inoue, Sachiko; Tsubota, Kazuo

    2016-04-01

    To examine the effect of a combined dietary supplement containing fish oil, lactoferrin, zinc, vitamin C, lutein, vitamin E, γ-aminobutanoic acid, and Enterococcus faecium WB2000 on dry eye. A preliminary study in a rat model and a prospective, randomized, double-blind, placebo-controlled study in humans were conducted. Forty Japanese volunteers aged 22 to 59 years were randomized into combined dietary supplement (2 capsules/day; 20 participants) and placebo (vehicle; 19 participants) groups and treated once daily for 8 weeks. Rats received the combined dietary supplement components (10 or 50 mg/kg orally) or vehicle (2% DMSO), and dry eye was mechanically induced for 2 days. Tear production was measured in rats after dry eye was induced. Humans were assessed at baseline and weeks 4 and 8 post-supplementation based on keratoconjunctival epithelial damage; fluorescein tear film breakup time; tear production; biochemical data; information regarding subjective dry eye symptoms by answering a questionnaire; and information regarding adverse events via medical interviews. Supplementation dose-dependently mitigated the decrease in tear production in rats. Among subjects with confirmed dry eye, clinical symptoms improved at weeks 4 and 8 more significantly in the supplementation group than in the placebo group (Peye symptoms. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Uncertainty sources in radiopharmaceuticals clinical studies

    International Nuclear Information System (INIS)

    Degenhardt, Aemilie Louize; Oliveira, Silvia Maria Velasques de

    2014-01-01

    The radiopharmaceuticals should be approved for consumption by evaluating their quality, safety and efficacy. Clinical studies are designed to verify the pharmacodynamics, pharmacological and clinical effects in humans and are required for assuring safety and efficacy. The Bayesian analysis has been used for clinical studies effectiveness evaluation. This work aims to identify uncertainties associated with the process of production of the radionuclide and radiopharmaceutical labelling as well as the radiopharmaceutical administration and scintigraphy images acquisition and processing. For the development of clinical studies in the country, the metrological chain shall assure the traceability of the surveys performed in all phases. (author)

  10. A whey-protein supplement increases fat loss and spares lean muscle in obese subjects: a randomized human clinical study

    Directory of Open Access Journals (Sweden)

    Ward Loren S

    2008-03-01

    Full Text Available Abstract Background This study evaluated a specialized whey fraction (Prolibra™, high in leucine, bioactive peptides and milk calcium for use as a dietary supplement to enhance weight loss. Methods This was a randomized, double-blind, parallel-arm, 12-week study. Caloric intake was reduced 500 calories per day. Subjects consumed Prolibra or an isocaloric ready-to-mix beverage 20 minutes before breakfast and 20 minutes before dinner. Body fat and lean muscle tissue were measured by dual-energy x-ray absorptiometry (DEXA. Body weight and anthropometric measurements were recorded every 4 weeks. Blood samples were taken at the beginning and end of the study. Statistical analyses were performed on all subjects that completed (completer analysis and all subjects that lost at least 2.25 kg of body weight (responder analysis. Within group significance was determined at P Results Both groups lost a significant amount of weight and the Prolibra group tended to lose more weight than the control group; however the amount of weight loss was not significantly different between groups after 12 weeks. Prolibra subjects lost significantly more body fat compared to control subjects for both the completer (2.81 vs. 1.62 kg P = 0.03 and responder (3.63 vs. 2.11 kg, P = 0.01 groups. Prolibra subjects lost significantly less lean muscle mass in the responder group (1.07 vs. 2.41 kg, P = 0.02. The ratio of fat to lean loss (kg fat lost/kg lean lost was much larger for Prolibra subjects for both completer (3.75 vs. 1.05 and responder (3.39 vs. 0.88 groups. Conclusion Subjects in both the control and treatment group lost a significant amount of weight with a 500 calorie reduced diet. Subjects taking Prolibra lost significantly more body fat and showed a greater preservation of lean muscle compared to subjects consuming the control beverage. Because subjects taking Prolibra lost 6.1% of their body fat mass, and because a 5% reduction of body fat mass has been shown to

  11. ANTIPLAQUE AND ANTIGINGIVITIS EFFECTS OF A GEL CONTAINING PUNICA GRANATUM LINN EXTRACT. A DOUBLE-BLIND CLINICAL STUDY IN HUMANS

    Science.gov (United States)

    Salgado, Alexandre Daher Yunes; Maia, Juliana Lemos; Pereira, Sérgio Luís da Silva; de Lemos, Telma Leda Gomes; Mota, Olívia Morais de Lima

    2006-01-01

    Objectives: The antiplaque and antigingivitis effects of a gel containing 10% Punica granatum Linn extract were evaluated using a 21-day partial-mouth experimental model of gingivitis. Methods: 23 volunteers participated in this cross-over, doubleblind study, carried out in 2 phases of 21 days each. For each period of the experiment, an acrylic toothshield was made for each volunteer to carry the test or placebo gel as well as to avoid brushing of the 4 experimental teeth (posterior teeth in the lower left quadrant). The subjects were randomly assigned to use either the placebo gel (control group) or the test gel (experimental group) and were instructed to brush the remaining teeth normally 3 times a day. On days 0 and 21, the visible plaque index (VPI) and gingival bleeding index (GBI) were recorded. Results: The results did not show statistically significant difference between control and experimental groups for either of the indices (VPI and GBI). Conclusion: The gel containing 10% Punica granatum Linn extract was not efficient in preventing supragingival dental plaque formation and gingivitis. PMID:19089066

  12. Silver percutaneous absorption after exposure to silver nanoparticles: a comparison study of three human skin graft samples used for clinical applications.

    Science.gov (United States)

    Bianco, C; Adami, G; Crosera, M; Larese, F; Casarin, S; Castagnoli, C; Stella, M; Maina, G

    2014-11-01

    Silver nanoparticles (AgNPs) are increasingly applied to a wide range of materials for biomedical use. These enable a close contact with human skin, thanks to the large release of silver ions that is responsible for a broad spectrum of antimicrobial activity. Silver can permeate the skin; however, there are no data available on silver permeation through skin grafts commonly used in burns recovery. The aim of our study was to evaluate silver penetration using fresh, cryopreserved, and glycerolized human skin grafts after exposure to a suspension of AgNPs in synthetic sweat using a Franz diffusion cell apparatus for 24 h. Silver permeation profiles revealed a significantly higher permeation through glycerolized skin compared with both fresh and cryopreserved skin: 24-h silver flux penetration was 0.2 ng cm(-2) h(-1) (lag time: 8.2 h) for fresh skin, 0.3 ng cm(-2) h(-1) (lag time: 10.9 h) for cryopreserved skin, and 3.8 ng cm(-2) h(-1) (lag time: 6.3 h) for glycerolized skin. Permeation through glycerolized skin is significantly higher compared to both fresh and cryopreserved skin. This result can generate relevant clinical implications for burns treatment with products containing AgNPs. Copyright © 2014 Elsevier Ltd and ISBI. All rights reserved.

  13. An alkaline comet assay study on the antimalarial drug atovaquone in human peripheral blood lymphocytes: a study based on clinically relevant concentrations.

    Science.gov (United States)

    Dinter, Domagoj; Gajski, Goran; Garaj-Vrhovac, Vera

    2013-01-01

    Atovaquone, a hydroxynaphthoquinone, is an anti-parasite drug, selectively targeting the mitochondrial respiratory chain of malaria parasite. It is used for both the treatment and prevention of malaria, usually in a fixed combination with proguanil. Although atovaquone has not often been associated with severe adverse reactions in the recommended dosages and has a relatively favorable side effect profile, the present study was undertaken to evaluate its cytogenotoxic potential towards human peripheral blood lymphocytes. Two different concentrations of atovaquone found in plasma when used in fixed-dose combination with proguanile hydrochloride were used with and without S9 metabolic activation: 2950 ng ml(-1) used for prophylactic treatment and 11 800 ng ml(-1) used in treatment of malaria. The results showed that lymphocyte viability was not affected after the treatment, suggesting that atovaquone was not cytotoxic in the given concentrations. With the alkaline comet assay we demonstrated that in human peripheral blood lymphocytes no significant changes in comet parameters occurred after the treatment. There were no differences in tested parameters with the addition of S9 metabolic activation, indicating that atovaquone either has no metabolite or it is not toxic in the given concentrations. Since no effects were observed after the treatment, it is to be concluded that atovaquone is safe from the aspect of genototoxicity in the recommended dosages. Copyright © 2011 John Wiley & Sons, Ltd.

  14. Comparative studies on drug binding to the purified and pharmaceutical-grade human serum albumins: Bridging between basic research and clinical applications of albumin.

    Science.gov (United States)

    Ashrafi-Kooshk, Mohammad Reza; Ebrahimi, Farangis; Ranjbar, Samira; Ghobadi, Sirous; Moradi, Nastaran; Khodarahmi, Reza

    2015-09-01

    Human serum albumin (HSA), the most abundant protein in blood plasma, is a monomeric multidomain protein that possesses an extraordinary capacity for binding, so that serves as a circulating depot for endogenous and exogenous compounds. During the heat sterilization process, the structure of pharmaceutical-grade HSA may change and some of its activities may be lost. In this study, to provide deeper insight on this issue, we investigated drug-binding and some physicochemical properties of purified albumin (PA) and pharmaceutical-grade albumin (PGA) using two known drugs (indomethacin and ibuprofen). PGA displayed significantly lower drug binding capacity compared to PA. Analysis of the quenching and thermodynamic parameters indicated that intermolecular interactions between the drugs and the proteins are different from each other. Surface hydrophobicity as well as the stability of PGA decreased compared to PA, also surface hydrophobicity of PA and PGA increased upon drugs binding. Also, kinetic analysis of pseudo-esterase activities indicated that Km and Vmax parameters for PGA enzymatic activity are more and less than those of PA, respectively. This in vitro study demonstrates that the specific drug binding of PGA is significantly reduced. Such studies can act as connecting bridge between basic research discoveries and clinical applications. Copyright © 2015 The International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

  15. Eggshell membrane: A possible new natural therapeutic for joint and connective tissue disorders. Results from two open-label human clinical studies

    Directory of Open Access Journals (Sweden)

    Kevin J Ruff

    2009-05-01

    Full Text Available Kevin J Ruff1, Dale P DeVore2, Michael D Leu3, Mark A Robinson41ESM Technologies, LLC, Carthage, MO, USA; 2Membrell, LLC, Carthage, MO, USA; 3Private Practice, Jenks, OK, USA; 4Robinson Family Health Center, Carthage, MO, USABackground: Natural Eggshell Membrane (NEM® is a novel dietary supplement that contains naturally occurring glycosaminoglycans and proteins essential for maintaining healthy joint and connective tissues. Two single center, open-label human clinical studies were conducted to evaluate the efficacy and safety of NEM® as a treatment for pain and inflexibility associated with joint and connective tissue disorders. Methods: Eleven (single-arm trial and 28 (double-arm trial patients received oral NEM® 500 mg once daily for four weeks. The primary outcome measure was to evaluate the change in general pain associated with the treatment joints/areas (both studies. In the single-arm trial, range of motion (ROM and related ROM-associated pain was also evaluated. The primary treatment response endpoints were at seven and 30 days. Both clinical assessments were performed on the intent-to-treat (ITT population within each study.Results: Single-arm trial: Supplementation with NEM® produced a significant treatment response at seven days for flexibility (27.8% increase; P = 0.038 and at 30 days for general pain (72.5% reduction; P = 0.007, flexibility (43.7% increase; P = 0.006, and ROM-associated pain (75.9% reduction; P = 0.021. Double-arm trial: Supplementation with NEM® produced a significant treatment response for pain at seven days for both treatment arms (X: 18.4% reduction; P = 0.021. Y: 31.3% reduction; P = 0.014. There was no clinically meaningful difference between treatment arms at seven days, so the Y arm crossed over to the X formulation for the remainder of the study. The significant treatment response continued through 30 days for pain (30.2% reduction; P = 0.0001. There were no adverse events reported during either

  16. Technology for Large-Scale Translation of Clinical Practice Guidelines: A Pilot Study of the Performance of a Hybrid Human and Computer-Assisted Approach.

    Science.gov (United States)

    Van de Velde, Stijn; Macken, Lieve; Vanneste, Koen; Goossens, Martine; Vanschoenbeek, Jan; Aertgeerts, Bert; Vanopstal, Klaar; Vander Stichele, Robert; Buysschaert, Joost

    2015-10-09

    The construction of EBMPracticeNet, a national electronic point-of-care information platform in Belgium, began in 2011 to optimize quality of care by promoting evidence-based decision making. The project involved, among other tasks, the translation of 940 EBM Guidelines of Duodecim Medical Publications from English into Dutch and French. Considering the scale of the translation process, it was decided to make use of computer-aided translation performed by certificated translators with limited expertise in medical translation. Our consortium used a hybrid approach, involving a human translator supported by a translation memory (using SDL Trados Studio), terminology recognition (using SDL MultiTerm terminology databases) from medical terminology databases, and support from online machine translation. This resulted in a validated translation memory, which is now in use for the translation of new and updated guidelines. The objective of this experiment was to evaluate the performance of the hybrid human and computer-assisted approach in comparison with translation unsupported by translation memory and terminology recognition. A comparison was also made with the translation efficiency of an expert medical translator. We conducted a pilot study in which two sets of 30 new and 30 updated guidelines were randomized to one of three groups. Comparable guidelines were translated (1) by certificated junior translators without medical specialization using the hybrid method, (2) by an experienced medical translator without this support, and (3) by the same junior translators without the support of the validated translation memory. A medical proofreader who was blinded for the translation procedure, evaluated the translated guidelines for acceptability and adequacy. Translation speed was measured by recording translation and post-editing time. The human translation edit rate was calculated as a metric to evaluate the quality of the translation. A further evaluation was made of

  17. A Human Clinical, Histological, Histomorphometrical, and Radiographical Study on Biphasic HA-Beta-TCP 30/70 in Maxillary Sinus Augmentation.

    Science.gov (United States)

    Mangano, Carlo; Sinjari, Bruna; Shibli, Jamil A; Mangano, Francesco; Hamisch, Sabine; Piattelli, Adriano; Perrotti, Vittoria; Iezzi, Giovanna

    2015-06-01

    By mixing hydroxyapatite (HA) and tricalcium phosphate (TCP), biphasic calcium phosphate ceramics can be obtained, and by varying their ratio it is possible to tailor the characteristics of the biomaterial. The aim of the present human study was to evaluate the histological and radiographical aspects of bone formation in maxillary sinus augmentation using a 30/70 HA-beta-TCP with a reticular structure. A total of 12 patients, undergoing two-stage sinus augmentation procedure using HA-beta-TCP at a ratio of 30/70, were included in the present study. After a 6-month healing period, during implant insertion, radiographical analysis was performed, and then the bone core biopsies were harvested and processed for histology. At radiographic evaluation, the bone gain was on average 6.85 ± 0.60 mm. HA-beta-TCP 30/70 appeared to be lined by newly formed bone, with no gaps at the interface. The histomorphometric analysis revealed 26 ± 2% of residual grafted biomaterial, 29 ± 3% of newly formed bone, and 45 ± 2% of marrow spaces. The present results indicate histologically the high biocompatibility and osteoconductivity of HA-beta-TCP 30/70, and clinically its successful use for sinus augmentation procedures. © 2013 Wiley Periodicals, Inc.

  18. Bilateral Transplantation of Allogenic Adult Human Bone Marrow-Derived Mesenchymal Stem Cells into the Subventricular Zone of Parkinson’s Disease: A Pilot Clinical Study

    Directory of Open Access Journals (Sweden)

    N. K. Venkataramana

    2012-01-01

    Full Text Available The progress of PD and its related disorders cannot be prevented with the medications available. In this study, we recruited 8 PD and 4 PD plus patients between 5 to 15 years after diagnosis. All patients received BM-MSCs bilaterally into the SVZ and were followed up for 12 months. PD patients after therapy reported a mean improvement of 17.92% during “on” and 31.21% during “off” period on the UPDRS scoring system. None of the patients increased their medication during the follow-up period. Subjectively, the patients reported clarity in speech, reduction in tremors, rigidity, and freezing attacks. The results correlated with the duration of the disease. Those patients transplanted in the early stages of the disease (less than 5 years showed more improvement and no further disease progression than the later stages (11–15 years. However, the PD plus patients did not show any change in their clinical status after stem cell transplantation. This study demonstrates the safety of adult allogenic human BM-MSCs transplanted into the SVZ of the brain and its efficacy in early-stage PD patients.

  19. Quality of life changes and clinical outcomes in thyroid cancer patients undergoing radioiodine remnant ablation (RRA) with recombinant human TSH (rhTSH): a randomized controlled study.

    Science.gov (United States)

    Taïeb, D; Sebag, F; Cherenko, M; Baumstarck-Barrau, K; Fortanier, C; Farman-Ara, B; De Micco, C; Vaillant, J; Thomas, S; Conte-Devolx, B; Loundou, A; Auquier, P; Henry, J F; Mundler, O

    2009-07-01

    Recombinant human TSH (rhTSH) has become the modality of choice for radioiodine remnant ablation (RRA) in low-risk thyroid cancer patients. The aims of the present prospective randomized study were to evaluate the impact of TSH stimulation procedure (hypothyroidism vs. rhTSH) on quality of life (QoL) of thyroid cancer patients undergoing RRA and to evaluate efficacy of both procedures. L-T4 was initiated in both groups after thyroidectomy. After randomization, L-T4 was discontinued in hypothyroid (hypo) group and continued in rhTSH group. A measure of 3.7 GBq of radioiodine was given to both groups. The functional assessment of chronic illness therapy-fatigue (FACIT-F) was administered from the early postoperative period to 9 months. Socio-demographic parameters, anxiety and depression scales were also evaluated (CES-D, BDI and Spielberger state-trait questionnaires). At 9 months, patients underwent an rhTSH stimulation test, diagnostic (131)I whole body scan (dxWBS) and neck ultrasonography. A total of 74 patients were enrolled for the study. There was a significant decrease in QoL from baseline (t0) to t1 (RRA period) in the hypothyroid group with significant differences in FACIT-F TOI (P hypothyrodism. However, there is a wide heterogeneity in the clinical impact of hypothyroidism.

  20. Human exploration mission studies

    Science.gov (United States)

    Cataldo, Robert L.

    1989-01-01

    The Office of Exploration has established a process whereby all NASA field centers and other NASA Headquarters offices participate in the formulation and analysis of a wide range of mission strategies. These strategies were manifested into specific scenarios or candidate case studies. The case studies provided a systematic approach into analyzing each mission element. First, each case study must address several major themes and rationale including: national pride and international prestige, advancement of scientific knowledge, a catalyst for technology, economic benefits, space enterprise, international cooperation, and education and excellence. Second, the set of candidate case studies are formulated to encompass the technology requirement limits in the life sciences, launch capabilities, space transfer, automation, and robotics in space operations, power, and propulsion. The first set of reference case studies identify three major strategies: human expeditions, science outposts, and evolutionary expansion. During the past year, four case studies were examined to explore these strategies. The expeditionary missions include the Human Expedition to Phobos and Human Expedition to Mars case studies. The Lunar Observatory and Lunar Outpost to Early Mars Evolution case studies examined the later two strategies. This set of case studies established the framework to perform detailed mission analysis and system engineering to define a host of concepts and requirements for various space systems and advanced technologies. The details of each mission are described and, specifically, the results affecting the advanced technologies required to accomplish each mission scenario are presented.

  1. clinical and experimental study

    OpenAIRE

    Tornow, Christoph

    2011-01-01

    Posterior capsule opacity (PCO) is a frequent complication in extracapsular cataract extraction in conjunction with an intraocular lens implant. Different studies have shown that a reduction in PCO frequency can be achieved via a number of factors. Lens design is a significant criterion in this process. In this study, two multifocal intraocular lenses (MIOLs) were compared. The design of these lenses differed due to their varying optical principles. They are the refractive MIOL A...

  2. Consumption of an aqueous cyanophyta extract derived from Arthrospira platensis is associated with reduction of chronic pain: results from two human clinical pilot studies

    Directory of Open Access Journals (Sweden)

    Jensen GS

    2016-05-01

    Full Text Available Gitte S Jensen,1 Victoria L Attridge,1 Steve G Carter,1 Jesse Guthrie,2 Axel Ehmann,2 Kathleen F Benson1 1NIS Labs, 2Cerule LLC, Klamath Falls, OR, USA Objectives: The aim of this study was to evaluate the effects of consumption of an aqueous cyanophyta extract (ACE from Arthrospira platensis on chronic pain in humans, in two clinical pilot studies. Design and interventions: The two pilot studies each involved 12 subjects experiencing chronic pain. The initial study followed an open-label 4-week study design involving consumption of 1 g ACE per day. A subsequent placebo-controlled, single-blind, crossover study involved consumption of 500 mg ACE, 250 mg ACE, or 0 mg ACE (placebo per day for 1-week duration, separated by 1-week washout period. Subjects: Adult subjects of both sexes, with chronic joint-related pain for at least 6 months prior to enrollment, were recruited after obtaining written informed consent. Outcome measures: Visual analog scales were used to score pain at rest and during physical activity for each person's primary and secondary areas of chronic pain. An activities of daily living questionnaire was used to collect data on physical functioning. Results: The data showed rapid reduction of chronic pain in people consuming ACE, where the reduction in pain scores for each person's primary pain area reached a high level of statistical significance after 2 weeks of consumption (P<0.01, both when at rest and when being physically active. Secondary pain areas when physically active showed highly significant improvements within 1 week of consumption of 1 g/d (P<0.001 and borderline significant improvements within 1 week of consuming 500 mg/d (P<0.065 and 250 mg/d (P<0.05. This was accompanied by an increased ability to perform daily activities (P<0.05. A small but significant weight loss was observed during the 4-week study, as the average body mass index dropped from 31.4 to 29.4 (P<0.01. Conclusion: Consumption of ACE was associated

  3. VENOUS AIR-EMBOLISM, PRESERVATION REPERFUSION INJURY, AND THE PRESENCE OF INTRAVASCULAR AIR COLLECTIONS IN HUMAN DONOR LIVERS - A RETROSPECTIVE CLINICAL-STUDY

    NARCIS (Netherlands)

    WOLF, RFE; SLUITER, WJ; BALLAST, A; VANDAM, RM; SLOOFF, MJH

    In human liver transplantation, air embolism is seldom encountered after graft reperfusion. Nevertheless, despite adequate flushing and clamping routines, air emboli have been reported in transesophageal echocardiography (TEE) studies performed during the reperfusion phase, We retrospectively

  4. Objective measurement of intraocular forward light scatter using Hartmann-Shack spot patterns from clinical aberrometers. Model-eye and human-eye study.

    Science.gov (United States)

    Cerviño, Alejandro; Bansal, Dheeraj; Hosking, Sarah L; Montés-Micó, Robert

    2008-07-01

    To apply software-based image-analysis tools to objectively determine intraocular scatter determined from clinically derived Hartmann-Shack patterns. Aston Academy of Life Sciences, Aston University, Birmingham, United Kingdom, and Department of Optics, University of Valencia, Valencia, Spain. Purpose-designed image-analysis software was used to quantify scatter from centroid patterns obtained using a clinical Hartmann-Shack analyzer (WASCA, Zeiss/Meditec). Three scatter values, as the maximum standard deviation within a lenslet for all lenslets in the pattern, were obtained in 6 model eyes and 10 human eyes. In the model-eye sample, patterns were obtained in 4 sessions: 2 without realigning between measurements, 1 with realignment, and 1 with an angular shift of 6 degrees from the instrument axis. Three measurements were made in the human eyes with the C-Quant straylight meter (Oculus) to obtain psychometric and objective measures of retinal straylight. Analysis of variance, intraclass correlation coefficients, coefficient of repeatability (CoR), and correlations were used to determine intrasession and intersession repeatability and the relationship between measures. No significant differences were found between the sessions in the model eye (P=.234). The mean CoR was less than 10% in all model- and human-eye sessions. After incomplete patterns were removed, good correlation was achieved between psychometric and objective scatter measurements despite the small sample size (n=6; r=-0.831; P=.040). The methodology was repeatable in model and human eyes, strong against realignment and misalignment, and sensitive. Clinical application would benefit from effective use of the sensor's dynamic range.

  5. Clinical epidemiology of human AE in Europe.

    Science.gov (United States)

    Vuitton, D A; Demonmerot, F; Knapp, J; Richou, C; Grenouillet, F; Chauchet, A; Vuitton, L; Bresson-Hadni, S; Millon, L

    2015-10-30

    This review gives a critical update of the situation regarding alveolar echinococcosis (AE) in Europe in humans, based on existing publications and on findings of national and European surveillance systems. All sources point to an increase in human cases of AE in the "historic endemic areas" of Europe, namely Germany, Switzerland, Austria and France and to the emergence of human cases in countries where the disease had never been recognised until the end of the 20th century, especially in central-eastern and Baltic countries. Both increase and emergence could be only due to methodological biases; this point is discussed in the review. One explanation may be given by changes in the animal reservoir of the parasite, Echinococcus multilocularis (increase in the global population of foxes in Europe and its urbanisation, as well as a possible increased involvement of pet animals as definitive infectious hosts). The review also focuses onto 2 more original approaches: (1) how changes in therapeutic attitudes toward malignant and chronic inflammatory diseases may affect the epidemiology of AE in the future in Europe, since a recent survey of such cases in France showed the emergence of AE in patients with immune suppression since the beginning of the 21st century; (2) how setting a network of referral centres in Europe based on common studies on the care management of patients might contribute to a better knowledge of AE epidemiology in the future. Copyright © 2015. Published by Elsevier B.V.

  6. Concept and benefits of the Inverted Classroom method for a competency-based biochemistry course in the pre-clinical stage of a human medicine course of studies.

    Science.gov (United States)

    Kühl, Susanne J; Toberer, Matthias; Keis, Oliver; Tolks, Daniel; Fischer, Martin R; Kühl, Michael

    2017-01-01

    Background: Medical students often have a problem recognising the relevance of basic science subjects for their later professional work in the pre-clinical stage of their studies. This can lead to a lower motivation to learn biochemical content and dissatisfaction in the courses amongst the students. Alternative teaching methods such as the Inverted Classroom (IC) method can address this deficiency. The goal of this study was: to analyse the motivation and satisfaction of the students in a biochemistry seminar through the use of the e-learning-based IC method, to investigate the acceptance against the IC teaching method in biochemistry, and to compare the learning success achieved using the IC approach with that of a traditional course. We also investigated how a biochemistry course in the pre-clinical stage of a human medicine course of studies can be successfully organised according to the IC method. Furthermore, we examined the benefits of the IC method over conventional teaching formats. Method: The IC method was implemented in accordance with the guidelines of the GMA committee "New Media" [30] in a biochemistry seminar for two student IC intervention groups with 42 students. A part of the factual knowledge from the on-site phase in the form of teaching videos together with self-learning control tasks were provided online before the seminar for both IC intervention groups. Exporting content to the self-learning phase creates new free time in the on-site phase, during which the content can be critically considered and processed and additional competency-based learning objectives can be taught. Identical biochemistry teaching content was taught in parallel control groups (14 student groups with n=299 students), but no material was handed out beforehand for a self-learning phase. These students only received the materials after the on-site phase. Motivation and satisfaction as well as the acceptance for the teaching methods were recorded by questionnaires, the

  7. Concept and benefits of the Inverted Classroom method for a competency-based biochemistry course in the pre-clinical stage of a human medicine course of studies

    Directory of Open Access Journals (Sweden)

    Kühl, Susanne J.

    2017-08-01

    Full Text Available Background: Medical students often have a problem recognising the relevance of basic science subjects for their later professional work in the pre-clinical stage of their studies. This can lead to a lower motivation to learn biochemical content and dissatisfaction in the courses amongst the students. Alternative teaching methods such as the Inverted Classroom (IC method can address this deficiency. The goal of this study was: We also investigated how a biochemistry course in the pre-clinical stage of a human medicine course of studies can be successfully organised according to the IC method. Furthermore, we examined the benefits of the IC method over conventional teaching formats. Method: The IC method was implemented in accordance with the guidelines of the GMA committee “New Media” in a biochemistry seminar for two student IC intervention groups with 42 students. A part of the factual knowledge from the on-site phase in the form of teaching videos together with self-learning control tasks were provided online before the seminar for both IC intervention groups. Exporting content to the self-learning phase creates new free time in the on-site phase, during which the content can be critically considered and processed and additional competency-based learning objectives can be taught. Identical biochemistry teaching content was taught in parallel control groups (14 student groups with n=299 students, but no material was handed out beforehand for a self-learning phase. These students only received the materials after the on-site phase. Motivation and satisfaction as well as the acceptance for the teaching methods were recorded by questionnaires, the acquisition of knowledge by MC exams.Results: On a Likert scale from 1 (strongly disagree to 6 (strongly agree, the students in the IC intervention groups could be seen to be much more motivated (5.53 than students in the control group (4.01. Students in the IC intervention groups also recognised the

  8. Human plasma concentrations of tolbutamide and acetaminophen extrapolated from in vivo animal pharmacokinetics using in vitro human hepatic clearances and simple physiologically based pharmacokinetic modeling for radio-labeled microdose clinical studies

    International Nuclear Information System (INIS)

    Yamazaki, Hiroshi; Kunikane, Eriko; Nishiyama, Sayako; Murayama, Norie; Shimizu, Makiko; Sugiyama, Yuichi; Chiba, Koji; Ikeda, Toshihiko

    2015-01-01

    The aim of the current study was to extrapolate the pharmacokinetics of drug substances orally administered in humans from rat pharmacokinetic data using tolbutamide and acetaminophen as model compounds. Adjusted animal biomonitoring equivalents from rat studies based on reported plasma concentrations were scaled to human biomonitoring equivalents using known species allometric scaling factors. In this extrapolation, in vitro metabolic clearance data were obtained using liver preparations. Rates of tolbutamide elimination were roughly similar in rat and human liver microsome experiments, but acetaminophen elimination by rat liver microsomes and cytosolic preparations showed a tendency to be faster than those in humans. Using a simple physiologically based pharmacokinetic (PBPK) model, estimated human plasma concentrations of tolbutamide and acetaminophen were consistent with reported concentrations. Tolbutamide cleared in a roughly similar manner in humans and rats, but medical-dose levels of acetaminophen cleared (dependent on liver metabolism) more slowly from plasma in humans than it did in rats. The data presented here illustrate how pharmacokinetic data in combination with a simple PBPK model can be used to assist evaluations of the pharmacological/toxicological potential of new drug substances and for estimating human radiation exposures from radio-labeled drugs when planning human studies. (author)

  9. Novel, broad-spectrum anticonvulsants containing a sulfamide group: advancement of N-((benzo[b]thien-3-yl)methyl)sulfamide (JNJ-26990990) into human clinical studies.

    Science.gov (United States)

    Parker, Michael H; Smith-Swintosky, Virginia L; McComsey, David F; Huang, Yifang; Brenneman, Douglas; Klein, Brian; Malatynska, Ewa; White, H Steve; Milewski, Michael E; Herb, Mark; Finley, Michael F A; Liu, Yi; Lubin, Mary Lou; Qin, Ning; Iannucci, Robert; Leclercq, Laurent; Cuyckens, Filip; Reitz, Allen B; Maryanoff, Bruce E

    2009-12-10

    In seeking broad-spectrum anticonvulsants to treat epilepsy and other neurological disorders, we synthesized and tested a group of sulfamide derivatives (4a-k, 5), which led to the clinical development of 4a (JNJ-26990990). This compound exhibited excellent anticonvulsant activity in rodents against audiogenic, electrically induced, and chemically induced seizures, with very weak inhibition of human carbonic anhydrase-II (IC(50) = 110 microM). The pharmacological profile for 4a supports its potential in the treatment of multiple forms of epilepsy, including pharmacoresistant variants. Mechanistically, 4a inhibited voltage-gated Na(+) channels and N-type Ca(2+) channels but was not effective as a K(+) channel opener. The pharmacokinetics and metabolic properties of 4a are discussed.

  10. Cell-Based Therapies Used to Treat Lumbar Degenerative Disc Disease: A Systematic Review of Animal Studies and Human Clinical Trials

    Directory of Open Access Journals (Sweden)

    David Oehme

    2015-01-01

    Full Text Available Low back pain and degenerative disc disease are a significant cause of pain and disability worldwide. Advances in regenerative medicine and cell-based therapies, particularly the transplantation of mesenchymal stem cells and intervertebral disc chondrocytes, have led to the publication of numerous studies and clinical trials utilising these biological therapies to treat degenerative spinal conditions, often reporting favourable outcomes. Stem cell mediated disc regeneration may bridge the gap between the two current alternatives for patients with low back pain, often inadequate pain management at one end and invasive surgery at the other. Through cartilage formation and disc regeneration or via modification of pain pathways stem cells are well suited to enhance spinal surgery practice. This paper will systematically review the current status of basic science studies, preclinical and clinical trials utilising cell-based therapies to repair the degenerate intervertebral disc. The mechanism of action of transplanted cells, as well as the limitations of published studies, will be discussed.

  11. Factors for incomplete adherence to antiretroviral therapy including drug refill and clinic visits among older adults living with human immunodeficiency virus - cross-sectional study in South Africa.

    Science.gov (United States)

    Barry, Abbie; Ford, Nathan; El-Khatib, Ziad

    2018-03-01

    To assess adherence outcomes to antiretroviral therapy (ART) of recipients ≥50 years in Soweto, South Africa. This was a secondary data analysis for a cross-sectional study at two HIV clinics in Soweto. Data on ART adherence and covariates were gathered through structured interviews with HIV 878 persons living with HIV (PLHIV) receiving ART. Logistic regression analysis was used to assess associations. PLHIV ≥50 years (n = 103) were more likely to miss clinic visits during the last six months than PLHIV aged 25-49 (OR 2.15; 95%CI 1.10-4.18). PLHIV ≥50 years with no or primary-level education were less likely to have missed a clinic visit during the last six months than PLHIV with secondary- or tertiary-level education in the same age category (OR 0.3; 95%CI 0.1-1.1), as were PLHIV who did not disclose their status (OR 0.2; 95%CI 0-1.1). There was no evidence of increased risk for non-adherence to ART pills and drug refill visits among older PLHIV. Missing a clinic visit was more common among older PLHIV who were more financially vulnerable. Further studies are needed to verify these findings and identify new risk factors associated with ART adherence. © 2017 John Wiley & Sons Ltd.

  12. Clinical potentials of human pluripotent stem cells.

    Science.gov (United States)

    Mora, Cristina; Serzanti, Marialaura; Consiglio, Antonella; Memo, Maurizio; Dell'Era, Patrizia

    2017-08-01

    Aging, injuries, and diseases can be considered as the result of malfunctioning or damaged cells. Regenerative medicine aims to restore tissue homeostasis by repairing or replacing cells, tissues, or damaged organs, by linking and combining different disciplines including engineering, technology, biology, and medicine. To pursue these goals, the discipline is taking advantage of pluripotent stem cells (PSCs), a peculiar type of cell possessing the ability to differentiate into every cell type of the body. Human PSCs can be isolated from the blastocysts and maintained in culture indefinitely, giving rise to the so-called embryonic stem cells (ESCs). However, since 2006, it is possible to restore in an adult cell a pluripotent ESC-like condition by forcing the expression of four transcription factors with the rejuvenating reprogramming technology invented by Yamanaka. Then the two types of PSC can be differentiated, using standardized protocols, towards the cell type necessary for the regeneration. Although the use of these derivatives for therapeutic transplantation is still in the preliminary phase of safety and efficacy studies, a lot of efforts are presently taking place to discover the biological mechanisms underlying genetic pathologies, by differentiating induced PSCs derived from patients, and new therapies by challenging PSC-derived cells in drug screening.

  13. Melatonin: a chemical photoperiodic signal with clinical significance in humans.

    Science.gov (United States)

    Pang, S F; Pang, C S; Poon, A M; Lee, P P; Liu, Z M; Shiu, S Y

    1998-03-01

    Secretion of pineal melatonin exhibits a diumal rhythm and a seasonal rhythm in humans. Night-time melatonin is high at 3-5 year-old and decreases with age. Many drugs and pathological conditions also change melatonin levels in the circulation. Melatonin has a mild sedative effect and has been used effectively in synchronizing the sleep-wake cycle of patients with sleep disorders. Immunoenhancing, anti-cancer, anti-aging and anti-oxidant effects of melatonin have been proposed. Recent studies suggest that melatonin receptors are present in central and peripheral tissues. The importance of melatonin receptors on the nervous, reproductive, immune and renal functions is implicated. Studies on the molecular biology, physiology and pathology of melatonin receptors in different tissues are progressing rapidly. The physiological and pathological changes in melatonin secretion, multifarious melatonin actions, and diverse melatonin receptors reported suggest that melatonin is a photoperiodic signal with clinical significance in humans.

  14. The development of human visual cortex and clinical implications

    Directory of Open Access Journals (Sweden)

    Siu CR

    2018-04-01

    Full Text Available Caitlin R Siu,1 Kathryn M Murphy1,2 1McMaster Integrative Neuroscience Discovery and Study (MiNDS Program, McMaster University, Hamilton, ON, Canada; 2Department of Psychology, Neuroscience & Behaviour, McMaster University, Hamilton, ON, Canada Abstract: The primary visual cortex (V1 is the first cortical area that processes visual information. Normal development of V1 depends on binocular vision during the critical period, and age-related losses of vision are linked with neurobiological changes in V1. Animal studies have provided important details about the neurobiological mechanisms in V1 that support normal vision or are changed by visual diseases. There is very little information, however, about those neurobiological mechanisms in human V1. That lack of information has hampered the translation of biologically inspired treatments from preclinical models to effective clinical treatments. We have studied human V1 to characterize the expression of neurobiological mechanisms that regulate visual perception and neuroplasticity. We have identified five stages of development for human V1 that start in infancy and continue across the life span. Here, we describe these stages, compare them with visual and anatomical milestones, and discuss implications for translating treatments for visual disorders that depend on neuroplasticity of V1 function. Keywords: development, human visual cortex, amblyopia, synaptic plasticity, glutamatergic, GABAergic, receptors

  15. A validated HPLC-MS/MS assay for quantifying unstable pharmacologically active metabolites of clopidogrel in human plasma: application to a clinical pharmacokinetic study.

    Science.gov (United States)

    Furlong, Michael T; Savant, Ishani; Yuan, Moucun; Scott, Laura; Mylott, William; Mariannino, Thomas; Kadiyala, Pathanjali; Roongta, Vikram; Arnold, Mark E

    2013-05-01

    Clopidogrel is prescribed for the treatment of Acute Coronary Syndrome and recent myocardial infarction, recent stroke, or established peripheral arterial disease. A sensitive and reliable high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) assay was developed and validated to enable reliable quantification of four diastereomeric and chemically reactive thiol metabolites, two of which are pharmacologically active, in human plasma. The metabolites were stabilized by alkylation of their reactive thiol moieties with 2-bromo-3'-methoxyacetophenone (MPB). Following organic solvent mediated-protein precipitation in a 96-well plate format, chromatographic separation was achieved by gradient elution on an Ascentis Express RP-amide column. Chromatographic conditions were optimized to ensure separation of the four derivatized active metabolites. Derivatized metabolites and stable isotope-labeled internal standards were detected by positive ion electrospray tandem mass spectrometry. The HPLC-MS/MS assay was validated over concentration ranges of 0.125-125 ng/mL for metabolites H1-H3 and 0.101-101 ng/mL for H4. Intra- and inter-assay precision values for replicate quality control samples were within 14.3% for all analytes during the assay validation. Mean quality control accuracy values were within ±6.3% of nominal values for all analytes. Assay recoveries were high (>79%). The four derivatized analytes were stable in human blood for at least 2 h at room temperature and on ice. The analytes were also stable in human plasma for at least 25 h at room temperature, 372 days at -20 °C and -70 °C, and following at least five freeze-thaw cycles. The validated assay was successfully applied to the quantification of all four thiol metabolites in human plasma in support of a human pharmacokinetic study. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. CLINICAL AND VIROLOGIC FOUNDATION FOR PATHOGENETIC THERAPY OF HUMAN HERPES VIRUS TYPE 6 INFECTION IN CHILDREN

    Directory of Open Access Journals (Sweden)

    N.A. Myukke

    2006-01-01

    Full Text Available Information about an infection caused by human herpes virus type 6, its' epidemiology, pathogenesis and clinical variants, is reviewed. Clinical cases, diagnosed at a time of study, are briefly reviewed.Key words: human herpes virus type 6, exanthema subitum (roseola infantum, fever of unknown origin, mononucleosis like syndrome, meningoencephalitis, children.

  17. Epidemiology, Clinical Characteristics, and Antimicrobial Susceptibility Profiles of Human Clinical Isolates of Staphylococcus intermedius Group.

    Science.gov (United States)

    Yarbrough, Melanie L; Lainhart, William; Burnham, C A

    2018-03-01

    The veterinary pathogens in the Staphylococcus intermedius group (SIG) are increasingly recognized as causes of human infection. Shared features between SIG and Staphylococcus aureus may result in the misidentification of SIG in human clinical cultures. This study examined the clinical and microbiological characteristics of isolates recovered at a tertiary-care academic medical center. From 2013 to 2015, 81 SIG isolates were recovered from 62 patients. Patients were commonly ≥50 years old, diabetic, and/or immunocompromised. Documentation of dog exposure in the electronic medical record was not common. Of the 81 SIG isolates, common sites of isolation included 37 (46%) isolates from wound cultures and 17 (21%) isolates from respiratory specimens. Although less common, 10 (12%) bloodstream infections were documented in 7 unique patients. The majority of SIG (65%) isolates were obtained from polymicrobial cultures. In comparison to S. aureus isolates from the same time period, significant differences were noted in proportion of SIG isolates that were susceptible to doxycycline (74% versus 97%, respectively; P SIG isolates. All MR isolates detected by an oxacillin disk diffusion test would have been misclassified as methicillin susceptible using a cefoxitin disk diffusion test. Thus, SIG is recovered from human clinical specimens, and distinction of SIG from S. aureus is critical for the accurate characterization of MR status in these isolates. Copyright © 2018 American Society for Microbiology.

  18. Effect of human papillomavirus (HPV) vaccination on clinical indicators of sexual behaviour among adolescent girls: the Ontario Grade 8 HPV Vaccine Cohort Study.

    Science.gov (United States)

    Smith, Leah M; Kaufman, Jay S; Strumpf, Erin C; Lévesque, Linda E

    2015-02-03

    Suboptimal human papillomavirus (HPV) vaccine coverage in some jurisdictions is partly attributed to fears that vaccination may increase risky sexual behaviour. We assessed the effect of HPV vaccination on clinical indicators of sexual behaviour among adolescent girls in Ontario. Using Ontario's administrative health databases, we identified a population-based cohort of girls in grade 8 in the 2 years before (2005/06 and 2006/07) and after (2007/08 and 2008/09) implementation of Ontario's grade 8 HPV vaccination program. For each girl, we then obtained data on vaccine receipt in grades 8 and 9 and data on indicators of sexual behaviour (pregnancy and non-HPV-related sexually transmitted infections) in grades 10-12. Using a quasi-experimental method known as regression discontinuity, we estimated, for each outcome, the risk difference (RD) and relative risk (RR) attributable to vaccination and to program eligibility. The cohort comprised 260 493 girls, of whom 131 781 were ineligible for the program and 128 712 were eligible. We identified 15 441 (5.9%) cases of pregnancy and sexually transmitted infection and found no evidence that vaccination increased the risk of this composite outcome: RD per 1000 girls -0.61 (95% confidence interval [CI] -10.71 to 9.49) and RR 0.96 (95% CI 0.81 to 1.14). Similarly, we found no discernible effect of program eligibility: RD per 1000 girls -0.25 (95% CI -4.35 to 3.85) and RR 0.99 (95% CI 0.93 to 1.06). The findings were similar when outcomes were assessed separately. We present strong evidence that HPV vaccination does not have any significant effect on clinical indicators of sexual behaviour among adolescent girls. These results suggest that concerns over increased promiscuity following HPV vaccination are unwarranted and should not deter from vaccinating at a young age. © 2015 Canadian Medical Association or its licensors.

  19. Human papillomavirus genotypes and clinical management of ...

    African Journals Online (AJOL)

    Background. Genital human papillomavirus (HPV) infection is the most common sexually transmitted viral disease in the world. HPV infection of the genital epithelium is associated with genital warts and malignancies of the lower genital tract. Objectives. To describe the distribution, phenotypic appearance and HPV type ...

  20. Randomised clinical study: inulin short-chain fatty acid esters for targeted delivery of short-chain fatty acids to the human colon.

    Science.gov (United States)

    Polyviou, T; MacDougall, K; Chambers, E S; Viardot, A; Psichas, A; Jawaid, S; Harris, H C; Edwards, C A; Simpson, L; Murphy, K G; Zac-Varghese, S E K; Blundell, J E; Dhillo, W S; Bloom, S R; Frost, G S; Preston, T; Tedford, M C; Morrison, D J

    2016-10-01

    Short-chain fatty acids (SCFA) produced through fermentation of nondigestible carbohydrates by the gut microbiota are associated with positive metabolic effects. However, well-controlled trials are limited in humans. To develop a methodology to deliver SCFA directly to the colon, and to optimise colonic propionate delivery in humans, to determine its role in appetite regulation and food intake. Inulin SCFA esters were developed and tested as site-specific delivery vehicles for SCFA to the proximal colon. Inulin propionate esters containing 0-61 wt% (IPE-0-IPE-61) propionate were assessed in vitro using batch faecal fermentations. In a randomised, controlled, crossover study, with inulin as control, ad libitum food intake (kcal) was compared after 7 days on IPE-27 or IPE-54 (10 g/day all treatments). Propionate release was determined using (13) C-labelled IPE variants. In vitro, IPE-27-IPE-54 wt% propionate resulted in a sevenfold increase in propionate production compared with inulin (P inulin (439.5 vs. 703.9 kcal, P = 0.025) and IPE-54 (439.5 vs. 659.3 kcal, P = 0.025), whereas IPE-54 was not significantly different from inulin control. IPE-27 significantly reduced food intake suggesting colonic propionate plays a role in appetite regulation. Inulin short-chain fatty acid esters provide a novel tool for probing the diet-gut microbiome-host metabolism axis in humans. © 2016 The Authors. Alimentary Pharmacology & Therapeutics Published by John Wiley & Sons Ltd.

  1. Evaluation of pre-existing antibody presence as a risk factor for posttreatment anti-drug antibody induction: analysis of human clinical study data for multiple biotherapeutics.

    Science.gov (United States)

    Xue, Li; Rup, Bonita

    2013-07-01

    Biotherapeutic-reactive antibodies in treatment-naïve subjects (i.e., pre-existing antibodies) have been commonly detected during clinical immunogenicity assessments; however information on pre-existing antibody prevalence, physiological effects, and impact on posttreatment anti-drug antibody (ADA) induction remains limited. In this analysis, pre-existing antibody prevalence and impact on posttreatment ADA induction were determined using ADA data from 12 biotherapeutics analyzed in 32 clinical studies. Approximately half (58%) of the biotherapeutics were associated with some level of pre-existing antibodies and 67% of those were associated with posttreatment ADA induction. Across all studies, 5.6% of study subjects demonstrated presence of pre-existing antibodies, among which, 17% of the individual subjects had posttreatment increases in their ADA titers while 16% had decreased titers and 67% had no change in titers. However, in studies conducted in the rheumatoid arthritis (RA) population, 14.8% of RA patients were associated with pre-existing antibodies and 30% of those had posttreatment titer increases. The results suggest that in most study subjects, pre-existing antibodies pose a low risk for posttreatment ADA induction. That said, the high risk of induction implicated for RA patients, primarily observed in treatments evaluating novel antibody-based constructs, indicates that further understanding of the contribution of product and disease-specific factors is needed. Cross-industry efforts to collect and analyze a larger data set would enhance understanding of the prevalence, nature, and physiological consequences of pre-existing antibodies, better inform the immunogenicity risk profiles of products associated with these antibodies and lead to better fit-for-purpose immunogenicity management and mitigation strategies.

  2. Clinical Relevance of KRAS in Human Cancers

    Directory of Open Access Journals (Sweden)

    Sylwia Jančík

    2010-01-01

    Full Text Available The KRAS gene (Ki-ras2 Kirsten rat sarcoma viral oncogene homolog is an oncogene that encodes a small GTPase transductor protein called KRAS. KRAS is involved in the regulation of cell division as a result of its ability to relay external signals to the cell nucleus. Activating mutations in the KRAS gene impair the ability of the KRAS protein to switch between active and inactive states, leading to cell transformation and increased resistance to chemotherapy and biological therapies targeting epidermal growth factor receptors. This review highlights some of the features of the KRAS gene and the KRAS protein and summarizes current knowledge of the mechanism of KRAS gene regulation. It also underlines the importance of activating mutations in the KRAS gene in relation to carcinogenesis and their importance as diagnostic biomarkers, providing clues regarding human cancer patients' prognosis and indicating potential therapeutic approaches.

  3. Comparative value of clinical, cytological, and histopathological features in feline mammary gland tumors; an experimental model for the study of human breast cancer.

    Science.gov (United States)

    Shafiee, Radmehr; Javanbakht, Javad; Atyabi, Nahid; Bahrami, Alimohammad; Kheradmand, Danial; Safaei, Reyhaneh; Khadivar, Farshid; Hosseini, Ehsan

    2013-08-13

    regions, local invasiveness and enlarged nuclei were observed. The samples included 3 tumors of mammary glands mammary tumors were complex carcinomas (n = 2) and adenocarcinoma (n = 1). The histological grades of the 3 cases were as follows: grade II, (1/3); grade III, (2/3) with high mitotic index. The preferential localization of mammary neoplasms was in the inguinal lobe (1/3 case) and abdominal lobes (2/3 cases). Furthermore, 1case of the inguinal mass affected the left caudo-inguinal lobe and 2cases right cranio and caudo abdominal lobes. The study concluded that cytology could be used as a quick, rapid, field diagnostic technique in combination with histopathology for the diagnosis of feline mammary tumors (FMTs). Our findings in feline MTs indicate that FMTs could be useful as an animal model of human breast cancer. Moreover, because of the similarity of the cytohistopathological findings in the human and feline mammary gland tumours, it is possible to use the same cytopathological criteria applied in human pathology for the diagnosis of feline mammary gland tumours. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2047361423103295.

  4. Study of the stability of packaging and storage conditions of human mesenchymal stem cell for intra-arterial clinical application in patient with critical limb ischemia.

    Science.gov (United States)

    Gálvez-Martín, Patricia; Hmadcha, Abdelkrim; Soria, Bernat; Calpena-Campmany, Ana C; Clares-Naveros, Beatriz

    2014-04-01

    Critical limb ischemia (CLI) is associated with significant morbidity and mortality. In this study, we developed and characterized an intra-arterial cell suspension containing human mesenchymal stem cells (hMSCs) for the treatment of CLI. Equally, the stability of cells was studied in order to evaluate the optimal conditions of storage that guarantee the viability from cell processing to the administration phase. Effects of various factors, including excipients, storage temperature and time were evaluated to analyze the survival of hMSCs in the finished medicinal product. The viability of hMSCs in different packaging media was studied for 60 h at 4 °C. The best medium to maintain hMSCs viability was then selected to test storage conditions (4, 8, 25 and 37 °C; 60 h). The results showed that at 4 °C the viability was maintained above 80% for 48 h, at 8 °C decreased slightly, whereas at room temperature and 37 °C decreased drastically. Its biocompatibility was assessed by cell morphology and cell viability assays. During stability study, the stored cells did not show any change in their phenotypic or genotypic characteristics and physicochemical properties remained constant, the ability to differentiate into adipocytes and osteocytes and sterility requirements were also unaltered. Finally, our paper proposes a packing media composed of albumin 20%, glucose 5% and Ringer's lactate at a concentration of 1×10(6) cells/mL, which must be stored at 4 °C as the most suitable to maintain cell viability (>80%) and without altering their characteristics for more than 48 h. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. Microanatomical and immunohistochemical study of the human lateral antebrachial cutaneous nerve of forearm at the antecubital fossa and its clinical implications.

    Science.gov (United States)

    Marx, S Chakravarthy; Kumar, Pramod; Dhalapathy, S; Prasad, Keerthana; Marx, C Anitha

    2010-09-01

    Changes in the intraneural anatomy with age can cause poor prognosis of nerve repair in patients after nerve injury. The occurrence of Complex Regional Pain Syndrome-Type II, secondary to peripheral nerve injury, is common. The purpose of this study is to asses changes in cross-sectional anatomy of the lateral antebrachial cutaneous nerve of forearm (LCNF) at the antecubital fossa in the fascicular, nonfascicular components (adipose and nonadipose tissue), and sympathetic fibers area with respect to age. For the purpose of the study, 32 human (37-88 years) fresh cadaveric LCNF were collected from left-antecubital fossae and processed for histological, morphometric analysis [total cross-sectional (Asc), fascicular (Af), and nonfascicular area (Anonf)], and immunohistochemical method (tyrosine hydroxylase) for sympathetic fibers. The LCNF's average total cross-sectional area was 3.024 mm(2), and fascicular area was 0.582 mm(2). The average number of fascicles per mm(2) was 3.09. The cross-sectional area in the nerve was mainly occupied by nonfascicular connective tissue (80.75%). There was increased adipose tissue deposition (48.48% of Asc) and decreased collagen fibers (32.24% of Asc) in interfascicular domains without any definite relationship with age. The average sympathetic fiber area was 0.026 mm(2) within the nerve fascicular area without any correlation with age. In LCNF, there was more adipose tissue and less collagen fibers deposition in the interfascicular domains of all age cases, and this may act as an obstacle for nerve fiber regeneration on using LCNF as an interpositional nerve graft.

  6. SU-E-QI-21: Iodinated Contrast Agent Time Course In Human Brain Metastasis: A Study For Stereotactic Synchrotron Radiotherapy Clinical Trials

    Energy Technology Data Exchange (ETDEWEB)

    Obeid, L; Esteve, F; Adam, J [Grenoble Institut des Neurosciences, La Tronche, Isere (France); Tessier, A; Balosso, J [Centre Hospitalier Universitaire, La Tronche, Isere (France)

    2014-06-15

    Purpose: Synchrotron stereotactic radiotherapy (SSRT) is an innovative treatment combining the selective accumulation of heavy elements in tumors with stereotactic irradiations using monochromatic medium energy x-rays from a synchrotron source. Phase I/II clinical trials on brain metastasis are underway using venous infusion of iodinated contrast agents. The radiation dose enhancement depends on the amount of iodine in the tumor and its time course. In the present study, the reproducibility of iodine concentrations between the CT planning scan day (Day 0) and the treatment day (Day 10) was assessed in order to predict dose errors. Methods: For each of days 0 and 10, three patients received a biphasic intravenous injection of iodinated contrast agent (40 ml, 4 ml/s, followed by 160 ml, 0.5 ml/s) in order to ensure stable intra-tumoral amounts of iodine during the treatment. Two volumetric CT scans (before and after iodine injection) and a multi-slice dynamic CT of the brain were performed using conventional radiotherapy CT (Day 0) or quantitative synchrotron radiation CT (Day 10). A 3D rigid registration was processed between images. The absolute and relative differences of absolute iodine concentrations and their corresponding dose errors were evaluated in the GTV and PTV used for treatment planning. Results: The differences in iodine concentrations remained within the standard deviation limits. The 3D absolute differences followed a normal distribution centered at zero mg/ml with a variance (∼1 mg/ml) which is related to the image noise. Conclusion: The results suggest that dose errors depend only on the image noise. This study shows that stable amounts of iodine are achievable in brain metastasis for SSRT treatment in a 10 days interval.

  7. Relevance of human anatomy in daily clinical practice.

    Science.gov (United States)

    Arráez-Aybar, Luis-Alfonso; Sánchez-Montesinos, Indalecio; Mirapeix, Rosa-M; Mompeo-Corredera, Blanca; Sañudo-Tejero, Jose-Ramón

    2010-12-20

    the aim of this study has been to evaluate the relevance of gross human anatomy in daily clinical practice and to compare it to that of other basic sciences (biochemistry, bioethics, cytohistology, microbiology, pharmacology, physiology, psychology). a total of 1250 questionnaires were distributed among 38 different medical speciality professionals. Answers were analyzed taking into account speciality (medical, surgery and others), professional status (training physician or staff member) and professional experience. the response rate was 42.9% (n=536). Gross human anatomy was considered the most relevant basic discipline for surgical specialists, while pharmacology and physiology were most relevant for medical specialists. Knowledge of anatomy was also considered fundamental for understanding neurological or musculoskeletal disorders. In undergraduate programmes, the most important focuses in teaching anatomy were radiological, topographical and functional anatomy followed by systematic anatomy. In daily medical practice anatomy was considered basic for physical examination, symptom interpretation and interpretation of radiological images. When professional status or professional experience was considered, small variations were shown and there were no significant differences related to gender or community. our results underline the relevance of basic sciences (gross anatomy, physiology, and pharmacology) in daily professional activity. Evidence-based studies such as ours, lend greater credibility and objectivity to the role of gross anatomy in the undergraduate training of health professionals and should help to establish a more appropriate curriculum for future professionals. 2010 Elsevier GmbH. All rights reserved.

  8. A Clinical Study on Hypothyroidism

    International Nuclear Information System (INIS)

    Park, Keun Jo; Park, Sun Yang; Park, Jung Sik; Lee, Myung Chul; Koh, Chang Soon; Lee, Mun Ho

    1976-01-01

    A clinical study was made on 263 patients of hypothyroidism among the 5,970 patients of Various thyroid diseases diagnosed and treated at the Radioisotope Clinic and Laboratory, Seoul National University Hospital from May, 1960 to Aug, 1975. The results obtained with this study are as follows: 1) The etiological classification of hypothyroidism revealed 244 cases (93%) of primary hypothyroidism and 19 cases (7%) of secondary hypothyroidism. 2) The most frequent cause of the thyroprivic primary hypothyroidism was post radioiodine therapy with 109 cases (41.4%). 3) There were 37 cases (14%) of male and 226 cases (86%) of female, showing a ratio of 1 : 6. 4) The majority of patients were between the ages of 30 and 60 with the peak incidence (87 cases, 33%) in their fourth decades of lives. 5) The major symptoms and signs were weakness (97%), edema of face and extremities (92%); Decreased Achilles tendon reflex (87%), cold intolerance (82%), gain in weight (76%), constipation (58%) and cold skin (51%). 6) The cumulative incidence of hypothyroidism in patient treated with 131 I (3-8 mci) was 7.2% at first year, 33.3% at tenth year and the 50% at fourteenth year and the annual increment was 2.9%. 7) The incidence of hypothyroidism related to the numbers of 131 I therapy was not linear. 8) The diagnostic compatibilities of the various tests to hypothyroidism were TSH (100%), T 4 (93.8%), 24-hour-RNIU (91.5%), ATR (86.7%), T 3 RU (66.1%) and BMR (64.9%).

  9. A Clinical Study on Hypothyroidism

    Energy Technology Data Exchange (ETDEWEB)

    Park, Keun Jo; Park, Sun Yang; Park, Jung Sik; Lee, Myung Chul; Koh, Chang Soon; Lee, Mun Ho [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1976-03-15

    A clinical study was made on 263 patients of hypothyroidism among the 5,970 patients of Various thyroid diseases diagnosed and treated at the Radioisotope Clinic and Laboratory, Seoul National University Hospital from May, 1960 to Aug, 1975. The results obtained with this study are as follows: 1) The etiological classification of hypothyroidism revealed 244 cases (93%) of primary hypothyroidism and 19 cases (7%) of secondary hypothyroidism. 2) The most frequent cause of the thyroprivic primary hypothyroidism was post radioiodine therapy with 109 cases (41.4%). 3) There were 37 cases (14%) of male and 226 cases (86%) of female, showing a ratio of 1 : 6. 4) The majority of patients were between the ages of 30 and 60 with the peak incidence (87 cases, 33%) in their fourth decades of lives. 5) The major symptoms and signs were weakness (97%), edema of face and extremities (92%); Decreased Achilles tendon reflex (87%), cold intolerance (82%), gain in weight (76%), constipation (58%) and cold skin (51%). 6) The cumulative incidence of hypothyroidism in patient treated with {sup 131}I (3-8 mci) was 7.2% at first year, 33.3% at tenth year and the 50% at fourteenth year and the annual increment was 2.9%. 7) The incidence of hypothyroidism related to the numbers of {sup 131}I therapy was not linear. 8) The diagnostic compatibilities of the various tests to hypothyroidism were TSH (100%), T{sub 4} (93.8%), 24-hour-RNIU (91.5%), ATR (86.7%), T{sub 3}RU (66.1%) and BMR (64.9%).

  10. A syphilis co-infection study in human papilloma virus patients attended in the sexually transmitted infection ambulatory clinic, Santa Casa de Misericórdia Hospital, Rio de Janeiro, Brazil

    Directory of Open Access Journals (Sweden)

    Lúcia Maria de Sena Souza

    Full Text Available Despite the prevalence of syphilis worldwide, little is known about its manifestations when associated with other Sexually Transmitted Infections (STI, specifically the Human Papilloma Virus (HPV. Current epidemiological studies show that there is a high incidence of both diseases in ambulatory clinics all over Brazil. This study aims to estimate the incidence of syphilis - HPV co-infections, among patients from the STI ambulatory clinic at the Santa Casa da Misericórdia Hospital, Rio de Janeiro, Brazil. Two-hundred and seven patients were seen in the clinic between March and December 2005, of which 113 (54.6% sought care for an HPV infection. Blood samples were taken from all patients to check syphilis serology using the flocculation and the non-treponemic test or VDRL (Venereal Disease Research Laboratory and the TPHA (Treponema Pallidum Hemagglutination Assay treponemic and confirmatory method. Of the 207 patients, 113 (54.6% consulted referring to HPV as their primary complaint, and of these, 18 (15.9% also presented with positive syphilis serology, demonstrating a high incidence of coinfection. The average age of the patients varied between 20 and 25 years, 203 (98.1% were male and 4 (1.9% were female. The predominance of the male sex in this sample confirms the profile usually treated in STI clinics across the country, and the age range is that of typically high sexually activity. Conclusion: The results demonstrated the need for a differentiated examination of all STD patients.

  11. Controlled clinical studies of homeopathy.

    Science.gov (United States)

    Mathie, Robert T

    2015-10-01

    Observations about controlled clinical trials expressed by Max Haidvogl in the book Ultra High Dilution (1994) have been appraised from a perspective two decades later. The present commentary briefly examines changes in homeopathy research evidence since 1994 as regards: the published number of randomised controlled trials (RCTs), the use of individualised homeopathic intervention, the 'proven efficacy of homeopathy', and the quality of the evidence. The commentary reflects the details of RCTs that are available in a recently published literature review and by scrutiny of systematic reviews of RCTs in homeopathy. The homeopathy RCT literature grew by 309 records in the 18 years that immediately followed Haidvogl's article, with more than a doubling of the proportion that investigated individualised homeopathy. Discounting one prior publication, the entire systematic review literature on homeopathy RCTs post-dates 1994. A total of 36 condition-specific systematic reviews have been identified in the peer-reviewed literature: 16 of them reported positive, or tentatively positive, conclusions about homeopathy's clinical effectiveness; the other 20 were negative or non-conclusive. Reviews typically have been restricted in the strength of their conclusions by the low quality of the original RCT evidence. Three comprehensive systematic reviews concluded, cautiously, that homeopathy may differ from placebo; a fourth such review reached negative conclusions. A recent high-quality meta-analysis concluded that medicines prescribed in individualised homeopathic treatment may have small, specific, effects. Despite important growth in research activity since 1994, concerns about study quality limit the interpretation of available RCT data. The question whether homeopathic intervention differs from placebo awaits decisive answer. Copyright © 2015 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.

  12. A rapid, LC-MS/MS assay for quantification of piperacillin and tazobactam in human plasma and pleural fluid; application to a clinical pharmacokinetic study.

    Science.gov (United States)

    Popowicz, Natalia D; O'Halloran, Sean J; Fitzgerald, Deirdre; Lee, Y C Gary; Joyce, David A

    2018-04-01

    Piperacillin, in combination with tazobactam is a common first-line antibiotic used for the treatment of pleural infection, however its pleural pharmacokinetics and penetration has not previously been reported. The objective of this work was to develop and validate a rapid and sensitive liquid chromatography with tandem mass spectrometry (LC-MS/MS) assay for quantification of piperacillin (PIP) and tazobactam (TAZ). PIP and TAZ were extracted from both human plasma and pleural fluid samples by protein precipitation in methanol containing the internal standards (IS) piperacillin-d 5 (PIP-d 5 ) and sulbactam (SUL). Briefly, 5 μL of sample was mixed with 125 μL of methanol containing IS, vortexed and centrifuged. Supernatant (50 μL) was diluted into 500 μL of mobile phase containing 10 mM of ammonium bicarbonate in LCMS grade water and transferred to the autosampler tray. Electrospray ionization in positive mode and multiple reaction monitoring (MRM) were used for PIP and PIP-d 5 at the transitions m/z 518.2 → 143.2 and m/z 523.2 → 148.2 respectively, and electrospray ionization in negative mode and MRM were used for TAZ and SUL at the transitions m/z 299.1 → 138.1 and m/z 232.4 → 140.1. The chromatographic separation was achieved using an Acquity BEH C-18 column with gradient elution of mobile phase containing 10 mmol/L ammonium bicarbonate in water and methanol. A linear range was observed over the concentration range of 0.25-352 mg/L and 0.25-50.5 mg/L for PIP and TAZ respectively. Complete method validation was performed according to US FDA guidelines for selectivity, specificity, precision and accuracy, LLOQ, matrix effects, recovery and stability, with all results within acceptable limits. This method was successfully applied to two patients with pleural infection and is suitable for further pharmacokinetic studies and therapeutic drug monitoring. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

  13. Clinical Trials

    Medline Plus

    Full Text Available ... Clinical Trials About Clinical Trials Clinical trials are research studies that explore whether a medical strategy, treatment, or ... humans. What Are Clinical Trials? Clinical trials are research studies that explore whether a medical strategy, treatment, or ...

  14. The Human Thioredoxin System: Modifications and Clinical Applications

    Directory of Open Access Journals (Sweden)

    Seyed Isaac Hashemy

    2011-03-01

    Full Text Available The thioredoxin system, comprising thioredoxin (Trx, thioredoxin reductase (TrxR and NADPH, is one of the major cellular antioxidant systems, implicated in a large and growing number of biological functions. Trx acts as an oxidoreductase via a highly conserved dithiol/disulfide motif located in the active site (-Trp-Cys-Gly-Pro-Cys-Lys-. Different factors are involved in the regulation of Trx activity, including its expression level, localization, protein-protein interactions, post-translational modifications and some chemical inhibitors. Mammalian TrxRs are selenoproteins which have a –Cys-Val-Asn-Val-Gly-Cys- N-terminal active site, as well as a C-terminal selenium-containing active site. Besides two Cys-residues in the redox-regulatory domain of cytosolic Trx (Trx1, human Trx1 has three additional Cys-residues. Post-translational modifications of human Trx1 which are involved in the regulation of its activity can happen via modification of Cys-residues including thiol oxidation, glutathionylation and S-nitrosylation or via modification of other amino acid residues such as nitration of Tyr-49. Because of the numerous functions of the thioredoxin system, its inhibition (mainly happens via the targeting TrxR can result in major cellular consequences, which are potentially pro-oxidant in nature, leading to cell death via necrosis or apoptosis if overexpression of Trx and other antioxidative enzymes can not recuperate cell response. Considering this feature, several anticancer drugs have been used which can inhibit TrxR. Elevated levels of Trx and/or TrxR have been reported in many different human malignancies, positively correlated with aggressive tumor growth and poor prognosis. Moreover, anti-oxidative and anti-apoptotic effects of Trx are reasons to study its clinical application as a drug.

  15. Potential use of recombinant human interleukin-6 in clinical oncology

    NARCIS (Netherlands)

    Veldhuis, GJ; Willemse, PHB; Mulder, NH; Limburg, PC; deVries, EGE

    Recombinant human IL-6 (rhIL-6) is a pleiotropic cytokine with stimulatory actions on the hematopoietic system, the immune system and hepatocytes. Clinical interest in the use of this cytokine was raised because of its thrombopoietic properties and also because of its anti-tumor activity, which was

  16. The Abbott RealTime High Risk HPV test is a clinically validated human papillomavirus assay for triage in the referral population and use in primary cervical cancer screening in women 30 years and older: a review of validation studies.

    Science.gov (United States)

    Poljak, Mario; Oštrbenk, Anja

    2013-01-01

    Human papillomavirus (HPV) testing has become an essential part of current clinical practice in the management of cervical cancer and precancerous lesions. We reviewed the most important validation studies of a next-generation real-time polymerase chain reaction-based assay, the RealTime High Risk HPV test (RealTime)(Abbott Molecular, Des Plaines, IL, USA), for triage in referral population settings and for use in primary cervical cancer screening in women 30 years and older published in peer-reviewed journals from 2009 to 2013. RealTime is designed to detect 14 high-risk HPV genotypes with concurrent distinction of HPV-16 and HPV-18 from 12 other HPV genotypes. The test was launched on the European market in January 2009 and is currently used in many laboratories worldwide for routine detection of HPV. We concisely reviewed validation studies of a next-generation real-time polymerase chain reaction (PCR)-based assay: the Abbott RealTime High Risk HPV test. Eight validation studies of RealTime in referral settings showed its consistently high absolute clinical sensitivity for both CIN2+ (range 88.3-100%) and CIN3+ (range 93.0-100%), as well as comparative clinical sensitivity relative to the currently most widely used HPV test: the Qiagen/Digene Hybrid Capture 2 HPV DNA Test (HC2). Due to the significantly different composition of the referral populations, RealTime absolute clinical specificity for CIN2+ and CIN3+ varied greatly across studies, but was comparable relative to HC2. Four validation studies of RealTime performance in cervical cancer screening settings showed its consistently high absolute clinical sensitivity for both CIN2+ and CIN3+, as well as comparative clinical sensitivity and specificity relative to HC2 and GP5+/6+ PCR. RealTime has been extensively evaluated in the last 4 years. RealTime can be considered clinically validated for triage in referral population settings and for use in primary cervical cancer screening in women 30 years and older.

  17. Evaluation of effectiveness of hyaluronic acid in combination with bioresorbable membrane (poly lactic acid-poly glycolic acid for the treatment of infrabony defects in humans: A clinical and radiographic study

    Directory of Open Access Journals (Sweden)

    Bhumika Sehdev

    2016-01-01

    Full Text Available Background: The combination of biomaterials, bone graft substitutes along with guided tissue regeneration (GTR has been shown to be an effective modality of periodontal regenerative therapy for infrabony defects. Therefore, the present randomized controlled clinical study was undertaken to evaluate the effectiveness of hyaluronic acid (HA in combination with bioresorbable membrane for the treatment of human infrabony defects. Materials and Methods: Twenty four infrabony defects in 20 systemically healthy patients were randomly assigned to test (HA in combination with bioresorbable membrane and control (bioresorbable membrane alone treatment groups. Probing pocket depth (PPD, relative attachment level, and relative gingival margin level were measured with a computerized Florida disc probe at baseline and at 6 months follow-up. Radiographic measurements were also evaluated at baseline and at 6 months of postsurgery. Results: At 6 months, the mean reduction in PPD in test group and control group was 4.52 mm and 2.97 mm, respectively. Significantly higher clinical attachment level with a gain of 2.20 mm was found in the test group as compared to control group. In addition, statistically significant greater reduction of radiographic defect depth was observed in the test group. Conclusion: Regenerative approach using hyaloss in combination with GTR for the treatment of human infrabony defects resulted in a significant added benefit in terms of CAL gains, PPD reductions and radiographic defect fill, as well as LBG, compared to the GTR alone.

  18. Expression and clinical value of EGFR in human meningiomas

    Directory of Open Access Journals (Sweden)

    Magnus B. Arnli

    2017-03-01

    Full Text Available Background Meningiomas are common intracranial tumors in humans that frequently recur despite having a predominantly benign nature. Even though these tumors have been shown to commonly express EGFR/c-erbB1 (epidermal growth factor receptor, results from previous studies are uncertain regarding the expression of either intracellular or extracellular domains, cellular localization, activation state, relations to malignancy grade, and prognosis. Aims This study was designed to investigate the expression of the intracellular and extracellular domains of EGFR and of the activated receptor as well as its ligands EGF and TGFα in a large series of meningiomas with long follow-up data, and investigate if there exists an association between antibody expression and clinical and histological data. Methods A series of 186 meningiomas consecutively operated within a 10-year period was included. Tissue microarrays were constructed and immunohistochemically analyzed with antibodies targeting intracellular and extracellular domains of EGFR, phosphorylated receptor, and EGF and TGFα. Expression levels were recorded as a staining index (SI. Results Positive immunoreactivity was observed for all antibodies in most cases. There was in general high SIs for the intracellular domain of EGFR, phosphorylated EGFR, EGF, and TGFα but lower for the extracellular domain. Normal meninges were negative for all antibodies. Higher SIs for the phosphorylated EGFR were observed in grade II tumors compared with grade I (p = 0.018. Survival or recurrence was significantly decreased in the time to recurrence analysis (TTR with high SI-scores of the extracellular domain in a univariable survival analysis (HR 1.152, CI (1.036–1.280, p = 0.009. This was not significant in a multivariable analysis. Expression of the other antigens did not affect survival. Conclusion EGFR is overexpressed and in an activated state in human meningiomas. High levels of ligands also support this

  19. Hurdles to clinical translation of human induced pluripotent stem cells.

    Science.gov (United States)

    Neofytou, Evgenios; O'Brien, Connor Galen; Couture, Larry A; Wu, Joseph C

    2015-07-01

    Human pluripotent stem cells are known to have the capacity to renew indefinitely, being intrinsically able to differentiate into many different cell types. These characteristics have generated tremendous enthusiasm about the potential applications of these cells in regenerative medicine. However, major challenges remain with the development and testing of novel experimental stem cell therapeutics in the field. In this Review, we focus on the nature of the preclinical challenges and discuss potential solutions that could help overcome them. Furthermore, we discuss the use of allogeneic versus autologous stem cell products, including a review of their respective advantages and disadvantages, major clinical requirements, quality standards, time lines, and costs of clinical grade development.

  20. Human Locomotion in Hypogravity: From Basic Research to Clinical Applications

    Directory of Open Access Journals (Sweden)

    Francesco Lacquaniti

    2017-11-01

    Full Text Available We have considerable knowledge about the mechanisms underlying compensation of Earth gravity during locomotion, a knowledge obtained from physiological, biomechanical, modeling, developmental, comparative, and paleoanthropological studies. By contrast, we know much less about locomotion and movement in general under sustained hypogravity. This lack of information poses a serious problem for human space exploration. In a near future humans will walk again on the Moon and for the first time on Mars. It would be important to predict how they will move around, since we know that locomotion and mobility in general may be jeopardized in hypogravity, especially when landing after a prolonged weightlessness of the space flight. The combination of muscle weakness, of wearing a cumbersome spacesuit, and of maladaptive patterns of locomotion in hypogravity significantly increase the risk of falls and injuries. Much of what we currently know about locomotion in hypogravity derives from the video archives of the Apollo missions on the Moon, the experiments performed with parabolic flight or with body weight support on Earth, and the theoretical models. These are the topics of our review, along with the issue of the application of simulated hypogravity in rehabilitation to help patients with deambulation problems. We consider several issues that are common to the field of space science and clinical rehabilitation: the general principles governing locomotion in hypogravity, the methods used to reduce gravity effects on locomotion, the extent to which the resulting behavior is comparable across different methods, the important non-linearities of several locomotor parameters as a function of the gravity reduction, the need to use multiple methods to obtain reliable results, and the need to tailor the methods individually based on the physiology and medical history of each person.

  1. Human Locomotion in Hypogravity: From Basic Research to Clinical Applications.

    Science.gov (United States)

    Lacquaniti, Francesco; Ivanenko, Yury P; Sylos-Labini, Francesca; La Scaleia, Valentina; La Scaleia, Barbara; Willems, Patrick A; Zago, Myrka

    2017-01-01

    We have considerable knowledge about the mechanisms underlying compensation of Earth gravity during locomotion, a knowledge obtained from physiological, biomechanical, modeling, developmental, comparative, and paleoanthropological studies. By contrast, we know much less about locomotion and movement in general under sustained hypogravity. This lack of information poses a serious problem for human space exploration. In a near future humans will walk again on the Moon and for the first time on Mars. It would be important to predict how they will move around, since we know that locomotion and mobility in general may be jeopardized in hypogravity, especially when landing after a prolonged weightlessness of the space flight. The combination of muscle weakness, of wearing a cumbersome spacesuit, and of maladaptive patterns of locomotion in hypogravity significantly increase the risk of falls and injuries. Much of what we currently know about locomotion in hypogravity derives from the video archives of the Apollo missions on the Moon, the experiments performed with parabolic flight or with body weight support on Earth, and the theoretical models. These are the topics of our review, along with the issue of the application of simulated hypogravity in rehabilitation to help patients with deambulation problems. We consider several issues that are common to the field of space science and clinical rehabilitation: the general principles governing locomotion in hypogravity, the methods used to reduce gravity effects on locomotion, the extent to which the resulting behavior is comparable across different methods, the important non-linearities of several locomotor parameters as a function of the gravity reduction, the need to use multiple methods to obtain reliable results, and the need to tailor the methods individually based on the physiology and medical history of each person.

  2. Antimicrobial Susceptibilities of Geographically Diverse Clinical Human Isolates of Leptospira▿

    OpenAIRE

    Ressner, Roseanne A.; Griffith, Matthew E.; Beckius, Miriam L.; Pimentel, Guillermo; Miller, R. Scott; Mende, Katrin; Fraser, Susan L.; Galloway, Renee L.; Hospenthal, Duane R.; Murray, Clinton K.

    2008-01-01

    Although antimicrobial therapy of leptospirosis has been studied in a few randomized controlled clinical studies, those studies were limited to specific regions of the world and few have characterized infecting strains. A broth microdilution technique for the assessment of antibiotic susceptibility has been developed at Brooke Army Medical Center. In the present study, we assessed the susceptibilities of 13 Leptospira isolates (including recent clinical isolates) from Egypt, Thailand, Nicarag...

  3. Comparative studies on the human serum albumin binding of the clinically approved EGFR inhibitors gefitinib, erlotinib, afatinib, osimertinib and the investigational inhibitor KP2187.

    Science.gov (United States)

    Dömötör, Orsolya; Pelivan, Karla; Borics, Attila; Keppler, Bernhard K; Kowol, Christian R; Enyedy, Éva A

    2018-05-30

    Binding interactions between human serum albumin (HSA) and four approved epidermal growth factor receptor (EGFR) inhibitors gefitinib (GEF), erlotinib (ERL), afatinib (AFA), osimertinib (OSI), as well as the experimental drug KP2187, were investigated by means of spectrofluorometric and molecular modelling methods. Steady-state and time resolved spectrofluorometric techniques were carried out, including direct quenching of protein fluorescence and site marker displacement measurements. Proton dissociation processes and solvent dependent fluorescence properties were investigated as well. The EGFR inhibitors were predominantly presented in their single protonated form (HL + ) at physiological pH except ERL, which is charge-neutral. Significant solvent dependent fluorescence properties were found for GEF, ERL and KP2187, namely their emission spectra show strong dependence on the polarity and the hydrogen bonding ability of the solvents. The inhibitors proved to be bound at site I of HSA (in subdomain IIA) in a weak-to-moderate fashion (logK' 3.9-4.9) using spectrofluorometry. OSI (logK' 4.3) and KP2187 can additionally bind in site II (in subdomain IIIA), while GEF, ERL and AFA clearly show no interaction here. Docking methods qualitatively confirmed binding site preferences of compounds GEF and KP2187, and indicated that they probably bind to HSA in their neutral forms. Binding constants calculated on the basis of the various experimental data indicate a weak-to-moderate binding on HSA, only OSI exhibits somewhat higher affinity towards this protein. However, model calculations performed at physiological blood concentrations of HSA resulted in high (ca. 90%) bound fractions for the inhibitors, highlighting the importance of plasma protein binding. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. Clinical Characteristics and Genetic Variability of Human Rhinovirus in Mexico

    Directory of Open Access Journals (Sweden)

    Hilda Montero

    2012-01-01

    Full Text Available Human rhinovirus (HRV is a leading cause of acute respiratory infection (ARI in young children and infants worldwide and has a high impact on morbidity and mortality in this population. Initially, HRV was classified into two species: HRV-A and HRV-B. Recently, a species called HRV-C and possibly another species, HRV-D, were identified. In Mexico, there is little information about the role of HRV as a cause of ARI, and the presence and importance of species such as HRV-C are not known. The aim of this study was to determine the clinical characteristics and genetic variability of HRV in Mexican children. Genetic characterization was carried out by phylogenetic analysis of the 5′-nontranslated region (5′-NTR of the HRV genome. The results show that the newly identified HRV-C is circulating in Mexican children more frequently than HRV-B but not as frequently as HRV-A, which was the most frequent species. Most of the cases of the three species of HRV were in children under 2 years of age, and all species were associated with very mild and moderate ARI.

  5. Analysis of APC mutation in human ameloblastoma and clinical significance.

    Science.gov (United States)

    Li, Ning; Liu, Bing; Sui, Chengguang; Jiang, Youhong

    2016-01-01

    As a highly conserved signaling pathway, Wnt/β-catenin signal transduction pathway plays an important role in many processes. Either in the occurrence or development of tumor, activation of this pathway takes an important place. APC inhibits Wnt/β-catenin pathway to regulate cell proliferation and differentiation. This study aimed to investigate the function of cancer suppressor gene. PCR amplification and sequencing method was used to analyze APC mutations of human clinical specimens. The pathological specimens were collected for PCR and clear electrophoretic bands were obtained after electrophoresis. The gene sequence obtained after purification and sequencing analysis was compared with the known APC gene sequence (NM_000038.5). Base mutations at APC 1543 (T → C), APC-4564 (G → A), APC-5353 (T → G), APC-5550 (T → A) and APC-5969 (G → A) locus existed in 22 (27.5 %), 12 (15 %), 5 (6.25 %), 13 (16.25 %) and 12 patients (15 %), respectively. Gene mutations existed in ameloblastoma, and the mutation loci were 1543 locus (T → C), 4564 locus (G → A), 5353 locus (T → G), 5550 locus (T → A) and 5969 locus (G → A) 15 %, respectively. APC mutation plays a certain role in monitoring the tumor malignant degree as it may indicate the transition process of ameloblastoma malignant phenotype.

  6. [The clinical use of cryopreserved human skin allografts for transplantation].

    Science.gov (United States)

    Martínez-Flores, Francisco; Chacón-Gómez, María; Madinaveitia-Villanueva, Juan Antonio; Barrera-Lopez, Araceli; Aguirre-Cruz, Lucinda; Querevalu-Murillo, Walter

    2015-01-01

    The biological recovery of human skin allografts is the gold standard for preservation in Skin Banks. However, there is no worldwide consensus about specific allocation criteria for preserved human skin allografts with living cells. A report is presented on the results of 5 years of experience of using human skin allografts in burned patient in the Skin and Tissue Bank at the "Instituto Nacional de Rehabilitacion" The human skin allografts were obtained from multi-organ donors. processed and preserved at -80 °C for 12 months. Allocation criteria were performed according to blood type match, clinical history, and burned body surface. Up to now, the Skin and Tissue Bank at 'Instituto Nacional de Rehabilitacion" has processed and recovered 125,000 cm(2) of human skin allografts. It has performed 34 surgical implants on 21 burned patients. The average of burn body surface was 59.2%. More than two-thirds (67.7%) of recipients of skin allografts were matched of the same to type blood of the donor, and 66.6% survived after 126 days hospital stay. It is proposed to consider recipient's blood group as allocation criteria to assign tissue; and use human skin allografts on patiens affected with burns over 30% of body surface (according the "rule of the 9"). Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

  7. [Introduction of neuroethics: out of clinic, beyond academia in human brain research].

    Science.gov (United States)

    Fukushi, Tamami; Sakura, Osamu

    2008-11-01

    Higher cognitive function in human brain is one of well-developed fields of neuroscience research in the 21st century. Especially functional magnetic resonance imaging (fMRI) and near infrared recording system have brought so many non-clinical researchers whose background is such as cognitive psychology, economics, politics, pedagogy, and so on, to the human brain mapping study. Authors have introduced the ethical issues related to incidental findings during the fMRI recording for non-clinical purpose, which is a typical problem derived from such expanded human brain research under non clinical condition, that is, neuroethics. In the present article we would introduce neuroethical issues in contexts of "out of clinic" and "beyond academia".

  8. Review of clinical and laboratory features of human Brucellosis

    Directory of Open Access Journals (Sweden)

    Mantur B

    2007-01-01

    Full Text Available Infection with Brucella spp. continues to pose a human health risk globally despite strides in eradicating the disease from domestic animals. Brucellosis has been an emerging disease since the discovery of Brucella melitensis by Sir David Bruce in 1887. Although many countries have eradicated B. abortus from cattle, in some areas B. melitensis and B. suis have emerged as causes of this infection in cattle, leading to human infections. Currently B. melitensis remains the principal cause of human brucellosis worldwide including India. The recent isolation of distinct strains of Brucella from marine mammals as well as humans is an indicator of an emerging zoonotic disease. Brucellosis in endemic and non-endemic regions remains a diagnostic puzzle due to misleading non-specific manifestations and increasing unusual presentations. Fewer than 10% of human cases of brucellosis may be clinically recognized and treated or reported. Routine serological surveillance is not practiced even in Brucella - endemic countries and we suggest that this should be a part of laboratory testing coupled with a high index of clinical suspicion to improve the level of case detection. The screening of family members of index cases of acute brucellosis in an endemic area should be undertaken to pick up additional unrecognised cases. Rapid and reliable, sensitive and specific, easy to perform and automated detection systems for Brucella spp. are urgently needed to allow early diagnosis and adequate antibiotic therapy in time to decrease morbidity / mortality. The history of travel to endemic countries along with exposure to animals and exotic foods are usually critical to making the clinical diagnosis. Laboratory testing is indispensable for diagnosis. Therefore alertness of clinician and close collaboration with microbiologist are essential even in endemic areas to correctly diagnose and treat this protean human infection. Existing treatment options, largely based on

  9. A combination of various functional food ingredients as a weight management program: randomized, placebo-controlled, and double-blind human clinical studies

    Directory of Open Access Journals (Sweden)

    Harunobu Amagase

    2011-12-01

    Full Text Available ABSTRACT:Background: Lycium barbarum increased the postprandial energy expenditure (PPEE. Negative energy balance caused by the systematic procedure (TAIslim® System, including increasing metabolic rate through physical activity, use of Lycium barbarum-containing TAIslim (Product A, and decreasing caloric intake by consuming a chewable confection (TAIslim SKINNY=Product B, and a meal replacement shake (TAIslim SHAKE=Product C, would be successful for weight loss.Methods: We examined TAIslim System on anthropometrics, appetite in Study 1 and PPEE in Study 2, both in a randomized, placebo-controlled, double-blind manner. 1 A total of 67 participants were randomized into 2 groups (placebo or TAIslim System. Intake procedures were: Product A, 60 ml (20 kcal b.i.d. immediately before breakfast and lunch, Product B, 1 chew (20 kcal t.i.d. between meals and after dinner; Product C, 40.5 g (158 kcal as breakfast. A calorie-restricted diet with multi-vitamin supplementation and daily exercise was required. Anthropometric parameters were assessed at baseline, 4, 8, and 12 w. 2 Appetite was measured using a subjective visual analog scale during the initial 3-7 days of intake. 3 For PPEE evaluation, 12 participants consumed a single bout of TAIslim System products or placebo, and took part in 6 study sessions. EE was measured by an indirect calorimeter immediately before (baseline and at 1, 2, and 4 h post-intake of samples.Results: 1 Body weight was significantly reduced by 6.2±0.7%, compared to pre-intervention with TAIslim System (P<0.01. Waist circumference, total body fat, blood pressure, and fasting blood glucose levels were also significantly reduced by TAIslim System, in a range of 3.8-9.9%. TAIslim System was significantly more effective than the placebo (P<0.05. The placebo group showed -0.1-3.9% reduction from pre-intervention with no significant difference. 2 TAIslim Functional Foods in Health and Disease 2011, 1(12:555-573System also

  10. Humanizing Oral Health Care through Continuing Education on Social Determinants of Health: Evaluative Case Study of a Canadian Private Dental Clinic.

    Science.gov (United States)

    Lévesque, Martine; Levine, Alissa; Bedos, Christophe

    2016-01-01

    Primary care practitioners are frequently unprepared to take into account the effects of social determinants on underprivileged patients' health and health management. To address this issue among dental professionals, an original onsite continuing education (CE) course on poverty was co-developed by researchers, dental professionals, and community organizations. Integrating patient narratives and a short film, course material aims to elicit critical reflection and provide coaching for practice improvements. A qualitative case study conducted with a large Montreal Canada dental team reveals CE course participants' newfound understandings and increased sensitivity to the causes of poverty and the nature of life on welfare. Participants also describe revised interpretations of certain patient behaviors, subtle changes in communication with patients and improved equity in appointment-giving policy. Unintended outcomes include reinforced judgment and a tendency to moralize certain patient categories. Implications for health professional educators, researchers, and dental regulatory authorities are discussed.

  11. Clinical Trials

    Medline Plus

    Full Text Available ... Clinical Trials About Clinical Trials Clinical trials are research studies that explore whether a medical strategy, treatment, ... required to have an IRB. Office for Human Research Protections The U.S. Department of Health and Human ...

  12. Preliminary clinical applications of DTI in human cervical spinal cord

    International Nuclear Information System (INIS)

    Song Ting; Mai Weiwen; Liang Biling; Shen Jun; Huang Suiqiao; Hu Chunhong

    2007-01-01

    Objective: To condcut preliminary study of the value of DTI(diffusion tensor imaging) in human cervical spinal cord. Methods: Twenty-one patients suffering from cervical spondylotic myelopathy and twenty volunteers without any clinical symptoms underwent routine MRI and DTI examination. DTI was performed in six non-collinear directions with single-shot fast spin echo echo, planar imaging sequence(b value = 400 s·mm -2 ). ADC(apparent diffusion coefficient) and FA(fractional anisotropy)values were measured by ROIs(regions of interest) in 4 different level segment spinal cord (C 2/3 , C 3/4 , C 4/5 , C 5/6 ) in normal volunteers, in lesions and normal segmental spinal cord in clinical cases respectively. DTI original images were automatically processed by using IDL (Version 5.6) soft- ware to produce color tensor images. SPSS11.0 software for windows was used for t-test and one-way ANOVA analysis. The difference was considered statistically significant if P 2/3 , C 3/4 , C 4/5 , C 5/6 , were analyzed and it was found that FA value between them had a significant difference by ANOVA, F=159.24, P 2/3 level. However, ADC value between 4 segments had no significant difference(F=2.191, P>0.05). (2)In patients of cervical spondylotic myelopathy, routine MRI T2WI showed abnormal signal in 9 cases, and showed no abnormal signal in 12 dases. In sixteen cases it was found that abnormal patchy green signal on colorized tensor maps appeared on the normal blue spinal cord. Also, in patients of cervical spondylotic myelopathy, there was significant difference in ADC and FA value between lesions and normal spinal cord (paired t test, for ADC, t=2.88, P 2/3 level segment spinal cord in normal volunteers (0.85 ± 0.03) is the highest among other segments. FA value decreases gradually along cervical spinal cord towards the caudal direction. However, the difference of ADC values amongst 4 segments is not significant. DTI colorized tensor maps can show more lesions than routine MRI

  13. Clinical application of antibody monoclonal humanized anti-EGFrnimotuzumab labeled

    International Nuclear Information System (INIS)

    Perera Pintado, Alejandro; Peña Quián, Yamilé; Batista Cuéllar, Juan F.; Prats Capote, Anaís; Torres Aroche, Leonel A.; Casacó Santana, Caridad; Sánchez Mendosa, Elvia L.; Sánchez González, Yolaine; Romero Collado, Susana; Quesada Pozo, Rodobaldo; Valladares Oviedo, Lourdes; Masquida García, Elsa M.; Leyva Montaña, René; Casacó, Angel; Ramos Suzarte, Mayra; Crombet, Tania

    2016-01-01

    Most malignant tumors are of epithelial origin. These are characterized by overexpression of the receptor of epidermal growth factor (EGFR), which the neoplastic cells escape the regulatory mechanisms are allowed, so its high concentration of membrane is generally associated with a poor prognosis . By binding an antibody specifically to this receptor, preventing binding of EGF latter and activation mechanism tyrosine kinase inhibiting cell mitosis and apoptosis causing tumor cell. For this reason, the EGFr has been considered as an attractive target for anti-tumor therapy. The humanized monoclonal antibody anti-EGFr nimotuzumab was developed by the Center of Molecular Immunology (Havana, Cuba). Numerous clinical trials have been developed in the Department of Clinical Research Center Isotopes (Cuba), in which it has been applied this antibody, both labeled with 99mTc for immuno gammagraphic detection of tumors, as labeled with 188 Re for radioimmunotherapy of gliomas high degree of malignancy. The aim of this paper is to show the experience of the Department of Clinical Research of CENTIS in various clinical trials with marking for both immuno gammagraphics detection of tumors, such as for radioimmunotherapy nimotuzumab. (author)

  14. [Clinical research XXIV. From clinical judgment to ethics in research on humans].

    Science.gov (United States)

    Pérez-Rodríguez, Marcela; Palacios-Cruz, Lino; Rivas-Ruiz, Rodolfo; Talavera, Juan O

    2014-01-01

    Bioethics in research is an essential part of the structured review process of an article and it is based on three fundamental principles: respect for persons, beneficence and justice. In addition to not providing valid knowledge, a research with inadequate design, execution and statistical analysis is not ethical either, since these methodological deficiencies will produce information that will not be useful and, therefore, the risks that the participants were exposed to will have been in vain. Beyond scientific validity, there are other aspects that outline if an investigation is ethical, such as the clinical and social value of a study, a fair selection of participants, favorable risk-benefit balance, an independent review, the informed consent and respect for participants and potential participants. Throughout the article here presented, the documents that profile the behavior of investigators to protect the participants, such as the Declaration of Helsinki, the national regulations that rule us and the differences between research without risk, with minimal risk and with greater than minimal risk are discussed. That like in daily life, behavior in research involving human participants must be self-regulated, ie, people with knowledge of the existence of the law discover that the man is outside the realm of nature where work is done under the necessity of natural causality, and falls within the scope of the will; only if the man is free to decide their actions may be a law regulating their action.

  15. Quantification of human motion: gait analysis-benefits and limitations to its application to clinical problems.

    Science.gov (United States)

    Simon, Sheldon R

    2004-12-01

    The technology supporting the analysis of human motion has advanced dramatically. Past decades of locomotion research have provided us with significant knowledge about the accuracy of tests performed, the understanding of the process of human locomotion, and how clinical testing can be used to evaluate medical disorders and affect their treatment. Gait analysis is now recognized as clinically useful and financially reimbursable for some medical conditions. Yet, the routine clinical use of gait analysis has seen very limited growth. The issue of its clinical value is related to many factors, including the applicability of existing technology to addressing clinical problems; the limited use of such tests to address a wide variety of medical disorders; the manner in which gait laboratories are organized, tests are performed, and reports generated; and the clinical understanding and expectations of laboratory results. Clinical use is most hampered by the length of time and costs required for performing a study and interpreting it. A "gait" report is lengthy, its data are not well understood, and it includes a clinical interpretation, all of which do not occur with other clinical tests. Current biotechnology research is seeking to address these problems by creating techniques to capture data rapidly, accurately, and efficiently, and to interpret such data by an assortment of modeling, statistical, wave interpretation, and artificial intelligence methodologies. The success of such efforts rests on both our technical abilities and communication between engineers and clinicians.

  16. Human bartonellosis: seroepidemiological and clinical features with an emphasis on data from Brazil - A review

    Directory of Open Access Journals (Sweden)

    C Lamas

    2008-05-01

    Full Text Available Bartonellae are fastidious Gram-negative bacteria that are widespread in nature with several animal reservoirs (mainly cats, dogs, and rodents and insect vectors (mainly fleas, sandflies, and human lice. Thirteen species or subspecies of Bartonella have been recognized as agents causing human disease, including B. bacilliformis, B. quintana, B. vinsonii berkhoffii, B. henselae, B. elizabethae, B. grahamii, B. washoensis, B. koehlerae, B. rocha-limaea, and B. tamiae. The clinical spectrum of infection includes lymphadenopathy, fever of unknown origin, endocarditis, neurological and ophthalmological syndromes, Carrion's disease, and others. This review provides updated information on clinical manifestations and seroepidemiological studies with an emphasis on data available from Brazil.

  17. How important are human immunodeficiency virus (HIV) clinical markers to the long-term formal employment among people living with HIV in developing countries? A study in South Africa.

    Science.gov (United States)

    Odek, W O; Glendinning, A; Charalambous, S

    2014-01-01

    To examine the relationship of Human Immunodeficiency Virus (HIV) clinical markers and socio-demographic characteristics with long-term formal employment among people living with HIV (PLHIV). 554 adults, 55% females, on HIV treatment for at least two years at two public hospitals in Johannesburg, South Africa. A retrospective cohort design, tracing changes in study participants' formal employment status since the first HIV-positive diagnosis. Data collection included historical medical records review and interviewer-administered questionnaires. 44% of all study participants (39% and 49% among males and females, respectively) were formally employed at the time of the study, primarily in low-skilled jobs in the private sector. The majority (83%) of males and 60% of females remained in formal employment since being diagnosed as HIV-positive. Female gender, education to grade 12 or higher, a smaller household size and being married were significantly associated with current formal employment. Formal employment was unrelated to HIV treatment indicators (CD4 count, viral load and duration since diagnosis). Of those in formal employment, 68 (28%) were aware of HIV policies at their workplaces, which was also positively associated with the duration in their current employment. PLHIV in developing country contexts can enter into and maintain formal employment, especially when treatment and workplace support are available. Thus, employer organisations should implement effective workplace HIV policies to enhance employment experiences of their workforce living with HIV. Care and support services for people on HIV treatment should also address their career development needs.

  18. Prospective study of the impact of the Prosigna assay on adjuvant clinical decision-making in unselected patients with estrogen receptor positive, human epidermal growth factor receptor negative, node negative early-stage breast cancer.

    Science.gov (United States)

    Martín, Miguel; González-Rivera, Milagros; Morales, Serafín; de la Haba-Rodriguez, Juan; González-Cortijo, Lucía; Manso, Luis; Albanell, Joan; González-Martín, Antonio; González, Sónia; Arcusa, Angels; de la Cruz-Merino, Luis; Rojo, Federico; Vidal, María; Galván, Patricia; Aguirre, Elena; Morales, Cristina; Ferree, Sean; Pompilio, Kristen; Casas, Maribel; Caballero, Rosalía; Goicoechea, Uxue; Carrasco, Eva; Michalopoulos, Steven; Hornberger, John; Prat, Aleix

    2015-06-01

    Improved understanding of risk of recurrence (ROR) is needed to reduce cases of recurrence and more effectively treat breast cancer patients. The purpose of this study was to examine how a gene-expression profile (GEP), identified by Prosigna, influences physician adjuvant treatment selection for early breast cancer (EBC) and the effects of this influence on optimizing adjuvant treatment recommendations in clinical practice. A prospective, observational, multicenter study was carried out in 15 hospitals across Spain. Participating medical oncologists completed pre-assessment, post-assessment, and follow-up questionnaires recording their treatment recommendations and confidence in these recommendations, before and after knowing the patient's ROR. Patients completed questionnaires on decision-making, anxiety, and health status. Between June 2013 and January 2014, 217 patients enrolled and a final 200 were included in the study. Patients were postmenopausal, estrogen receptor positive, human epidermal growth hormone factor negative, and node negative with either stage 1 or stage 2 tumors. After receiving the GEP results, treatment recommendations were changed for 40 patients (20%). The confidence of medical oncologists in their treatment recommendations increased in 41.6% and decreased in 6.5% of total cases. Patients reported lower anxiety after physicians made treatment recommendations based on the GEP results (p anxiety about the selected adjuvant therapy decreased with use of the GEP.

  19. Clinical studies of biomarkers in suicide prediction

    OpenAIRE

    Jokinen, Jussi

    2007-01-01

    Suicide is a major clinical problem in psychiatry and suicidal behaviours can be seen as a nosological entity per se. Predicting suicide is difficult due to its low base-rate and the limited specificity of clinical predictors. Prospective biological studies suggest that dysfunctions in the hypothalamo pituitary adrenal (HPA) axis and the serotonergic system have predictive power for suicide in mood disorders. Suicide attempt is the most robust clinical predictor making suici...

  20. CLINICAL STUDY OF DUODENAL PERFORATION

    Directory of Open Access Journals (Sweden)

    Sambasiva Rao

    2016-04-01

    Full Text Available BACKGROUND The duodenal injury can pose a formidable challenge to the surgeon and failure to manage it properly may have devastating results. Over the centuries, there was little to offer the patient of acute abdomen beyond cupping, purgation and enemas, all of which did more harm than good. It was not until 1884 that Mikulicz made an attempt to repair a perforation. Recent statistics indicate roughly 10% of population develop gastric or duodenal ulcer in life time. Roughly 1-3% of population above the age of 20 years have some degree of peptic ulcer activity during any annual period. A detailed history with regards to the signs and symptoms of the patient, a meticulous examination, radiological and biochemical investigations help to arrive at a correct preoperative diagnosis. In this study, a sincere effort has been put to understand the demographic patterns, to understand the underlying aetiology and to understand the effectiveness of the standard methods of investigation and treatment in use today. METHODS This is a 24 months prospective study i.e., from September 2011 to September 2013 carried out at Dr. Pinnamaneni Siddhartha Institute of Medical Sciences & Research Foundation. The study included the patients presenting to Dr. Pinnamaneni Siddhartha Institute of Medical Sciences & Research Foundation to emergency ward with signs and symptoms of hollow viscus perforation. The sample size included 30 cases of duodenal perforation. RESULTS Duodenal ulcer perforation commonly occurs in the age group of 30-60 years, but it can occur in any age group. Majority of the patients were male. Smoking and alcohol consumption were risk factors in most cases (53.3% for the causation of duodenal ulcer perforation. Sudden onset of abdominal pain, situated at epigastrium and right hypochondrium was a constant symptom (100%. Vomiting, constipation and fever were not so common. CONCLUSION The emergency surgical management for perforated duodenal ulcer is by

  1. CLINICAL STUDY OF CONCOMITANT SQUINT

    Directory of Open Access Journals (Sweden)

    Vijay Chopra

    2017-07-01

    Full Text Available BACKGROUND Malalignment in the visual axes of the two eyes is called strabismus. Fusion of both images is replaced either by diplopia or suppression of one image. Squint leads to loss of binocular single vision. Concomitant squint is a type of manifest squint in which the amount of deviation in the squinting eye is same in all gazes. Binocular single vision and ocular movement coordination are not present since birth, but are acquired in the early childhood. This process starts by the age of 3-6 months and is completed up to 5-6 years. Any hindrance in the development of these processes may result in concomitant squint. MATERIALS AND METHODS In 100 cases of concomitant squint, patients were included in our study. Detailed history was taken regarding the onset of squint and duration. Past history and family history was also elicited. General examination was done to detect any abnormalities of central nervous system. Routine ophthalmic examination including best corrected visual acuity, cover test performed to detect the type of deviation whether uniocular or alternating and the type of fixation. Angle of deviation was measured by Hirschberg’s test and on the synoptophore. Binocular single vision was assessed using Worth’s 4-dot test and synoptophore. Cycloplegic refraction and fundus evaluation done in all patients. Inclusion Criteria- All primary non-paralytic deviations, sensory deprivation strabismus. Exclusion Criteria- Paralytic strabismus, strabismus associated with neurological disorders, consecutive strabismus and palpebral fissure abnormalities patients. RESULTS Majority of cases of concomitant squint were of esotropic type. Most common form of esotropia seen was infantile esotropia. Most common form of exotropia was intermittent exotropia. 19% of cases were secondary to other ocular diseases namely cataract, macular lesion, high myopia, etc. Amblyopia was present in 54% patients and of very dense type, which could not be treated

  2. Korean Clinic Based Outcome Measure Studies

    OpenAIRE

    Jongbae Park

    2003-01-01

    Background: Evidence based medicine has become main tools for medical practice. However, conducting a highly ranked in the evidence hierarchy pyramid is not easy or feasible at all times and places. There remains a room for descriptive clinical outcome measure studies with admitting the limit of the intepretation. Aims: Presents three Korean clinic based outcome measure studies with a view to encouraging Korean clinicians to conduct similar studies. Methods: Three studies are presented...

  3. Depletion of Human DNA in Spiked Clinical Specimens for Improvement of Sensitivity of Pathogen Detection by Next-Generation Sequencing

    OpenAIRE

    Hasan, Mohammad R.; Rawat, Arun; Tang, Patrick; Jithesh, Puthen V.; Thomas, Eva; Tan, Rusung; Tilley, Peter

    2016-01-01

    Next-generation sequencing (NGS) technology has shown promise for the detection of human pathogens from clinical samples. However, one of the major obstacles to the use of NGS in diagnostic microbiology is the low ratio of pathogen DNA to human DNA in most clinical specimens. In this study, we aimed to develop a specimen-processing protocol to remove human DNA and enrich specimens for bacterial and viral DNA for shotgun metagenomic sequencing. Cerebrospinal fluid (CSF) and nasopharyngeal aspi...

  4. Inhibitory Interneurons of The Human Neocortex after Clinical Death

    Directory of Open Access Journals (Sweden)

    V. A. Akulinin

    2016-01-01

    Full Text Available Objective: to analyze the human neocortex interneurons (areas 4, 10, 17 and 21 by Brodmann after cardiac arrest (clinical death.Materials and methods. The main group included patients (n=7, men who survived 7—10 days and 70—90 days after cardiac arrest and later died due to heart failure. The control group (n=4, men included individuals after sudden fatal accidents. The morphometric and histological analysis of 420 neocortical fields (Nissl#staining,calbindin D28k, neuropeptide Y was performed using light and confocal microscopy.Results. We verified all main types of interneurons (Basket, Martinotti, and neurogliaform interneurons in neocortex based on the morphology of their bodies and dendritic processes in both groups. The number of calbindin- and NPY-positive neurons in the neocortex was similar in the control and in the postoperative period.However, calbindin- and NPY-immunopositive structure fields including neuronal cell bodies and their dendrites were significantly more represented in neocortex of patients from the main group. Maximum increase in common square in the relative areas of calbindin-immunopositive structures was observed 90 days after ischemia. The squares of NPY#immunopositive fields became larger seven days after resuscitation and remained increased on 90th day post-resuscitation.Conclusion. Our findings demonstrate an increase of calbindin and NPY expression in human neocortex after clinical death, which can be explained by a compensatory  eaction of undamaged inhibitory cortical interneurons directed to protectbrain from ischemia.

  5. Digital communication to support clinical supervision: considering the human factors.

    Science.gov (United States)

    Mather, Carey; Marlow, Annette; Cummings, Elizabeth

    2013-01-01

    During the last three years the School of Nursing and Midwifery at the University of Tasmania has used a needs assessment survey to explore the needs of organizations and nursing professionals that facilitate and clinically supervise Bachelor of Nursing students in the workplace. Findings from the survey indicated that staff at healthcare organizations wanted a communication strategy that was easily accessible by clinicians who supervised students during work integrated learning placements. In particular they wanted to receive timely information related to the role and function of supervisors in practice. The development of the digital strategy to strengthen the development of a community of practice between the University, organizations, facilities and clinical supervisors was identified as the key method of improving communication. Blogging and micro blogging were selected as methods of choice for the implementation of the digital strategy because they were easy to set up, use and enable equity of access to geographically dispersed practitioners in urban and rural areas. Change champions were identified to disseminate information about the strategy within their workplaces. Although clinicians indicated electronic communication as their preferred method, there were a number of human factors at a systems and individual level identified to be challenges when communicating with clinical supervisors who were based off-campus. Information communication technology policies and embedded culture towards social presence were impediments to using this approach in some organizations. Additionally, it was found that it is necessary for this group of clinicians to be educated about using digital methods to undertake their role as clinical supervisors in their varied clinical practice environments.

  6. Clinical study of CT colonography

    International Nuclear Information System (INIS)

    Nakazawa, Saburo; Hattori, Toshiyuki; Inui, Kazuo

    2011-01-01

    We studied the usefulness of CT colonography (CTC) for colon cancer diagnosis. CTC and optical colonoscopy were performed for 150 cases mainly including patients with a positive fecal occult blood test (FOBT). The results were compared and analyzed. The following are the final diagnoses given to the patients: advanced colon cancer: 41 cases; early cancer: 25 cases; adenoma: 74 cases; hyperplasia: 3 cases; submucosal tumor: 1 case; and no lesion: 6 cases. In terms of diagnostic performance of CTC, accuracy was found to be 96%, sensitivity was found to be 97.9%, and specificity was found to be 50%. Cancer stage-specific sensitivity was as follows: advanced colon cancer: 100%; early cancer: 96.3%; adenoma: 71.2%; and hyperplasia: 47.4%. Lesion site-specific sensitivity was as follows: caecum: 76.2%; ascending colon: 57.6%; transverse colon: 66.2%; descending colon: 83.3%; sigmoid colon: 85.1%; and rectum: 78.0%. Lesion size-specific sensitivity was as follows: 2 to 5 mm: 56.7%; 6 to 9 mm: 88.1%; 10 mm or more: 92.5%; and 6 mm or more: 90.9%. Therefore, the diagnostic sensitivity of CTC was confirmed to be high. The results suggest that CTC would be useful for colon cancer screening. (author)

  7. Clinical studies on Bell's palsy

    International Nuclear Information System (INIS)

    Yamada, Yoshio

    1985-01-01

    The purpose of this study was to evaluate the diagnostic value of the salivary gland scintigraphy using sup(99m)Tc-pertechnetate for the prognosis of Bell's palsy. The salivary gland scintigraphy was performed in 40 patients with Bell's palsy and 15 normal subjects. After intravenous injection of 10 mCt of sup(99m)Tc-pertechnetate, sequential scintigrams were taken with a scintillation camera every one minute for 25 minutes. At 15 minutes after injection, both of normal subjects and patients were given ascorbic acid to stimulate the secretion of saliva. By the present method, the time activity curve was examined for the regions of interest over the parotid and submandibular glands and backgrounds. In normal subjects, values of the concentration and excretory ratio between the right and left sides of the parotid and submandibular glands were more than 80%. Some patients with Bell's palsy showed a decreased concentration and/or excretory ratio less than 80% between the normal and affected sides of the parotid glands. This suggests a functional involvement of the facial nerve in the salivary secretion from the parotid glands. On examination within 10 days of the onset of Bell's palsy, 31 cases with complete recovery showed values of the concentration ratio and/or excretory ratio more than 80% between the normal and affected sides of the submandibular glands. In contrast, 9 cases with imcomplete recovery showed low values of the concentration ratio and excretory ratio less than 80%. In the latter, more active treatments such as decompression operation should be considerd in the early stage of the palsy. The salivary scintigraphy using sup(99m)Tc-pertechnetate is more valuable as an early prognostic indicator for Bell's palsy compared with other prognostic tests such as the lid vibration test, the stapedial reflex test, the electrogustometry, the nerve excitability test and the evoked electromyography. (author)

  8. Timing of HAART initiation and clinical outcomes in human immunodeficiency virus type 1 seroconverters

    NARCIS (Netherlands)

    Jonsson, Michele; Fusco, Jennifer S.; Cole, Stephen R.; Thomas, James C.; Porter, Kholoud; Kaufman, Jay S.; Davidian, Marie; White, Alice D.; Hartmann, Katherine E.; Eron, Joseph J.; del Amo, Julia; Meyer, Laurence; Bucher, Heiner C.; Chene, Geneviève; Pillay, Deenan; Prins, Maria; Rosinska, Magda; Sabin, Caroline; Touloumi, Giota; Lodi, Sara; Coughlin, Kate; Walker, Sarah; Babiker, Abdel; de Luca, Andrea; Fisher, Martin; Muga, Roberto; Kaldor, John; Kelleher, Tony; Ramacciotti, Tim; Gelgor, Linda; Cooper, David; Smith, Don; Gill, John; Jørgensen, Louise Bruun; Nielsen, Claus; Pedersen, Court; Lutsar, Irja; Dabis, Francois; Thiebaut, Rodolphe; Masquelier, Bernard; Costagliola, Dominique; Guiguet, Marguerite; Vanhems, Philippe; Chaix, Marie-Laure; Ghosn, Jade; Boufassa, Faroudy; Hamouda, Osamah; Geskus, Ronald; van der Helm, Jannie; Schuitemaker, Hanneke

    2011-01-01

    To estimate the clinical benefit of highly active antiretroviral therapy (HAART) initiation vs deferral in a given month in patients with CD4 cell counts less than 800/μL. In this observational cohort study of human immunodeficiency virus type 1 seroconverters from CASCADE (Concerted Action on

  9. GC-MS determination of creatinine in human biological fluids as pentafluorobenzyl derivative in clinical studies and biomonitoring: Inter-laboratory comparison in urine with Jaffé, HPLC and enzymatic assays.

    Science.gov (United States)

    Tsikas, Dimitrios; Wolf, Alexander; Mitschke, Anja; Gutzki, Frank-Mathias; Will, Wolfgang; Bader, Michael

    2010-10-01

    In consideration of its relatively constant urinary excretion rate, creatinine in urine is a useful biochemical parameter to correct the urinary excretion rate of endogenous and exogenous biomolecules. Assays based on the reaction of creatinine and picric acid first reported by Jaffé in 1886 still belong to the most frequently used laboratory approaches for creatinine measurement in urine. Further analytical methods for creatinine include HPLC-UV, GC-MS, and LC-MS and LC-MS/MS approaches. In the present article we report on the development, validation and biomedical application of a new GC-MS method for the reliable quantitative determination of creatinine in human urine, plasma and serum. This method is based on the derivatization of creatinine (d(0)-Crea) and the internal standard [methyl-trideutero]creatinine (d(3)-Crea) with pentafluorobenzyl (PFB) bromide in the biological sample directly or after dilution with phosphate buffered saline, extraction of the reaction products with toluene and quantification in 1-μl aliquots of the toluene extract by selected-ion monitoring of m/z 112 for d(0)-Crea-PFB and m/z 115 for d(3)-Crea-PFB in the electron-capture negative-ion chemical ionization mode. The limit of detection of the method is 100 amol of creatinine. In an inter-laboratory study on urine samples from 100 healthy subjects, the GC-MS method was used to test the reliability of currently used Jaffé, enzymatic and HPLC assays in clinical and occupational studies. The results of the inter-laboratory study indicate that all three tested methods allow for satisfactory quantification of creatinine in human urine. The GC-MS method is suitable for use as a reference method for urinary creatinine in humans. In serum, creatine was found to contribute to creatinine up to 20% when measured by the present GC-MS method. The application of the GC-MS method can be extended to other biological samples such as saliva. Copyright © 2010 Elsevier B.V. All rights reserved.

  10. Radio sterilized human ligaments and their clinical application

    International Nuclear Information System (INIS)

    Luna Z, D.; Reyes F, M. L.; Diaz M, I.; Hernandez R, G.

    2009-10-01

    The ligaments are human tissues that are used in the transplantation area. A ligament is an anatomical structure in band form, composed by resistant fibers that connect the tissues that unite the bones with the articulations. In an articulation, the ligaments allow and facilitate the movement inside the natural anatomical directions, while it restricts those movements that are anatomically abnormal, impeding lesions that could arise of this type of movements. The kneecap ligament is a very important tissue in the knee mobility and of walking in the human beings. This ligament can injure it because of automobile accidents, for sport lesions or illnesses, and in many cases the only form of recovering the knee movement is carried out a transplant with the purpose of replacing the damage ligament by allo gen kneecap ligament processed in specialized Tissue Banks where the tissue is sterilized with gamma radiation of 60 Co at very low temperatures, obtaining high quality ligaments for clinical application in injured patients. The kneecap ligaments are processed in the Tissue Banks with a segment of kneecap bone, a segment of tibial bone, the contained ligament between both bones and in some cases a fraction of the quadriceps tendon. In this work is given a description of the selection method of the tissue that includes the donor's serologic control, the kneecap ligament processing in the Radio Sterilized Tissues Bank, its sterilization with gamma radiation of 60 Co, also it is indicated like the clinical application of the allo gen ligament was realized in a hasty patient and whose previous crossed ligament was injured. Finally the results are presented from the tissue obtaining until the clinical application of it is, and in this case is observed a favorable initial evolution of the transplantation patient. (Author)

  11. Liver Effects of Clinical Drugs Differentiated in Human Liver Slices

    Directory of Open Access Journals (Sweden)

    Alison E. M. Vickers

    2017-03-01

    Full Text Available Drugs with clinical adverse effects are compared in an ex vivo 3-dimensional multi-cellular human liver slice model. Functional markers of oxidative stress and mitochondrial function, glutathione GSH and ATP levels, were affected by acetaminophen (APAP, 1 mM, diclofenac (DCF, 1 mM and etomoxir (ETM, 100 μM. Drugs targeting mitochondria more than GSH were dantrolene (DTL, 10 μM and cyclosporin A (CSA, 10 μM, while GSH was affected more than ATP by methimazole (MMI, 500 μM, terbinafine (TBF, 100 μM, and carbamazepine (CBZ 100 μM. Oxidative stress genes were affected by TBF (18%, CBZ, APAP, and ETM (12%–11%, and mitochondrial genes were altered by CBZ, APAP, MMI, and ETM (8%–6%. Apoptosis genes were affected by DCF (14%, while apoptosis plus necrosis were altered by APAP and ETM (15%. Activation of oxidative stress, mitochondrial energy, heat shock, ER stress, apoptosis, necrosis, DNA damage, immune and inflammation genes ranked CSA (75%, ETM (66%, DCF, TBF, MMI (61%–60%, APAP, CBZ (57%–56%, and DTL (48%. Gene changes in fatty acid metabolism, cholestasis, immune and inflammation were affected by DTL (51%, CBZ and ETM (44%–43%, APAP and DCF (40%–38%, MMI, TBF and CSA (37%–35%. This model advances multiple dosing in a human ex vivo model, plus functional markers and gene profile markers of drug induced human liver side-effects.

  12. Resistance to antivirals in human cytomegalovirus: mechanisms and clinical significance.

    Science.gov (United States)

    Pérez, J L

    1997-09-01

    Long term therapies needed for managing human cytomegalovirus (HCMV) infections in immunosupressed patients provided the background for the emergence of the resistance to antivirals active against HCMV. In addition, laboratory selected mutants have also been readily achieved. Both clinical and laboratory resistant strains share the same determinants of resistance. Ganciclovir resistance may be due to a few mutations in the HCMV UL97 gene and/or viral DNA pol gene, the former being responsible for about 70% of clinical resistant isolates. Among them, V464, V594, S595 and F595 are the most frequent mutations. Because of their less extensive clinical use, much less is known about resistance to foscarnet and cidofovir (formerly, HPMPC) but in both cases, it has been associated to mutations in the DNA pol. Ganciclovir resistant strains showing DNA pol mutations are cross-resistant to cidofovir and their corresponding IC50 are normally higher than those from strains harboring only mutations at the UL97 gene. To date, foscarnet resistance seems to be independent of both ganciclovir and cidofovir resistance.

  13. Translation of Human iPSCs: From Clinical Trial in a Dish to Precision Medicine

    Science.gov (United States)

    Sayed, Nazish; Liu, Chun; Wu, Joseph C.

    2016-01-01

    The prospect of changing the plasticity of terminally differentiated cells toward pluripotency has completely altered the outlook of biomedical research. Human induced pluripotent stem cells (iPSCs) provide a new source of therapeutic cells free from the ethical issues or immune barriers of human embryonic stem cells. iPSCs also confer considerable advantages over conventional methods of studying human diseases. Since its advent, iPSC technology has expanded, with 3 major applications: disease modeling; regenerative therapy; and drug discovery. Here we discuss, in a comprehensive manner, the recent advances in iPSC technology in relation to basic, clinical, and population health. PMID:27151349

  14. A simple, rapid and stability indicating validated method for quantification of lamotrigine in human plasma and dry plasma spot using LC-ESI-MS/MS: Application in clinical study.

    Science.gov (United States)

    Namdev, Kuldeep Kumar; Dwivedi, Jaya; Chilkoti, Deepak Chandra; Sharma, Swapnil

    2018-01-01

    Lamotrigine (LTZ) is a phenyltriazine derivative which belongs to anti-epileptic drugs (AEDs) class and prescribed as mono- or adjunctive-therapy in treatment of epilepsy. Therapeutic drug monitoring (TDM) of AEDs provides a valid clinical tool in optimization of overall therapy. However, TDM is challenging due to the high biological samples (plasma/blood) storage/shipment costs and the limited availability of laboratories providing TDM services. Sampling in the form of dry plasma spot (DPS) or dry blood spot (DBS) are suitable alternative to overcome these issues. We developed and validated a new method for quantification of LTZ in human plasma and DPS. The extraction of LTZ from plasma and DPS was performed using liquid-liquid extraction with diethyl ether and an extraction solution composed of diethyl ether- methyl tert-butyl ether- acetone (50:30:20, v/v/v), respectively. Lamotrigine- 13C3, d3 was used as internal standard (ISTD) and the chromatographic separation was achieved on Hypurity Advance C18 column (150×4.6mm, 5μm). Quantitative estimation of LTZ and ISTD was performed on a liquid chromatography tandem mass spectrometer coupled with electrospray ionization interface operated under positive mode of ionization. Calibration curves were linear (r 2 >0.99) over the concentration range of 10-3020ng/mL for both plasma and DPS. Statistical analysis provides insignificant difference between LTZ concentration extracted from plasma and DPS samples. The method is found suitable for application in clinical study and in therapeutic monitoring of LTZ. To the best of our knowledge this is the first report which describing a validated stability indicating assay for quantification of LTZ in dry plasma spot. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Development and validation of a liquid chromatography-tandem mass spectrometry method for the simultaneous quantification of tamoxifen, anastrozole, and letrozole in human plasma and its application to a clinical study.

    Science.gov (United States)

    Beer, Beate; Schubert, Birthe; Oberguggenberger, Anne; Meraner, Verena; Hubalek, Michael; Oberacher, Herbert

    2010-10-01

    There is substantial evidence that circulating estrogens promote the proliferation of breast cancer. Consequently, adjuvant hormonal treatment strategies targeting estrogen action have been established. Such hormonal therapies include selective estrogen receptor modulators, such as tamoxifen, which interfere at the estrogen receptors directly, or non-steroidal aromatase inhibitors, such as anastrozole and letrozole, which inhibit estrogen synthesis through blocking the aromatase, a key enzyme of estrogen production. Despite considerable therapeutic success, in several cases, the use of these drugs is limited by side effects that have been described to significantly impair the adherence of patients to endocrine treatment. However, objective data concerning patient adherence and its clinical relevance are limited. One promising approach to check patient-reported adherence is drug monitoring in human plasma. Therefore, a liquid chromatography-tandem mass spectrometry method to determine the plasma concentrations of tamoxifen, anastrozole, and letrozole has been developed and fully validated according to guidelines for clinical and forensic toxicology. The validation criteria evaluated were selectivity, linearity, accuracy and precision, limit of quantification, recovery and matrix effects, sample stability, and carryover. The six-point calibration curves showed linearity over the range of concentrations from 25 to 500 ng/ml for tamoxifen, 5 to 200 ng/ml for anastrozole, and 10 to 300 ng/ml for letrozole. The intra- and inter-day precision and accuracies were always better than 15%. The validated procedure was successfully applied to a clinical study (Patient-Reported Outcomes in Breast Cancer Patients undergoing Endocrine Therapy, PRO-BETh). A major aim of PRO-BETh study is the comprehensive evaluation of adherence to treatment in pre- and post-menopausal women with breast cancer. Plasma samples of 310 breast cancer patients undergoing anti-estrogen therapy were

  16. Palaeoproteomics for human evolution studies

    Science.gov (United States)

    Welker, Frido

    2018-06-01

    The commonplace sequencing of Neanderthal, Denisovan and ancient modern human DNA continues to revolutionize our understanding of hominin phylogeny and interaction(s). The challenge with older fossils is that the progressive fragmentation of DNA even under optimal conditions, a function of time and temperature, results in ever shorter fragments of DNA. This process continues until no DNA can be sequenced or reliably aligned. Ancient proteins ultimately suffer a similar fate, but are a potential alternative source of biomolecular sequence data to investigate hominin phylogeny given their slower rate of fragmentation. In addition, ancient proteins have been proposed to potentially provide insights into in vivo biological processes and can be used to provide additional ecological information through large scale ZooMS (Zooarchaeology by Mass Spectrometry) screening of unidentifiable bone fragments. However, as initially with ancient DNA, most ancient protein research has focused on Late Pleistocene or Holocene samples from Europe. In addition, only a limited number of studies on hominin remains have been published. Here, an updated review on ancient protein analysis in human evolutionary contexts is given, including the identification of specific knowledge gaps and existing analytical limits, as well as potential avenues to overcome these.

  17. Advances in clinical study of curcumin.

    Science.gov (United States)

    Yang, Chunfen; Su, Xun; Liu, Anchang; Zhang, Lin; Yu, Aihua; Xi, Yanwei; Zhai, Guangxi

    2013-01-01

    Curcumin has been estimated as a potential agent for many diseases and attracted great attention owing to its various pharmacological activities, including anti-cancer, and anti-inflammatory. Now curcumin is being applied to a number of patients with breast cancer, rheumatoid arthritis, Alzheimer's disease, colorectal cancer, psoriatic, etc. Several clinical trials have stated that curcumin is safe enough and effective. The objective of this article was to summarize the clinical studies of curcumin, and give a reference for future studies.

  18. Clinical Trials

    Medline Plus

    Full Text Available ... go to the NHLBI's Children and Clinical Studies Web page. Children and Clinical Studies Learn more about ... Protections The U.S. Department of Health and Human Services’ (HHS’) Office for Human Research Protections (OHRP) oversees ...

  19. Medical humanitarianism, human rights and political advocacy: the case of the Israeli Open Clinic.

    Science.gov (United States)

    Gottlieb, Nora; Filc, Dani; Davidovitch, Nadav

    2012-03-01

    In the context of neo-liberal retrenchments humanitarian NGOs have become alternative healthcare providers that partially fill the vacuum left by the welfare state's withdrawal from the provision of services to migrants and other marginalized populations. In many cases they thus help to build legitimacy for the state's retreat from social responsibilities. Human rights organizations play an important role in advocating for migrants' rights, but in many cases they represent a legalistic and individualized conceptualization of the right to health that limits their claims for social justice. This paper analyzes the interactions and tensions between the discourses of medical humanitarianism, human rights and political advocacy using the example of an "Open Clinic" run by an Israeli human rights organization as a case-study: In 2007 dramatically increasing patient numbers provoked an intense internal debate concerning the proposal to temporarily close the "Open Clinic" in order to press the government to take action. Based on protocols from internal meetings and parliamentary hearings and in-depth interviews, we have analyzed divergent contextualizations of the Clinic's closure. These reflect conflicting notions regarding the Clinic's variegated spectrum of roles--humanitarian, political, legitimizing, symbolic, empowering and organizational--and underlying conceptualizations of migrants' "deservingness". Our case-study thus helps to illuminate NGOs' role in the realm of migrant healthcare and points out options for a possible fruitful relationship between the divergent paradigms of medical humanitarianism, human rights and political advocacy. Copyright © 2011. Published by Elsevier Ltd.

  20. Clinically unrecognized miliary tuberculosis: an autopsy study.

    Science.gov (United States)

    Savic, Ivana; Trifunovic-Skodric, Vesna; Mitrovic, Dragan

    2016-01-01

    Miliary tuberculosis (TB) usually presents with atypical clinical manifestations; thus it is often recognized only at autopsy. Our objectives were to study the frequency of MT diagnosed at autopsy and determine clinical diagnoses that masked TB, as well as causes of death and comorbidities. Retrospective study of all autopsies performed between 2008 and 2014. Institute of Pathology, Belgrade, Serbia. in subjects where autopsy showed the presence of MT that was not recognized clinically, we recorded the clinical diagnoses (presumed causes of death) as reported in autopsy request forms, as well as actual cause of death and comorbidities as determined at autopsy. Clinically unrecognized MT. The total number of autopsies in this period was 6206. thirty-five individuals showed clinically unrecognized MT (0.56% of all autopsies, age: 62.2 [17.2] years, M:F=2:3). Common clinical diagnoses masking pulmonary MT were exacerbation of COPD (25%) and pulmonary thromboembolism (25%), with common radiological presentation of diffuse pulmonary infiltrates (56.3%). Dominant clinical diagnoses in patients with generalized MT were adult respiratory distress syndrome, sepsis, gastrointestinal bleeding and meningoencephalitis. Disseminated MT was often associated with secondary anemia or thrombocytopenia (15.8%) and recent surgery (15.8%). Frequent comorbidities included chronic renal failure and malignancies, whereas MT was a dominant cause of death. Greater awareness of MT is needed to improve recognition in clinical settings. In particular, MT should be considered in patients with atypical clinical presentation and diffuse pulmonary infiltrates on chest X-ray, particularly if they have chronic renal failure, malignancy, hematological disorders or a history of recent surgery. None.

  1. Development and clinical application of human gastrin radioimmunoassay

    International Nuclear Information System (INIS)

    Ginabreda, M.G.P.; Borghi, V.C.; Bettarello, A.

    1988-08-01

    The determination of human gastrin levels in the blood is very important for diagnosis of gastrointestinal disorders. This work describes the radioimmunoassay of gastrin developed according to Russell et al. and its clinical application measuring fasting levels of this hormone in normal subjects, gastrectomized, chagasics, patients with chronic renal failure (CRF), pernicious anemia (PA) and Zollinger-Ellison syndrome (ZES). Synthetic human gastrin was used for radioiodination and as standard, while the specific antibody was raised in rabbits. Gastrin was radioiodinated by a modification of the chloramine T technique and purified by anion exchange chromatography in QAE-Sephadex A-25 to a specific activity around 200 uCi/ug. The assays were performed by incubation of 125 I-gastrin, standard gastrin (zero to 500 pmol/l) or unknown samples with the antiserum for 4 days at 4 0 C. The antibody bound and free 125 I-gastrin was separated by adsorption of the latter to the charcoal. The basal gastrin values of normal subjects ranged from 2 to 74 pmol/l, being these levels higher in the chagasics (from 6 to 261 pmol/l). Higher levels of gastrin were determined in patients with CRF (from 12 to 350 pmol/l), PA (from 160 to 680 pmol/l) and with ZES(1010 pmol/l), while very low levels were confirmed in gastrectomized (from 1 to 8 pmol/l). (author) [pt

  2. Risk factors for human-directed canine aggression in a referral level clinical population.

    Science.gov (United States)

    Lord, M; Casey, R A; Loftus, B A; Blackwell, E J

    2017-07-07

    Risk factors for human-directed aggression were investigated using retrospective analysis of data from a referral-level clinical behaviour population in the UK. A sample of 200 cases involving human-directed canine aggression and 200 control cases involving no instance of human-directed aggression were selected at random from a population of 746 cases. The final model suggested that clinical cases with human-directed aggression were significantly younger than those presenting with other undesired behaviours (P=0.008) and that male dogs were 1.4 times more likely to be aggressive towards human beings than female dogs (P=0.019). Dogs were 1.7 times more likely to be aggressive towards people if they had attended more than five puppy classes than if they had never attended puppy class (P=0.015) and that dogs were 2.8 times more likely to be aggressive towards human beings if there was another dog between 0 months and 24 months of age in the home (P=0.004). These factors only account for 7 per cent to 10 per cent of the variance between the human-directed aggression population and the control population, but factors such as attendance at puppy classes and numbers of dogs in the household suggest the need for longitudinal studies to investigate temporal relationships.

  3. Talocalcaneal luxation: an anatomic and clinical study

    International Nuclear Information System (INIS)

    Gorse, M.J.; Purinton, P.T.; Penwick, R.C.; Aron, D.N.; Roberts, R.E.

    1990-01-01

    Talocalcaneal luxation in dogs was studied by anatomic dissection of the talocalcaneal joint in cadavers and review of five clinical cases. The integrity of the talocalcaneal joint was maintained by two strong ligaments traversing the tarsal sinus between the two bones. The joint was found to be a low motion joint. Luxation in clinical cases was not always apparent on standard radiographic views. Three dogs were treated surgically with a screw inserted in lag fashion from talus to calcaneus. One luxation was treated surgically with figure-of-eight orthopedic wires and one was treated with external coaptation. Four dogs returned to their previous levels of function without clinically detectable lameness

  4. Clinical-grade production of human mesenchymal stromal cells: occurrence of aneuploidy without transformation.

    Science.gov (United States)

    Tarte, Karin; Gaillard, Julien; Lataillade, Jean-Jacques; Fouillard, Loic; Becker, Martine; Mossafa, Hossein; Tchirkov, Andrei; Rouard, Hélène; Henry, Catherine; Splingard, Marie; Dulong, Joelle; Monnier, Delphine; Gourmelon, Patrick; Gorin, Norbert-Claude; Sensebé, Luc

    2010-02-25

    Clinical-grade human mesenchymal stromal cells (MSCs) have been expanded in vitro for tissue engineering or immunoregulatory purposes without standardized culture conditions or release criteria. Although human MSCs show poor susceptibility for oncogenic transformation, 2 recent studies described their capacity to accumulate chromosomal instability and to give rise to carcinoma in immunocompromised mice after long-term culture. We thus investigated the immunologic and genetic features of MSCs expanded with fetal calf serum and fibroblast growth factor or with platelet lysate in 4 cell-therapy facilities during 2 multicenter clinical trials. Cultured MSCs showed a moderate expression of human leukocyte antigen-DR without alteration of their low immunogenicity or their immunomodulatory capacity. Moreover, some transient and donor-dependent recurring aneuploidy was detected in vitro, independently of the culture process. However, MSCs with or without chromosomal alterations showed progressive growth arrest and entered senescence without evidence of transformation either in vitro or in vivo.

  5. Data sharing platforms for de-identified data from human clinical trials.

    Science.gov (United States)

    Huser, Vojtech; Shmueli-Blumberg, Dikla

    2018-04-01

    Data sharing of de-identified individual participant data is being adopted by an increasing number of sponsors of human clinical trials. In addition to standardizing data syntax for shared trial data, semantic integration of various data elements is the focus of several initiatives that define research common data elements. This perspective article, in the first part, compares several data sharing platforms for de-identified clinical research data in terms of their size, policies and supported features. In the second part, we use a case study approach to describe in greater detail one data sharing platform (Data Share from National Institute of Drug Abuse). We present data on the past use of the platform, data formats offered, data de-identification approaches and its use of research common data elements. We conclude with a summary of current and expected future trends that facilitate secondary research use of data from completed human clinical trials.

  6. Human Intestinal Cells Modulate Conjugational Transfer of Multidrug Resistance Plasmids between Clinical Escherichia coli Isolates

    DEFF Research Database (Denmark)

    Machado, Ana Manuel; Sommer, Morten

    2014-01-01

    Bacterial conjugation in the human gut microbiota is believed to play a major role in the dissemination of antibiotic resistance genes and virulence plasmids. However, the modulation of bacterial conjugation by the human host remains poorly understood and there is a need for controlled systems...... to study this process. We established an in vitro co-culture system to study the interaction between human intestinal cells and bacteria. We show that the conjugation efficiency of a plasmid encoding an extended spectrum beta-lactamase is reduced when clinical isolates of Escherichia coli are co...... of the intestinal cells exposed to bacteria leading to a two-fold reduction in conjugation efficiency. These results show that human gut epithelial cells can modulate bacterial conjugation and may have relevance to gene exchange in the gut....

  7. A review of human factors principles for the design and implementation of medication safety alerts in clinical information systems.

    Science.gov (United States)

    Phansalkar, Shobha; Edworthy, Judy; Hellier, Elizabeth; Seger, Diane L; Schedlbauer, Angela; Avery, Anthony J; Bates, David W

    2010-01-01

    The objective of this review is to describe the implementation of human factors principles for the design of alerts in clinical information systems. First, we conduct a review of alarm systems to identify human factors principles that are employed in the design and implementation of alerts. Second, we review the medical informatics literature to provide examples of the implementation of human factors principles in current clinical information systems using alerts to provide medication decision support. Last, we suggest actionable recommendations for delivering effective clinical decision support using alerts. A review of studies from the medical informatics literature suggests that many basic human factors principles are not followed, possibly contributing to the lack of acceptance of alerts in clinical information systems. We evaluate the limitations of current alerting philosophies and provide recommendations for improving acceptance of alerts by incorporating human factors principles in their design.

  8. Does Awareness of Status and Risks of Human Immunodeficiency Virus Impact Risky Transmission Behavior Among Infected Adolescents? A Case Study of Clients Attending an Antiretroviral Therapy (ART) Clinic in Kano, Kano State, Nigeria.

    Science.gov (United States)

    Lawan, Umar Muhammad; Envuladu, Esther Awazzi; Abubakar, Sanusi

    2016-01-01

    Human immunodeficiency virus (HIV)-positive adolescents by virtue of their position are prone to dangerous behaviors including risk-taking for HIV transmission. To determine the awareness of HIV status and risk factors for HIV transmission among HIV-positive adolescents, and how these impact their behavior. A case study approach was used to study a random sample of 400 HIV-positive adolescent children attending an antiretroviral (ART) clinic in Kano, Kano State, Nigeria. Data were analyzed using Statistical Package for the Social Sciences (SPSS) 16.0 computer statistical software. The mean age of the adolescents was 14.9 ± 3.15 years. The majority were females (54.8%) from a polygamous family (57.5%). About two-thirds or 251 (62.8%) patients knew their HIV status. The age of 14 years and above (z = 11.36, P = 0.0001) and having at least secondary school level of education (z = 2.78, P = 0.005) were significantly associated with awareness of HIV status on binary logistic regression. Up to 311 (77.8%) patients had good awareness of the risks of HIV transmission. Awareness of risk of HIV transmission was associated with awareness of HIV status (X(2) = 166.2, P = 0.0001). There was a significant variation in the behaviors between those who were aware of their HIV status and those who were not. Paradoxically, the percentage differences in risk-taking were remarkably high in all the variables examined, and were all in the direction of the adolescents who had good knowledge of the risk factors for HIV transmission. Health ministries, development partners working in this field, and behavioral change communication experts should develop formidable strategies for addressing this menace. There is also a dire need for further research in this area.

  9. Characterization of Listeria monocytogenes isolated from Ganges water, human clinical and milk samples at Varanasi, India.

    Science.gov (United States)

    Soni, Dharmendra K; Singh, Rakesh K; Singh, Durg V; Dubey, Suresh K

    2013-03-01

    Listeria monocytogenes isolated from Ganges water, human clinical and milk samples were characterized by antibiotic susceptibility, serotype identification, detection of virulence genes and ERIC- and REP-PCR fingerprint analyses. All isolates were uniformly resistant to ampicillin, except two isolates, and showed variable resistance to gentamicin, cotrimoxazole, ofloxacin, rifampicin and tetracycline. Of the 20 isolates found positive for pathogens, seven (four human and three water isolates) belong to serogroups 4b, 4d and 4e; six (one human and five water isolates) belong to serogroups 1/2c and 3c; four milk isolates belong to serogroups 1/2b and 3b; and three milk isolates belong to serogroups 1/2a and 3a. Two water isolates, all human isolates, except one (Pb1) lacking inlJ gene, and three milk isolates possess inlA, inlC, plcA, prfA, actA, hlyA and iap genes. The remaining water and milk isolates showed variable presence of inlJ, plcA, prfA, and iap genes. ERIC- and REP-PCR based analyses collectively indicated that isolates of human clinical samples belong to identical or similar clone and isolates of water and milk samples belong to different clones. Overall study demonstrates the prevalence of pathogenic L. monocytogenes species in the environmental and clinical samples. Most of the isolates were resistant to commonly used antibiotics. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. High purity of human oligodendrocyte progenitor cells obtained from neural stem cells: suitable for clinical application.

    Science.gov (United States)

    Wang, Caiying; Luan, Zuo; Yang, Yinxiang; Wang, Zhaoyan; Wang, Qian; Lu, Yabin; Du, Qingan

    2015-01-30

    Recent studies have suggested that the transplantation of oligodendrocyte progenitor cells (OPCs) may be a promising potential therapeutic strategy for a broad range of diseases affecting myelin, such as multiple sclerosis, periventricular leukomalacia, and spinal cord injury. Clinical interest arose from the potential of human stem cells to be directed to OPCs for the clinical application of treating these diseases since large quantities of high quality OPCs are needed. However, to date, there have been precious few studies about OPC induction from human neural stem cells (NSCs). Here we successfully directed human fetal NSCs into highly pure OPCs using a cocktail of basic fibroblast growth factor, platelet-derived growth factor, and neurotrophic factor-3. These cells had typical morphology of OPCs, and 80-90% of them expressed specific OPC markers such as A2B5, O4, Sox10 and PDGF-αR. When exposed to differentiation medium, 90% of the cells differentiated into oligodendrocytes. The OPCs could be amplified in our culture medium and passaged at least 10 times. Compared to a recent published method, this protocol had much higher stability and repeatability, and OPCs could be obtained from NSCs from passage 5 to 38. It also obtained more highly pure OPCs (80-90%) via simpler and more convenient manipulation. This study provided an easy and efficient method to obtain large quantities of high-quality human OPCs to meet clinical demand. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Linking ClinicalTrials.gov and PubMed to track results of interventional human clinical trials.

    Directory of Open Access Journals (Sweden)

    Vojtech Huser

    Full Text Available OBJECTIVE: In an effort to understand how results of human clinical trials are made public, we analyze a large set of clinical trials registered at ClinicalTrials.gov, the world's largest clinical trial registry. MATERIALS AND METHODS: We considered two trial result artifacts: (1 existence of a trial result journal article that is formally linked to a registered trial or (2 the deposition of a trial's basic summary results within the registry. RESULTS: The study sample consisted of 8907 completed, interventional, phase 2-or-higher clinical trials that were completed in 2006-2009. The majority of trials (72.2% had no structured trial-article link present. A total of 2367 trials (26.6% deposited basic summary results within the registry. Of those, 969 trials (10.9% were classified as trials with extended results and 1398 trials (15.7% were classified as trials with only required basic results. The majority of the trials (54.8% had no evidence of results, based on either linked result articles or basic summary results (silent trials, while a minimal number (9.2% report results through both registry deposition and publication. DISCUSSION: Our study analyzes the body of linked knowledge around clinical trials (which we refer to as the "trialome". Our results show that most trials do not report results and, for those that do, there is minimal overlap in the types of reporting. We identify several mechanisms by which the linkages between trials and their published results can be increased. CONCLUSION: Our study shows that even when combining publications and registry results, and despite availability of several information channels, trial sponsors do not sufficiently meet the mandate to inform the public either via a linked result publication or basic results submission.

  12. Summary reports for key Hoodia clinical studies

    CSIR Research Space (South Africa)

    Maharaj, VJ

    2011-12-01

    Full Text Available The CSIR has acquired the reports to 14 clinical studies in which Hoodia has been assesses, using crude extracts and concentrated active ingredients formulated in a number of different ways. In many of the studies Hoodia was found to be generally...

  13. Tea and Health: Studies in Humans

    Science.gov (United States)

    Khan, Naghma; Mukhtar, Hasan

    2014-01-01

    Tea, next to water is the cheapest beverage humans consume. Drinking the beverage tea has been considered a health-promoting habit since ancient times. The modern medicinal research is providing a scientific basis for this belief. The evidence supporting the health benefits of tea drinking grows stronger with each new study that is published in the scientific literature. Tea plant Camellia sinensis has been cultivated for thousands of years and its leaves have been used for medicinal purposes. Tea is used as a popular beverage worldwide and its ingredients are now finding medicinal benefits. Encouraging data showing cancer-preventive effects of green tea from cell-culture, animal and human studies have emerged. Evidence is accumulating that black tea may have similar beneficial effects. Tea consumption has also been shown to be useful for prevention of many debilitating human diseases that include maintenance of cardiovascular and metabolic health. Various studies suggest that polyphenolic compounds present in green and black tea are associated with beneficial effects in prevention of cardiovascular diseases, particularly of atherosclerosis and coronary heart disease. In addition, anti-aging, antidiabetic and many other health beneficial effects associated with tea consumption are described. Evidence is accumulating that catechins and theaflavins, which are the main polyphenolic compounds of green and black tea, respectively, are responsible for most of the physiological effects of tea. This article describes the evidences from clinical and epidemiological studies in the prevention of chronic diseases like cancer and cardiovascular diseases and general health promotion associated with tea consumption. PMID:23448443

  14. Implications of human tissue studies

    International Nuclear Information System (INIS)

    Kathren, R.L.

    1986-10-01

    Through radiochemical analysis of voluntary tissue donations, the United States Transuranium and Uranium Registries are gaining improved understanding of the distribution and biokinetics of actinide elements in occupationally exposed persons. Evaluation of the first two whole body contributions to the Transuranium Registry revealed an inverse proportionality between actinide concentration and bone ash fraction. The analysis of a whole body with a documented 241 Am deposition indicated a significantly shorter half-time in liver and a greater fraction resident in the skeleton than predicted by existing models. Other studies of the Registries are designed to evaluate in vivo estimates of actinide deposition with those derived from postmortem tissue analysis, compare results of animal experiments with human data, and reviw histopathologic slides for tissue toxicity that might be attributable to exposure to uranium and the transuranic elements. The implications of these recent findings and other work of the Registries are discussed from the standpoint of their potential impact on biokinetic modeling, internal dose assessment, safety standards, and operational health physics practices

  15. [Clinical impact of opening a human milk bank in a neonatal unit].

    Science.gov (United States)

    Vázquez-Román, S; Bustos-Lozano, G; López-Maestro, M; Rodríguez-López, J; Orbea-Gallardo, C; Samaniego-Fernández, M; Pallás-Alonso, C R

    2014-09-01

    The benefits of donor human milk compared with artificial formulas have been well demonstrated; nevertheless the impact in the clinical practice of opening a human milk bank within a neonatal unit has not yet been studied. The main aim of this study was to analyze the impact on the clinical practice of opening a human milk bank in a neonatal unit to provide donor human milk for preterm infants ≤ 32 weeks of gestational age. A before and after study was designed, with the intervention being the opening a human milk bank. Preterm infants ≤ 32 weeks of gestational age born in the Hospital 12 Octubre from July to December 2005 and January to June 2008 (firsts 6 months after opening the human milk bank) were included. After opening the human milk bank, enteral feedings were started 31h before (Partificial formula, the exposure to formula in the first 15 days of life was reduced from 50% to 16.6%, and it's consumption during the first 28 days of life was significantly reduced. There was a higher consumption of own mother's milk during the hospital stay, and a higher rate of exclusive breastfeeding at hospital discharge (54% vs 40%). The availability of donor human milk has led to quicker progression with enteral feedings and earlier withdrawal of parenteral nutrition. It has reduced the exposure to artificial formulas, and has also increased the intake of own mother's milk during the hospital stay and the rate of exclusive breastfeeding at hospital discharge. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  16. Genetic association with overall survival of taxane-treated lung cancer patients - a genome-wide association study in human lymphoblastoid cell lines followed by a clinical association study

    International Nuclear Information System (INIS)

    Niu, Nifang; Cunningham, Julie M; Li, Liang; Sun, Zhifu; Yang, Ping; Wang, Liewei; Schaid, Daniel J; Abo, Ryan P; Kalari, Krishna; Fridley, Brooke L; Feng, Qiping; Jenkins, Gregory; Batzler, Anthony; Brisbin, Abra G

    2012-01-01

    Taxane is one of the first line treatments of lung cancer. In order to identify novel single nucleotide polymorphisms (SNPs) that might contribute to taxane response, we performed a genome-wide association study (GWAS) for two taxanes, paclitaxel and docetaxel, using 276 lymphoblastoid cell lines (LCLs), followed by genotyping of top candidate SNPs in 874 lung cancer patient samples treated with paclitaxel. GWAS was performed using 1.3 million SNPs and taxane cytotoxicity IC50 values for 276 LCLs. The association of selected SNPs with overall survival in 76 small or 798 non-small cell lung cancer (SCLC, NSCLC) patients were analyzed by Cox regression model, followed by integrated SNP-microRNA-expression association analysis in LCLs and siRNA screening of candidate genes in SCLC (H196) and NSCLC (A549) cell lines. 147 and 180 SNPs were associated with paclitaxel or docetaxel IC50s with p-values <10 -4 in the LCLs, respectively. Genotyping of 153 candidate SNPs in 874 lung cancer patient samples identified 8 SNPs (p-value < 0.05) associated with either SCLC or NSCLC patient overall survival. Knockdown of PIP4K2A, CCT5, CMBL, EXO1, KMO and OPN3, genes within 200 kb up-/downstream of the 3 SNPs that were associated with SCLC overall survival (rs1778335, rs2662411 and rs7519667), significantly desensitized H196 to paclitaxel. SNPs rs2662411 and rs1778335 were associated with mRNA expression of CMBL or PIP4K2A through microRNA (miRNA) hsa-miR-584 or hsa-miR-1468. GWAS in an LCL model system, joined with clinical translational and functional studies, might help us identify genetic variations associated with overall survival of lung cancer patients treated paclitaxel

  17. Genetic association with overall survival of taxane-treated lung cancer patients - a genome-wide association study in human lymphoblastoid cell lines followed by a clinical association study

    Directory of Open Access Journals (Sweden)

    Niu Nifang

    2012-09-01

    Full Text Available Abstract Background Taxane is one of the first line treatments of lung cancer. In order to identify novel single nucleotide polymorphisms (SNPs that might contribute to taxane response, we performed a genome-wide association study (GWAS for two taxanes, paclitaxel and docetaxel, using 276 lymphoblastoid cell lines (LCLs, followed by genotyping of top candidate SNPs in 874 lung cancer patient samples treated with paclitaxel. Methods GWAS was performed using 1.3 million SNPs and taxane cytotoxicity IC50 values for 276 LCLs. The association of selected SNPs with overall survival in 76 small or 798 non-small cell lung cancer (SCLC, NSCLC patients were analyzed by Cox regression model, followed by integrated SNP-microRNA-expression association analysis in LCLs and siRNA screening of candidate genes in SCLC (H196 and NSCLC (A549 cell lines. Results 147 and 180 SNPs were associated with paclitaxel or docetaxel IC50s with p-values -4 in the LCLs, respectively. Genotyping of 153 candidate SNPs in 874 lung cancer patient samples identified 8 SNPs (p-value PIP4K2A, CCT5, CMBL, EXO1, KMO and OPN3, genes within 200 kb up-/downstream of the 3 SNPs that were associated with SCLC overall survival (rs1778335, rs2662411 and rs7519667, significantly desensitized H196 to paclitaxel. SNPs rs2662411 and rs1778335 were associated with mRNA expression of CMBL or PIP4K2A through microRNA (miRNA hsa-miR-584 or hsa-miR-1468. Conclusions GWAS in an LCL model system, joined with clinical translational and functional studies, might help us identify genetic variations associated with overall survival of lung cancer patients treated paclitaxel.

  18. Human genetics after the bomb: Archives, clinics, proving grounds and board rooms.

    Science.gov (United States)

    Lindee, Susan

    2016-02-01

    In this paper I track the history of post-1945 human genetics and genomics emphasizing the importance of ideas about risk to the scientific study and medical management of human heredity. Drawing on my own scholarship as it is refracted through important new work by other scholars both junior and senior, I explore how radiation risk and then later disease risk mattered to the development of genetics and genomics, particularly in the United States. In this context I excavate one of the central ironies of post-war human genetics: while studies of DNA as the origin and cause of diseases have been lavishly supported by public institutions and private investment around the world, the day-to-day labor of intensive clinical innovation has played a far more important role in the actual human experience of genetic disease and genetic risk for affected families. This has implications for the archival record, where clinical interactions are less readily accessible to historians. This paper then suggests that modern genomics grew out of radiation risk; that it was and remains a risk assessment science; that it is temporally embedded as a form of both prediction and historical reconstruction; and that it has become a big business focused more on risk and prediction (which can be readily marketed) than on effective clinical intervention. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Coupled Human-Space Suit Mobility Studies

    Data.gov (United States)

    National Aeronautics and Space Administration — Current EVA mobility studies only allow for comparisons of how the suit moves when actuated by a human and how the human moves when unsuited. There are now new...

  20. The Effect of Noise on Human Performance: A Clinical Trial

    Directory of Open Access Journals (Sweden)

    P Nassiri

    2013-04-01

    Full Text Available Background: Noise is defined as unwanted or meaningless sound that apart from auditory adverse health effects may distract attention from cues that are important for task performance. Human performance is influenced by many job-related factors and workplace conditions including noise level. Objective: To study the effect of noise on human performance. Methods: The participants included 40 healthy male university students. The experimental design consisted of 3 (sound pressure level x 3 (noise schedule x 2 (noise type factors. To investigate occupational skill performance, some specific test batteries were used: 1 steadiness test, 2 Minnesota manual dexterity test, 3 hand tool dexterity test, and 4 two-arm coordination test. Time duration of test completion was measured as speed response; to determine error response, the time taken during committing an error by participants while performing a task was measured. Results: Speed response obtained from the 4 tests in combined conditions of noise schedule, harmonic index, and sound pressure level was highest for (intermittent, treble, 95 dB, (continuous, treble, 95 dB, (continuous, treble, 85 dB and (intermittent, treble, 95 dB, respectively. Conclusion: Treble noise was found significant in reducing human performance; also, intermittent noise, especially at high pressure levels, was responsible for worsening environmental conditions during performing a task.

  1. Clinical Trials

    Medline Plus

    Full Text Available ... medical strategy, treatment, or device is safe and effective for humans. What Are Clinical Trials? Clinical trials ... medical strategy, treatment, or device is safe and effective for humans. These studies also may show which ...

  2. Marketing and clinical trials: a case study

    Directory of Open Access Journals (Sweden)

    Entwistle Vikki A

    2007-11-01

    Full Text Available Abstract Background Publicly funded clinical trials require a substantial commitment of time and money. To ensure that sufficient numbers of patients are recruited it is essential that they address important questions in a rigorous manner and are managed well, adopting effective marketing strategies. Methods Using methods of analysis drawn from management studies, this paper presents a structured assessment framework or reference model, derived from a case analysis of the MRC's CRASH trial, of 12 factors that may affect the success of the marketing and sales activities associated with clinical trials. Results The case study demonstrates that trials need various categories of people to buy in – hence, to be successful, trialists must embrace marketing strategies to some extent. Conclusion The performance of future clinical trials could be enhanced if trialists routinely considered these factors.

  3. Marketing and clinical trials: a case study.

    Science.gov (United States)

    Francis, David; Roberts, Ian; Elbourne, Diana R; Shakur, Haleema; Knight, Rosemary C; Garcia, Jo; Snowdon, Claire; Entwistle, Vikki A; McDonald, Alison M; Grant, Adrian M; Campbell, Marion K

    2007-11-20

    Publicly funded clinical trials require a substantial commitment of time and money. To ensure that sufficient numbers of patients are recruited it is essential that they address important questions in a rigorous manner and are managed well, adopting effective marketing strategies. Using methods of analysis drawn from management studies, this paper presents a structured assessment framework or reference model, derived from a case analysis of the MRC's CRASH trial, of 12 factors that may affect the success of the marketing and sales activities associated with clinical trials. The case study demonstrates that trials need various categories of people to buy in - hence, to be successful, trialists must embrace marketing strategies to some extent. The performance of future clinical trials could be enhanced if trialists routinely considered these factors.

  4. A clinical study of geriatric dermatoses

    OpenAIRE

    Leena Raveendra

    2014-01-01

    Introduction: The geriatric population is composed of persons over 65 years of age and very few studies are available on the dermatologic diseases in this group. This study was done to study the spectrum of cutaneous manifestations and prevalence of physiological and pathological changes in the skin of elderly people. Material and Methods: Two hundred consecutive patients aged more than 65 years of age attending the outpatient clinic or admitted as inpatients in the Department of Dermato...

  5. The Impact of Human Papilloma Viruses, Matrix Metallo-Proteinases and HIV Protease Inhibitors on the Onset and Progression of Uterine Cervix Epithelial Tumors: A Review of Preclinical and Clinical Studies

    Directory of Open Access Journals (Sweden)

    Giovanni Barillari

    2018-05-01

    Full Text Available Infection of uterine cervix epithelial cells by the Human Papilloma Viruses (HPV is associated with the development of dysplastic/hyperplastic lesions, termed cervical intraepithelial neoplasia (CIN. CIN lesions may regress, persist or progress to invasive cervical carcinoma (CC, a leading cause of death worldwide. CIN is particularly frequent and aggressive in women infected by both HPV and the Human Immunodeficiency Virus (HIV, as compared to the general female population. In these individuals, however, therapeutic regimens employing HIV protease inhibitors (HIV-PI have reduced CIN incidence and/or clinical progression, shedding light on the mechanism(s of its development. This article reviews published work concerning: (i the role of HPV proteins (including HPV-E5, E6 and E7 and of matrix-metalloproteinases (MMPs in CIN evolution into invasive CC; and (ii the effect of HIV-PI on events leading to CIN progression such as basement membrane and extracellular matrix invasion by HPV-positive CIN cells and the formation of new blood vessels. Results from the reviewed literature indicate that CIN clinical progression can be monitored by evaluating the expression of MMPs and HPV proteins and they suggest the use of HIV-PI or their derivatives for the block of CIN evolution into CC in both HIV-infected and uninfected women.

  6. Clinical uses of melatonin: evaluation of human trials.

    Science.gov (United States)

    Sánchez-Barceló, E J; Mediavilla, M D; Tan, D X; Reiter, R J

    2010-01-01

    During the last 20 years, numerous clinical trials have examined the therapeutic usefulness of melatonin in different fields of medicine. The objective of this article is to review, in depth, the science regarding clinical trials performed to date. The efficacy of melatonin has been assessed as a treatment of ocular diseases, blood diseases, gastrointestinal tract diseases, cardiovascular diseases, diabetes, rheumatoid arthritis, fibromyalgia, chronic fatigue syndrome, infectious diseases, neurological diseases, sleep disturbances, aging and depression. Melatonin has been also used as a complementary treatment in anaesthesia, hemodialysis, in vitro fertilization and neonatal care. The conclusion of the current review is that the use of melatonin as an adjuvant therapy seems to be well funded for macular degeneration, glaucoma, protection of the gastric mucosa, irritable bowel syndrome, arterial hypertension, diabetes, side effects of chemotherapy and radiation in cancer patients or hemodialysis in patients with renal insufficiency and, especially, for sleep disorders of circadian etiology (jet lag, delayed sleep phase syndrome, sleep deterioration associated with aging, etc.) as well as in those related with neurological degenerative diseases (Alzheimer, etc.,) or Smith-Magenis syndrome. The utility of melatonin in anesthetic procedures has been also confirmed. More clinical studies are required to clarify whether, as the preliminary data suggest, melatonin is useful for treatment of fibromyalgia, chronic fatigue syndrome, infectious diseases, neoplasias or neonatal care. Preliminary data regarding the utility of melatonin in the treatment of ulcerative colitis, Crohn's disease, rheumatoid arthritis are either ambiguous or negative. Although in a few cases melatonin seems to aggravate some conditions, the vast majority of studies document the very low toxicity of melatonin over a wide range of doses.

  7. Left ventricular noncompaction: Clinical-echocardiographic study

    Directory of Open Access Journals (Sweden)

    Nikolić Aleksandra

    2012-01-01

    Full Text Available Background/Aim. Left ventricular noncompaction (LVNC is a disorder in endomyocardial morphogenesis, seen either isolated (in the absence of other cardiac anomalies or in association with congenital heart disease and some neuromuscular diseases. Intrauterine arrest of the compaction of myocardial fibers is postulated to be the reason of LVNC. Recognition of this condition is extremely important due to its high mortality and morbidity that lead to progressive heart failure, ventricular arrhythmias and thromboembolic events. The aim of this study was to determine the prevalence and clinical presentation of LVNC among consecutive outpatients according to clinical and echocardiographyic findings. Methode. A total of 3,854 consecutive patients examined at the Institute for Cardiovascular Diseases within a period January 2006 - January 2007 were included in the study. All the patients underwent echocardiographic examination using the same equipment (Vivid 7, GE Medical System. Echocardiographic parameters and clinical presentation in patients with echocardiographic criteria for LVNC were analyzed. Results. Analyzing 3,854 consecutive outpatients, using two-dimensional Color Doppler echocardiography from January 2006 to January 2007, 12 patients met the criteria for LVNC. Seven of them were male. The mean age at diagnosis was 45 ± 15 years. Analyzing clinical manifestation of LVNC it was found that seven patients had signs of heart failure, six had arrhythmias with no embolic events. Conclusion. Our results suggest that the real prevalence of LVNC may be higher than expected. New studies have to be done to solve this problem.

  8. Clinical significance of melatonin receptors in the human myometrium.

    Science.gov (United States)

    Olcese, James; Beesley, Stephen

    2014-08-01

    To review and update the research on melatonin receptor expression in the human myometrium, in particular as it pertains to uterine contractility at labor. Summary of previous studies with the addition of new data on the transcriptional regulation of melatonin receptor expression in human myometrial cells. Not applicable. Late-term pregnant volunteers. Biopsy collection for in vitro analyses provided the original data. More recently, uterine contractions in late-term pregnant volunteers were assessed before, during, and after acute white-light exposure. Melatonin receptor signaling in myometrial cells and uterine contractions in late-term pregnant volunteers. Melatonin acts through the MTNR1B melatonin receptor that is expressed in the myometrium at late term to synergistically enhance oxytocin-dependent signaling and contractions. Acute inhibition of endogenous melatonin levels with light reversibly suppresses uterine contractions. These results point to a significant role for circulating melatonin in the timing and degree of uterine contractions in late-term pregnancy. Understanding the regulation of melatonin receptors remains a future objective. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  9. Clinical Pharmacology Studies in Critically Ill Children

    Science.gov (United States)

    Thakkar, Nilay; Salerno, Sara; Hornik, Christoph P.; Gonzalez, Daniel

    2016-01-01

    Developmental and physiological changes in children contribute to variation in drug disposition with age. Additionally, critically ill children suffer from various life-threatening conditions that can lead to pathophysiological alterations that further affect pharmacokinetics (PK). Some factors that can alter PK in this patient population include variability in tissue distribution caused by protein binding changes and fluid shifts, altered drug elimination due to organ dysfunction, and use of medical interventions that can affect drug disposition (e.g., extracorporeal membrane oxygenation and continuous renal replacement therapy). Performing clinical studies in critically ill children is challenging because there is large inter-subject variability in the severity and time course of organ dysfunction; some critical illnesses are rare, which can affect subject enrollment; and critically ill children usually have multiple organ failure, necessitating careful selection of a study design. As a result, drug dosing in critically ill children is often based on extrapolations from adults or non-critically ill children. Dedicated clinical studies in critically ill children are urgently needed to identify optimal dosing of drugs in this population. This review will summarize the effect of critical illness on pediatric PK, the challenges associated with performing studies in this vulnerable subpopulation, and the clinical PK studies performed to date for commonly used drugs. PMID:27585904

  10. Phase I/II clinical and pharmacokinetic study evaluating a fully human monoclonal antibody against EGFr (HuMax-EGFr) in patients with advanced squamous cell carcinoma of the head and neck

    DEFF Research Database (Denmark)

    Bastholt, Lars; Specht, Lena; Jensen, Kenneth

    2007-01-01

    PURPOSE: To assess safety, tolerability, pharmacokinetics and clinical activity of HuMax-EGFr in patients with SCCHN. PATIENTS AND METHODS: Twenty-eight patients with SCCHN were enrolled. The study comprised a single-dose escalation part for assessment of safety issues followed by a repeat dose e...

  11. Clinical Trials

    Medline Plus

    Full Text Available ... or device is safe and effective for humans. What Are Clinical Trials? Clinical trials are research studies ... parents, clinicians, researchers, children, and the general public. What to Expect During a clinical trial, doctors, nurses, ...

  12. Clinical experience in humans with radiolabeled antibody for tumor detection

    International Nuclear Information System (INIS)

    Morrison, R.T.; Lyster, D.M.; Szasz, I.; Alcorn, L.N.; Huckell, V.F.; Rhodes, B.; Breslow, K.; Burchiel, S.

    1982-01-01

    I-131 and Tc-99m labeled polyclonal or monoclonal antibody and fragments of antibody, specific to human chorionic gonadotropin (hCG) or to a melanoma cell surface antigen (MCSA) were injected into proven cancer patients. Using standard homeostasis parameters, and scanning techniques, the safety and efficacy of each antibody was evaluated. Antibody fragments were expected to clear faster from the circulation allowing for earlier imaging and a better target-to-non-target ratio. The technetium label may perturb the antiboby's kinetics so that clearance is more rapid for both whole antibody and fragments. After a statistical evaluation of all parameters measured pre and post injection it was concluded that no acute toxicity reactions were present in any patient studied. Scan results were not acceptable for a tumor detecting procedure used in routine practice. Tumor upake was seen in less than 10% of scans

  13. Clinical effects of prior trastuzumab on combination eribulin mesylate plus trastuzumab as first-line treatment for human epidermal growth factor receptor 2 positive locally recurrent or metastatic breast cancer: results from a Phase II, single-arm, multicenter study

    Directory of Open Access Journals (Sweden)

    Puhalla S

    2016-12-01

    treatment with eribulin plus trastuzumab for metastatic disease (median time between neo/adjuvant and study treatment: 23 months. In trastuzumab-naïve patients (n=31 compared with those who had received prior trastuzumab, objective response rate was 77.4% versus 61.9%, respectively; duration of response was 11.8 versus 9.5 months, respectively; clinical benefit rate was 87.1% versus 81.0%, respectively; and median progression-free survival was 12.2 versus 11.5 months, respectively. The most common grade 3/4 treatment-emergent adverse events (occuring in ≥5% of patients in patients who received prior trastuzumab versus trastuzumab naïve patients, respectively, were neutropenia (47.6% vs 32.3%, peripheral neuropathy (14.3% vs 25.8%, febrile neutropenia (14.3% vs 3.2%, fatigue (9.5% vs 6.5%, nausea (9.5% vs 0%, vomiting (9.5% vs 3.2%, and leukopenia (9.5% vs 3.2%. In patients with human epidermal growth factor receptor 2 positive metastatic breast cancer, first-line eribulin/trastuzumab treatment demonstrated substantial antitumor activity and was well tolerated, regardless of prior neo/adjuvant trastuzumab treatment. Keywords: oncology, breast neoplasms, advanced breast cancer, chemotherapy, eribulin mesylate, trastuzumab, HER2

  14. Atlas of the clinical genetics of human dilated cardiomyopathy

    DEFF Research Database (Denmark)

    Haas, Jan; Frese, Karen S; Peil, Barbara

    2015-01-01

    AIM: Numerous genes are known to cause dilated cardiomyopathy (DCM). However, until now technological limitations have hindered elucidation of the contribution of all clinically relevant disease genes to DCM phenotypes in larger cohorts. We now utilized next-generation sequencing to overcome...... these limitations and screened all DCM disease genes in a large cohort. METHODS AND RESULTS: In this multi-centre, multi-national study, we have enrolled 639 patients with sporadic or familial DCM. To all samples, we applied a standardized protocol for ultra-high coverage next-generation sequencing of 84 genes...... disease variants, we find titin, plakophilin-2, myosin-binding protein-C 3, desmoplakin, ryanodine receptor 2, desmocollin-2, desmoglein-2, and SCN5A variants among the most commonly mutated genes. The overlap between DCM, hypertrophic cardiomyopathy (HCM), and channelopathy causing mutations...

  15. [Clinical studies on flomoxef in neonates].

    Science.gov (United States)

    Tabuki, K; Nishimura, T

    1993-07-01

    Clinical studies on flomoxef (FMOX) were performed in neonates and the results obtained are summarized as follows. Treatment with FMOX was made in 4 cases of neonatal bacterial infections; 2 cases of sepsis (suspected) and 1 case each of infection of umbilicus and staphylococcal scalded skin syndrome. Results obtained were excellent in 1 case, good in 3 cases. No significant side effects due to the drug were observed in any cases.

  16. Nail disorders in children, a clinical study

    Directory of Open Access Journals (Sweden)

    Ayşe Akbaş

    2016-04-01

    Full Text Available Introduction: Aims of the study to investigate the frequency and the nature ofnail disorders in children significant clinical data is available. Nail disorders although common in children in some parts of our country. This study was carried out to document the clinical and demographic pattern of nail disorders in a dermatology outpatient clinic of a pediatric hospital in Ankara, Turkey. Material and Methods: All consecutive patients a total of 3000 children from age 0-16 were admitted to dermatology outpatient clinic of Ankara Pediatric Hematology and Oncology Education and Research Hospital during January 2011 to December 2011 were studied and retrospectively evaluated for age, gender, drug use, diseases, systemic or genetic disorders and demographic features. Diagnostic evaluation results were noted and patients were categorized for demographic features and diagnosis. Results: These 133 patients (M: F 58:75, %44 vs 56, respectively were under 16 years of age and have 17 different dermatological disorders related with nail symptoms. Fifty three of (39,8% these patient were under 2 years of age, 31 (23.3% were between 3-5 years, 30 (22.5% were between 6-11 years old, 19 of 133 (14%, 2 were between 11-16 years of age. Through all of ages and independent of gender the most etiologies of nail disorders were, onychomadesis, paronychia, onycholysis, onychomycosis and systemic nail presentation of systemic dermatosis. Conclusion: Nail disorders are different in children than in adults. In our study, the first 5 years of age was found in 53% of nail disorders. Nail disorders are uncommon but may be seen as a part of a systemic disease and may be associated with cosmetic and psychologic problem.

  17. Marketing and clinical trials: a case study

    OpenAIRE

    Entwistle Vikki A; Snowdon Claire; Garcia Jo; Knight Rosemary C; Shakur Haleema; Elbourne Diana R; Roberts Ian; Francis David; McDonald Alison M; Grant Adrian M; Campbell Marion K

    2007-01-01

    Abstract Background Publicly funded clinical trials require a substantial commitment of time and money. To ensure that sufficient numbers of patients are recruited it is essential that they address important questions in a rigorous manner and are managed well, adopting effective marketing strategies. Methods Using methods of analysis drawn from management studies, this paper presents a structured assessment framework or reference model, derived from a case analysis of the MRC's CRASH trial, o...

  18. Clinical and experimental studies on radiation proctitis

    International Nuclear Information System (INIS)

    Honke, Yoshifumi

    1988-01-01

    Clinical and experimental studies were performed to clarify the mechanism of developing radiation proctitis. The results were as follows; (1) In the clinical study with 38 uterine cervix cancer patients, who received radiotherapy, diarrhea was observed in 44.7% at the acute stage, while rectal bleeding in 36.7% about 1 year after radiation. However, no clinical correlation was observed between diarrhea and rectal bleeding. (2) Colon fiberscopic examination revealed little change at the acute stage. However, erosion, ulcer and remarkable redness were found at the late stage. By the magnified fiberscope, unit degeneration was found in 72.8% at the acute stage. (3) Concerning the histopathological changes, edema and inflammatory change were observed immediately after irradiation. Fibrosis was observed in 83.3% at the late stage. (4) The number of the immunoglobulin containing cells decreased by radiation. However, its recovered as time passed after radiation. (5) In experimental study with rats by microangiography, there were ramarkable changes of the small vessels, such as bending, tortuosity and capillary hyperplasia at the acute stage. However, these changes returned to normal soon. At the late stage, decreased number of blood vessels were observed. The above results indicated that rectal bleeding after exposure to radiation are developed by secondary circulation abnormality caused by fibrosis of the perivascular tissues. (author) 52 refs

  19. The clinic-statistic study of osteoporosis

    Directory of Open Access Journals (Sweden)

    Florin MARCU

    2008-05-01

    Full Text Available Osteoporosis is the most common metabolic bone disease and is characterized by the shrinkage in bone mass and the distruction of bone quality, thus conferring a higher risk for fractures and injuries. Osteoporosis reaches clinical attention when it is severe enough to induce microfractures and the collapsing of vertebral bodies manifesting with back aches or predisposition to other bone fractures. The aim of the study was to establish a statistic-numeric report between women and men in subjects diagnosed with osteoporosis through DEXA that present with a clinical simptomatology. We studied a group of subjects of masculine and feminine genders that have been diagnosed with osteoporosis through DEXA at the EURORAD clinic in Oradea from 01.01.2007-to present time .The result of the study was that the simptomatology of osteoporosis with pain and even cases of fractures is more obvious in female subjects then in male patients; statistically ,a woman/man report of 6.1/1 was established.

  20. Clinical and Statistical Study on Canine Impaction

    Directory of Open Access Journals (Sweden)

    Adina-Simona Coșarcă

    2013-08-01

    Full Text Available Aim: The aim of this study was to perform a clinical and statistical research on permanent impacted canine patients among those with dental impaction referred to and treated at the Oral and Maxillo-Facial Surgery Clinic of Tîrgu Mureș, over a four years period (2009-2012. Materials and methods: The study included 858 patients having dental impaction, and upon clinical records, different parameters, like frequency, gender, age, quadrant involvement, patient residence, associated complications, referring specialist and type of treatment, related to canine impaction, were assessed. Results: The study revealed: about 10% frequency of canine impaction among dental impactions; more frequent in women, in the first quadrant (tooth 13; most cases diagnosed between the age of 10-19 years; patients under 20 were referred by an orthodontist, those over 20 by a dentist; surgical exposure was more often performed than odontectomy. Conclusions: Canine impaction is the second-most frequent dental impaction in dental arch after third molars; it occurs especially in women. Due to its important role, canine recovery within dental arch is a goal to be achieved, whenever possible. Therefore, diagnose and treatment of canine impaction requires an interdisciplinary approach (surgical and orthodontic

  1. Annals of Humanities and Development Studies

    African Journals Online (AJOL)

    The Annals of Humanities and Development Studies publishes papers in all aspects of humanities and rural, social and cultural development, including peace and international cooperation activities related to societal transformation in developing countries. Papers arising from original research and case studies or forming ...

  2. Angular cheilitis: A clinical and microbial study

    Directory of Open Access Journals (Sweden)

    Nirima Oza

    2017-01-01

    Full Text Available Aims: The aim of the present study was to examine clinical types and microbiological flora isolated from angular chelitis. Materials and Methods: An eroded and/or erythematous, with or without fissure formation, nonvesicular lesion radiating from the angle of the mouth was considered to be angular chelitis. A sample of the present study comprised of 40 patients having unilateral or bilateral angular chelitis and 20 healthy individuals without any lip lesions. Clinical examination was done. In both test and control groups, the sample for microbial analysis was obtained from angle of the mouth. Results: Clinically, four types of angular cheilitis lesions were found, Type I, II, III, and IV. The most common type of lesion found was Type I lesion. Microorganisms isolated from the lesion were Staphylococcus aureus, Candida or Streptococci in 33 (82.5% cases either in pure culture or mixed culture. Among these 33 patients, S. aureus was found in 25 (75.5% cases, Candida in 16 (48.4% cases, and Streptococci in 5 (13.5% cases, respectively. Out of 16 cases positive for Candida, in 13 cases further isolation of Candida was possible. Candida albicans was found in 6 cases and Candida stellastodia in 7 cases. In majority of the dentulous and edentulous patients, S. aureus showed profuse growth. Conclusions: There are microorganisms associated with angular cheilitis.

  3. [ilin Pills for oligoasthenospermia: Advances in clinical studies].

    Science.gov (United States)

    Zhang, Kai-Shu; Fu, Long-Long; Shang, Xue-Jun; Gu, Yi-Qun

    2017-10-01

    Industrialization and environmental pollution are bringing more problems to human reproduction and increasing the prevalence of male infertility. Western medicine has shown its limitations in the management of male infertility, especially that of oligoasthenospermia. Traditional Chinese medicine (TCM), however, has long and rich experiences in the treatment of oligoasthenospermia, with a large variety of medicinal prescriptions based on the TCM theories, among which Qilin Pills shows a particularly significant therapeutic effect on oligoasthenospermia, especially when combined with Western medicine. At present, published studies on Qilin Pills are mainly in the stage of clinical observation, while basic researches and studies on its relevant mechanisms are rarely seen.

  4. Cell-mediated immune response: a clinical review of the therapeutic potential of human papillomavirus vaccination.

    Science.gov (United States)

    Meyer, Sonja Izquierdo; Fuglsang, Katrine; Blaakaer, Jan

    2014-12-01

    This clinical review aims to assess the efficacy of human papillomavirus 16/18 (HPV16/18) vaccination on the cell-mediated immune response in women with existing cervical intraepithelial neoplasia or cervical cancer induced by HPV16 or HPV18. A focused and thorough literature search conducted in five different databases found 996 publications. Six relevant articles were chosen for further review. In total, 154 patients (>18 years of age) were enrolled in prospective study trials with 3-15 months of follow up. The vaccine applications were administered two to four times. The vaccines contained different combinations of HPV16 and HPV18 and early proteins, E6 and E7. The primary outcome was the cell-mediated immune response. Correlation to clinical outcome (histopathology) and human leukocyte antigen genes were secondary endpoints. All vaccines triggered a detectable cell-mediated immune response, some of which were statistically significant. Correlations between immunological response and clinical outcome (histopathology) were not significant, so neoplasms may not be susceptible to vaccine-generated cytotoxic T cells (CD8(+)). Prophylactic HPV vaccines have been introduced to reduce the incidence of cervical cancer in young women. Women already infected with HPV could benefit from a therapeutic HPV vaccination. Hence, it is important to continue the development of therapeutic HPV vaccines to lower the rate of HPV-associated malignancies and crucial to evaluate vaccine efficacy clinically. This clinical review represents an attempt to elucidate the theories supporting the development of an HPV vaccine with a therapeutic effect on human papillomavirus-induced malignancies of the cervix. © 2014 Nordic Federation of Societies of Obstetrics and Gynecology.

  5. Communication in a Human biomonitoring study

    DEFF Research Database (Denmark)

    Exley, Karen; Cano, Noemi; Aerts, Dominique

    2015-01-01

    A communication strategy was developed by The Consortium to Perform Human Biomonitoring on a European Scale (COPHES), as part of its objectives to develop a framework and protocols to enable the collection of comparable human biomonitoring data throughout Europe. The framework and protocols were...... tested in the pilot study DEMOCOPHES (Demonstration of a study to Coordinate and Perform Human biomonitoring on a European Scale). The aims of the communication strategy were to raise awareness of human biomonitoring, encourage participation in the study and to communicate the study results...... and stakeholders, followed by dissemination at European level. Several lessons were learnt that may assist other future human biomonitoring studies. Recruitment took longer than anticipated and so social scientists, to help with community engagement, should be part of the research team from the start...

  6. Estimating individual glomerular volume in the human kidney: clinical perspectives.

    Science.gov (United States)

    Puelles, Victor G; Zimanyi, Monika A; Samuel, Terence; Hughson, Michael D; Douglas-Denton, Rebecca N; Bertram, John F; Armitage, James A

    2012-05-01

    Measurement of individual glomerular volumes (IGV) has allowed the identification of drivers of glomerular hypertrophy in subjects without overt renal pathology. This study aims to highlight the relevance of IGV measurements with possible clinical implications and determine how many profiles must be measured in order to achieve stable size distribution estimates. We re-analysed 2250 IGV estimates obtained using the disector/Cavalieri method in 41 African and 34 Caucasian Americans. Pooled IGV analysis of mean and variance was conducted. Monte-Carlo (Jackknife) simulations determined the effect of the number of sampled glomeruli on mean IGV. Lin's concordance coefficient (R(C)), coefficient of variation (CV) and coefficient of error (CE) measured reliability. IGV mean and variance increased with overweight and hypertensive status. Superficial glomeruli were significantly smaller than juxtamedullary glomeruli in all subjects (P IGV mean and variability. Overall, mean IGV was particularly reliable with nine or more sampled glomeruli (R(C) > 0.95, IGV and estimated total glomerular number. Multiple comorbidities for CKD are associated with increased IGV mean and variance within subjects, including overweight, obesity and hypertension. Zonal selection and the number of sampled glomeruli do not represent drawbacks for future longitudinal biopsy-based studies of glomerular size and distribution.

  7. Human tibial torsion - Morphometric assessment and clinical relevance

    Directory of Open Access Journals (Sweden)

    Swati Gandhi

    2014-02-01

    Full Text Available Background: Tibial torsion is an important anatomical parameter in clinical practice and displays variability among individuals. These variations are extremely significant in view of alignment guides such as those related to rotational landmarks of tibia in total knee arthroplasty. Further, precise knowledge and information pertaining to angle of tibial torsion also helps in correction of traumatic malunion or congenital maltorsion of tibia. Methods: The present study was carried out to determine the angle of tibial torsion in 100 adult dry tibia bones in the Department of Anatomy, Government Medical College, Amritsar. The study group comprised 50 males and 50 females with equal number of right- and left-sided bones. The measurements were meticulously recorded and the data were subjected to statistical analysis. The results were analyzed and discussed in the light of existing literature. Results: On the right side, it was found to be 29.84° ± 4.86°° (range = 22.00° -38.00° in males and 28.92° ± 5.10°° (range = 15.00°-38.00° in females. On the left side, it was found to be 28.00° ± 4.94°° (range = 20.00°-40.00°° in males and 28.12° ± 4.28°° (range = 20.00°-37.00°° in females. Conclusion: The present study is an endeavor to provide baseline data with reference to the angle of tibial torsion in the Indian population. The results of the study assume special importance in view of the technical advancements in reconstructive surgical procedures in orthopedic practice.

  8. Clinical relevance of liquid chromatography tandem mass spectrometry as an analytical method in microdose clinical studies.

    Science.gov (United States)

    Yamane, Naoe; Tozuka, Zenzaburo; Kusama, Makiko; Maeda, Kazuya; Ikeda, Toshihiko; Sugiyama, Yuichi

    2011-08-01

    To investigate the potency of LC-MS/MS by means of sensitivity and the applicability for cassette dosing in microdose clinical trials. Thirty one top-selling 31 drugs were spiked to human plasma, extracted, and analyzed by LC-MS/MS. The lower limits of quantification for each drug varied from 0.08 to 50 pg/mL, and were lower than one eighth of the assumed maximum plasma concentration at microdose in all drugs except for losartan, indicating the high performance in acquisition of full pharmacokinetic profiles at microdose. We also succeeded in simultaneous analysis of multiple compounds, assuming a situation of cassette dosing in which multiple drug candidates would be administrated simultaneously. Together with the features of LC-MS/MS, such as immediate verification, the utilization of non-radiolabeled drugs and no special facilities, we suppose that LC-MS/MS analysis would be widely applicable in conducting microdose clinical studies.

  9. Variation in clinical phenotype of human infection among genetic groups of Blastomyces dermatitidis

    Science.gov (United States)

    Meece, Jennifer K.; Anderson, Jennifer L.; Gruszka, Sarah; Sloss, Brian L.; Sullivan, Bradley; Reed, Kurt D.

    2013-01-01

    Background. Blastomyces dermatitidis, the etiologic agent of blastomycosis, has 2 genetic groups and shows varied clinical presentation, ranging from silent infections to fulminant respiratory disease and dissemination. The objective of this study was to determine whether clinical phenotype and outcomes vary based on the infecting organism's genetic group.Methods. We used microsatellites to genotype 227 clinical isolates of B. dermatitidis from Wisconsin patients. For each isolate, corresponding clinical disease characteristics and patient demographic information were abstracted from electronic health records and Wisconsin Division of Health reportable disease forms and questionnaires.Results. In univariate analysis, group 1 isolates were more likely to be associated with pulmonary-only infections (P 1 month (P smoking status (P = .0001) remained predictors for group 2 infections.Conclusions. This study identified previously unknown associations between clinical phenotype of human infection and genetic groups of B. dermatitidis and provides a framework for further investigations of the genetic basis for virulence in B. dermatitidis.

  10. Clinical Correlates of Diarrhea and Gut Parasites among Human Immunodeficiency Virus Seropositive Patients

    Directory of Open Access Journals (Sweden)

    Elvis Bisong

    2017-09-01

    Full Text Available Cluster differentiation 4 (CD4 count estimation, which is not readily available in most resource poor settings in Nigeria, is an important indexdetermining commencement of antiretroviral therapy (ART. It is imperative for physicians who come in contact with these patients in such settings to recognize other parameters to evaluate these patients. The clinical correlates of diarrhea and gut parasites among human immunodeficiency virus (HIV-seropositive patients attending our special treatment clinic were studied. Three hundred and forty consenting HIV-positive adult subjects were enrolled. Their stool and blood specimens were collected for a period of three months. Stool samples were analyzed for the presence of diarrhea and gut parasites. The patients were clinically evaluated by physical examination for the presence of pallor, dehydration, oral thrush, wasting lymphadenopathy, dermatitis, skin hyperpigmentation, and finger clubbing. Participants with diarrhea represented 14.1% of the population, while 21.5% harbored one or more parasites. In the subjects with diarrhea, 14.6% harbored gut parasites. The presence of diarrhea was associated with a low CD4 count. Clinically, oral thrush, wasting, and rashes were more reliable predictors of low CD4 count levels; whereas, the presence of pallor, dehydration, wasting, and rashes correlated with the presence of diarrhea. HIV patients presenting with pallor, dehydration, wasting, and rashes should be evaluated for the presence of diarrhea. The clinical variables associated with low CD4 count in this study may guide commencing antiretroviral therapy in resource poor settings.

  11. A clinical study of papular urticaria

    International Nuclear Information System (INIS)

    Raza, N.; Lodhi, M.S.; Ali, L.

    2008-01-01

    To determine the clinical features and demographic profile of the patients having papular urticaria. Individuals of all age groups and either gender either suspected of or having definite history of insect bite were included in the study. A specially-designed proforma was filled for each patient separately. The proforma included demographic features, information regarding clothing and sleeping habits, personal or family history of atopy and clinical patterns of the lesions. Computer programme SPSS 10 was used to manage and analyze the data. Out of 280 patients, 201 (71.8%) were children upto 12 years of age, 178 (63.6%) were males, 91 (32.5%) had atopy, 194 (69.3%) were non-locals, 212 (75.7%) came from urban/peri-urban areas and 173 (61.8%) presented during May-August. Lesions were present over exposed parts of the body in 36 (12.9%), arranged in groups in 152 (54.3%) and were papular urticaria in 185 (66.1%) patients. Children, adult males, non-locals and those belonging to urban/peri-urban areas are more vulnerable to papular urticaria in a particular region. Papular and urticarial lesions arranged in groups over both exposed as well as covered body parts of a single patient is the most common clinical pattern. (author)

  12. Dual-gated cardiac PET-clinical feasibility study

    Energy Technology Data Exchange (ETDEWEB)

    Teraes, Mika; Kokki, Tommi; Noponen, Tommi; Hoppela, Erika; Sipilae, Hannu T.; Knuuti, Juhani [Turku PET Centre, PO BOX 52, Turku (Finland); Durand-Schaefer, Nicolas [General Electric Medical Systems, Buc (France); Pietilae, Mikko [Turku University Hospital, Department of Internal Medicine, Turku (Finland); Kiss, Jan [Turku University Hospital, Department of Surgery, Turku (Finland)

    2010-03-15

    Both respiratory and cardiac motions reduce image quality in myocardial imaging. For accurate imaging of small structures such as vulnerable coronary plaques, simultaneous cardiac and respiratory gating is warranted. This study tests the feasibility of a recently developed robust method for cardiac-respiratory gating. List-mode data with triggers from respiratory and cardiac cycles are rearranged into dual-gated segments and reconstructed with standard algorithms of a commercial PET/CT scanner. Cardiac gates were defined as three fixed phases and one variable diastolic phase. Chest motion was measured with a respiratory gating device and post-processed to determine gates. Preservation of quantification in dual-gated images was tested with an IEC whole-body phantom. Minipig and human studies were performed to evaluate the feasibility of the method. In minipig studies, a coronary catheter with radioactive tip was guided in coronary artery for in vivo and ex vivo acquisitions. Dual gating in humans with suspected cardiac disorders was performed using 18-F-FDG as a tracer. The method was found feasible for in vivo imaging and the radioactive catheter tip was better resolved in gated images. In human studies, the dual gating was found feasible and easy for clinical routine. Maximal movement of myocardial surface in cranio-caudal direction was over 20 mm. The shape of myocardium was clearly different between the gates and papillary muscles become more visible in diastolic images. The first clinical experiences using robust cardiac-respiratory dual gating are encouraging. Further testing in larger clinical populations using tracers designed especially for plaque imaging is warranted. (orig.)

  13. Dual-gated cardiac PET-clinical feasibility study

    International Nuclear Information System (INIS)

    Teraes, Mika; Kokki, Tommi; Noponen, Tommi; Hoppela, Erika; Sipilae, Hannu T.; Knuuti, Juhani; Durand-Schaefer, Nicolas; Pietilae, Mikko; Kiss, Jan

    2010-01-01

    Both respiratory and cardiac motions reduce image quality in myocardial imaging. For accurate imaging of small structures such as vulnerable coronary plaques, simultaneous cardiac and respiratory gating is warranted. This study tests the feasibility of a recently developed robust method for cardiac-respiratory gating. List-mode data with triggers from respiratory and cardiac cycles are rearranged into dual-gated segments and reconstructed with standard algorithms of a commercial PET/CT scanner. Cardiac gates were defined as three fixed phases and one variable diastolic phase. Chest motion was measured with a respiratory gating device and post-processed to determine gates. Preservation of quantification in dual-gated images was tested with an IEC whole-body phantom. Minipig and human studies were performed to evaluate the feasibility of the method. In minipig studies, a coronary catheter with radioactive tip was guided in coronary artery for in vivo and ex vivo acquisitions. Dual gating in humans with suspected cardiac disorders was performed using 18-F-FDG as a tracer. The method was found feasible for in vivo imaging and the radioactive catheter tip was better resolved in gated images. In human studies, the dual gating was found feasible and easy for clinical routine. Maximal movement of myocardial surface in cranio-caudal direction was over 20 mm. The shape of myocardium was clearly different between the gates and papillary muscles become more visible in diastolic images. The first clinical experiences using robust cardiac-respiratory dual gating are encouraging. Further testing in larger clinical populations using tracers designed especially for plaque imaging is warranted. (orig.)

  14. Current nonclinical testing paradigm enables safe entry to First-In-Human clinical trials: The IQ consortium nonclinical to clinical translational database.

    Science.gov (United States)

    Monticello, Thomas M; Jones, Thomas W; Dambach, Donna M; Potter, David M; Bolt, Michael W; Liu, Maggie; Keller, Douglas A; Hart, Timothy K; Kadambi, Vivek J

    2017-11-01

    The contribution of animal testing in drug development has been widely debated and challenged. An industry-wide nonclinical to clinical translational database was created to determine how safety assessments in animal models translate to First-In-Human clinical risk. The blinded database was composed of 182 molecules and contained animal toxicology data coupled with clinical observations from phase I human studies. Animal and clinical data were categorized by organ system and correlations determined. The 2×2 contingency table (true positive, false positive, true negative, false negative) was used for statistical analysis. Sensitivity was 48% with a 43% positive predictive value (PPV). The nonhuman primate had the strongest performance in predicting adverse effects, especially for gastrointestinal and nervous system categories. When the same target organ was identified in both the rodent and nonrodent, the PPV increased. Specificity was 84% with an 86% negative predictive value (NPV). The beagle dog had the strongest performance in predicting an absence of clinical adverse effects. If no target organ toxicity was observed in either test species, the NPV increased. While nonclinical studies can demonstrate great value in the PPV for certain species and organ categories, the NPV was the stronger predictive performance measure across test species and target organs indicating that an absence of toxicity in animal studies strongly predicts a similar outcome in the clinic. These results support the current regulatory paradigm of animal testing in supporting safe entry to clinical trials and provide context for emerging alternate models. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Phenotypic and genotypic evaluation of 18 Nocardia isolates from human clinical samples in Mexico.

    Science.gov (United States)

    Sánchez-Herrera, K; Sandoval, H; Couble, A; Mouniee, D; Ramírez-Durán, N; Uzcategui de Morillo, M; Serrano, J A; Bergeron, E; Boiron, P; Rodríguez-Nava, V

    2012-03-01

    Mexico has the largest number of clinical cases of actinomycetoma in North and South America. Species originally identified by less specific methods have been recently reclassified as other known species or as new species. To assess, by 16S rRNA gene sequencing and phenotypic methods, the species distribution of 18 human clinical isolates originally identified as N. brasiliensis, some of them isolated between 1947 and 1959 in Mexico City. Clinical isolates came from the Hospital General, "Dr. Manuel Gea Gonzalez", and Instituto Nacional de Diagnóstico y Referencia Epidemiológica (INDRE) in Mexico, D.F. The strains used in this study included 15 clinical strains isolated between 1947 and 1959 that were originally identified as N. brasiliensis and three more strains obtained in 2007 identified as Nocardia spp. The isolates were identified genotypically by sequencing the 16S rRNA gene, and their phenotypic profiles were obtained with the API Coryne(®) system. Antibiotic susceptibility patterns were tested according to the protocol of the Comité de l'antibiogramme de la Société française de microbiologie[4]. According to 16S rRNA gene, sequencing were identified among 18 human clinical isolates as Nocardia farcinica (n=11) and Nocardia brasiliensis (n=7). A high number of the strains were susceptible to the majority of the antibiotics tested. The phenotypic profiles of the strains were quite uniform for N. farcinica and some variability was observed for N. brasiliensis strains. N. farcinica was the most prevalent species identified. Modern methodologies should be applied in clinical laboratories to accurately identify etiological agents. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  16. Clinical implications of microRNAs in human glioblastoma

    Directory of Open Access Journals (Sweden)

    Masahiro eMizoguchi

    2013-02-01

    Full Text Available Glioblastoma (GBM is one of the most common and dismal brain tumors in adults. Further elucidation of the molecular pathogenesis of GBM is mandatory to improve the overall survival of patients. A novel small non-coding RNA molecule, microRNA (miRNA, appears to represent one of the most attractive target molecules contributing to the pathogenesis of various types of tumors. Recent global analyses have revealed that several miRNAs are clinically implicated in GBM, with some reports indicating the association of miRNA dysregulation with acquired temozolomide (TMZ resistance. More recent studies have revealed that miRNAs could play a role in cancer stem cell (CSC properties, contributing to treatment resistance. In addition, greater impact might be expected from miRNA-targeted therapies based on tumor-derived exosomes that contain numerous functional miRNAs, which could be transferred between tumor cells and surrounding structures. Tumor-derived miRNAs are now considered to be a novel molecular mechanism promoting the progression of GBM. Establishment of miRNA-targeted therapies based on miRNA dysregulation of CSCs could provide effective therapeutic strategies for TMZ-resistant GBM. Recent progress has revealed that miRNAs are not only putative biological markers for diagnosis, but also one of the most promising targets for GBM treatment. Herein, we summarize the translational aspects of miRNAs in the diagnosis and treatment of GBM.

  17. A clinical and investigational study of donovanosis

    Directory of Open Access Journals (Sweden)

    Veeranna S

    2003-03-01

    Full Text Available A clinical and investigational study of 25 cases of Donovanosis was undertaken. The incidence was found to be 1.53% of all STD cases and 2.9% of GUD. M:F ratio was 2.12:1. Incidence was more in unmarried people. Fleshy exuberant type was seen in 88% of cases. Two patients (8% had extragenital ulcers. Donovan bodies were found in 88%. Pseudo elephantiasis was seen in 8 patients. Biopsy was done in 8 cases and showed ocanthosis, plasma cell infiltration and pseudo epitheliomatous hyperplasia. One patient developed squamous cell carcinoma of vulva.

  18. Technological advances for studying human behavior

    Science.gov (United States)

    Roske-Hofstrand, Renate J.

    1990-01-01

    Technological advances for studying human behavior are noted in viewgraph form. It is asserted that performance-aiding systems are proliferating without a fundamental understanding of how they would interact with the humans who must control them. Two views of automation research, the hardware view and the human-centered view, are listed. Other viewgraphs give information on vital elements for human-centered research, a continuum of the research process, available technologies, new technologies for persistent problems, a sample research infrastructure, the need for metrics, and examples of data-link technology.

  19. [Clinical aspects of human infection by the avian influenza virus].

    Science.gov (United States)

    Goubau, P

    2009-01-01

    The species barrier is not perfect for Influenza A and numerous transmissions of the virus from pigs or poultry to humans have been described these years. Appearing in 1997 and becoming epidemic in 2003, influenza A/H5N1 provoked many deadly enzootics in poultry batteries (highly pathogenic avian influenza of HPAI). Starting in Asia, many countries throughout Africa and Europe were affected. Sporadic human cases were described in direct contact with diseased chicken or other poultry. Half of the cases are lethal, but human to human transmission occurs with difficulty. From January 2003 to August 11th 2009, 438 cases were declared worldwide with 262 deaths. Many countries declared cases, but recently most cases occurred in Egypt. Measures in hospital were taken which were copied from the measures for SARS (Severe Acute Respiratory Syndrome), but these were probably excessive in this case, considering the low rate of secondary cases with A/H5N1. In many human infections, signs of severe respiratory distress develop and multi organ failure. It was feared that this deadly virus could become easily transmitted between humans, leading to a new pandemic. This was not the case up to now. The strong pathogenicity of the virus is still not completely explained, but the deep location of infection in the lungs and the deregulation of cytokine production by the target cells, particularly macrophages, may be part of the explanation.

  20. Clinic-Radiological Study of facial paralysis

    International Nuclear Information System (INIS)

    Olier, J.; Bacaicoa, M.C.; Guridi, J.; Gil, J.L.; Elcarte, F.; Delgado, G.

    1992-01-01

    We have gathered 159 cases of facial paralysis from recent records in our hospital, including paralyses of central as well as peripheral origin, and presenting as the only symptom or as one of several major symptoms of the discomfort of each patient. Sixty-four percent of them were studied by CT scan and/or MR, confirming the existence of alterations in the pathway of nerve pair VII in 50% of the patients who underwent radiological study. Idiopathic facial paralysis was the most common type (42% of the total); while tumors and post-traumatic findings were the most constant radiological findings. From the analysis of the data, the importance of the clinical criteria for selection of the patients in the study and the protocol for radiological diagnosis employed can be deduced. (author)

  1. Quality of clinical brain tumor MR spectra judged by humans and machine learning tools.

    Science.gov (United States)

    Kyathanahally, Sreenath P; Mocioiu, Victor; Pedrosa de Barros, Nuno; Slotboom, Johannes; Wright, Alan J; Julià-Sapé, Margarida; Arús, Carles; Kreis, Roland

    2018-05-01

    To investigate and compare human judgment and machine learning tools for quality assessment of clinical MR spectra of brain tumors. A very large set of 2574 single voxel spectra with short and long echo time from the eTUMOUR and INTERPRET databases were used for this analysis. Original human quality ratings from these studies as well as new human guidelines were used to train different machine learning algorithms for automatic quality control (AQC) based on various feature extraction methods and classification tools. The performance was compared with variance in human judgment. AQC built using the RUSBoost classifier that combats imbalanced training data performed best. When furnished with a large range of spectral and derived features where the most crucial ones had been selected by the TreeBagger algorithm it showed better specificity (98%) in judging spectra from an independent test-set than previously published methods. Optimal performance was reached with a virtual three-class ranking system. Our results suggest that feature space should be relatively large for the case of MR tumor spectra and that three-class labels may be beneficial for AQC. The best AQC algorithm showed a performance in rejecting spectra that was comparable to that of a panel of human expert spectroscopists. Magn Reson Med 79:2500-2510, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

  2. Isolation and clinical sample typing of human leptospirosis cases in Argentina.

    Science.gov (United States)

    Chiani, Yosena; Jacob, Paulina; Varni, Vanina; Landolt, Noelia; Schmeling, María Fernanda; Pujato, Nazarena; Caimi, Karina; Vanasco, Bibiana

    2016-01-01

    Leptospira typing is carried out using isolated strains. Because of difficulties in obtaining them, direct identification of infective Leptospira in clinical samples is a high priority. Multilocus sequence typing (MLST) proved highly discriminatory for seven pathogenic species of Leptospira, allowing isolate characterization and robust assignment to species, in addition to phylogenetic evidence for the relatedness between species. In this study we characterized Leptospira strains circulating in Argentina, using typing methods applied to human clinical samples and isolates. Phylogenetic studies based on 16S ribosomal RNA gene sequences enabled typing of 8 isolates (6 Leptospira interrogans, one Leptospira wolffii and one Leptospira broomii) and 58 out of 85 (68.2%) clinical samples (55 L. interrogans, 2 Leptospira meyeri, and one Leptospira kirschneri). MLST results for the L. interrogans isolates indicated that five were probably Canicola serogroup (ST37) and one was probably Icterohaemorrhagiae serogroup (ST17). Eleven clinical samples (21.6%), provided MLST interpretable data: five were probably Pyrogenes serogroup (ST13), four Sejroe (ST20), one Autumnalis (ST22) and one Canicola (ST37). To the best of our knowledge this study is the first report of the use of an MLST typing scheme with seven loci to identify Leptospira directly from clinical samples in Argentina. The use of clinical samples presents the advantage of the possibility of knowing the infecting strain without resorting to isolates. This study also allowed, for the first time, the characterization of isolates of intermediate pathogenicity species (L. wolffii and L. broomii) from symptomatic patients. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Clinical and neuroradiological studies on internuclear ophthalmoplegia

    Energy Technology Data Exchange (ETDEWEB)

    Ito, Michiko; Uchiyama, Shinichiro; Endo, Riuko; Aikawa, Takashi; Kobayashi, Itsuro; Takemiya, Toshiko; Maruyama, Shoichi (Tokyo Women' s Medical Coll. (Japan))

    1989-06-01

    In this study 14 cases of internuclear ophthalmoplegia (INO) were analysed. The correlation of clinical symptoms with localization of the responsible lesions was studied in these patients. The subjects included 9 patients with CVD, 2 with MS, 1 with Fisher's syndrome, 1 with cranial polyneuritis and one with unknown etiology. Nine patients with unilateral INO are all associated with brainstem infarction. The other 5 patients including 2 MS had bilateral INO. CT showed abnormal findings in brain stem in 7 out of 14 patients. As for MRI an abnormality was found in 5 out of the 8 patients examined. Two of the 7 patients without any abnormality on CT had abnormal signals on MRI. We divided INO into 3 groups based on the clinical symptoms: (1) anterior type in which convergence was involved concomitantly with adduction paralysis, (2) typical type in which dissociated nystagmus was more marked in the abducting eye, and convergence was preserved, (3) posterior type in which abduction is impaired without adduction disturbance. There were 5 cases of anterior type, 9 of typical type, and none of posterior type. On MRI two patients of anterior type had abnormalities in the dorsal midbrain, and one patient had an abnormality in the pons, and two patients of typical type had abnormalities in the upper or middle dorsal pons to the dorsal midbrain. CT failed to demontrate any responsible lesions in 2 patients in whom the responsible legions were clearly identified on MRI. (J.P.N.).

  4. A Guide to Studying Human Hair Follicle Cycling In Vivo.

    Science.gov (United States)

    Oh, Ji Won; Kloepper, Jennifer; Langan, Ewan A; Kim, Yongsoo; Yeo, Joongyeub; Kim, Min Ji; Hsi, Tsai-Ching; Rose, Christian; Yoon, Ghil Suk; Lee, Seok-Jong; Seykora, John; Kim, Jung Chul; Sung, Young Kwan; Kim, Moonkyu; Paus, Ralf; Plikus, Maksim V

    2016-01-01

    Hair follicles (HFs) undergo lifelong cyclical transformations, progressing through stages of rapid growth (anagen), regression (catagen), and relative "quiescence" (telogen). Given that HF cycling abnormalities underlie many human hair growth disorders, the accurate classification of individual cycle stages within skin biopsies is clinically important and essential for hair research. For preclinical human hair research purposes, human scalp skin can be xenografted onto immunocompromised mice to study human HF cycling and manipulate long-lasting anagen in vivo. Although available for mice, a comprehensive guide on how to recognize different human hair cycle stages in vivo is lacking. In this article, we present such a guide, which uses objective, well-defined, and reproducible criteria, and integrates simple morphological indicators with advanced, (immuno)-histochemical markers. This guide also characterizes human HF cycling in xenografts and highlights the utility of this model for in vivo hair research. Detailed schematic drawings and representative micrographs provide examples of how best to identify human HF stages, even in suboptimally sectioned tissue, and practical recommendations are given for designing human-on-mouse hair cycle experiments. Thus, this guide seeks to offer a benchmark for human hair cycle stage classification, for both hair research experts and newcomers to the field. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Development and validation of a sensitive liquid chromatographic-tandem mass spectrometric method for the simultaneous analysis of granisetron and 7-hydroxy granisetron in human plasma and urine samples: application in a clinical pharmacokinetic study in pregnant subject.

    Science.gov (United States)

    Zhao, Yang; Chen, Hui-Jun; Caritis, Steve; Venkataramanan, Raman

    2016-02-01

    A liquid chromatography-tandem mass spectrometric method for the quantification of granisetron and its major metabolite, 7-hydroxy granisetron in human plasma and urine samples was developed and validated. Respective stable isotopically labeled granisetron and 7-hydroxy granisetron were used as internal standards (IS). Chromatography was performed using an Xselect HSS T3 analytical column with a mobile phase of 20% acetonitrile in water (containing 0.2 mM ammonium formate and 0.14% formic acid, pH 4) delivered in an isocratic mode. Tandem mass spectrometry operating in positive electrospray ionization mode with multiple reaction monitoring was used for quantification. The standard curves were linear in the concentration ranges of 0.5-100 ng/mL for granisetron and 0.1-100 ng/mL for 7-hydroxy granisetron in human plasma samples, and 2-2000 ng/mL for granisetron and 2-1000 ng/mL for 7-hydroxy granisetron in human urine samples, respectively. The accuracies were >85% and the precision as determined by the coefficient of variations was granisetron or 7-hydroxy granisetron in either plasma or urine samples. Granisetron was stable under various storage and experimental conditions. This validated method was successfully applied to a pharmacokinetic study after intravenous administration of 1 mg granisetron to a pregnant subject. Copyright © 2015 John Wiley & Sons, Ltd.

  6. Non-clinical studies in the process of new drug development - Part II: Good laboratory practice, metabolism, pharmacokinetics, safety and dose translation to clinical studies.

    Science.gov (United States)

    Andrade, E L; Bento, A F; Cavalli, J; Oliveira, S K; Schwanke, R C; Siqueira, J M; Freitas, C S; Marcon, R; Calixto, J B

    2016-12-12

    The process of drug development involves non-clinical and clinical studies. Non-clinical studies are conducted using different protocols including animal studies, which mostly follow the Good Laboratory Practice (GLP) regulations. During the early pre-clinical development process, also known as Go/No-Go decision, a drug candidate needs to pass through several steps, such as determination of drug availability (studies on pharmacokinetics), absorption, distribution, metabolism and elimination (ADME) and preliminary studies that aim to investigate the candidate safety including genotoxicity, mutagenicity, safety pharmacology and general toxicology. These preliminary studies generally do not need to comply with GLP regulations. These studies aim at investigating the drug safety to obtain the first information about its tolerability in different systems that are relevant for further decisions. There are, however, other studies that should be performed according to GLP standards and are mandatory for the safe exposure to humans, such as repeated dose toxicity, genotoxicity and safety pharmacology. These studies must be conducted before the Investigational New Drug (IND) application. The package of non-clinical studies should cover all information needed for the safe transposition of drugs from animals to humans, generally based on the non-observed adverse effect level (NOAEL) obtained from general toxicity studies. After IND approval, other GLP experiments for the evaluation of chronic toxicity, reproductive and developmental toxicity, carcinogenicity and genotoxicity, are carried out during the clinical phase of development. However, the necessity of performing such studies depends on the new drug clinical application purpose.

  7. A CLINICAL STUDY ON BLUNT INJURY ABDOMEN

    Directory of Open Access Journals (Sweden)

    G. Kishore Babu

    2016-10-01

    Full Text Available BACKGROUND Abdominal trauma continues to account for a large number of trauma-related injuries and deaths. Motor vehicle accidents and urban violence, respectively, are the leading causes of blunt and penetrating trauma to this area of the body. Unnecessary deaths and complications can be minimized by improved resuscitation, evaluation and treatment. The new techniques and diagnostic tools available are important in the management of abdominal trauma. These improved methods, however, still depend on experience and clinical judgment for application and determination of the best care for the injured patient. The aim of the study is to 1. Analyse the incidence, clinical characteristics, diagnosis, indications for laparotomy, therapeutic methods and morbidity & mortality rates. 2. To study nature of blunt abdominal trauma. 3. To assess patient for surgical intervention and to avoid negative laparotomy. 4. To assess morbidity rate in different organs injury. 5. To evaluate modalities of treatment, complications and prognosis. MATERIALS AND METHODS This study is a prospective study on 97 patients with Blunt injuries to the abdomen admitted in S.V.R.R.G.G. Hospital, Tirupati during October 2013-15. Inclusion Criteria Patients > 13 years, with Blunt injury to abdomen either by RTA, fall, object contact, assault giving written informed consent. Exclusion Criteria Patients <13 yrs. Blunt injuries due to blasts, patients with severe cardiothoracic and head injuries who are hemodynamically unstable. CONCLUSION Blunt Trauma to abdomen is on rise due to excessive use of motor vehicles. It poses a therapeutic and diagnostic dilemma for the attending surgeon due to wide range of clinical manifestations ranging from no early physical findings to progression to shock. So, the Trauma surgeon should rely on his physical findings in association with use of modalities like x-ray abdomen, USG abdomen and abdominal paracentesis. Hollow viscus perforations are

  8. Korean Clinic Based Outcome Measure Studies

    Directory of Open Access Journals (Sweden)

    Jongbae Park

    2003-02-01

    Full Text Available Background: Evidence based medicine has become main tools for medical practice. However, conducting a highly ranked in the evidence hierarchy pyramid is not easy or feasible at all times and places. There remains a room for descriptive clinical outcome measure studies with admitting the limit of the intepretation. Aims: Presents three Korean clinic based outcome measure studies with a view to encouraging Korean clinicians to conduct similar studies. Methods: Three studies are presented briefly here including 1 Quality of Life of liver cancer patients after 8 Constitutional acupuncture; 2 Developing a Korean version of Measuring yourself Medical Outcome profile (MYMOP; and 3 Survey on 5 Shu points: a pilot In the first study, we have included 4 primary or secondary liver cancer patients collecting their diagnostic X-ray film and clinical data f개m their hospital, and asked them to fill in the European Organization Research and Treatment of Cancer, Quality of Life Questionnaire before the commencement of the treatment. The acupuncture treatment is set up format but not disclosed yet. The translation and developing a Korean version of outcome measures that is Korean clinician friendly has been sought for MYMOP is one of the most appropriate one. The permission was granted, the translation into Korean was done, then back translated into English only based on the Korean translation by the researcher who is bilingual in both languages. The back translation was compared by the original developer of MYMOP and confirmed usable. In order to test the existence of acupoints and meridians through popular forms of Korean acupuncture regimes, we aim at collecting opinions from 101 Korean clinicians that have used those forms. The questions asked include most effective symptoms, 5 Shu points, points those are least likely to use due to either adverse events or the lack of effectiveness, theoretical reasons for the above proposals, proposing outcome measures

  9. Clinical studies on mercury poisoning in cattle

    Energy Technology Data Exchange (ETDEWEB)

    Sonoda, M; Nakamura, R; Too, K; Matsuhashi, A; Ishimoto, H; Sasaki, R; Ishida, K; Takahashi, M

    1956-01-01

    A sporadic outbreak of an unknown disease occurred among dairy cattle, from early February to late May 1955, in Japan. The characteristic symptoms of this disease were dyspnea and depilation; out of 29 cases, 8 died while 2 were slaughtered. Clinical studies have disclosed that the symptoms were similar to those found in cases of mercury poisoning as described by others. So the animals' feed was suspected of being the cause of the sickness. It was confirmed that the incident was due to poisoning resulting from ingestion of linseed meal treated with a mercurial fungicide. From the results of the testing anamnesis, it was found that 171 cattle were fed with the meal and 29 cases were affected. In veiw of the wide use of mercurial preparations for treating seed grains against fungi infection, a further experimental study was made on the effects of the feed and fungicide upon calves.

  10. Clinical and radiologic study of odontogenic keratocyst

    International Nuclear Information System (INIS)

    Kim, Sang Rae; Park, Tae Won

    1984-01-01

    The purpose of this article is to define further clinical behaviors and radiographic appearances of odontogenic keratocyst developed in jaws, with special interest in recurrent rate which is generally high. 32 patients whose microscopic examinations were verified as odontogenic keratocyst were examined in this study. The results of this study were as follows. 1. There was an apparent sex predilection for male. 2. The peak incidence was the second and third decades with gradual decline thereafter with a mean age of 31 years 7 months. 3. The most common site was a mandibular molar-ramus region, 22 cases (68.8%) occurred in the mandible and 10 cases (31.3%) in the maxilla.

  11. Clinical and radiologic study of odontogenic keratocyst

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sang Rae; Park, Tae Won [Department of Radiology, College of Dentistry, Seoul National University, Seoul (Korea, Republic of)

    1984-11-15

    The purpose of this article is to define further clinical behaviors and radiographic appearances of odontogenic keratocyst developed in jaws, with special interest in recurrent rate which is generally high. 32 patients whose microscopic examinations were verified as odontogenic keratocyst were examined in this study. The results of this study were as follows. 1. There was an apparent sex predilection for male. 2. The peak incidence was the second and third decades with gradual decline thereafter with a mean age of 31 years 7 months. 3. The most common site was a mandibular molar-ramus region, 22 cases (68.8%) occurred in the mandible and 10 cases (31.3%) in the maxilla.

  12. Laboratory and Clinical Aspects of Human Herpesvirus 6 Infections

    Science.gov (United States)

    Bonnafous, Pascale; Gautheret-Dejean, Agnès

    2015-01-01

    SUMMARY Human herpesvirus 6 (HHV-6) is a widespread betaherpesvirus which is genetically related to human cytomegalovirus (HCMV) and now encompasses two different species: HHV-6A and HHV-6B. HHV-6 exhibits a wide cell tropism in vivo and, like other herpesviruses, induces a lifelong latent infection in humans. As a noticeable difference with respect to other human herpesviruses, genomic HHV-6 DNA is covalently integrated into the subtelomeric region of cell chromosomes (ciHHV-6) in about 1% of the general population. Although it is infrequent, this may be a confounding factor for the diagnosis of active viral infection. The diagnosis of HHV-6 infection is performed by both serologic and direct methods. The most prominent technique is the quantification of viral DNA in blood, other body fluids, and organs by means of real-time PCR. Many active HHV-6 infections, corresponding to primary infections, reactivations, or exogenous reinfections, are asymptomatic. However, the virus may be the cause of serious diseases, particularly in immunocompromised individuals. As emblematic examples of HHV-6 pathogenicity, exanthema subitum, a benign disease of infancy, is associated with primary infection, whereas further virus reactivations can induce severe encephalitis cases, particularly in hematopoietic stem cell transplant recipients. Generally speaking, the formal demonstration of the causative role of HHV-6 in many acute and chronic human diseases is difficult due to the ubiquitous nature of the virus, chronicity of infection, existence of two distinct species, and limitations of current investigational tools. The antiviral compounds ganciclovir, foscarnet, and cidofovir are effective against active HHV-6 infections, but the indications for treatment, as well as the conditions of drug administration, are not formally approved to date. There are still numerous pending questions about HHV-6 which should stimulate future research works on the pathophysiology, diagnosis, and

  13. Studies on nerve terminations in human mucosa and skin

    OpenAIRE

    Hilliges, Marita

    1997-01-01

    - In spite of their accessibility and important sensory function,the nervous tissue components of human oral and vaginal mucosa and skin have beensubject to very few, if any, systematic investigations. Studies on the innervationof oral tissues have mainly focused on the dental pulp, the periodontium and thegingiva, probably because of specific clinical interest, thus largely neglectingthe mucosa. Genital studies comprise only in a few cases the vagina and when thevagina is i...

  14. Measurement and Clinical Significance of Biomarkers of Oxidative Stress in Humans

    Directory of Open Access Journals (Sweden)

    Ilaria Marrocco

    2017-01-01

    Full Text Available Oxidative stress is the result of the imbalance between reactive oxygen species (ROS formation and enzymatic and nonenzymatic antioxidants. Biomarkers of oxidative stress are relevant in the evaluation of the disease status and of the health-enhancing effects of antioxidants. We aim to discuss the major methodological bias of methods used for the evaluation of oxidative stress in humans. There is a lack of consensus concerning the validation, standardization, and reproducibility of methods for the measurement of the following: (1 ROS in leukocytes and platelets by flow cytometry, (2 markers based on ROS-induced modifications of lipids, DNA, and proteins, (3 enzymatic players of redox status, and (4 total antioxidant capacity of human body fluids. It has been suggested that the bias of each method could be overcome by using indexes of oxidative stress that include more than one marker. However, the choice of the markers considered in the global index should be dictated by the aim of the study and its design, as well as by the clinical relevance in the selected subjects. In conclusion, the clinical significance of biomarkers of oxidative stress in humans must come from a critical analysis of the markers that should give an overall index of redox status in particular conditions.

  15. Evidence Based Studies in Clinical Transfusion Medicine

    NARCIS (Netherlands)

    A.J.G. Jansen (Gerard)

    2007-01-01

    textabstractAfter the introduction of blood component therapy in the 1960s, more and more attention is given to clinical transfusion medicine. Although blood transfusion is an important treatment in different clinical settings, there are still lack of much randomized clinical trials. Nowadays

  16. ACSNI study group on human factors

    International Nuclear Information System (INIS)

    1993-01-01

    Organisational failures are now recognised as being as important as mechanical failures or individual human errors in causing major accidents such as the capsize of the Herald of Free Enterprise or the Pipa Alpha disaster. The Human Factors Study Group of the Advisory Committee on the Safety of Nuclear Installations was set up to look at the part played by human factors in nuclear risk and its reduction. The third report of the Study Group considers the role played by organisational factors and management in promoting nuclear safety. Actions to review and promote a safety culture are suggested. Three main conclusions are drawn and several recommendations made. (UK)

  17. Experimental and clinical studies on CT lymphography

    International Nuclear Information System (INIS)

    Hirata, Yuzo; Kono, Michio

    1982-01-01

    Indirect lymphography using computed tomographic apparatus (CT Lymphography) was attempted in 15 dogs with newly devised contrast medium for the opacification of hilar and mediastinal lymphnodes. Clinical application was performed in 2 cases of lung cancer. Newly devised contrast material is an emulsion, which consists of oily contrast medium, non-ionic surfactant and glucose solution. The contrast medium was injected percutaneously into subdiaphragmatic space, or into bronchial walls by bronchofiberscopic technique. CT was able to demonstrate the opacified hilar and mediastinal nodes much more in number than demonstrated in conventional radiograms. It was true in 6 to 11 cases when injected into subdiaphragmatic spaces, and in 2 of 4 cases with an injection into bronchial walls. In clinical studies, CT revealed opacification of mediastinal nodes in one case of lung cancer. Although the procedure is still inferior to the demonstrability of routine indirect lymphography for the evaluation of the fine structure of each node, it showed no remarkable side effects. As the satisfactory method of opacifying hilar and mediastinal nodes has not yet been established, our method is thought to be of value in applying for detection of the metastatic lymphnodes. (author)

  18. Controlled outcome studies of child clinical hypnosis.

    Science.gov (United States)

    Adinolfi, Barbara; Gava, Nicoletta

    2013-09-01

    Background Hypnosis is defined as "as an interaction in which the hypnotist uses suggested scenarios ("suggestions") to encourage a person's focus of attention to shift towards inner experiences". Aim of the work The focus of this review is to summarize the findings of controlled outcome studies investigating the potential of clinical hypnosis in pediatric populations. We will examine the following themes: anesthesia, acute and chronic pain, chemotherapy-related distress, along with other specific medical issues. Results Hypnosis is an effective method to reduce pain and anxiety before, during and after the administration of anesthetics, during local dental treatments, invasive medical procedures and in burn children. Hypnosis can be successfully used to manage recurrent headaches, abdominal pain, irritable bowel syndrome and chemotherapy-related distress. Hypnosis has an important role in managing symptoms and improving the quality of life of children suffering from asthma and cystic fibrosis and in facilitating the treatment of insomnia in school-age children. Finally, hypnosis can be effectively used for the treatment of some habitual disorders such as nocturnal enuresis and dermatologic conditions, including atopic dermatitis and chronic eczema Conclusions Clinical hypnosis seems to be a useful, cheap and side-effects free tool to manage fear, pain and several kinds of stressful experiences in pediatric populations. Children who receive self-hypnosis trainings achieve significantly greater improvements in their physical health, quality of life, and self-esteem.

  19. Biomedical and Clinical Promises of Human Pluripotent Stem Cells for Neurological Disorders

    Directory of Open Access Journals (Sweden)

    Nopporn Jongkamonwiwat

    2013-01-01

    Full Text Available Neurological disorders are characterized by the chronic and progressive loss of neuronal structures and functions. There is a variability of the onsets and causes of clinical manifestations. Cell therapy has brought a new concept to overcome brain diseases, but the advancement of this therapy is limited by the demands of specialized neurons. Human pluripotent stem cells (hPSCs have been promised as a renewable resource for generating human neurons for both laboratory and clinical purposes. By the modulations of appropriate signalling pathways, desired neuron subtypes can be obtained, and induced pluripotent stem cells (iPSCs provide genetically matched neurons for treating patients. These hPSC-derived neurons can also be used for disease modeling and drug screening. Since the most urgent problem today in transplantation is the lack of suitable donor organs and tissues, the derivation of neural progenitor cells from hPSCs has opened a new avenue for regenerative medicine. In this review, we summarize the recent reports that show how to generate neural derivatives from hPSCs, and discuss the current evidence of using these cells in animal studies. We also highlight the possibilities and concerns of translating these hPSC-derived neurons for biomedical and clinical uses in order to fight against neurological disorders.

  20. Studies of human mutation rates: Progress report

    International Nuclear Information System (INIS)

    Neel, J.V.

    1988-01-01

    Progress was recorded between January 1 and July 1, 1987 on a project entitled ''Studies of Human Mutation Rates''. Studies underway include methodology for studying mutation at the DNA level, algorithms for automated analyses of two-dimensional polyacrylamide DNA gels, theoretical and applied population genetics, and studies of mutation frequency in A-bomb survivors

  1. Human mesenchymal stromal cells : biological characterization and clinical application

    NARCIS (Netherlands)

    Bernardo, Maria Ester

    2010-01-01

    This thesis focuses on the characterization of the biological and functional properties of human mesenchymal stromal cells (MSCs), isolated from different tissue sources. The differentiation capacity of MSCs from fetal and adult tissues has been tested and compared. Umbilical cord blood (UCB) has

  2. The humanization of catheter room design: its clinical practice

    International Nuclear Information System (INIS)

    Lin Hanying; Shi Fengxia; Guo Huiying

    2011-01-01

    American scholar Engeer has proposed biological, psychological and sociological medicine pattern, which has been well accepted by the society, It has manifested the medical arena humanism return and has made the profound influence on the nursing development. The idea, 'the human is a whole', has gradually become the mainstream of the nurse service concept, meanwhile, the environment has more and more become a beneficial part for diagnosing and treating in hospitalization. The improvement and more user-friendly design of the diagnosing and treating environment has already become an important ring linked with the whole nursing work. At the beginning of the fitting up design for the Catheter Lab Room of Interventional Radiology in General Hospital of PLA, the authors receive the idea 'the environment experience and admiration of the patient', put more attention to the humanization in the diagnosing and treating environmental construction. The functional compartments are separated clearly. The color, the background music as well as the video are designed to be coordinated with each other in order to produce a relaxing system. Practice for the past three years indicates that the use of humanization environment design can markedly reduce the patient intense and the anxious level in perioperative period, it can also significantly promote the patient to be restored to health. This article will describe user-friendly diagnosing and treating environmental construction practice in the Catheter Lab Room of Interventional Radiology in General Hospital of PLA. (authors)

  3. A clinical study of geriatric dermatoses

    Directory of Open Access Journals (Sweden)

    Leena Raveendra

    2014-07-01

    Full Text Available Introduction: The geriatric population is composed of persons over 65 years of age and very few studies are available on the dermatologic diseases in this group. This study was done to study the spectrum of cutaneous manifestations and prevalence of physiological and pathological changes in the skin of elderly people. Material and Methods: Two hundred consecutive patients aged more than 65 years of age attending the outpatient clinic or admitted as inpatients in the Department of Dermatology at Vydehi Institute of Medical Sciences and Research Centre were subjects for the study. A detailed history of cutaneous complaints, present and past medical ailments was taken. A complete general physical, systemic examination and dermatological examination was done and all findings were noted in a pre designed proforma. Skin changes observed due to ageing were classified as physiological and pathological. Findings were collated in a master chart and results analyzed. Results: Out of 200 patients studied, 71% were males and 29% were females. Pruritus was the single most common complaint elicited (44%. Among the physiological changes, xerosis was the commonest (93%. Among the pathological changes skin tumours, eczemas, infections were the common findings. Conclusions: The geriatric dermatoses are different in different populations as some of the skin changes seen in western skin and Indian skin are not identical.

  4. Redesign of a computerized clinical reminder for colorectal cancer screening: a human-computer interaction evaluation

    Directory of Open Access Journals (Sweden)

    Saleem Jason J

    2011-11-01

    Full Text Available Abstract Background Based on barriers to the use of computerized clinical decision support (CDS learned in an earlier field study, we prototyped design enhancements to the Veterans Health Administration's (VHA's colorectal cancer (CRC screening clinical reminder to compare against the VHA's current CRC reminder. Methods In a controlled simulation experiment, 12 primary care providers (PCPs used prototypes of the current and redesigned CRC screening reminder in a within-subject comparison. Quantitative measurements were based on a usability survey, workload assessment instrument, and workflow integration survey. We also collected qualitative data on both designs. Results Design enhancements to the VHA's existing CRC screening clinical reminder positively impacted aspects of usability and workflow integration but not workload. The qualitative analysis revealed broad support across participants for the design enhancements with specific suggestions for improving the reminder further. Conclusions This study demonstrates the value of a human-computer interaction evaluation in informing the redesign of information tools to foster uptake, integration into workflow, and use in clinical practice.

  5. CSAHi study-2: Validation of multi-electrode array systems (MEA60/2100) for prediction of drug-induced proarrhythmia using human iPS cell-derived cardiomyocytes: Assessment of reference compounds and comparison with non-clinical studies and clinical information.

    Science.gov (United States)

    Nozaki, Yumiko; Honda, Yayoi; Watanabe, Hitoshi; Saiki, Shota; Koyabu, Kiyotaka; Itoh, Tetsuji; Nagasawa, Chiho; Nakamori, Chiaki; Nakayama, Chiaki; Iwasaki, Hiroshi; Suzuki, Shinobu; Tanaka, Kohji; Takahashi, Etsushi; Miyamoto, Kaori; Morimura, Kaoru; Yamanishi, Atsuhiro; Endo, Hiroko; Shinozaki, Junko; Nogawa, Hisashi; Shinozawa, Tadahiro; Saito, Fumiyo; Kunimatsu, Takeshi

    2017-08-01

    With the aim of reconsidering ICH S7B and E14 guidelines, a new in vitro assay system has been subjected to worldwide validation to establish a better prediction platform for potential drug-induced QT prolongation and the consequent TdP in clinical practice. In Japan, CSAHi HEART team has been working on hiPS-CMs in the MEA (hiPS-CMs/MEA) under a standardized protocol and found no inter-facility or lot-to-lot variability for proarrhythmic risk assessment of 7 reference compounds. In this study, we evaluated the responses of hiPS-CMs/MEA to another 31 reference compounds associated with cardiac toxicities, and gene expression to further clarify the electrophysiological characteristics over the course of culture period. The hiPS-CMs/MEA assay accurately predicted reference compounds potential for arrhythmogenesis, and yielded results that showed better correlation with target concentrations of QTc prolongation or TdP in clinical setting than other current in vitro and in vivo assays. Gene expression analyses revealed consistent profiles in all samples within and among the testing facilities. This report would provide CiPA with informative guidance on the use of the hiPS-CMs/MEA assay, and promote the establishment of a new paradigm, beyond conventional in vitro and in vivo assays for cardiac safety assessment of new drugs. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Characterization of a 2016 Clinical Isolate of Zika Virus in Non-human Primates

    Directory of Open Access Journals (Sweden)

    Xiao-Feng Li

    2016-10-01

    Full Text Available Animal models are critical to understand disease and to develop countermeasures for the ongoing epidemics of Zika virus (ZIKV. Here we report a non-human primate model using a 2016 contemporary clinical isolate of ZIKV. Upon subcutaneous inoculation, rhesus macaques developed fever and viremia, with robust excretion of ZIKV RNA in urine, saliva, and lacrimal fluid. Necropsy of two infected animals revealed that systematic infections involving central nervous system and visceral organs were established at the acute phrase. ZIKV initially targeted the intestinal tracts, spleen, and parotid glands, and retained in spleen and lymph nodes till 10 days post infection. ZIKV-specific immune responses were readily induced in all inoculated animals. The non-human primate model described here provides a valuable platform to study ZIKV pathogenesis and to evaluate vaccine and therapeutics.

  7. "HUMAN AURICULAR MYIASIS CAUSED BY LUCILIA SERICATA: CLINICAL AND PARASITOLOGICAL CONSIDERATIONS"

    Directory of Open Access Journals (Sweden)

    R. Yaghoobi

    2005-05-01

    Full Text Available Myiasis is the invasion of body tissues of humans and animals by the larvae of the Diptera or two-winged flies. There are only sporadic reports in the literature concerning human ear myiasis. A 62-year-old bedridden woman in an intensive care unit was examined because of her intense swollen and erythematous right ear. Physical examination revealed 80 live larvae (maggots in the posterior part of right outer ear and external auditory canal. Entomological studies of the third instar larvae revealed it’s identity as Lucilia sericata. The entomological aspects, clinical and epidemiological characteristics are evaluated. In particular, we underline the rarity of myiasis because of both etiological agent and the anatomical site.

  8. Comparison of different culture conditions for human mesenchymal stromal cells for clinical stem cell therapy

    DEFF Research Database (Denmark)

    Haack-Sorensen, M.; Friis, T.; Bindslev, L.

    2008-01-01

    OBJECTIVE: Mesenchymal stromal cells (MSCs) from adult bone marrow (BM) are considered potential candidates for therapeutic neovascularization in cardiovascular disease. When implementing results from animal trials in clinical treatment, it is essential to isolate and expand the MSCs under...... conditions following good manufacturing practice (GMP). The aims of the study were first to establish culture conditions following GMP quality demands for human MSC expansion and differentiation for use in clinical trials, and second to compare these MSCs with MSCs derived from culture in four media commonly...... analysis showed that the plastic-adherent MSCs cultured in EMEA medium or in the other four media were identically negative for the haematopoietic surface markers CD45 and CD34 and positive for CD105, CD73, CD90, CD166 and CD13, which in combined expression is characteristic of MSCs. MSC stimulation...

  9. Hormones, Nicotine and Cocaine: Clinical Studies

    Science.gov (United States)

    Mello, Nancy K.

    2009-01-01

    Nicotine and cocaine each stimulate hypothalamic-pituitary-adrenal and -gonadal axis hormones, and there is increasing evidence that the hormonal milieu may modulate the abuse-related effects of these drugs. This review summarizes some clinical studies of the acute effects of cigarette smoking or IV cocaine on plasma drug and hormone levels, and subjective effects ratings. The temporal covariance between these dependent measures was assessed with a rapid (two min) sampling procedure in nicotine-dependent volunteers or current cocaine users. Cigarette smoking and IV cocaine each stimulated a rapid increase in LH and ACTH, followed by gradual increases in cortisol and DHEA. Positive subjective effects ratings increased immediately after initiation of cigarette smoking or IV cocaine administration. However, in contrast to cocaine’s sustained positive effects (hormones on nicotine dependence and cocaine abuse, and implications for treatment of these addictive disorders is discussed. PMID:19835877

  10. Experimental and clinical studies with intraoperative radiotherapy

    International Nuclear Information System (INIS)

    Sindelar, W.F.; Kinsella, T.; Tepper, J.; Travis, E.L.; Rosenberg, S.A.; Glatstein, E.

    1983-01-01

    Studies of normal tissue tolerance to intraoperative radiotherapy were done upon 65 dogs subjected to laparotomy and 11 million electron volt electron irradiation in doses ranging from zero to 5,000 rads. Results of studies indicated that intact aorta and vena cava tolerate up to 5,000 rads without loss of structural integrity. Ureteral fibrosis and stenosis develop at doses of 3,000 rads or more. Arterial anastomoses heal after doses of 4,500 rads, but fibrosis can lead to occlusion. Intestinal suture lines heal after doses of 4,500 rads. Bile duct fibrosis and stenosis develop at doses of 2,000 rads or more. Biliary-enteric anastomoses fail to heal at any dose level. A clinical trial of intraoperative radiotherapy combined with radical surgery was performed upon 20 patients with advanced malignant tumors which were considered unlikely to be cured by conventional therapies and which included carcinomas of the stomach, carcinomas of the pancreas, carcinomas involving the hilus of the liver, retroperitoneal sarcomas and osteosarcomas of the pelvis. All patients underwent resection of gross tumor, followed by intraoperative irradiation of the tumor bed and regional nodal basins. Some patients received additional postoperative external beam radiotherapy. Treatment mortality for combined operation and radiotherapy occurred in four of 20 patients. Postoperative complications occurred in four of the 16 surviving patients. Local tumor control was achieved in 11 of the 16 surviving patients, with an over-all median follow-up period of 18 months. The clinical trial suggested that intraoperative radiotherapy is a feasible adjunct to resection in locally advanced tumors, that the resulting mortality and morbidity is similar to that expected from operation alone and that local tumor control may be improved

  11. A CLINICAL STUDY OF HELLP SYNDROME

    Directory of Open Access Journals (Sweden)

    Irrinki Vasundhara Jyothi

    2017-01-01

    Full Text Available BACKGROUND HELLP syndrome is an acronym for Haemolysis (H, Elevated Liver Enzymes (EL and Low Platelet (LP. This is a rare complication of preeclampsia (10-15%. HELLP syndrome may develop even without hypertension. This syndrome is manifested by nausea, vomiting, epigastric or right upper quadrant pain along with haematological changes. Parenchymal necrosis of liver causes elevation in hepatic enzymes (AST and ALT >70 IU/L, LDH >600 IU/L and bilirubin (>1.2 mg/dL. There may be subcapsular haematoma formation (which is diagnosed by CT scanning and abnormal peripheral blood smear. Eventually, liver may rupture to cause sudden hypotension due to haemoperitoneum. Periportal haemorrhagic necrosis of the liver occurs due to thrombosis of the arterioles. The necrosis is seen at the periphery of the lobule. There may be subcapsular haemorrhage. Hepatic insufficiency seldom occurs because of the capacity and regenerative ability of liver cells. Liver function tests are especially abnormal in women with HELLP syndrome. A sincere effort has been put to study the HELLP syndrome incidence and its clinical prognosis and to understand its outcome. MATERIALS AND METHODS Forty patients were selected whose BP was recorded more than 140/80 mmHg after twenty weeks of gestation. Peripheral smear were taken to check for haemolysis or elevated indirect bilirubin or elevated LDH levels were checked, elevated liver enzymes and decreased platelet count <1,00,000/cumm was noted. Incidence of HELLP syndrome was found and various clinical features presented and the complications faced by the patients were recorded. Prompt treatment was given and the outcome of the disease was noted. All the statistical analysis was done using the latest SPSS software 2015 (California. RESULTS The mean age of the study group was found to be 26.72 years with a standard deviation of 5.62 years. In our study, the mean haemoglobin level was found to be 6.41 gm%, which is very low compared to the

  12. Human factors in resuscitation: Lessons learned from simulator studies

    Directory of Open Access Journals (Sweden)

    Hunziker S

    2010-01-01

    Full Text Available Medical algorithms, technical skills, and repeated training are the classical cornerstones for successful cardiopulmonary resuscitation (CPR. Increasing evidence suggests that human factors, including team interaction, communication, and leadership, also influence the performance of CPR. Guidelines, however, do not yet include these human factors, partly because of the difficulties of their measurement in real-life cardiac arrest. Recently, clinical studies of cardiac arrest scenarios with high-fidelity video-assisted simulations have provided opportunities to better delineate the influence of human factors on resuscitation team performance. This review focuses on evidence from simulator studies that focus on human factors and their influence on the performance of resuscitation teams. Similar to studies in real patients, simulated cardiac arrest scenarios revealed many unnecessary interruptions of CPR as well as significant delays in defibrillation. These studies also showed that human factors play a major role in these shortcomings and that the medical performance depends on the quality of leadership and team-structuring. Moreover, simulated video-taped medical emergencies revealed that a substantial part of information transfer during communication is erroneous. Understanding the impact of human factors on the performance of a complex medical intervention like resuscitation requires detailed, second-by-second, analysis of factors involving the patient, resuscitative equipment such as the defibrillator, and all team members. Thus, high-fidelity simulator studies provide an important research method in this challenging field.

  13. Epidemiology and clinical presentation of the four human parainfluenza virus types

    Directory of Open Access Journals (Sweden)

    Liu Wen-Kuan

    2013-01-01

    Full Text Available Abstract Background Human parainfluenza viruses (HPIVs are important causes of upper respiratory tract illness (URTI and lower respiratory tract illness (LRTI. To analyse epidemiologic and clinical characteristics of the four types of human parainfluenza viruses (HPIVs, patients with acute respiratory tract illness (ARTI were studied in Guangzhou, southern China. Methods Throat swabs (n=4755 were collected and tested from children and adults with ARTI over a 26-month period, and 4447 of 4755 (93.5% patients’ clinical presentations were recorded for further analysis. Results Of 4755 patients tested, 178 (3.7% were positive for HPIV. Ninety-nine (2.1% samples were positive for HPIV-3, 58 (1.2% for HPIV-1, 19 (0.4% for HPIV-2 and 8 (0.2% for HPIV-4. 160/178 (88.9% HPIV-positive samples were from paediatric patients younger than 5 years old, but no infant under one month of age was HPIV positive. Seasonal peaks of HPIV-3 and HPIV-1 occurred as autumn turned to winter and summer turned to autumn. HPIV-2 and HPIV-4 were detected less frequently, and their frequency of isolation increased when the frequency of HPIV-3 and HPIV-1 declined. HPIV infection led to a wide spectrum of symptoms, and more “hoarseness” (p=0.015, “abnormal pulmonary breathing sound” (p Conclusions HPIV infection led to a wide spectrum of symptoms, and similar clinical manifestations were found in the patients with four different types of HPIVs. The study suggested pathogenic activity of HPIV in gastrointestinal illness. The clinical presentation of HPIV infection may differ by patient age.

  14. Pregnancy - associated human listeriosis: Virulence and genotypic analysis of Listeria monocytogenes from clinical samples.

    Science.gov (United States)

    Soni, Dharmendra Kumar; Singh, Durg Vijai; Dubey, Suresh Kumar

    2015-09-01

    Listeria monocytogenes, a life-threatening pathogen, poses severe risk during pregnancy, may cause abortion, fetal death or neonatal morbidity in terms of septicemia and meningitis. The present study aimed at characterizing L. monocytogenes isolated from pregnant women based on serotyping, antibiotic susceptibility, virulence genes, in vivo pathogenicity test and ERIC- and REP-PCR fingerprint analyses. The results revealed that out of 3700 human clinical samples, a total of 30 (0.81%) isolates [12 (0.80%) from placental bit (1500), 18 (0.81%) from vaginal swab (2200)] were positive for L. monocytogenes. All the isolates belonged to serogroup 4b, and were + ve for virulence genes tested i.e. inlA, inlC, inlJ, plcA, prfA, actA, hlyA, and iap. Based on the mice inoculation tests, 20 isolates showed 100% and 4 isolates 60% relative virulence while 6 isolates were non-pathogenic. Moreover, 2 and 10 isolates were resistant to ciprofloxacin and cefoxitin, respectively, while the rest susceptible to other antibiotics used in this study. ERIC- and REP-PCR collectively depicted that the isolates from placental bit and vaginal swab had distinct PCR fingerprints except a few isolates with identical patterns. This study demonstrates prevalence of pathogenic strains mostly resistant to cefoxitin and/or ciprofloxacin. The results indicate the importance of isolating and characterizing the pathogen from human clinical samples as the pre-requisite for accurate epidemiological investigations.

  15. Microbiological and molecular characterization of human clinical isolates of Staphylococcus cohnii, Staphylococcus hominis, and Staphylococcus sciuri.

    Science.gov (United States)

    Garza-González, Elvira; Morfin-Otero, Rayo; Martínez-Vázquez, Manuel A; Gonzalez-Diaz, Esteban; González-Santiago, Omar; Rodríguez-Noriega, Eduardo

    2011-12-01

    The incidence of coagulase-negative staphylococci reported as causative agents of nosocomial infections has risen in the last decade. The aim of this study was to characterize biofilm formation, antibiotic resistance, SCCmec type, and genetic relatedness in clinical isolates of Staphylococcus cohnii, Staphylococcus hominis, and Staphylococcus sciuri recovered from humans. Clinically relevant isolates of S. cohnii (n = 15), S. hominis (n = 9), and S. sciuri (n = 6), were collected from patients. Biofilm formation was evaluated using crystal violet staining, drug susceptibility was assessed using the broth microdilution method, and methicillin resistance was measured using the cefoxitin disk test. SCCmec was typed using 2 different methodologies, and genetic relatedness was determined by pulsed-field gel electrophoresis (PFGE). Sixty percent (9/15) of S. cohnii, 33% (3/9) of S. hominis, and 50% (3/6) of S. sciuri isolates were categorized as weak producers of biofilm. None of the isolates were resistant to vancomycin or linezolid. All 3 species showed a high resistance (> 66%) to ampicillin, levofloxacin, erythromycin, and ceftriaxone, and the majority of the isolates were methicillin-resistant. PFGE revealed that the S. cohnii isolates comprised 1 dominant clone. The S. cohnii, S. hominis, and S. sciuri isolates analyzed in this study showed a high methicillin resistance and resistance to other antimicrobials. The results of this study strongly suggest that coagulase-negative staphylococci harbour new SCCmec elements. We report the first case of a clone of S. cohnii associated with human disease.

  16. Polymorphism of human haptoglobin and its clinical importance

    Directory of Open Access Journals (Sweden)

    Vânia Peretti de Albuquerque Wobeto

    2008-01-01

    Full Text Available Haptoglobin (Hp is a plasma glycoprotein, the main biological function of which is to bind free hemoglobin (Hb and prevent the loss of iron and subsequent kidney damage following intravascular hemolysis. Haptoglobin is also a positive acute-phase protein with immunomodulatory properties. In humans, the HP locus is polymorphic, with two codominant alleles (HP1 and HP2 that yield three distinct genotypes/phenotypes (Hp1-1, Hp2-1 and Hp2-2. The corresponding proteins have structural and functional differences that may influence the susceptibility and/or outcome in several diseases. This article summarizes the available data on the structure and functions of Hp and the possible effects of Hp polymorphism in a number of important human disorders.

  17. Hurdles to clinical translation of human induced pluripotent stem cells

    OpenAIRE

    Neofytou, Evgenios; O’Brien, Connor Galen; Couture, Larry A.; Wu, Joseph C.

    2015-01-01

    Human pluripotent stem cells are known to have the capacity to renew indefinitely, being intrinsically able to differentiate into many different cell types. These characteristics have generated tremendous enthusiasm about the potential applications of these cells in regenerative medicine. However, major challenges remain with the development and testing of novel experimental stem cell therapeutics in the field. In this Review, we focus on the nature of the preclinical challenges and discuss p...

  18. Influence of human papillomavirus on the clinical presentation of oropharyngeal carcinoma in the United States.

    Science.gov (United States)

    Stenmark, Matthew H; Shumway, Dean; Guo, Cui; Vainshtein, Jeffrey; Mierzwa, Michelle; Jagsi, Reshma; Griggs, Jennifer J; Banerjee, Mousumi

    2017-10-01

    Much of what is known about the significance of human papillomavirus (HPV) in oropharyngeal squamous cell carcinoma is derived from single-institution retrospective studies, post hoc analyses of tissue specimens from clinical trials, and tissue bank studies with a small sample size. The objective of this study is to investigate the impact of HPV on the frequency and clinical presentation of oropharyngeal carcinoma in a large, national sample with information from patients who underwent HPV testing. Retrospective, cross-sectional study. We identified a comprehensive national sample of 8,359 patients with oropharyngeal carcinoma and known HPV status diagnosed between 2010 and 2011 within the National Cancer Database. Multivariable logistic regression was used to assess correlates of patient and tumor characteristics on HPV status. Among patients with oropharyngeal carcinoma, the frequency of HPV-related squamous cell carcinoma in the United States was 65.4%. HPV-related oropharyngeal carcinoma was associated with younger age, male sex, and white race (P presentation (P clinical profile, supporting efforts to re-evaluate the staging and treatment paradigm for HPV-associated oropharyngeal cancer. 4. Laryngoscope, 127:2270-2278, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  19. A study on job satisfaction among clinical and non-clinical hospital ...

    African Journals Online (AJOL)

    Methods: Two hundred clinical and non-clinical hospital staff were invited to take part in the study. They completed a sociodemographic questionnaire and the Job Descriptive Index (JDI). Results: The results indicated that majority clinical and non-clinical staff were satisfied with their jobs as regards the parameters of the ...

  20. When clinical trials compete: prioritising study recruitment.

    Science.gov (United States)

    Gelinas, Luke; Lynch, Holly Fernandez; Bierer, Barbara E; Cohen, I Glenn

    2017-12-01

    It is not uncommon for multiple clinical trials at the same institution to recruit concurrently from the same patient population. When the relevant pool of patients is limited, as it often is, trials essentially compete for participants. There is evidence that such a competition is a predictor of low study accrual, with increased competition tied to increased recruitment shortfalls. But there is no consensus on what steps, if any, institutions should take to approach this issue. In this article, we argue that an institutional policy that prioritises some trials for recruitment ahead of others is ethically permissible and indeed prima facie preferable to alternative means of addressing recruitment competition. We motivate this view by appeal to the ethical importance of minimising the number of studies that begin but do not complete, thereby exposing their participants to unnecessary risks and burdens in the process. We then argue that a policy of prioritisation can be fair to relevant stakeholders, including participants, investigators and funders. Finally, by way of encouraging and helping to frame future debate, we propose some questions that would need to be addressed when identifying substantive ethical criteria for prioritising between studies. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  1. Clinical application of cerebral dynamic perfusion studies

    International Nuclear Information System (INIS)

    DeLand, F.H.

    1975-01-01

    Radionuclide cerebral perfusion studies are assuming a far greater importance in the detection and differential diagnosis of cerebral lesions. Perfusion studies not only contribute to the differential diagnosis of lesions but in certain cases are the preferred methods by which more accurate clinical interpretations can be made. The characteristic blood flow of arterio-venous malformations readily differentiates this lesion from neoplasms. The decreased perfusion or absent perfusion observed in cerebral infarctions is diagnostic without concurrent evidence from static images. Changes in rates and direction of blood flow contribute fundamental information to the status of stenosis and vascular occlusion and, in addition, offer valuable information on the competency and routes of collateral circulation. The degree of cerebral perfusion after cerebral vascular accidents appears to be directly related to patient recovery, particularly muscular function. Cerebral perfusion adds a new parameter in the diagnosis of subdural haematomas and concussion and in the differentiation of obscuring radioactivity from superficial trauma. Although pictorial displays of perfusion blood flow will offer information in most cerebral vascular problems, the addition of computer analysis better defines temporal relationships of regional blood flow, quantitative changes in flow and the detection of the more subtle increases or decreases in cerebral blood flow. The status of radionuclide cerebral perfusion studies has taken on an importance making it the primary modality for the diagnosis of cerebral lesions. (author)

  2. Human talent development processes in a specialty clinic in Pasto, Colombia

    Directory of Open Access Journals (Sweden)

    Jeraldine Milena Matabajoy-Montilla

    2018-01-01

    Full Text Available Introduction: Workers in the organization play a fundamental role in meeting the corporate objectives. In this sense, it is important to identify the processes of human talent development in the health sector since they contribute to human and organizational development. Objective: The processes of human talent development training, quality of work life, occupational health, organizational climate and performance evaluation were characterized in a specialty clinic in the city of Pasto, Colombia. Materials and methods: The study was addressed from the quantitative paradigm of descriptive type with a sample of 211 collaborators. The scale called "perception of human talent development processes" was built, whose Alfa de Cronbach was 0.97. Results: The results were systematized in the statistical program IBM SPSS statistics. Statistically significant differences were found in the training category (in the categories of needs detection, plan and programmes, training evaluation and follow-up, quality of working life (in the sub-categories: meaning of work and labor commitment and performance evaluation (in the subcategories: methods and results. Conclusions: The need to continue strengthening the processes of training, quality of work life and evaluation of performance is recognized.

  3. Statistical Issues in TBI Clinical Studies

    Directory of Open Access Journals (Sweden)

    Paul eRapp

    2013-11-01

    Full Text Available The identification and longitudinal assessment of traumatic brain injury presents several challenges. Because these injuries can have subtle effects, efforts to find quantitative physiological measures that can be used to characterize traumatic brain injury are receiving increased attention. The results of this research must be considered with care. Six reasons for cautious assessment are outlined in this paper. None of the issues raised here are new. They are standard elements in the technical literature that describes the mathematical analysis of clinical data. The purpose of this paper is to draw attention to these issues because they need to be considered when clinicians evaluate the usefulness of this research. In some instances these points are demonstrated by simulation studies of diagnostic processes. We take as an additional objective the explicit presentation of the mathematical methods used to reach these conclusions. This material is in the appendices. The following points are made:1. A statistically significant separation of a clinical population from a control population does not ensure a successful diagnostic procedure.2. Adding more variables to a diagnostic discrimination can, in some instances, actually reduce classification accuracy.3. A high sensitivity and specificity in a TBI versus control population classification does not ensure diagnostic successes when the method is applied in a more general neuropsychiatric population. 4. Evaluation of treatment effectiveness must recognize that high variability is a pronounced characteristic of an injured central nervous system and that results can be confounded by either disease progression or spontaneous recovery. A large pre-treatment versus post-treatment effect size does not, of itself, establish a successful treatment.5. A procedure for discriminating between treatment responders and nonresponders requires, minimally, a two phase investigation. This procedure must include a

  4. Hypothyroid myopathy. A clinical and pathologaical study.

    Science.gov (United States)

    McKeran, R O; Slavin, G; Ward, P; Paul, E; Mair, W G

    1980-09-01

    Ten patients with varying degrees of hypothroid myopathy were studied clinically and by serial percutaneous needle muscle biopsies before and during treatment with L-thyroxine. The biochemical evidence of hypothyroidism was related to the severity of the myopathic and signs before treatment. The severity of myopathic symptoms before and during treatment correlated with the biochemical evidence of hypothyrodism, a type II fibre atrophy and increased central nuclear counts. Likewise, the clinical evidence of a myopathy before and during treatment was correlated with both a type II fibre atrophy and loss and increased central nuclear counts but was not related to the biochemical parameters of hypothyroidism, except the level of thyroid stimulating hormone. In the muscle, before and during treatment, of the two most severely affected patients, intracellular glycogen inclusions were seen in scattered muscle fibres. On light microscopy and on electronmicroscopy, numerous mitochondria were seen responding to L-thyroxine with accumulations of subsarcolemmal honey-combing. Vesicular abnormalities, an electron dense matrix or occasional crystalline deposits were seen in muscle mitochondria from less severely azffected patients. Severely myopathic muscle contained excessive glycogen, membrane bound glycogen and excess lipid in a mainly perinuclear distribution. Occasional myelin and membranous bodies were seen and satellite cells during the recovery phase. A group of patients with hypothyroid myopathy who are likely to have a delayed recovery of full muscle strength on L-thyroxine may be recognised by the presence of severe proximal muscle weakness and characteristic changes on histochemical and electronmicroscopic examination of muscle. The spectrum of histochemical and electronmicroscopic abnormalities of muscle revealed with increasing degree of hypothyrodism, suggests that a generally reversible acquired glycogen storage and mictochondrial disorder is an important feature

  5. HUMAN HAND STUDY FOR ROBOTIC EXOSKELETON DELVELOPMENT

    Directory of Open Access Journals (Sweden)

    BIROUAS Flaviu Ionut

    2016-11-01

    Full Text Available This paper will be presenting research with application in the rehabilitation of hand motor functions by the aid of robotics. The focus will be on the dimensional parameters of the biological human hand from which the robotic system will be developed. The term used for such measurements is known as anthropometrics. The anthropometric parameters studied and presented in this paper are mainly related to the angular limitations of the finger joints of the human hand.

  6. HUMAN HAND STUDY FOR ROBOTIC EXOSKELETON DELVELOPMENT

    OpenAIRE

    BIROUAS Flaviu Ionut; NILGESZ Arnold

    2016-01-01

    This paper will be presenting research with application in the rehabilitation of hand motor functions by the aid of robotics. The focus will be on the dimensional parameters of the biological human hand from which the robotic system will be developed. The term used for such measurements is known as anthropometrics. The anthropometric parameters studied and presented in this paper are mainly related to the angular limitations of the finger joints of the human hand.

  7. CLINICAL STUDY OF POST LAPAROTOMY WOUND DEHISCENCE

    Directory of Open Access Journals (Sweden)

    Chanda Ramanachalam

    2017-04-01

    Full Text Available BACKGROUND The aim of the study is to- 1. Assess the association and prevalence of risk factors involved in causing post laparotomy wound dehiscence. 2. Identify the type of disease involved in causing abdominal wound dehiscence. 3. Effectively manage cases of wound dehiscence. MATERIALS AND METHODS Total 50 cases clinically presenting as gaping of abdominal wound and discharge from the site during the period of October 2014 to April 2016 were taken for study. Patients presenting with abdominal wound dehiscence after undergoing elective or emergency operation Each case was examined clinically and properly in systematic manner and an elaborative study of history based on chief complaints, significant risk factors, investigations, time and type of surgery performed and postoperative events and day of onset of wound dehiscence. RESULTS Males outnumbered females with 64% males and 36% females. Patients in the age group of 41-50 years and 51-60 years found to have highest incidence of abdominal wound dehiscence. Mean age of the patients affected was 48.02 years. Incidence of abdominal wound dehiscence is more common in patients with peritonitis due to duodenal and appendicular perforation than in case of intestinal obstruction. Incidence of abdominal wound dehiscence is more common in patients who are operated in emergency than elective (35:15. Surgical procedures, which included perforation closure carried higher incidence of wound dehiscence. Patients operated with midline incision carried higher risk for wound dehiscence than those operated with paramedian incisions. Incidence of abdominal wound dehiscence is more common in patients having their BMI >25 and anaemia (Hb% <10 g%. Average stay was 22 days, which increased both economic burden on patient and hospital. Out of 50 cases, 48 survivals and 2 were mortals. Partial wound dehiscence was conservative management, i.e. healing by secondary intention was observed in 32 patients and 8 patients had

  8. CLINICAL STUDY OF EARLY BREAST CARCINOMA

    Directory of Open Access Journals (Sweden)

    Kiran Kumar

    2016-01-01

    Full Text Available Carcinoma of the breast is one of the commonest cancers occurring in female and accounts for 1/3rd of all the malignant diseases occurring in them. It is mainly a disease of the developed countries and accounts for 1,00,000 deaths annually. Breast carcinoma is classified as Early breast cancer, Locally advanced breast cancer and Metastatic breast cancer. By definition early stage breast cancer constitutes breast tumors of clinical stages I, IIa and T2N1M0. Early breast cancer is the one diagnosed by mammography. Women when approaches at this stage, they can go for breast conservation surgery. Not all women are candidates for this approach, and some require mastectomy as part of their treatment. AIM To observe the incidence of early breast carcinoma with particular reference to the time taken by the patients to seek medical advice after the symptoms have developed i.e. the average time taken by the patients to seek medical advice, their appropriate management and prognosis. MATERIALS AND METHODS This prospective study was conducted over a period of 2 years from Oct-2012 to Oct-2014 in 30 female patients aged between 25-65 years who were presented with lump in breast of size ≤5cms with or without pain, with or without lymph nodes to the outpatient department. All the patients were thoroughly asked about history, examined clinically, investigated, staged and managed by surgery either Breast Conservation Surgery or Modified Radical Mastectomy. Postoperative complications were recorded and followed up regularly. RESULTS The incidence of early breast cancer in this study was 0.98% with peak age incidence between 40-60 years and duration of symptoms <6 months in 18 patients. Breast Conservation Surgery + axillary dissection + Radiotherapy was done in 23%. Prognosis was good in these patients with no local recurrence and death. CONCLUSION The prognosis of early stage breast carcinoma patients in this study was good. To have long term tumor free and

  9. HAMMLAB 2000 for human factor's studies

    International Nuclear Information System (INIS)

    Kvalem, J.

    1999-01-01

    The simulator-based Halden Man-Machine Laboratory (HAMMLAB) has, since its establishment in 1983, been the main vehicle for the human-machine systems research at the OECD Halden Reactor Project. The human factors programme relies upon HAMMLAB for performing experimental studies, but the laboratory is also utilised when evaluating computerised operator support systems, and for experimentation with advanced control room prototypes. The increased focus on experimentation as part of the research programme at the Halden Project, has led to a discussion whether today's laboratory will meet the demands of the future. A pre-project concluded with the need for a new laboratory, with extended simulation capabilities. Based upon these considerations, the HAMMLAB 2000 project was initiated with the goal of making HAMMLAB a global centre of excellence for the study of human-technology interaction in the management and control of industrial processes. This paper will focus on human factors studies to be performed in the new laboratory, and which requirements this will bring upon the laboratory infrastructure and simulation capabilities. The aim of the human factors research at the Halden Project is to provide knowledge which can be used by member organisations to enhance safety and efficiency in the operation of nuclear power plants by utilising research about the capabilities and limitations of the human operator in a control room environment. (author)

  10. Periodontal conditions in vegetarians: a clinical study.

    Science.gov (United States)

    Staufenbiel, I; Weinspach, K; Förster, G; Geurtsen, W; Günay, H

    2013-08-01

    Investigations about possible correlations between vegetarian diet and periodontal conditions are rare and characterized by small case numbers. The aim of this clinical study was to investigate the influence of a vegetarian diet on periodontal parameters with an appropriate sample size. A total of 200 patients, 100 vegetarians and 100 non-vegetarians, were included in the study. All patients were examined including a full mouth assessment of the periodontal and dental conditions. In addition, a questionnaire was handed out to ask for patients' oral hygiene habits and level of education. For statistical analysis the Mann-Whitney Test (χ(2) for analysis of the questionnaire) was applied (level of significance: Pvegetarians versus 41.72 years non-vegetarians). Vegetarians had significantly lower probing pocket depths (P=0.039), bleeding on probing (P=0.001), periodontal screening index (P=0.012), a better hygiene index (Pvegetarians. Furthermore, vegetarians had a higher level of education (PVegetarians revealed better periodontal conditions (less inflammation signs, less periodontal damage and a better dental home care). However, it should be considered that vegetarians are not only avoiding meat in their nutrition but are also characterized by an overall healthier life style.

  11. CLINICAL STUDY OF FISTULA IN ANO

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    Sushma Ramteke

    2017-02-01

    Full Text Available BACKGROUND Fistula in ano is one of the common problem faced in today’s world. Fistula in ano is track lined by granulation tissue that connect deeply in the anal canal or rectum and superficially on the skin around the anus. It usually results from cryptoglandular infection causing abscess, which burst spontaneously or was drained inadequately. The study is conducted to find most common aetiological factor and to evaluate various surgical technique and their outcome. The aim of the study is to- 1. Study the incidence of various aetiologies of fistula in ano. 2. Study the clinical presentation of fistula in ano. 3. Evaluate different modalities of surgical approach and their outcome. MATERIALS AND METHODS This prospective study was conducted at Late Lakhiram Agrawal Memorial Government Medical College, Raigarh, during the study period of July 2015 to July 2016. All the 50 cases were included in this study who were above 15 year of age diagnosed with fistula in ano on the basis of clinical examination who underwent surgical procedure. RESULTS In present study of 50 cases, 60% of cases were in the age group of 31-50 years. Male:female ratio was 9:1. 80% of cases belong to low socioeconomic status. The most common mode of presentation was discharging sinus in 96% of cases. 70% of patient had past history of burst abscess or surgical drainage of abscess. 90% of cases have single external opening. 80% of cases had posterior external opening. Most of the fistula are of low anal type, which was 92% and rest of the patient had an internal opening situated above the anorectal ring. The most common surgical approach done was fistulectomy. Only fistulectomy was done in 80% of patients. Fistulectomy with sphincterectomy was done in two patients. These two patients had associated anal fissure. Fistulectomy with seton placement was done in two patients of high level of fistula type. Fistulotomy was done in four patients (8%, these were of low fistula type

  12. Genetics in endocrinology: genetic variation in deiodinases: a systematic review of potential clinical effects in humans.

    Science.gov (United States)

    Verloop, Herman; Dekkers, Olaf M; Peeters, Robin P; Schoones, Jan W; Smit, Johannes W A

    2014-09-01

    Iodothyronine deiodinases represent a family of selenoproteins involved in peripheral and local homeostasis of thyroid hormone action. Deiodinases are expressed in multiple organs and thyroid hormone affects numerous biological systems, thus genetic variation in deiodinases may affect multiple clinical endpoints. Interest in clinical effects of genetic variation in deiodinases has clearly increased. We aimed to provide an overview for the role of deiodinase polymorphisms in human physiology and morbidity. In this systematic review, studies evaluating the relationship between deiodinase polymorphisms and clinical parameters in humans were eligible. No restrictions on publication date were imposed. The following databases were searched up to August 2013: Pubmed, EMBASE (OVID-version), Web of Science, COCHRANE Library, CINAHL (EbscoHOST-version), Academic Search Premier (EbscoHOST-version), and ScienceDirect. Deiodinase physiology at molecular and tissue level is described, and finally the role of these polymorphisms in pathophysiological conditions is reviewed. Deiodinase type 1 (D1) polymorphisms particularly show moderate-to-strong relationships with thyroid hormone parameters, IGF1 production, and risk for depression. D2 variants correlate with thyroid hormone levels, insulin resistance, bipolar mood disorder, psychological well-being, mental retardation, hypertension, and risk for osteoarthritis. D3 polymorphisms showed no relationship with inter-individual variation in serum thyroid hormone parameters. One D3 polymorphism was associated with risk for osteoarthritis. Genetic deiodinase profiles only explain a small proportion of inter-individual variations in serum thyroid hormone levels. Evidence suggests a role of genetic deiodinase variants in certain pathophysiological conditions. The value for determination of deiodinase polymorphism in clinical practice needs further investigation. © 2014 European Society of Endocrinology.

  13. Fibrin related antigens: assay development, clinical and kinetic studies

    Energy Technology Data Exchange (ETDEWEB)

    Kruskal, J B

    1987-08-01

    This thesis describes an assay which is able to measure and to determine the proportions of fibrin- and fibrinogen-related antigens (FRA) present in clinical samples. No assay exists at present which is capable of distinguishing between fibrin and fibrinogen degradation products concurrently and in a clinical setting. The assay may be used as a tool with which to gain further insight to pathophysiology of disorders characterized by activation of the coagulation and fibrinolytic pathways. This study provides and analysis of the FRA profiles in patients with disorders characterised by possible enhanced fibrinolytic activity. Studies have been undertaken on patients with acute and chronic liver diseases, on patients with the various syndromes of coronary artery disease and on patients with insulin-dependent diabetes mellitus with and without evidence of microvascular disease. Certain observations made it evident that further studies were required in order to explain previously undocumented fibrinolytic abnormalities in certain patient groups. Data obtained from patients with liver disease provided information compatible with the activation of their fibrinolytic pathways. The initial scope of this study was then extended to further investigate the deranged haemostatic mechanisms in patients with severe liver diseases. Kinetic studies were performed which required the development of specific technology to be able to measure certain previously undertermined parameters. Mathematical models describing the rates of fibrin formation and lysis were developed for human studies. Fibrin-derived D-dimer was radiolabelled and its validity as and intravenous tracer and maker of fibrin degradation established.

  14. [Clinical studies on flomoxef in acute tonsillitis].

    Science.gov (United States)

    Tomiyama, M

    1994-09-01

    To objectively evaluate the clinical efficacy and safety in acute tonsillitis, flomoxef (FMOX) was examined for the distribution of sensitivity of clinical strains to it and for its clinical usefulness. 1. The 80% minimum inhibitory concentration of 11 clinical strains of Gram-positive bacteria, 6 of Gram-negative bacteria and 5 of anaerobic bacteria was 0.39 microgram/ml. FMOX showed the strongest, most comprehensive antibacterial action among the drugs tested. 2. Thirty patients received FMOX. Clinical effectiveness was evaluated in 28 patients, and clinical usefulness and safety in 30. 3. The clinical efficacy rate ('excellent' and 'good') was 75% (21/28). 4. As for bacteriological response, bacterial elimination rates were 67% for Gram-positive bacteria, 100% for Gram-negative bacteria, 100% for anaerobic bacteria and 100% for mixed infections. 5. Side effects occurred in 2 (6%) patients: drug eruption and diarrhea in 1 patient each. These symptoms improved rapidly after discontinuation of the drug. 6. Although abnormal clinical test results were found in 7 (23%) patients, i.e., increases in GOT and GPT in 2, in GPT in 4 and in BUN in 1, they were transient. 7. The usefulness of FMOX was assessed in light of its efficacy and safety. It was highly satisfactory in 14 patients, satisfactory in 11, relatively satisfactory in 1, unsatisfactory in 2 and highly unsatisfactory in 2, and rate of usefulness was 83%. FMOX is considered to be highly useful for the treatment of severe acute tonsillitis.

  15. Human biomonitoring pilot study DEMOCOPHES in Germany

    DEFF Research Database (Denmark)

    Schwedler, Gerda; Seiwert, Margarete; Fiddicke, Ulrike

    2017-01-01

    , cadmium, cotinine and several phthalate metabolites in urine of 6–11 year old children and their mothers in an urban and a rural region. Seventeen European countries simultaneously conducted this cross-sectional DEMOCOPHES feasibility study. The German study population was taken in the city of Bochum...... and in the Higher Sauerland District, comprising 120 mother-child pairs. In the present paper features of the study implementation are presented. German exposure concentrations of the pollutants are reported and compared with European average concentrations from DEMOCOPHES and with those measured......Human biomonitoring (HBM) is an effective tool to assess human exposure to environmental pollutants, but comparable HBM data in Europe are lacking. In order to expedite harmonization of HBM studies on a European scale, the twin projects COPHES (Consortium to Perform Human Biomonitoring...

  16. Clinical Nonlinear Laser Imaging of Human Skin: A Review

    Science.gov (United States)

    Pavone, Francesco Saverio

    2014-01-01

    Nonlinear optical microscopy has the potential of being used in vivo as a noninvasive imaging modality for both epidermal and dermal imaging. This paper reviews the capabilities of nonlinear microscopy as a noninvasive high-resolution tool for clinical skin inspection. In particular, we show that two-photon fluorescence microscopy can be used as a diagnostic tool for characterizing epidermal layers by means of a morphological examination. Additional functional information on the metabolic state of cells can be provided by measuring the fluorescence decay of NADH. This approach allows differentiating epidermal layers having different structural and cytological features and has the potential of diagnosing pathologies in a very early stage. Regarding therapy follow-up, we demonstrate that nonlinear microscopy could be successfully used for monitoring the effect of a treatment. In particular, combined two-photon fluorescence and second-harmonic generation microscopy were used in vivo for monitoring collagen remodeling after microablative fractional laser resurfacing and for quantitatively monitoring psoriasis on the basis of the morphology of epidermal cells and dermal papillae. We believe that the described microscopic modalities could find in the near future a stable place in a clinical dermatological setting for quantitative diagnostic purposes and as a monitoring method for various treatments. PMID:25250337

  17. Clinical Nonlinear Laser Imaging of Human Skin: A Review

    Directory of Open Access Journals (Sweden)

    Riccardo Cicchi

    2014-01-01

    Full Text Available Nonlinear optical microscopy has the potential of being used in vivo as a noninvasive imaging modality for both epidermal and dermal imaging. This paper reviews the capabilities of nonlinear microscopy as a noninvasive high-resolution tool for clinical skin inspection. In particular, we show that two-photon fluorescence microscopy can be used as a diagnostic tool for characterizing epidermal layers by means of a morphological examination. Additional functional information on the metabolic state of cells can be provided by measuring the fluorescence decay of NADH. This approach allows differentiating epidermal layers having different structural and cytological features and has the potential of diagnosing pathologies in a very early stage. Regarding therapy follow-up, we demonstrate that nonlinear microscopy could be successfully used for monitoring the effect of a treatment. In particular, combined two-photon fluorescence and second-harmonic generation microscopy were used in vivo for monitoring collagen remodeling after microablative fractional laser resurfacing and for quantitatively monitoring psoriasis on the basis of the morphology of epidermal cells and dermal papillae. We believe that the described microscopic modalities could find in the near future a stable place in a clinical dermatological setting for quantitative diagnostic purposes and as a monitoring method for various treatments.

  18. A CLINICAL STUDY OF ACNE VULGARIS

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    Melathil Sadanandan Sadeep

    2017-11-01

    Full Text Available BACKGROUND Acne vulgaris is a highly prevalent chronic inflammatory disease of pilosebaceous unit affecting teenagers and young adults. Prognosis of acne is generally good, especially in mild acne. But, this disease reduces the self-esteem, their sense of identity and can severely compromise quality of life. All clinicians caring for children and adolescents should be familiar with this problem. Early diagnosis, proper treatment and timely counselling reduce the overall impact of disease to individuals. MATERIALS AND METHODS This is a prospective study conducted in the Department of Dermatology at Government Medical College, Kottayam, Kerala, in 200 patients who presented to the outpatient clinic with a clinical diagnosis of acne vulgaris who have not yet received any medical treatment for the disease and consented to participate in the study. RESULTS Male-to-female ratio of 1.43:1. 61.5% patients were in the 2nd decade. 4% were more than 30 years old. Duration of the disease at the time of presentation ranged from 3 weeks to 30 years. 42.5% complained of mild itching and 18.5% had burning sensation. 48.5% attribute exacerbation of disease after food intake. 72.5% acne patients had seborrhoea. Hirsutism and Acanthosis nigricans were present in 7.31% and 4.87% female patients, respectively. 50% with hirsutism and 25% with Acanthosis nigricans had polycystic ovarian disease and severe grades of acne. 25.6% females complained of premenstrual exacerbation of the disease. 26% of the patients showed exacerbation in summer. Smokers had severe grades of acne vulgaris compared to nonsmokers. Comedones were present in all and they were the predominant lesions in majority. Inflammatory papules were the 2nd most common lesions. Severe grades of acne were more common in patients with age ≥20 years. Severity of the disease increases with long duration of the disease. Relatively high incidence of post-acne scarring and post-inflammatory hyperpigmentation was

  19. EVA Health and Human Performance Benchmarking Study

    Science.gov (United States)

    Abercromby, A. F.; Norcross, J.; Jarvis, S. L.

    2016-01-01

    Multiple HRP Risks and Gaps require detailed characterization of human health and performance during exploration extravehicular activity (EVA) tasks; however, a rigorous and comprehensive methodology for characterizing and comparing the health and human performance implications of current and future EVA spacesuit designs does not exist. This study will identify and implement functional tasks and metrics, both objective and subjective, that are relevant to health and human performance, such as metabolic expenditure, suit fit, discomfort, suited postural stability, cognitive performance, and potentially biochemical responses for humans working inside different EVA suits doing functional tasks under the appropriate simulated reduced gravity environments. This study will provide health and human performance benchmark data for humans working in current EVA suits (EMU, Mark III, and Z2) as well as shirtsleeves using a standard set of tasks and metrics with quantified reliability. Results and methodologies developed during this test will provide benchmark data against which future EVA suits, and different suit configurations (eg, varied pressure, mass, CG) may be reliably compared in subsequent tests. Results will also inform fitness for duty standards as well as design requirements and operations concepts for future EVA suits and other exploration systems.

  20. Human pharmacology for addiction medicine: From evidence to clinical recommendations.

    Science.gov (United States)

    Quednow, Boris B; Herdener, Marcus

    2016-01-01

    Substance use disorders (SUD) are complex and often chronic diseases with negative health outcomes and social consequences. Pharmacological treatment options for SUD can be separated in medications for (i) intoxication, (ii) withdrawal, and (iii) reduction of use together with relapse prevention. This chapter will focus on approved or clinically established pharmacological strategies suited to manage symptoms of withdrawal, and to reduce substance use or to promote abstinence. Hereby SUD involving alcohol, nicotine, stimulants, and opioids are primarily discussed as these substances are considered most harmful for both the individual and the society. Moreover, the pharmacotherapy of SUD related to the use of cannabis, benzodiazepines, and gamma-hydroxybutyrate is also briefly reviewed. Since most approved pharmacological treatment options show only moderate effect sizes especially in the long term, the development of new treatment strategies including new drugs, new combinations of available compounds, and biomarkers for response prediction is still warranted. © 2016 Elsevier B.V. All rights reserved.

  1. Comparing the Effectiveness of a Clinical Registry and a Clinical Data Warehouse for Supporting Clinical Trial Recruitment: A Case Study

    Science.gov (United States)

    Weng, Chunhua; Bigger, J Thomas; Busacca, Linda; Wilcox, Adam; Getaneh, Asqual

    2010-01-01

    This paper reports a case study comparing the relative efficiency of using a Diabetes Registry or a Clinical Data Warehouse to recruit participants for a diabetes clinical trial, TECOS. The Clinical Data Warehouse generated higher positive predictive accuracy (31% vs. 6.6%) and higher participant recruitment than the Registry (30 vs. 14 participants) in a shorter time period (59 vs. 74 working days). We identify important factors that increase clinical trial recruitment efficiency and lower cost. PMID:21347102

  2. A CLINICAL STUDY OF ADHESIVE INTESTINAL OBSTRUCTION

    Directory of Open Access Journals (Sweden)

    Haricharan

    2015-09-01

    Full Text Available INTRODUCTION: Adhesive intestinal obstruction is an inevitable complication of abdominal surgeries. It has high morbidity with associated poor quality of life and predisposition to repeated hospitalization. Commonest cause of bowel obstruction in developed countries is postoperative adhesions with extrinsic compression of the intestine. Most of them can be managed conservatively. METHODS: A retrospective study of 30 patients admitted with the diagnosis of post - operative adhesive partial bowel obstruction was conducted by analyzing their medical records. Demographic data, clinical presentation including duration, previous surgical procedures, treatments received for the condition and successful conservative approach versus requirement of operative intervention were assesse d. RESULTS: The median age was 31yrs, most in their third decade of life. Male predominance was noted. Pelvic surgeries and gynecological surgeries (26% were found to be the most common cause of adhesive bowel obstruction followed by appendectomy (16%. M ore than two third of the patients (76.7% developed symptoms within two years of the initial surgery. Successful conservative treatment was noted in 22 patients (73.3% and discharged on fourth day of admission. Eight patients (26.6% underwent surgery. T hey all underwent adhesiolysis and had good outcome. CONCLUSIONS: The time - honored practice of expectant management of adhesive partial bowel obstruction has equally good outcome, as compared to various interventions practiced

  3. Clinical Study of Second Branchial Cleft Anomalies.

    Science.gov (United States)

    Lee, Dong Hoon; Yoon, Tae Mi; Lee, Joon Kyoo; Lim, Sang Chul

    2018-03-30

    The objective of this study was to review the clinical characteristics and surgical treatment outcomes of second branchial cleft anomalies, and to evaluate the usefulness and accuracy of preoperative fine-needle aspiration cytology (FNAC) in the diagnosis of branchial cleft cysts. A retrospective chart review was performed at Chonnam National University Hwasun Hospital from January 2010 to December 2016. Among 25 patients with second branchial cleft anomalies, in 23 patients (92.0%), these anomalies presented as cysts, and in the remaining 2 patients (8.0%), these anomalies presented as fistulas. Fine-needle aspiration cytology had a diagnostic sensitivity of 100%, a positive-predictive value of 100%, and accuracy of 100% for diagnosing second branchial cleft cyst. All patients of second branchial cleft anomalies were treated surgically under general anesthesia. No recurrence of second branchial cleft anomalies was observed. Branchial cleft cysts were the most common type of second branchial cleft anomalies. Preoperative FNAC is a useful and accurate method for preoperative evaluation of branchial cleft cysts. Surgical excision of second branchial cleft anomalies is the treatment of choice without any complications and with no recurrence.

  4. Clinical study of internal carotid artery occlusion

    International Nuclear Information System (INIS)

    Okada, Kyoko

    1989-01-01

    Fourteen patients with internal carotid artery (ICA) occlusion identified by cerebral angiography were studied for clinical features, computed tomographic findings, collateral circulation and risk factors. Eleven patients were males, and at age distribution it occurred more frequently in patients over 50 years to 60 years of age rather than other ages. As for the risk factors of cerebral infarction, smoking was more frequent in patients with thrombosis, and heart disease was more common in those with embolism. Stroke occurred progressively in patients with thrombosis whereas it occurred suddenly in those with embolism. The consciousness was more severely disturbed in patients with embolism than in those with thrombosis. On neuro-radiological findings, in the patients with thrombosis, the infarcted area on CT were small and emerged as deep or watershed types, and on the angiograms, occlusion at carotid bifurcation were found more frequently and the collateral circulation were well developed. In those with embolism, the infarcted areas were large and emerged as cortical types, and on the angiograms, occlusions were observed more frequently in the intracranial portion and collateral circulation were poorly developed. In many patients with thrombosis, platelet aggregation, hematocrit and blood viscosity increased, but in those with embolism did not. (author)

  5. Experimental infection of human volunteers with Haemophilus ducreyi: fifteen years of clinical data and experience.

    Science.gov (United States)

    Janowicz, Diane M; Ofner, Susan; Katz, Barry P; Spinola, Stanley M

    2009-06-01

    Haemophilus ducreyi causes chancroid, which facilitates transmission of human immunodeficiency virus type 1. To better understand the biology of H. ducreyi, we developed a human inoculation model. In the present article, we describe clinical outcomes for 267 volunteers who were infected with H. ducreyi. There was a relationship between papule formation and estimated delivered dose. The outcome (either pustule formation or resolution) of infected sites for a given subject was not independent; the most important determinants of pustule formation were sex and host effects. When 41 subjects were infected a second time, their outcomes segregated toward their initial outcome, confirming the host effect. Subjects with pustules developed local symptoms that required withdrawal from the study after a mean of 8.6 days. There were 191 volunteers who had tissue biopsy performed, 173 of whom were available for follow-up analysis; 28 (16.2%) of these developed hypertrophic scars, but the model was otherwise safe. Mutant-parent trials confirmed key features in H. ducreyi pathogenesis, and the model has provided an opportunity to study differential human susceptibility to a bacterial infection.

  6. Clinical Study of Uric Acid Urolithiasis

    Directory of Open Access Journals (Sweden)

    Yii-Her Chou

    2007-06-01

    Full Text Available Uric acid urolithiasis develops from various causes. To investigate the clinical and biochemical presentation of patients with uric acid urolithiasis, a retrospective study was designed. A total of 46 cases were enrolled between January 2004 and December 2005. The compositions of the stones were analyzed by infrared spectrophotometry. There were 39 males (84.8% and seven females (15.2%, with a mean age of 61.5 ± 10.6 years and mean body mass index (BMI of 26.7 ± 3.1 kg/m2. The stone location was kidney in 10 (21.7%, ureter in 22 (41.8%, and bladder in 14 (30.5%. Multiple stones were diagnosed in 36 patients (78.3%. Pre-existing comorbidities included diabetes mellitus in 11 patients (23.9%, hypertension in 23 (50%, gout in 13 (28.2%, and benign prostatic hyperplasia in 14 (30.4%. Mean serum creatinine and uric acid was 1.6 ± 0.6 mg/dL and 7.6 ± 1.8 mg/dL, respectively. There were 27 patients (58% with creatinine > 1.4 mg/dL. The mean urinary pH was 5.42 ± 0.46. Patients with uric acid urolithiasis were predominantly male, older, with higher BMI, multiple stone presentation, with lower urinary pH, and hyperuricemia. Exacerbation of the renal function should also be of concern because of the high proportion of patients with renal insufficiency diagnosed in this study.

  7. Uncertainty sources in radiopharmaceuticals clinical studies; Fontes de incertezas em estudos clinicos com radiofarmacos

    Energy Technology Data Exchange (ETDEWEB)

    Degenhardt, Aemilie Louize; Oliveira, Silvia Maria Velasques de, E-mail: silvia@cnen.gov.br, E-mail: amilie@bolsista.ird.gov.br [Instituto de Radioprotecao e Dosimetria, (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil)

    2014-07-01

    The radiopharmaceuticals should be approved for consumption by evaluating their quality, safety and efficacy. Clinical studies are designed to verify the pharmacodynamics, pharmacological and clinical effects in humans and are required for assuring safety and efficacy. The Bayesian analysis has been used for clinical studies effectiveness evaluation. This work aims to identify uncertainties associated with the process of production of the radionuclide and radiopharmaceutical labelling as well as the radiopharmaceutical administration and scintigraphy images acquisition and processing. For the development of clinical studies in the country, the metrological chain shall assure the traceability of the surveys performed in all phases. (author)

  8. Wearable Internet of Things - from human activity tracking to clinical integration.

    Science.gov (United States)

    Kumari, Poonam; Lopez-Benitez, Miguel; Gyu Myoung Lee; Tae-Seong Kim; Minhas, Atul S

    2017-07-01

    Wearable devices for human activity tracking have been emerging rapidly. Most of them are capable of sending health statistics to smartphones, smartwatches or smart bands. However, they only provide the data for individual analysis and their data is not integrated into clinical practice. Leveraging on the Internet of Things (IoT), edge and cloud computing technologies, we propose an architecture which is capable of providing cloud based clinical services using human activity data. Such services could supplement the shortage of staff in primary healthcare centers thereby reducing the burden on healthcare service providers. The enormous amount of data created from such services could also be utilized for planning future therapies by studying recovery cycles of existing patients. We provide a prototype based on our architecture and discuss its salient features. We also provide use cases of our system in personalized and home based healthcare services. We propose an International Telecommunication Union based standardization (ITU-T) for our design and discuss future directions in wearable IoT.

  9. Clinically relevant known and candidate genes for obesity and their overlap with human infertility and reproduction.

    Science.gov (United States)

    Butler, Merlin G; McGuire, Austen; Manzardo, Ann M

    2015-04-01

    Obesity is a growing public health concern now reaching epidemic status worldwide for children and adults due to multiple problems impacting on energy intake and expenditure with influences on human reproduction and infertility. A positive family history and genetic factors are known to play a role in obesity by influencing eating behavior, weight and level of physical activity and also contributing to human reproduction and infertility. Recent advances in genetic technology have led to discoveries of new susceptibility genes for obesity and causation of infertility. The goal of our study was to provide an update of clinically relevant candidate and known genes for obesity and infertility using high resolution chromosome ideograms with gene symbols and tabular form. We used computer-based internet websites including PubMed to search for combinations of key words such as obesity, body mass index, infertility, reproduction, azoospermia, endometriosis, diminished ovarian reserve, estrogen along with genetics, gene mutations or variants to identify evidence for development of a master list of recognized obesity genes in humans and those involved with infertility and reproduction. Gene symbols for known and candidate genes for obesity were plotted on high resolution chromosome ideograms at the 850 band level. Both infertility and obesity genes were listed separately in alphabetical order in tabular form and those highlighted when involved with both conditions. By searching the medical literature and computer generated websites for key words, we found documented evidence for 370 genes playing a role in obesity and 153 genes for human reproduction or infertility. The obesity genes primarily affected common pathways in lipid metabolism, deposition or transport, eating behavior and food selection, physical activity or energy expenditure. Twenty-one of the obesity genes were also associated with human infertility and reproduction. Gene symbols were plotted on high resolution

  10. The next generation of sepsis clinical trial designs: what is next after the demise of recombinant human activated protein C?*.

    Science.gov (United States)

    Opal, Steven M; Dellinger, R Phillip; Vincent, Jean-Louis; Masur, Henry; Angus, Derek C

    2014-07-01

    The developmental pipeline for novel therapeutics to treat sepsis has diminished to a trickle compared to previous years of sepsis research. While enormous strides have been made in understanding the basic molecular mechanisms that underlie the pathophysiology of sepsis, a long list of novel agents have now been tested in clinical trials without a single immunomodulating therapy showing consistent benefit. The only antisepsis agent to successfully complete a phase III clinical trial was human recumbent activated protein C. This drug was taken off the market after a follow-up placebo-controlled trial (human recombinant activated Protein C Worldwide Evaluation of Severe Sepsis and septic Shock [PROWESS SHOCK]) failed to replicate the favorable results of the initial registration trial performed ten years earlier. We must critically reevaluate our basic approach to the preclinical and clinical evaluation of new sepsis therapies. We selected the major clinical studies that investigated interventional trials with novel therapies to treat sepsis over the last 30 years. Phase II and phase III trials investigating new treatments for sepsis and editorials and critiques of these studies. Selected manuscripts and clinical study reports were analyzed from sepsis trials. Specific shortcomings and potential pit falls in preclinical evaluation and clinical study design and analysis were reviewed and synthesized. After review and discussion, a series of 12 recommendations were generated with suggestions to guide future studies with new treatments for sepsis. We need to improve our ability to define appropriate molecular targets for preclinical development and develop better methods to determine the clinical value of novel sepsis agents. Clinical trials must have realistic sample sizes and meaningful endpoints. Biomarker-driven studies should be considered to categorize specific "at risk" populations most likely to benefit from a new treatment. Innovations in clinical trial design

  11. [Consensus statement of the National AIDS Plan Secretariat, Spanish Society of Emergency Medicine and AIDS Study Group of the Spanish Society of Infectious Diseases and Clinical Microbiology on Emergency and Human Immunodeficiency Virus Infection].

    Science.gov (United States)

    2013-01-01

    Supporting non-HIV specialist professionals in the treatment of patients with urgent diseases resulting from HIV infection. These recommendations have been agreed by an expert panel from the National AIDS Plan Secretariat, the Spanish Society of Emergency Medicine, and the AIDS Study Group. A review has been made of the safety and efficacy results of clinical trials and cohort studies published in biomedical journals (PubMed and Embase) or presented at conferences. The strength of each recommendation (A, B, C) and the level of supporting evidence (I, II, III) are based on a modification of the criteria of the Infectious Diseases Society of America. The data to be collected from the emergency medical history in order to recognize the patient at risk of HIV infection were specified. It stressed the basic knowledge of ART principles and its importance in terms of decline in morbidity and mortality of HIV+ patients and referring to the HIV specialist for follow-up, where appropriate, including drug interactions. Management of different emergency situations that may occur in patients with HIV infection is also mentioned. The non-HIV specialist professional, will find the necessary tools to approach HIV patients with an emergency disease. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  12. Engagement and practical wisdom in clinical practice: a phenomenological study.

    Science.gov (United States)

    Saraga, Michael; Boudreau, Donald; Fuks, Abraham

    2018-05-08

    In order to understand the lived experiences of physicians in clinical practice, we interviewed eleven expert, respected clinicians using a phenomenological interpretative methodology. We identified the essence of clinical practice as engagement. Engagement accounts for the daily routine of clinical work, as well as the necessity for the clinician to sometimes trespass common boundaries or limits. Personally engaged in the clinical situation, the clinician is able to create a space/time bubble within which the clinical encounter can unfold. Engagement provides an account of clinical practice as a unitary lived experience. This stands in stark contrast to the prevailing notion, referred to as a dual discourse, that describes medicine as the addition of humanism to science. Drawing on Aristotle's notion of phronesis and Sartre's definition of the situation, we illustrate how this novel perspective entwines clinical practice, the person of the clinician, and the clinician's situation.

  13. The human coronary collateral circulation: development and clinical importance.

    Science.gov (United States)

    Seiler, Christian; Stoller, Michael; Pitt, Bertram; Meier, Pascal

    2013-09-01

    Coronary collaterals are an alternative source of blood supply to myocardium jeopardized by ischaemia. In comparison with other species, the human coronary collateral circulation is very well developed. Among individuals without coronary artery disease (CAD), there are preformed collateral arteries preventing myocardial ischaemia during a brief vascular occlusion in 20-25%. Determinants of such anastomoses are low heart rate and the absence of systemic arterial hypertension. In patients with CAD, collateral arteries preventing myocardial ischaemia during a brief occlusion are present in every third individual. Collateral flow sufficient to prevent myocardial ischaemia during coronary occlusion amounts to one-fifth to one-fourth the normal flow through the open vessel. Myocardial infarct size, the most important prognostic determinant after such an event, is the product of coronary artery occlusion time, area at risk for infarction, and the inverse of collateral supply. Well-developed coronary collateral arteries in patients with CAD mitigate myocardial infarcts and improve survival. Approximately one-fifth of patients with CAD cannot be revascularized by percutaneous coronary intervention or coronary artery bypass grafting. Therapeutic promotion of collateral growth is a valuable treatment strategy in those patients. It should aim at growth of large conductive collateral arteries (arteriogenesis). Potential arteriogenic approaches include the treatment with granulocyte colony-stimulating factor, physical exercise training, and external counterpulsation.

  14. Clinical Trials

    Medline Plus

    Full Text Available ... best data available for health care decisionmaking. The purpose of clinical trials is research, so the studies ... Thus, research in humans is needed. For safety purposes, clinical trials start with small groups of patients ...

  15. A CLINICAL STUDY OF STROKE IN YOUNG

    Directory of Open Access Journals (Sweden)

    Kumbha Thulasi Ram

    2015-02-01

    Full Text Available NTRIDUCTION : Stroke is one of the important causes of morbidity and mortality all over the world. Incidence of stroke steadily increases with age. Experts are concerned of the emerging stroke epidemic in India. Stroke affecting the young has potentially devastating consequence son the individual and his family. Certain risk factors are unique to the young. I t needs more studies for identification and modification of risk factors. The study aims to evaluate clinical features, risk factors, etiology and mortality of stroke in young patients. METHODS : 74 young patients satisfying the inclusion criteria were included in this study. A detailed history was taken from young stroke patients, systemic examination and required investigations were done. Data was collected in standardized proforma and analysed. RESULTS: Stroke in young accounts for 7.95% of stroke cases of all age groups. The mean age of the patients was 34.66 ± 7.48 years. Among 74 patients, 47(63.51% were male and 27(36.49% were female. Seizures, decreased consciousness, speech involvement and motor deficit were observed in 33.78%, 44.59%, 22.97% and 100% of cases respectively. 82.43% patients had ischemic and 17.57% patients had hemorrhagic stroke. Among ischemic stroke, large artery atherosclerosis was 16.21%, tuberculous meningoencephalitis with vasculitis was 16.21%, lacunar stroke was 10.81%, CVT was 10.81% and cardio embolic stroke was 6.76%. Smoking (59.45%, alcoholism (58.10%, hypertension (43.24%, coronary artery disease (8.10%, diabetes mellitus (10.81%, elevated total cholesterol (25.67%, elevated low density lipo proteins (22.97%, elevated triglycerides (27.02% and low HDL (22.97% were important risk factors. Carotid doppler was abnormal in 9.45% of patients. 6.76% patients had mitral stenosis in echocardiogram. Low protein C and protein S were found in 1.35% of patients. Eight (10.81% patients died during the hospital stay. INTERPRETATION AND CONCLUSIONS: The major risk

  16. Human factors consideration in clinical applications of virtual reality.

    Science.gov (United States)

    Lewis, C H; Griffin, M J

    1997-01-01

    Virtual reality environments have many potential applications in medicine, including surgical training, tele-operated robotic surgery, assessment and rehabilitation of behavioural and neurological disorders and diagnosis, therapy and rehabilitation of physical disabilities. Although there is much potential for the use of immersive virtual reality environments in clinical applications, there are problems which could limit their ultimate usability. Some users have experienced side-effects during and after exposure to virtual reality environments. The symptoms include ocular problems, disorientation and balance disturbances, and nausea. Susceptibility to side-effects can be affected by age, ethnicity, experience, gender and physical fitness, as well as the characteristics of the display, the virtual environment and the tasks. The characteristics of the virtual reality system have also been shown to affect the ability of users to perform tasks in a virtual environment. Many of these effects can be attributed to delays between the sampling of head and limb positions and the presentation of an appropriate image on the display. The introduction of patients to virtual reality environments, for assessment, therapy or rehabilitation, raises particular safety and ethical issues. Patients exposed to virtual reality environments for assessment and rehabilitation may have disabilities which increase their susceptibility to certain side-effects. Special precautions therefore need to be taken to ensure the safety and effectiveness of such virtual reality applications. These precautions include minimisation of possible side-effects at the design stage. Factors are identified which are likely to affect the incidence of side-effects during and after exposures, and which need to be understood in order to minimise undesirable consequences. There is also a need for the establishment of protocols for monitoring and controlling exposures of patients to virtual reality environments. Issues

  17. [Changing surgical therapy because of clinical studies?].

    Science.gov (United States)

    Schwenk, W; Haase, O; Müller, J M

    2002-04-01

    The randomised controlled clinical trial (RCT) is a powerful instrument to evaluate different therapeutic regimens. In a survey among 115 physicians visiting the 25th annual meeting of the Surgical Society of Berlin and Brandenburg, the RCT was judged to be very important when changes of therapeutic strategies are discussed. 90 % of all participants claimed to use data from RCTs in the clinical routine and 89 % would participate in such a trial. In official (e. g. discussions during coffee breaks at scientific meetings) or non-medical (e. g. non-scientific press or media) sources of information were assessed as irrelevant for decisions regarding therapeutic strategies. However, in contrast to this view laparoscopic cholecystectomy was introduced into clinical practice rapidly because patients informed by external (non-medical) sources preferred to be operated on with the "modern" technique. Clinical trials with a high level of evidence had no relevant influence on the rapid distribution of laparoscopic cholecystectomy. Controversial discussions concerning the extent of lymphadenectomy with gastric resection for carcinoma demonstrate that the value of excellent clinical RCTs is low if their results challenge a stable paradigma of the surgical scientific society. To allow a rational judgement, new surgical technologies should undergo a scientific gradual evaluation in agreement with the principles of evidence based medicine.

  18. Effects of curcumin consumption on human chronic diseases: A narrative review of the most recent clinical data.

    Science.gov (United States)

    Mantzorou, Maria; Pavlidou, Eleni; Vasios, George; Tsagalioti, Eftychia; Giaginis, Constantinos

    2018-06-01

    Numerous clinical trials have investigated the potential beneficial effects of curcumin supplementation against several human chronic diseases. Up to now, it has been claimed that curcumin consumption may exert beneficial effects against several chronic diseases by promoting human health and preventing diseases. In this aspect, the present review aims to critically collect and in-depth summarize the most recent, well-designed clinical studies evaluating the potential beneficial effects of curcumin consumption on human health promotion and disease prevention. According to recent and well-designed clinical studies, curcumin consumption may benefit against obesity, metabolic syndrome, and diabetes. Moreover, curcumin consumption seems to exert a positive effect on people suffering from various types of cancer, fatty liver disease, depression, arthritis, skin diseases, gut inflammation, and symptoms of premenstrual syndrome. Due to the strong heterogeneity among the clinical studies concerning the exact effective curcumin dose and formulation, as well as the recommended treatment duration for each chronic disease, no precise and definitive conclusions could be drawn. Further large-scale prospective studies are strongly recommended, being well-designed as far as follow-up times, dosage, formulation, and duration of curcumin supplementation are concerned. Moreover, potential confounders in each specific chronic disease should carefully be taken into account in future studies. Copyright © 2018 John Wiley & Sons, Ltd.

  19. Supporting Clinical Cognition: A Human-Centered Approach to a Novel ICU Information Visualization Dashboard.

    Science.gov (United States)

    Faiola, Anthony; Srinivas, Preethi; Duke, Jon

    2015-01-01

    Advances in intensive care unit bedside displays/interfaces and electronic medical record (EMR) technology have not adequately addressed the topic of visual clarity of patient data/information to further reduce cognitive load during clinical decision-making. We responded to these challenges with a human-centered approach to designing and testing a decision-support tool: MIVA 2.0 (Medical Information Visualization Assistant, v.2). Envisioned as an EMR visualization dashboard to support rapid analysis of real-time clinical data-trends, our primary goal originated from a clinical requirement to reduce cognitive overload. In the study, a convenience sample of 12 participants were recruited, in which quantitative and qualitative measures were used to compare MIVA 2.0 with ICU paper medical-charts, using time-on-task, post-test questionnaires, and interviews. Findings demonstrated a significant difference in speed and accuracy with the use of MIVA 2.0. Qualitative outcomes concurred, with participants acknowledging the potential impact of MIVA 2.0 for reducing cognitive load and enabling more accurate and quicker decision-making.

  20. Clinical manifestation, serology marker & microscopic agglutination test (MAT) to mortality in human leptospirosis

    Science.gov (United States)

    Perdhana, S. A. P.; Susilo, R. S. B.; Arifin; Redhono, D.; Sumandjar, T.

    2018-03-01

    Leptospirosis is a potentially fatal zoonosis that is endemic in many tropical regions and causes large epidemics after heavy rainfall and flooding. Severe disease is estimated 5–15% of all human infections. Its mortality rate is 5-40%. MAT, isolation of the organism, or leptospiral DNA in PCR are used to confirm Leptospirosis. This cross-sectional analytic study recruited 26 hospitalized leptospirosis patients admitted to Dr. Moewardi Hospital Surakarta. The diagnosis was based on clinical, laboratory and epidemiological findings. The onset of the disease was the date when the first symptom started, and the end of the analysis was the date when the patient died or discharged. Modified Faine’s score ≥ 25 tend to die (45.5%) while modified Faine’s score 20 – 24 tend to heal (60%) (OR 1.250; CI 0.259-6.029; p=1.0). Seropositive IgM predicts mortality 7.8 times higher than seronegative IgM (OR 7.800; CI 1.162-52.353; p=0.038). MAT positive predict mortality 10.667 times higher than MAT negative (OR 10.667; CI 1.705-66.720; p=0.015). Clinical manifestation, MAT, and serologic marker are all correlated with mortality in Leptospirosis. However, statistically, clinical manifestation has an insignificant correlation.

  1. Indium-111 labelled platelets: experimental and clinical studies

    International Nuclear Information System (INIS)

    Gjerloeff Schmidt, K.

    1985-10-01

    The object of the present study became to develop a method of effective and gentle isolation and 111-In labelling of human platelets, as well as to employ these platelets in human clinical studies with the object of elucidating a number of physiological and pathophysiological mechanisms and processes in which platelets take part. 111-In-oxine presents obvious advantages over 51-Cr-sodium chromate; a high labelling efficiency, and more advantageous physical properties (a half life of 68 hours (against the half life of 28 days for 51-Cr) and considerably more effective gamma emission), making external registration by means of a gamma camera possible. Considering the role played by platelets in the development of atherosclerosis and its thromboembolic complications, in the early phases of deep venous thrombosis, and in graft rejection, it is natural that attempts have been made to use 111-In-labelled platelets for scintigraphic and kinetic evaluation of thromboembolic processes. Accumulation of 111-In-labelled platelets at sites of vessel wall injury, on pulmonary emboli (presumably on deep vein thrombi as well), and on catheter material has been demonstrated. Beyond this, the number of publications concerning the use of 111-In-labelled platelets for visualization of atherosclerosis, venous thromboembolism, arterial grafts, intracardiac thrombi, aortic aneurysms, renal allograft rejection, and other situations in which platelet thromboembolism takes place, provides evidence that a tool has finally been found for the study of their nature and response to therapeutic intervention. (eg)

  2. Communication: The Study of Human Interaction.

    Science.gov (United States)

    Mortensen, C. David

    Designed to provide a comprehensive and broadly based introduction to the study of human communication, this book presents the concept of communication as interrelated constituent processes that operate at varying levels of complexity and acquire significance only in the context of larger intrapersonal, interpersonal, or socio-cultural systems of…

  3. Human Challenge Pilot Study with Cyclospora cayetanensis

    OpenAIRE

    Alfano-Sobsey, Edith M.; Eberhard, Mark L.; Seed, John R.; Weber, David J.; Won, Kimberly Y.; Nace, Eva K.; Moe, Christine L.

    2004-01-01

    We describe a pilot study that attempted to infect human volunteers with Cyclospora cayetanensis. Seven healthy volunteers ingested an inoculum of Cyclospora oocysts (approximately 200–49,000 oocysts). The volunteers did not experience symptoms of gastroenteritis, and no oocysts were detected in any stool samples during the 16 weeks volunteers were monitored.

  4. Studies of Human Memory and Language Processing.

    Science.gov (United States)

    Collins, Allan M.

    The purposes of this study were to determine the nature of human semantic memory and to obtain knowledge usable in the future development of computer systems that can converse with people. The work was based on a computer model which is designed to comprehend English text, relating the text to information stored in a semantic data base that is…

  5. Towards Clinical Application of Neurotrophic Factors to the Auditory Nerve; Assessment of Safety and Efficacy by a Systematic Review of Neurotrophic Treatments in Humans

    NARCIS (Netherlands)

    Bezdjian, Aren; Kraaijenga, Véronique J C; Ramekers, Dyan; Versnel, Huib; Thomeer, Hans G X M; Klis, Sjaak F L; Grolman, Wilko

    2016-01-01

    Animal studies have evidenced protection of the auditory nerve by exogenous neurotrophic factors. In order to assess clinical applicability of neurotrophic treatment of the auditory nerve, the safety and efficacy of neurotrophic therapies in various human disorders were systematically reviewed.

  6. Effects of atorvastatin on biomarkers of immune activation, inflammation, and lipids in virologically suppressed, human immunodeficiency virus-1-infected individuals with low-density lipoprotein cholesterol <130 mg/dL (AIDS Clinical Trials Group Study A5275).

    Science.gov (United States)

    Nixon, Daniel E; Bosch, Ronald J; Chan, Ellen S; Funderburg, Nicholas T; Hodder, Sally; Lake, Jordan E; Lederman, Michael M; Klingman, Karin L; Aberg, Judith A

    Persistent immune activation and inflammation in virologically suppressed human immunodeficiency virus (HIV) infection are linked to excess cardiovascular risk. To evaluate atorvastatin as a strategy to reduce cardiovascular risk. A5275 was a multicenter, prospective, randomized, double-blind, placebo-controlled, cross-over pilot study of atorvastatin (10 mg/day for 4 weeks then 20 mg/day for 16 weeks) with a planned enrollment of 97 HIV-infected participants ≥18 years old, receiving boosted protease inhibitor-based antiretroviral therapy for ≥6 months, with plasma HIV-1 RNAs below limits of quantification ≥180 days, and fasting low-density lipoprotein (LDL) cholesterol ≥70 and atorvastatin treatment. Analyses were as-treated. Ninety-eight participants were enrolled at 31 U S sites and 73 completed study treatment. Atorvastatin treatment did not decrease T-lymphocyte or monocyte activation, circulating biomarker levels (interleukin-6, D-dimer, soluble CD14, soluble CD163, monocyte chemoattractant protein-1, interferon-gamma-induced protein-10, high-sensitivity C-reactive protein, CD40L, and P-selectin) or white blood cell Krüppel-like Factor 2/4 messenger RNA levels. Pre-to-post atorvastatin reductions in calculated LDL (-38%), oxidized-LDL (-33%), and lipoprotein-associated phospholipase A2 (-31%) were significant (P atorvastatin did not significantly decrease levels of soluble or cellular biomarkers of immune activation and inflammation but resulted in robust reductions in LDL cholesterol, oxLDL, and lipoprotein-associated phospholipase A 2 , biomarkers associated with cardiovascular risk. Copyright © 2016 National Lipid Association. All rights reserved.

  7. Comparison of the Effect of Two Human Milk Fortifiers on Clinical Outcomes in Premature Infants

    Directory of Open Access Journals (Sweden)

    Melissa Thoene

    2014-01-01

    Full Text Available The use of human milk fortifiers (HMF helps to meet the high nutritional requirements of the human milk-fed premature infant. Previously available powdered products have not met the protein requirements of the preterm infant population and many neonatologists add powder protein modulars to help meet protein needs. The use of powdered products is discouraged in neonatal intensive care units (NICU due to concern for invasive infection. The use of a commercially available acidified liquid product with higher protein content was implemented to address these two concerns. During the course of this implementation, poor growth and clinically significant acidosis of infants on Acidified Liquid HMF (ALHMF was observed. The purpose of this study was to quantify those observations by comparing infant outcomes between groups receiving the ALHMF vs. infants receiving powdered HMF (PHMF. A retrospective chart review compared outcomes of human milk-fed premature infants <2000 g receiving the ALHMF (n = 23 and the PHMF (n = 46. Infant growth, enteral feeding tolerance and provision, and incidence of necrotizing enterocolitis (NEC, metabolic acidosis, and diaper dermatitis were compared between the two groups. No infants were excluded from this study based on acuity. Use of ALHMF resulted in a higher incidence of metabolic acidosis (p = 0.002. Growth while on HMF as measured in both g/kg/day (10.59 vs. 15.37, p < 0.0001 and in g/day (23.66 vs. 31.27, p = 0.0001 was slower in the ALHMF group, on increased mean cal/kg/day (128.7 vs. 117.3, p = 0.13 with nearly twice as many infants on the ALHMF requiring increased fortification of enteral feedings beyond 24 cal/ounce to promote adequate growth (48% vs. 26%, p = 0.10. Although we were not powered to study NEC as a primary outcome, NEC was significantly increased in the ALHMF group. (13% vs. 0%, p = 0.03. Use of a LHMF in an unrestricted NICU population resulted in an increase in clinical complications within a high

  8. In vitro studies of human lung carcinogenesis.

    Science.gov (United States)

    Harris, C C; Lechner, J F; Yoakum, G H; Amstad, P; Korba, B E; Gabrielson, E; Grafstrom, R; Shamsuddin, A; Trump, B F

    1985-01-01

    Advances in the methodology to culture normal human lung cells have provided opportunities to investigate fundamental problems in biomedical research, including the mechanism(s) of carcinogenesis. Using the strategy schematically shown in Figure 1, we have initiated studies of the effects of carcinogens on the normal progenitor cells of the human cancers caused by these carcinogens. Extended lifespans and aneuploidy were found after exposure of mesothelial cells to asbestos and bronchial epithelial cells to nickel sulfate. These abnormal cells may be considered to be preneoplastic and at an intermediate position in the multistage process of carcinogenesis. Human bronchial epithelial cells can also be employed to investigate the role of specific oncogenes in carcinogenesis and tumor progression. Using the protoplast fusion method for high frequency gene transfection, vHa-ras oncogene initiates a cascade of events in the normal human bronchial cells leading to their apparent immortality, aneuploidy, and tumorigenicity in athymic nude mice. These results suggest that oncogenes may play an important role in human carcinogenesis.

  9. Clinical feasibility studies with newly devised instruments

    International Nuclear Information System (INIS)

    Cooper, M.

    1980-01-01

    This report summarizes work done in the production of C-11-labelled amino acids. The goals of this work are to minimize synthesis and purification times, to maximize reproducibility and to increase the radiochemical yield so that these tracers can be used clinically

  10. An Evaluative Study of Clinical Preceptorship.

    Science.gov (United States)

    Kaviani, Nayer; Stillwell, Yvonne

    2000-01-01

    A training institute to prepare nurses to serve as preceptors of undergraduate clinical experience was evaluated by focus groups of 6 preceptors, 13 students, and 2 nurse managers. Formal preceptorship training enhanced student learning and promoted positive relationships between nurse educators and practitioners. (SK)

  11. Double Shell Tank (DST) Human Factors Study

    International Nuclear Information System (INIS)

    CHAFFEE, G.A.

    1994-01-01

    This report documents the data collection and analyses that were performed in development of material to be used in the Human Factors chapter for the upgrade to the Safety Analysis Report (SAR) for the Double-Shell Tank Farms (DSTF). This study was conducted to collect the data that is necessary to prepare the Human Factors chapter for the upgrade of the SAR for the DSTF. Requirements for the HF chapter of the SAR generally dictate that the facility management describe how the consideration of operator capabilities and limitations and operating experience are used in ensuring the safe and effective operation of the facility. Additionally, analysis to indicate the contribution of human error to the safety basis accidents or events must be reported. Since the DSTF is a mature operating facility and the requirement to prepare a HF chapter is new, it was not expected that the consideration of HF principles would be an explicit part of DSTF operations. It can be expected, however, that the programs that guide the daily operations at the DSTF contain provisions for the consideration of the needs of their operating personnel and lessons learned from prior experience. Consideration of both the SAR requirements and the nature of the DSTF operations led to the following objectives being defined for the study: (1) to identify the programs at the OSTF where human performance may be considered; (2) to describe how HF principles and operating experience are used to ensure safe and reliable human performance at the DSTF; (3) to describe how HF principles and operating experience are considered as modifications or improvements are made at the DSTF; and (4) to perform task analysis sufficient to understand the potential for human error in OSTF operations

  12. METHODOLOGICAL APPROACHES TO EXPERT EVALUATION OF PRECLINICAL AND CLINICAL TRIALS OF HUMAN IMMUNOGLOBULIN PRODUCTS

    Directory of Open Access Journals (Sweden)

    V. B. Ivanov

    2017-01-01

    Full Text Available The article considers the experience of Russian and leading foreign regulatory agencies in organisation and conduction of preclinical and clinical trials of human immunoglobulin products. The authors suggest a classification of human immunoglobulins and provide updated information on authorization of these products in Russia. The article summarizes methodological approaches, basic scientific principles and criteria relating to expert evaluation of preclinical and clinical trials of blood products. The authors further define the expert body’s requirements for data on preclinical and clinical trials of human normal immuniglobulins and human specific immunoglobulins for the prevention and/or treatment of infectious and non-infectious diseases which are submitted as part of applications for marketing authorization or marketing authorization variation. The article suggests programs of preclinical and clinical trials for human normal immunoglobulins and human specific immunoglobulins for the prevention and/or treatment of infectious and non-infectious diseases that are aligned with the Russian legislation and Eurasian Economic Union’s regulations on medicines circulation, and have been elaborated with respect to the guidelines of the European Medicines Agency.

  13. Using Clinical Gait Case Studies to Enhance Learning in Biomechanics

    Science.gov (United States)

    Chester, Victoria

    2011-01-01

    Clinical case studies facilitate the development of clinical reasoning strategies through knowledge and integration of the basic sciences. Case studies have been shown to be more effective in developing problem-solving abilities than the traditional lecture format. To enhance the learning experiences of students in biomechanics, clinical case…

  14. The human immune response to streptococcal extracellular antigens: clinical, diagnostic, and potential pathogenetic implications.

    Science.gov (United States)

    Johnson, Dwight R; Kurlan, Roger; Leckman, James; Kaplan, Edward L

    2010-02-15

    Determination of an immune response to group A Streptococcus (GAS) antigens, frequently anti-streptolysin O and anti-DNase B, is crucial for documentation of bona fide GAS infection. Although the importance of immunologic confirmation of infection is widely accepted, the immediate and long-term immunokinetics of the human antibody response are incompletely documented and poorly understood. Pediatric study participants (n = 160) were followed during a 2-year study with monthly throat cultures (n = 3491) and blood samples (n = 1679) obtained every 13 weeks. Recovered GAS were characterized; serum anti-streptolysin O and anti-DNase B antibody titers were determined. Antibody titers and GAS culture results were temporally correlated and analyzed. The analyses clearly document, in some instances for the first time, that an increase in antibody titer more accurately defines infection than does an absolute titer (eg, "upper limit of normal"), that antibody titers can remain elevated for many months even without GAS, and that some individuals may harbor GAS continuously for months or years without symptoms of infection and without an associated immune response. Measuring 2 different antibodies is more accurate in defining infection. Single time-point cultures and single antibody titers are often misleading. Sequential samples more accurately define infection, allowing correlation of titer increases with temporal confirmation of GAS acquisition. Understanding kinetics of the immune response(s) to GAS infection is necessary in formulating accurate clinical diagnostic conclusions, to appropriate design of clinical and epidemiological studies examining the association of GAS with subsequent sequelae, and to providing insight into pathogenetic mechanisms associated with this important human pathogen.

  15. Variability in anatomical features of human clavicle: Its forensic anthropological and clinical significance

    Directory of Open Access Journals (Sweden)

    Jagmahender Singh Sehrawat

    2016-06-01

    Full Text Available Bones can reflect the basic framework of human body and may provide valuable information about the biological identity of the deceased. They, often, survive the morphological alterations, taphonomic destructions, decay/mutilation and decomposition insults. In-depth knowledge of variations in clavicular shape, size and its dimensions is very important from both clinical (fixation of clavicular fractures using external or inter-medullary devices, designing orthopedic fixation devices as well as forensic anthropological perspectives. Human clavicle is the most frequently fractured bone of human skeleton, possessing high degree of variability in its anatomical, biomechanical and morphological features. Extended period of skeletal growth (up to third decade in clavicle imparts it an additional advantage for forensic identification purposes. In present study, five categories of clavicular features like lengths, diameters, angles, indices and robustness were examined to explore the suitability of collarbone for forensic and clinical purposes. For this purpose, 263 pairs of adult clavicles (195 Males and 68 Females were collected from autopsied cadavers and were studied for 13 anatomical features. Gender and occupational affiliations of cadavers were found to have significant influences on anatomical dimensions of their clavicles. Product index, weight and circumference of collarbone were found the best univariate variables, discriminating sex of more than 80% individuals. The best multivariate Function-I (DF: -17.315 + 0.054 CL-L+0.196 CC-R+0.184 DM-L could identify sex and occupation of 89.4% (89.2% Male and 89.7% Female and 65.4% individuals, respectively. All clavicular variables were found bilaterally asymmetric; left clavicles being significantly longer in length, lighter in weight, smooth in texture and less curved than the right side bones. Among non-metric traits, sub-clavian groove, nutrient foramina and ‘type’ of clavicle exhibited

  16. Human eye modelling for ophthalmic simulators project for clinic applications

    International Nuclear Information System (INIS)

    Sanchez, Andrea; Santos, Adimir dos; Yoriyaz, Helio

    2002-01-01

    Most of eye tumors are treated by surgical means, which involves the enucleation of affected eyes. In terms of treatment and control of diseases, there is brachytherapy, which often utilizes small applicator of Co-60, I-125, Ru-106, Ir-192, etc. These methods are shown to be very efficient but highly cost. The objective of this work is propose a detailed simulator modelling for eye characterization. Additionally, this study can contribute to design and build a new applicator in order to reduce the cost and to allow more patients to be treated

  17. Clinical application of human serum apolipoprotein B ria

    International Nuclear Information System (INIS)

    He Rongxia

    1988-01-01

    The serum apolipoprotein B (Apo B) was measured in 89 normal subjects with radioimmunoassay method established by the authors, among them 50 patients with coronary heart disease (CHD), 19 patients with cerebrae-vascular accident (CVA) and 46 patients with hyperlipemia. Meanwhile the serum cholesterol and triglyceride were also measured. Although cholesterol, triglyceride, and Apo B levels in disease groups were all significantly higher than control group, there are more overlap between the control and disease group for cholesterol and triglyceride. The Apo B level was 723.9 +- 195.9 mg/L in control group, 1097 +- 236.0 mg/L in CHD group and in CVA group, and this difference was highly significant (P < 0.001). Besides, less overlap of the Apo B value between disease and countrol group was observed in both disease groups. When the Apo B was used as single parameter for the diagnosis CHD, the accuracy rate reached 82%. The results of this study indicated that measurement of Apo B can offer important prediction for coronary artery disease, especially in those having normal levels of plasma cholesterol. In conclusion, the study of apolipoprotein is more significant than lipid component in discriminating between atherosclerotic patients and normal persons

  18. A radiopharmacological study without human radiation exposure

    International Nuclear Information System (INIS)

    Loew, D.; Graul, E.H.; Kunkel, R.

    1984-01-01

    The development, study and control of new drugs today is hardly conceivable without nuclear medicine studies. Nuclear physicians on ethical commissions bear great responsibility in the planning and execution of such studies. In order to protect subjects and patients those nuclear techniques are therefore to be welcome which do not include exposure to radiation. Nuclear techniques used in in-vitro diagnostics (RIA) and the determination of naturally occurring nuclides incorporated in the human body belong to this category. With the aid of a clinico-pharmacological study of a new combination of diuretics it is shown that both methods supply valuable pharmacodynamic evidence. (orig.) [de

  19. Validation of In Vitro Cell-Based Human Blood-Brain Barrier Model Using Clinical Positron Emission Tomography Radioligands To Predict In Vivo Human Brain Penetration

    International Nuclear Information System (INIS)

    Mabondzo, A.; Guyot, A.C.; Bottlaender, M.; Deverre, J.R.; Tsaouin, K.; Balimane, P.V.

    2010-01-01

    We have evaluated a novel in vitro cell-based human blood-brain barrier (BBB) model that could predict in vivo human brain penetration for compounds with different BBB permeabilities using the clinical positron emission tomography (PET) data. Comparison studies were also performed to demonstrate that the in vitro cell-based human BBB model resulted in better predictivity over the traditional permeability model in discovery organizations, Caco-2 cells. We evaluated the in vivo BBB permeability of [ 18 F] and [ 11 C]-compounds in humans by PET imaging. The in vivo plasma-brain exchange parameters used for comparison were determined in humans by PET using a kinetic analysis of the radiotracer binding. For each radiotracer, the parameters were determined by fitting the brain kinetics of the radiotracer using a two-tissue compartment model of the ligand-receptor interaction. Bidirectional transport studies with the same compounds as in in vivo studies were carried out using the in vitro cell-based human BBB model as well as Caco-2 cells. The in vitro cell-based human BBB model has important features of the BBB in vivo and is suitable for discriminating between CNS and non-CNS marketed drugs. A very good correlation (r 2 =0.90; P≤0.001) was demonstrated between in vitro BBB permeability and in vivo permeability coefficient. In contrast, a poor correlation (r 2 = 0.17) was obtained between Caco-2 data and in vivo human brain penetration. This study highlights the potential of this in vitro cell-based human BBB model in drug discovery and shows that it can be an extremely effective screening tool for CNS programs. (authors)

  20. Abnormal neuronal migration: radiologic-clinic study

    International Nuclear Information System (INIS)

    Martinez Fernandez, M.; Menor Serrano, F.; Bordon Ferre, F.; Garcia Tena, J.; Esteban Hernandez, E.; Sanguesa Nebot, C.; Marti Bonnati, L.

    1994-01-01

    We present our experience in 18 pediatric patients with abnormal neuronal migration. Seven cases of heterotopia of the gray matter, 7 agyria-pachygyria complexes, 1 case of polymicrogyria, 2 cases of schizencephaly and 1 case of hemimegalencephaly were diagnosed by means of ultrasonography, computed tomography and magnetic resonance. The clinical picture was reviewed in each case, with special attention to the occurrence of convulsions, psycho motor development and visual changes. In general, the greater the morphological change, the greater the neurological involvement in these patients. However, the two cases of schizencephaly presented mild clinical expression. Magnetic resonance increases the diagnostic yield in neuronal migration disorders. Nevertheless, either ultrasonography or, especially, computed tomography is useful as a first diagnostic approach in these malformative disorders. (Author)

  1. Clinical experimental stress studies: methods and assessment.

    Science.gov (United States)

    Bali, Anjana; Jaggi, Amteshwar Singh

    2015-01-01

    Stress is a state of threatened homeostasis during which a variety of adaptive processes are activated to produce physiological and behavioral changes. Stress induction methods are pivotal for understanding these physiological or pathophysiological changes in the body in response to stress. Furthermore, these methods are also important for the development of novel pharmacological agents for stress management. The well-described methods to induce stress in humans include the cold pressor test, Trier Social Stress Test, Montreal Imaging Stress Task, Maastricht Acute Stress Test, CO2 challenge test, Stroop test, Paced Auditory Serial Addition Task, noise stress, and Mannheim Multicomponent Stress Test. Stress assessment in humans is done by measuring biochemical markers such as cortisol, cortisol awakening response, dexamethasone suppression test, salivary α-amylase, plasma/urinary norepinephrine, norepinephrine spillover rate, and interleukins. Physiological and behavioral changes such as galvanic skin response, heart rate variability, pupil size, and muscle and/or skin sympathetic nerve activity (microneurography) and cardiovascular parameters such as heart rate, blood pressure, and self-reported anxiety are also monitored to assess stress response. This present review describes these commonly employed methods to induce stress in humans along with stress assessment methods.

  2. On-site preparation of technetium-99m labeled human serum albumin for clinical application

    International Nuclear Information System (INIS)

    Wang Yuhfeng; Chuang Meihua; Cham Thauming; Chung Meiing; Chiu Jainnshiun

    2007-01-01

    Technetium-99m labeled human serum albumin (Tc-99m HSA) is an important radiopharmaceutical for clinical applications, such as cardiac function tests or protein-losing gastroenteropathy assessment. However, because of transfusion-induced infectious diseases, the safety of serum products is a serious concern. In this context, serum products acquired from patients themselves are the most ideal tracer. However, the development of rapid separation and easy clinical labeling methods is not yet well established. Under such situation, products from the same ethnic group or country are now recommended by the World Health Organization as an alternative preparation. This article describes the on-site preparation of Tc-99m HSA from locally supplied serum products. Different formulations were prepared and the labeling efficiency and stability were examined. Radio-labeling efficiencies were more than 90% in all preparation protocols, except for one that omitted the stannous solution. The most cost-effective protocol contained HSA 0.1 mg, treated with stannous fluoride 0.2 mg, and mixed with Tc-99m pertechnetate 30 mCi. A biodistribution study was performed in rats using a gamma camera immediately after intravenous administration of radiolabeled HSA. Tissue/organ uptake was obtained by measuring the radioactivity in organs after sacrificing the rats at timed intervals. The biologic half-life was about 32 min, determined from sequential venous blood collections. These data indicate that our preparation of Tc-99m HSA is useful and potentially applicable clinically. In addition, this on-site preparation provides the possibility of labeling a patient's own serum for subsequent clinical application. (author)

  3. Clinical usefulness of human-mouse chimeric Fab monoclonal antibody A7 for radioimmunoguided surgery

    International Nuclear Information System (INIS)

    Yamamoto, Kazuhito

    1999-01-01

    This study was designed to determine the clinical usefulness of radioimmunoguided surgery (RIGS) using the human-mouse chimeric Fab monoclonal antibody A7 (chA7Fab) for colorectal cancer patients. Whole murine monoclonal antibody A7 (whole A7) and chA7Fab were labelled with 125 I and 131 I, and their biodistributions were investigated experimentally and clinically. Radioactivities of the antibodies in the tissues were measured by a portable gamma detecting probe (GDP) purchased from Neoprobe Corp.. Of the four labelled antibodies used in a mouse model, 125 I-chA7Fab revealed the highest tumor/surrounding tissue ratio and all values were greater than 2.0. All tumor/surrounding tissue ratios of 131 I-chA7Fab were greater than 1.5, but the values were lower than those of 125 I-chA7Fab. Due to the limited clinical use of 125 I in Japan, 131 I was used as a radio-tracer for chA7Fab in the clinical trial. RIGS using 131 I-chA7Fab was performed on ten colorectal cancer patients. Tumor localization was intraoperatively determined in four of ten patients using the GDP. Liver metastasis and lymph node metastasis were identified in two patients and one patient, respectively. The GDP revealed tumor/surrounding tissue ratios of 1.5 or greater in eight of the ten resected tumors. Although radioimmunoguided surgery using chA7Fab is a promising tool to intraoperatively determine the tumor localization of colorectal cancer, 125 I and not 131 I should be used as a tracer for radioimmunoguided surgery to increase the accuracy of chA7Fab. (author)

  4. [Organizational ethics: a study in ophthalmologic clinics].

    Science.gov (United States)

    Sanches, Maria Aparecida; Scarpi, Marinho Jorge

    2005-01-01

    Research on the field of organizational ethics to investigate to which extent ophthalmologic clinics, inserted in the competitive atmosphere, in the condition of organizations in search of survival, subordinate ethics to competitiveness in the managerial praxis, that is, in the administrative sphere. Kohlberg is taken as theoretical reference, approaching the theme of ethical subordination to competitiveness. The instrument to evaluate moral behaviors of organizations, elaborated by Licht, is applied. The quantitative method is used, adopting analytic instruments, such as Q of Yule and non parametric tests, when dealing with the data of 41 ophthalmologic clinics. The results of the research seem to indicate that administrators of ophthalmologic clinics of greater performance subordinate ethical principles to competitiveness, seeking to assure the survival of the company and, when confronted with the instrument to evaluate their moral behavior, proposed by Kohlberg, have a significantly smaller presence in the postconventional stage than administrators of ophthalmologic clinics with a smaller performance. One may affirm, according to non parametric tests, at the level of significance of 0.05, that the levels of moral development of the two groups differ significantly. The obtained results are according to the literature, especially concerning the "paradox of the ethical subordination and competitiveness". They also suggest that the warrant of the survival of the company tends to reduce the perception of the groups in power regarding the problems that happen in the community, and that a reduction of the ethical values subordinated to competition occurs, and such reduction provokes growing feelings of economical disputes in the social sphere.

  5. Celiac Patients: A Randomized, Controlled Clinical Study

    Directory of Open Access Journals (Sweden)

    Giuseppe Mazzarella

    2012-01-01

    Full Text Available A lifelong gluten-free diet (GFD is mandatory for celiac disease (CD but has poor compliance, justifying novel strategies. We found that wheat flour transamidation inhibited IFN-γ secretion by intestinal T cells from CD patients. Herein, the primary endpoint was to evaluate the ability of transamidated gluten to maintain GFD CD patients in clinical remission. Secondary endpoints were efficacy in prevention of the inflammatory response and safety at the kidney level, where reaction products are metabolized. In a randomized single blinded, controlled 90-day trial, 47 GFD CD patients received 3.7 g/day of gluten from nontransamidated (12 or transamidated (35 flour. On day 15, 75% and 37% of patients in the control and experimental groups, respectively, showed clinical relapse (=0.04 whereas intestinal permeability was mainly altered in the control group (50% versus 20%, =0.06. On day 90, 0 controls and 14 patients in the experimental group completed the challenge with no variation of antitransglutaminase IgA (=0.63, Marsh-Oberhuber grading (=0.08, or intestinal IFN-γ mRNA (>0.05. Creatinine clearance did not vary after 90 days of treatment (=0.46. In conclusion, transamidated gluten reduced the number of clinical relapses in challenged patients with no changes of baseline values for serological/mucosal CD markers and an unaltered kidney function.

  6. Development and validation of a high-performance liquid chromatography-tandem mass spectrometry method for the simultaneous determination of irinotecan and its main metabolites in human plasma and its application in a clinical pharmacokinetic study.

    Directory of Open Access Journals (Sweden)

    Elena Marangon

    Full Text Available Irinotecan is currently used in several cancer regimens mainly in colorectal cancer (CRC. This drug has a narrow therapeutic range and treatment can lead to side effects, mainly neutropenia and diarrhea, frequently requiring discontinuing or lowering the drug dose. A wide inter-individual variability in irinotecan pharmacokinetic parameters and pharmacodynamics has been reported and associated to patients' genetic background. In particular, a polymorphism in the UGT1A1 gene (UGT1A1*28 has been linked to an impaired detoxification of SN-38 (irinotecan active metabolite to SN-38 glucuronide (SN-38G leading to increased toxicities. Therefore, therapeutic drug monitoring of irinotecan, SN-38 and SN-38G is recommended to personalize therapy. In order to quantify simultaneously irinotecan and its main metabolites in patients' plasma, we developed and validated a new, sensitive and specific HPLC-MS/MS method applicable to all irinotecan dosages used in clinic. This method required a small plasma volume, addition of camptothecin as internal standard and simple protein precipitation. Chromatographic separation was done on a Gemini C18 column (3 μM, 100 mm x 2.0 mm using 0.1% acetic acid/bidistilled water and 0.1% acetic acid/acetonitrile as mobile phases. The mass spectrometer worked with electrospray ionization in positive ion mode and selected reaction monitoring. The standard curves were linear (R2 ≥0.9962 over the concentration ranges (10-10000 ng/mL for irinotecan, 1-500 ng/mL for SN-38 and SN-38G and 1-5000 ng/mL for APC and had good back-calculated accuracy and precision. The intra- and inter-day precision and accuracy, determined on three quality control levels for all the analytes, were always <12.3% and between 89.4% and 113.0%, respectively. Moreover, we evaluated this bioanalytical method by re-analysis of incurred samples as an additional measure of assay reproducibility. This method was successfully applied to a pharmacokinetic study in

  7. A Comparative Study of Human Saposins

    Directory of Open Access Journals (Sweden)

    María Garrido-Arandia

    2018-02-01

    Full Text Available Saposins are small proteins implicated in trafficking and loading of lipids onto Cluster of Differentiation 1 (CD1 receptor proteins that in turn present lipid antigens to T cells and a variety of T-cell receptors, thus playing a crucial role in innate and adaptive immune responses in humans. Despite their low sequence identity, the four types of human saposins share a similar folding pattern consisting of four helices linked by three conserved disulfide bridges. However, their lipid-binding abilities as well as their activities in extracting, transporting and loading onto CD1 molecules a variety of sphingo- and phospholipids in biological membranes display two striking characteristics: a strong pH-dependence and a structural change between a compact, closed conformation and an open conformation. In this work, we present a comparative computational study of structural, electrostatic, and dynamic features of human saposins based upon their available experimental structures. By means of structural alignments, surface analyses, calculation of pH-dependent protonation states, Poisson-Boltzmann electrostatic potentials, and molecular dynamics simulations at three pH values representative of biological media where saposins fulfill their function, our results shed light into their intrinsic features. The similarities and differences in this class of proteins depend on tiny variations of local structural details that allow saposins to be key players in triggering responses in the human immune system.

  8. A new high-performance liquid chromatography-tandem mass spectrometry method for the determination of paclitaxel and 6α-hydroxy-paclitaxel in human plasma: Development, validation and application in a clinical pharmacokinetic study.

    Directory of Open Access Journals (Sweden)

    Bianca Posocco

    Full Text Available Paclitaxel belongs to the taxanes family and it is used, alone or in multidrug regimens, for the therapy of several solid tumours, such as breast-, lung-, head and neck-, and ovarian cancer. Standard dosing of chemotherapy does not take into account the many inter-patient differences that make drug exposure highly variable, thus leading to the insurgence of severe toxicity. This is particularly true for paclitaxel considering that a relationship between haematological toxicity and plasma exposure was found. Therefore, in order to treat patients with the correct dose of paclitaxel, improving the overall benefit-risk ratio, Therapeutic Drug Monitoring is necessary. In order to quantify paclitaxel and its main metabolite, 6α-hydroxy-paclitaxel, in patients' plasma, we developed a new, sensitive and specific HPLC-MS/MS method applicable to all paclitaxel dosages used in clinical routine. The developed method used a small volume of plasma sample and is based on quick protein precipitation. The chromatographic separation of the analytes was achieved with a SunFire™ C18 column (3.5 μM, 92 Å, 2,1 x 150 mm; the mobile phases were 0.1% formic acid/bidistilled water and 0.1% formic acid/acetonitrile. The electrospray ionization source worked in positive ion mode and the mass spectrometer operated in selected reaction monitoring mode. Our bioanalytical method was successfully validated according to the FDA-EMA guidelines on bioanalytical method validation. The calibration curves resulted linear (R2 ≥0.9948 over the concentration ranges (1-10000 ng/mL for paclitaxel and 1-1000 ng/mL for 6α-hydroxy-paclitaxel and were characterized by a good accuracy and precision. The intra- and inter-day precision and accuracy were determined on three quality control concentrations for paclitaxel and 6α-hydroxy-paclitaxel and resulted respectively <9.9% and within 91.1-114.8%. In addition, to further verify the assay reproducibility, we tested this method by re

  9. 77 FR 14531 - Proposed Collection; Comment Request; Web-Based Assessment of the NHLBI Clinical Studies Support...

    Science.gov (United States)

    2012-03-12

    ... (PRCs) have become an important quality standard in clinical trials and research involving human... study protocols developed under NHLBI funded Clinical Trial Networks. These committees are composed of... research areas. The NHLBI is charged with ensuring the highest quality of each Institute-funded clinical...

  10. Black tea: Phytochemicals, cancer chemoprevention, and clinical studies.

    Science.gov (United States)

    Singh, Brahma N; Rawat, A K S; Bhagat, R M; Singh, B R

    2017-05-03

    Tea (Camellia sinensis L.) is the most popular, flavored, functional, and therapeutic non-alcoholic drink consumed by two-thirds of the world's population. Black tea leaves are reported to contain thousands of bioactive constituents such as polyphenols, amino acids, volatile compounds, and alkaloids that exhibit a range of promising pharmacological properties. Due to strong antioxidant property, black tea inhibits the development of various cancers by regulating oxidative damage of biomolecules, endogenous antioxidants, and pathways of mutagen and transcription of antioxidant gene pool. Regular drinking of phytochemicals-rich black tea is linked to regulate several molecular targets, including COX-2, 5-LOX, AP-1, JNK, STAT, EGFR, AKT, Bcl2, NF-κB, Bcl-xL, caspases, p53, FOXO1, TNFα, PARP, and MAPK, which may be the basis of how dose of black tea prevents and cures cancer. In vitro and preclinical studies support the anti-cancer activity of black tea; however, its effect in human trails is uncertain, although more clinical experiments are needed at molecular levels to understand its anti-cancer property. This review discusses the current knowledge on phytochemistry, chemopreventive activity, and clinical applications of black tea to reveal its anti-cancer effect.

  11. Clinical evaluation of the radiolanthanide terbium-152: first-in-human PET/CT with 152Tb-DOTATOC.

    Science.gov (United States)

    Baum, Richard P; Singh, Aviral; Benešová, Martina; Vermeulen, Christiaan; Gnesin, Silvano; Köster, Ulli; Johnston, Karl; Müller, Dirk; Senftleben, Stefan; Kulkarni, Harshad R; Türler, Andreas; Schibli, Roger; Prior, John O; van der Meulen, Nicholas P; Müller, Cristina

    2017-10-31

    The existence of theragnostic pairs of radionuclides allows the preparation of radiopharmaceuticals for diagnostic and therapeutic purposes. Radiolanthanides, such as 177 Lu, are successfully used for therapeutic purposes; however, a perfect diagnostic match is currently not available for clinical use. A unique, multi-disciplinary study was performed using 152 Tb (T 1/2 = 17.5 h, Eβ + average = 1140 keV, Iβ + = 20.3%), which resulted in the first-in-human PET/CT images with this promising radionuclide. For this purpose, 152 Tb was produced via a spallation process followed by mass separation at ISOLDE, CERN. The chemical separation and quality control, performed at PSI, resulted in a pure product in sufficient yields. Clinical PET phantom studies revealed an increased image noise level, because of the smaller β + branching ratio of 152 Tb as compared to standard PET nuclides at matched activity concentrations; however, the expected recovery would be comparable at matched signal-to-noise ratios in clinical PET. 152 Tb was used for labeling DOTATOC, at Zentralklinik Bad Berka, and administered to a patient for a first-in-human clinical study. PET scans were performed over a period of 24 h, allowing the visualization of even small metastases with increased tumor-to-background contrast over time. Based on the results obtained in this work, it can be deduced that PET/CT imaging with 152 Tb-labeled targeting agents has promise for clinical application and may be particularly interesting for pre-therapeutic dosimetry.

  12. Studies in human skin epithelial cell carcinogenesis

    International Nuclear Information System (INIS)

    Lehman, T.A.

    1987-01-01

    Metabolism and DNA adduct formation of benzo[a]pyrene (BP) by human epidermal keratinocytes pretreated with inhibitors or inducer of cytochrame P450 was studied. To study DNA adduct analysis, cultures were pretreated as described above, and then treated with non-radiolabeled BP. DNA was prepared from these cultures, digested to the nucleotide level, and 32 P-postlabeled for adduct analysis. Cultures pretreated with BHA, 7,8-BF or disulfiralm formed significantly fewer BPDE I-dB adducts than non-pretreated cultures, while cultures pretreated with MeBHA formed more BPDE-I-dG adducts. MeBHA increased BP activation and adduct formation inhuman keratinocyte in cultures by inducing a specific isoenzyme of cytochrome P450 which preferentially increases the oxidative metabolism of BP to 7,8 diol BP and 7,8 diol BP to BPDE I. To approximate an in vivo human system, metabolism of BPDE I by human skin xenografts treated with cell cycles modulators was studied. When treated with BPDE I, specific carcinogen-DNA adducts were formed. Separation and identification of these adducts by the 32 P-postlabeling technique indicated that the 7R- and 7S-BPDE I-dG adducts were the major adducts

  13. Noninvasive studies of human visual cortex using neuromagnetic techniques

    International Nuclear Information System (INIS)

    Aine, C.J.; George, J.S.; Supek, S.; Maclin, E.L.

    1990-01-01

    The major goals of noninvasive studies of the human visual cortex are: to increase knowledge of the functional organization of cortical visual pathways; and to develop noninvasive clinical tests for the assessment of cortical function. Noninvasive techniques suitable for studies of the structure and function of human visual cortex include magnetic resonance imaging (MRI), positron emission tomography (PET), single photon emission tomography (SPECT), scalp recorded event-related potentials (ERPs), and event-related magnetic fields (ERFs). The primary challenge faced by noninvasive functional measures is to optimize the spatial and temporal resolution of the measurement and analytic techniques in order to effectively characterize the spatial and temporal variations in patterns of neuronal activity. In this paper we review the use of neuromagnetic techniques for this purpose. 8 refs., 3 figs

  14. Cardioprotective effects of cocoa: clinical evidence from randomized clinical intervention trials in humans.

    Science.gov (United States)

    Arranz, Sara; Valderas-Martinez, Palmira; Chiva-Blanch, Gemma; Casas, Rosa; Urpi-Sarda, Mireia; Lamuela-Raventos, Rosa M; Estruch, Ramon

    2013-06-01

    Cocoa is an important source of polyphenols, which comprise 12-18% of its total dry weight. The major phenolic compounds in cocoa and cocoa products are mainly flavonoids such as epicatechin, catechin, and proanthocyanidins. These products contain higher amounts of flavonoids than other polyphenol-rich foods. However, the bioavailability of these compounds depends on other food constituents and their interactions with the food matrix. Many epidemiological and clinical intervention trials have concluded that the ingestion of flavonoids reduces the risk factors of developing cardiovascular disease. This review summarizes the new findings regarding the effects of cocoa and chocolate consumption on cardiovascular risk factors. The mechanisms involved in the cardioprotective effects of cocoa flavonoids include reduction of oxidative stress, inhibition of low-density lipoproteins oxidation and platelet aggregation, vasodilatation of blood vessels, inhibition of the adherence of monocytes to vascular endothelium, promotion of fibrinolysis, and immunomodulatory and anti-inflammatory activity. Scientific evidence supports a cause and effect relationship between consumption of cocoa flavonoids and the maintenance of normal endothelium-dependent vasodilation, which contributes to normal blood flow. However, larger randomized trials are required to definitively establish the impact of cocoa and cocoa products consumption on hard cardiovascular outcomes. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Occurance of Staphylococcus nepalensis strains in different sources including human clinical material.

    Science.gov (United States)

    Nováková, Dana; Pantůcek, Roman; Petrás, Petr; Koukalová, Dagmar; Sedlácek, Ivo

    2006-10-01

    Five isolates of coagulase-negative staphylococci were obtained from human urine, the gastrointestinal tract of squirrel monkeys, pig skin and from the environment. All key biochemical characteristics of the tested strains corresponded with the description of Staphylococcus xylosus species. However, partial 16S rRNA gene sequences obtained from analysed strains corresponded with those of Staphylococcus nepalensis reference strains, except for two strains which differed in one residue. Ribotyping with EcoRI and HindIII restriction enzymes, whole cell protein profile analysis performed by SDS-PAGE and SmaI macrorestriction analysis were used for more precise characterization and identification of the analysed strains. Obtained results showed that EcoRI and HindIII ribotyping and whole cell protein fingerprinting are suitable and reliable methods for the differentiation of S. nepalensis strains from the other novobiocin resistant staphylococci, whereas macrorestriction analysis was found to be a good tool for strain typing. The isolation of S. nepalensis is sporadic, and according to our best knowledge this study is the first report of the occurrence of this species in human clinical material as well as in other sources.

  16. Liver afferents contribute to water drinking-induced sympathetic activation in human subjects: a clinical trial.

    Directory of Open Access Journals (Sweden)

    Marcus May

    Full Text Available Water drinking acutely increases sympathetic activity in human subjects. In animals, the response appears to be mediated through transient receptor potential channel TRPV4 activation on osmosensitive hepatic spinal afferents, described as osmopressor response. We hypothesized that hepatic denervation attenuates water drinking-induced sympathetic activation. We studied 20 liver transplant recipients (44±2.6 years, 1.2±0.1 years post transplant as model of hepatic denervation and 20 kidney transplant recipients (43±2.6 years, 0.8±0.1 years post transplant as immunosuppressive drug matched control group. Before and after 500 ml water ingestion, we obtained venous blood samples for catecholamine analysis. We also monitored brachial and finger blood pressure, ECG, and thoracic bioimpedance. Plasma norepinephrine concentration had changed by 0.01±0.07 nmol/l in liver and by 0.21±0.07 nmol/l in kidney transplant recipients (p<0.05 between groups after 30-40 minutes of water drinking. While blood pressure and systemic vascular resistance increased in both groups, the responses tended to be attenuated in liver transplant recipients. Our findings support the idea that osmosensitive hepatic afferents are involved in water drinking-induced sympathetic activation in human subjects.ClinicalTrials.gov NCT01237431.

  17. Liver Afferents Contribute to Water Drinking-Induced Sympathetic Activation in Human Subjects: A Clinical Trial

    Science.gov (United States)

    May, Marcus; Gueler, Faikah; Barg-Hock, Hannelore; Heiringhoff, Karl-Heinz; Engeli, Stefan; Heusser, Karsten; Diedrich, André; Brandt, André; Strassburg, Christian P.; Tank, Jens; Sweep, Fred C. G. J.; Jordan, Jens

    2011-01-01

    Water drinking acutely increases sympathetic activity in human subjects. In animals, the response appears to be mediated through transient receptor potential channel TRPV4 activation on osmosensitive hepatic spinal afferents, described as osmopressor response. We hypothesized that hepatic denervation attenuates water drinking-induced sympathetic activation. We studied 20 liver transplant recipients (44±2.6 years, 1.2±0.1 years post transplant) as model of hepatic denervation and 20 kidney transplant recipients (43±2.6 years, 0.8±0.1 years post transplant) as immunosuppressive drug matched control group. Before and after 500 ml water ingestion, we obtained venous blood samples for catecholamine analysis. We also monitored brachial and finger blood pressure, ECG, and thoracic bioimpedance. Plasma norepinephrine concentration had changed by 0.01±0.07 nmol/l in liver and by 0.21±0.07 nmol/l in kidney transplant recipients (pwater drinking. While blood pressure and systemic vascular resistance increased in both groups, the responses tended to be attenuated in liver transplant recipients. Our findings support the idea that osmosensitive hepatic afferents are involved in water drinking-induced sympathetic activation in human subjects. Trial Registration ClinicalTrials.gov NCT01237431 PMID:22016786

  18. Systematic Review and Meta-Analysis of Randomized Clinical Trials in the Treatment of Human Brucellosis

    Science.gov (United States)

    Solís García del Pozo, Julián; Solera, Javier

    2012-01-01

    Background Brucellosis is a persistent health problem in many developing countries throughout the world, and the search for simple and effective treatment continues to be of great importance. Methods and Findings A search was conducted in MEDLINE and in the Cochrane Central Register of Controlled Trials (CENTRAL). Clinical trials published from 1985 to present that assess different antimicrobial regimens in cases of documented acute uncomplicated human brucellosis were included. The primary outcomes were relapse, therapeutic failure, combined variable of relapse and therapeutic failure, and adverse effect rates. A meta-analysis with a fixed effect model was performed and odds ratio with 95% confidence intervals were calculated. A random effect model was used when significant heterogeneity between studies was verified. Comparison of combined doxycycline and rifampicin with a combination of doxycycline and streptomycin favors the latter regimen (OR = 3.17; CI95% = 2.05–4.91). There were no significant differences between combined doxycycline-streptomycin and combined doxycycline-gentamicin (OR = 1.89; CI95% = 0.81–4.39). Treatment with rifampicin and quinolones was similar to combined doxycycline-rifampicin (OR = 1.23; CI95% = 0.63–2.40). Only one study assessed triple therapy with aminoglycoside-doxycycline-rifampicin and only included patients with uncomplicated brucellosis. Thus this approach cannot be considered the therapy of choice until further studies have been performed. Combined doxycycline/co-trimoxazole or doxycycline monotherapy could represent a cost-effective alternative in certain patient groups, and further studies are needed in the future. Conclusions Although the preferred treatment in uncomplicated human brucellosis is doxycycline-aminoglycoside combination, other treatments based on oral regimens or monotherapy should not be rejected until they are better studied. Triple therapy should not be considered the current

  19. Pro-inflammatory cytokine levels in human apical periodontitis: Correlation with clinical and histological findings.

    Science.gov (United States)

    Jakovljevic, Aleksandar; Knezevic, Aleksandra; Karalic, Danijela; Soldatovic, Ivan; Popovic, Branka; Milasin, Jelena; Andric, Miroslav

    2015-08-01

    This study aimed to compare the levels of tumour necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) between apical periodontitis lesions with different clinical and histological features. Based on clinical data and history of disease, 100 human apical periodontitis lesions were categorised as either asymptomatic or symptomatic lesions. According to histological examination, lesions were divided into periapical granulomas and radicular cysts. Pulp tissues of 25 impacted wisdom teeth were used as controls. Homogenised tissue samples were centrifuged and supernatants were used for the determination of cytokine levels by enzyme-linked immunosorbent assay. Significantly higher levels of IL-1β and IL-6 were found in symptomatic lesions compared with asymptomatic lesions and control tissues (P < 0.001, P < 0.001, respectively). The concentration of IL-1β was significantly higher in radicular cysts compared with periapical granulomas (P = 0.003). Symptomatic lesions, as judged by high local production of IL-1β and IL-6, represent an immunologically active stage of the disease. © 2014 Australian Society of Endodontology.

  20. Work, Productivity, and Human Performance: Practical Case Studies in Ergonomics, Human Factors and Human Engineering.

    Science.gov (United States)

    Fraser, T. M.; Pityn, P. J.

    This book contains 12 case histories, each based on a real-life problem, that show how a manager can use common sense, knowledge, and interpersonal skills to solve problems in human performance at work. Each case study describes a worker's problem and provides background information and an assignment; solutions are suggested. The following cases…

  1. Challenges in Evaluating Clinical Governance Systems in Iran: A Qualitative Study

    Science.gov (United States)

    Hooshmand, Elaheh; Tourani, Sogand; Ravaghi, Hamid; Ebrahimipour, Hossein

    2014-01-01

    Background: In spite of the pivotal role of clinical governance in enhancing quality of services provided by hospitals across the country, a scientific framework with specific criteria for evaluating hospitals has not been developed so far. Objectives: This study was conducted with the aim to identify the challenges involved in evaluating systems of clinical governance in Iran. Materials and Methods: For the purposes of this qualitative study, 15 semi-structured interviews with experts in the field were conducted in 2011 and the data were analyzed using framework analysis method. Results: Five major challenges in evaluating clinical governance include managing human resources, improving clinical quality, managing development, organizing clinical governance, and providing patient-oriented healthcare system. Conclusions: Healthcare system in Iran requires a clinical governance program which has a patient-oriented approach in philosophy, operation, and effectiveness in order to meet the challenges ahead. PMID:24910799

  2. The Effect of Learning Styles, Critical Thinking Disposition, and Critical Thinking on Clinical Judgment in Senior Baccalaureate Nursing Students during Human Patient Simulation

    Science.gov (United States)

    McCormick, Kiyan

    2014-01-01

    Simulated learning experiences using high-fidelity human patient simulators (HPS) are increasingly being integrated into baccalaureate nursing programs. Thus, the purpose of this study was to examine relationships among learning style, critical thinking disposition, critical thinking, and clinical judgment during high-fidelity human patient…

  3. Composition and function of macroencapsulated human embryonic stem cell-derived implants: comparison with clinical human islet cell grafts.

    Science.gov (United States)

    Motté, Evi; Szepessy, Edit; Suenens, Krista; Stangé, Geert; Bomans, Myriam; Jacobs-Tulleneers-Thevissen, Daniel; Ling, Zhidong; Kroon, Evert; Pipeleers, Daniel

    2014-11-01

    β-Cells generated from large-scale sources can overcome current shortages in clinical islet cell grafts provided that they adequately respond to metabolic variations. Pancreatic (non)endocrine cells can develop from human embryonic stem (huES) cells following in vitro derivation to pancreatic endoderm (PE) that is subsequently implanted in immune-incompetent mice for further differentiation. Encapsulation of PE increases the proportion of endocrine cells in subcutaneous implants, with enrichment in β-cells when they are placed in TheraCyte-macrodevices and predominantly α-cells when they are alginate-microencapsulated. At posttransplant (PT) weeks 20-30, macroencapsulated huES implants presented higher glucose-responsive plasma C-peptide levels and a lower proinsulin-over-C-peptide ratio than human islet cell implants under the kidney capsule. Their ex vivo analysis showed the presence of single-hormone-positive α- and β-cells that exhibited rapid secretory responses to increasing and decreasing glucose concentrations, similar to isolated human islet cells. However, their insulin secretory amplitude was lower, which was attributed in part to a lower cellular hormone content; it was associated with a lower glucose-induced insulin biosynthesis, but not with lower glucagon-induced stimulation, which together is compatible with an immature functional state of the huES-derived β-cells at PT weeks 20-30. These data support the therapeutic potential of macroencapsulated huES implants but indicate the need for further functional analysis. Their comparison with clinical-grade human islet cell grafts sets references for future development and clinical translation. Copyright © 2014 the American Physiological Society.

  4. Prevalence and clinical symptoms of human metapneumovirus infection in hospitalized patients

    NARCIS (Netherlands)

    B.G. van den Hoogen (Bernadette); G.J.J. van Doornum (Gerard); J.C. Fockens (John); J.J. Cornelissen (Jan); W.E.Ph. Beyer (Walter); R. de Groot (Ronald); A.D.M.E. Osterhaus (Albert); R.A.M. Fouchier (Ron)

    2003-01-01

    textabstractDuring a 17-month period, we performed retrospective analyses of the prevalence of and clinical symptoms associated with human metapneumovirus (hMPV) infection, among patients in a university hospital in The Netherlands. All available nasal-aspirate, throat-swab, sputum, and

  5. Pragmatic trial of an intervention to increase human papillomavirus vaccination in safety-net clinics

    Directory of Open Access Journals (Sweden)

    Maureen Sanderson

    2017-02-01

    Full Text Available Abstract Background Human papillomavirus (HPV infection has been causally linked to six cancers, and many disproportionately affect minorties. This study reports on the development and effectiveness of an intervention aimed at increasing HPV vaccine uptake among African American and Hispanic pediatric patients in safety-net clinics. Methods Formative research, community engagement, and theory guided development of the intervention. A clustered, non-randomized controlled pragmatic trial was conducted in four clinics providing healthcare for the underserved in Tennessee, U.S., with two intervention sites and two usual care sites. Patients aged 9-18 years (N = 408 and their mothers (N = 305 enrolled, with children clustered within families. The intervention consisted of two provider/staff training sessions and provision of patient education materials, consisting of a video/flyer promoting HPV vaccine. Medical records were reviewed before/after the initial visit and after 12 months. Results At the initial visit, provision of patient education materials and provider recommendation were higher at intervention sites versus usual care sites, and receipt of HPV vaccine was higher at intervention sites (45.4% versus 32.9% but not significantly after adjusting for patient’s age and mother’s education. Provider recommendation, but not education materials, increased the likelihood of vaccine receipt at the initial visit, although over one-third of intervention mothers cited the flyer/video as motivating vaccination. Completion of the 3-dose series at follow-up was lower in the intervention arm. Conclusions Future interventions should combine patient education, intensive provider/staff education, and patient reminders. Research should compare patient education focusing on HPV vaccine only versus all adolescent vaccines. Trial registration Retrospectively registered with ClinicalTrials.gov NCT02808832 , 9/12/16

  6. Clinical Features, Presence of Human Herpesvirus-8 and Treatment Results in Classic Kaposi Sarcoma

    Directory of Open Access Journals (Sweden)

    Özlem Su

    2008-12-01

    Full Text Available Background and Design: Classic Kaposi sarcoma (KS occurs predominantly among the elderly, with Jews, Italians and Greeks. Classic KS has been seen relatively frequently in Turkey. Our aim was to evaluate the demographic, clinical features of Kaposi sarcoma and etiopathological role of human herpesvirus-8 (HHV-8. Treatment results of 18 classic Kaposi’s sarcoma were also concluded.Material and Method: Eighteen cases of classic Kaposi sarcoma diagnosed as clinically and histopathologically between January 2001 and August 2008 in our dermatology department were taken to this study. Demographic, clinical features and treatment results were reviewed retrospectively in all patients. HHV-8 was investigated in the lesional skin of 7 patients.Results: A male/female ratio of 2/1 was found. Mean age at diagnosis was 67.2 (37-94 years. Bilaterally lower extremities were involved in 15 patients (83.3%, the trunk was involved in 3 patients (16.6%. Plaques and nodules were the common type of lesions (66.6% and 55.5%. Nine patients had no symptoms (50%. Edema was the most common symptom (38.8%. A second primary malignancy was found in 2 patients (11.1%. HHV-8 was detected in 6 of the 7 patients(85.7%. Majority of the patients were treated with interferon alfa (subcutaneously and cryotherapy as a monotherapy or a combination therapy. Imiquimod was the second agent in combined treatment (27.7%. Conclusion: We suggest that interferon alfa and imiquimod can be used as first line therapy agents with their antiviral and immunmodulatuar features in the treatment of KKS. (Turkderm 2008; 42: 122-6

  7. Frequency and clinical relevance of human bocavirus infection in acute exacerbations of chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Felix C Ringshausen

    2009-02-01

    Full Text Available Felix C Ringshausen1, Ai-Yui M Tan1, Tobias Allander2, Irmgard Borg1, Umut Arinir1, Juliane Kronsbein1, Barbara M Hauptmeier1, Gerhard Schultze-Werninghaus1, Gernot Rohde11Clinical Research Group “Significance of viral infections in chronic respiratory diseases of children and adults,” University Hospital Bergmannsheil, Department of Internal Medicine III–Pneumology, Allergology and Sleep Medicine, Bochum, Germany; 2Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, and Department of Clinical Microbiology, Karolinska University Hospital, Stockholm, SwedenObjective: Human bocavirus (HBoV is a recently discovered parvovirus associated with acute respiratory tract infections in children. The objective of the present study was to determine the frequency and clinical relevance of HBoV infection in adult patients with acute exacerbation of chronic obstructive pulmonary disease (AE-COPD.Methods: We retrospectively tested 212 COPD patients, 141 (66.5% with AE-COPD and 71 (33.5% with stable disease, of whom nasal lavage and induced sputum had been obtained for the presence of HBoV deoxyribonucleic acid (DNA. The specificity of positive polymerase chain reaction results was confirmed by sequencing.Results: Two hundred two of 212 patients for whom PCR results were available both for nasal lavage and induced sputum samples were eligible for data analysis. HBoV DNA was detected in three patients (1.5%. Of those, only one patient had AE-COPD. Thus, the frequency of HBoV infection demonstrated to be low in both AE-COPD (0.8% and stable COPD (2.9%. HBoV was found in two sputum and one nasal lavage sample in different patients, respectively. Sequencing revealed >99% sequence identity with the reference strain.Conclusion: HBoV detection was infrequent. Since we detected HBoV in both upper and lower respiratory tract specimens and in AE-COPD as well as stable disease, a major role of HBoV infection in adults with AE-COPD is unlikely

  8. Hand osteoarthritis: Clinical and imaging study

    African Journals Online (AJOL)

    Abir Naguib

    2011-09-09

    Sep 9, 2011 ... Methods: This study was carried out on thirty patients with primary hand OA, and fifteen healthy subjects .... history about their hand condition including morning stiffness, ..... They found the US method of direct visualiza-.

  9. Human reliability data bank: feasibility study

    International Nuclear Information System (INIS)

    Comer, K.; Miller, D.P.; Donovan, M.

    1984-01-01

    The US Nuclear Regulatory Commission and Sandia National Laboratories have been developing a plan for a human reliability data bank since August 1981. This research is in response to the data needs of the nuclear power industry's probabilistic risk assessment community. The three phases of the program are to: (A) develop the data bank concept, (B) develop an implementation plan and conduct a feasibility study, and (C) assist a sponsor in implementing the data bank. The program is now in Phase B. This paper describes the methods used in the feasibility study. Decisions to be made in the future regarding full-scale implementation will be based, in part, on the outcome of this study. 3 references, 2 figures

  10. Challenges in implementing clinical governance: A qualitative study ...

    African Journals Online (AJOL)

    Design: A qualitative study. Setting: Hospitals affiliated to Shahid Sadoughi University of Medical Sciences in Yazd, Iran. Subjects: Thirteen participants selected among clinical governance executives of under study hospitals and members of clinical governance office in curative deputy of the University. Results: Eight major ...

  11. Clinical findings versus imaging studies in the diagnosis of infantile ...

    African Journals Online (AJOL)

    Background: Infantile hypertrophic pyloric stenosis is the most common surgical cause of vomiting in early infancy and can be diagnosed clinically or by imaging studies. Objectives: The aim of this study was to assess the accuracy of clinical examination compared with ultrasound and upper gastrointestinal contrast imaging ...

  12. Can the hair follicle become a model for studying selected aspects of human ocular immune privilege?

    Science.gov (United States)

    Kinori, Michael; Kloepper, Jennifer E; Paus, Ralf

    2011-06-23

    Immune privilege (IP) is important in maintaining ocular health. Understanding the mechanism underlying this dynamic state would assist in treating inflammatory eye diseases. Despite substantial progress in defining eye IP mechanisms, because of the scarcity of human ocular tissue for research purposes, most of what we know about ocular IP is based on rodent models (of unclear relevance to human eye immunology) and on cultured human eye-derived cells that cannot faithfully mirror the complex cell-tissue interactions that underlie normal human ocular IP in situ. Therefore, accessible, instructive, and clinically relevant human in vitro models are needed for exploring the general principles of why and how IP collapses under clinically relevant experimental conditions and how it can be protected or even restored therapeutically. Among the few human IP sites, the easily accessible and abundantly available hair follicle (HF) may offer one such surrogate model. There are excellent human HF organ culture systems for the study of HF IP in situ that instructively complement in vivo autoimmunity research in the human system. In this article, we delineate that the human eye and HF, despite their obvious differences, share key molecular and cellular mechanisms for maintaining IP. We argue that, therefore, human scalp HFs can provide an unconventional, but highly instructive, accessible, easily manipulated, and clinically relevant preclinical model for selected aspects of ocular IP. This essay is an attempt to encourage professional eye researchers to turn their attention, with appropriate caveats, to this candidate surrogate model for ocular IP in the human system.

  13. Clinical Music Study Quality Assessment Scale (MUSIQUAS)

    NARCIS (Netherlands)

    Jaschke, A.C.; Eggermont, L.H.P.; Scherder, E.J.A.; Shippton, M.; Hiomonides, I.

    2013-01-01

    AIMS Quality assessment of studies is essential for the understanding and application of these in systematic reviews and meta analyses, the two “gold standards” of medical sciences. Publications in scientific journals have extensively used assessment scales to address poor methodological quality,

  14. A CLINICAL STUDY OF ADHESIVE INTESTINAL OBSTRUCTION

    OpenAIRE

    Haricharan; Murali Krishna; Koti Reddy; Nara Hari

    2015-01-01

    INTRODUCTION: Adhesive intestinal obstruction is an inevitable complication of abdominal surgeries. It has high morbidity with associated poor quality of life and predisposition to repeated hospitalization. Commonest cause of bowel obstruction in developed countries is postoperative adhesions with extrinsic compression of the intestine. Most of them can be managed conservatively. METHODS: A retrospective study of 30 patients admit...

  15. [Foot reflexology massage: a clinical study].

    Science.gov (United States)

    Kesselring, A

    1999-02-01

    The aim of the study was to investigate the possible usefulness of foot reflexology on the recovery after a surgical intervention. 130 patients participated in the study. They underwent abdominal surgery under full anesthesia for different, but exclusively gynecological reasons. Foot reflexology investigated in this study was applied only for a few days for each patient. The following parameters were recorded: the subjective, self-assessed, general condition, pain intensity, movement of the bowels, micturition and sleep, beginning on the day before operation until day 10. Two other treatments served as controls, a simple massage of the foot or a personal conversation. The simple massage turned out to be a relaxing, positive experience, whereas foot reflexology had various effects, some of them were even negative. The conclusion was that foot reflexology is not recommended for acute, abdominal postsurgical situations in gynecology because it can occasionally trigger abdominal pain. This project is one of the few studies planned, conducted and performed by the nursing staff.

  16. MONOAMINE OXIDASE: RADIOTRACER DEVELOPMENT AND HUMAN STUDIES.

    Energy Technology Data Exchange (ETDEWEB)

    FOWLER,J.S.; LOGAN,J.; VOLKOW,N.D.; WANG,G.J.; MACGREGOR,R.R.; DING,Y.S.

    2000-09-28

    PET is uniquely capable of providing information on biochemical transformations in the living human body. Although most of the studies of monoamine oxidase (MAO) have focused on measurements in the brain, the role of peripheral MAO as a phase 1 enzyme for the metabolism of drugs and xenobiotics is gaining attention (Strolin Benedetti and Tipton, 1998; Castagnoli et al., 1997.). MAO is well suited for this role because its concentration in organs such as kidneys, liver and digestive organs is high sometimes exceeding that in the brain. Knowledge of the distribution of the MAO subtypes within different organs and different cells is important in determining which substrates (and which drugs and xenobiotics) have access to which MAO subtypes. The highly variable subtype distribution with different species makes human studies even more important. In addition, the deleterious side effects of combining MAO inhibitors with other drugs and with foodstuffs makes it important to know the MAO inhibitory potency of different drugs both in the brain and in peripheral organs (Ulus et al., 2000). Clearly PET can play a role in answering these questions, in drug research and development and in discovering some of the factors which contribute to the highly variable MAO levels in different individuals.

  17. Challenges of clinical translation in nanomedicine: A qualitative study.

    Science.gov (United States)

    Satalkar, Priya; Elger, Bernice Simon; Hunziker, Patrick; Shaw, David

    2016-05-01

    Clinical translation of breakthroughs in nanotechnology and nanomedicine is expected to significantly improve diagnostic tools and therapeutic modalities for various diseases. This will not only improve human health and well-being, but is also likely to reduce health care costs in the long run. However, clinical translation is a long, arduous, resource intensive process that requires priority setting, resource mobilization, successful national and international collaboration, and effective coordination between key stakeholders. The aim of this paper is to describe various challenges faced by the stakeholders involved in translational nanomedicine while planning and conducting first in human clinical trials. We draw on insights obtained from 46 in-depth qualitative interviews with key stakeholders from Europe and North America. Translational research is a crucial step in bringing basic research into clinical reality. This is particularly important in a new field like nanomedicine. Clinical translation is a long and resource intensive process with difficulties along the way. In this article, the authors looked at the challenges faced by various parties in order to help identify ways to overcome these challenges. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Phase I clinical studies with WR-2721

    International Nuclear Information System (INIS)

    Kligerman, M.M.; Shaw, M.T.; Slavik, M.; Yuhas, J.M.

    1980-01-01

    Toxicity studies of S-2-(3 aminopropylamino)-ethylphosphorothioic acid (WR-2721) access patients in remission following radiation therapy. The dose has been escalated from 25 to 250 mg/m2 without significant symptoms. Inconsistent variation in the systolic blood pressure in some patients has been observed over an 8-10-point range without producing any symptoms. Combining WR-2721 with conventional radiotherapy is contemplated by intravenous injection the drug 20 to 30 minutes before irradiation. This will start as weekly injections, and the number of weekly injections will be increased progessively. Animal studies suggest that the level already safely reached could give significant protection to the normal tissues without protecting tumor

  19. IMPACT OF NEW PRODUCTS WITH A FLOUR DIETARY SUPPLEMENTS "RAPAMID" ON CLINICAL STATE OF THE HUMAN

    Directory of Open Access Journals (Sweden)

    E. I. Kireevа

    2015-01-01

    Full Text Available Summary. Тhe principal problems, which the food industry of Ukraine is confronted with, is to provide the population with foodstuffs of high biological value. At the moment the technology of producing traditional foodstuffs is being improved and new generation of foodstuffs, which meet today’s requirements, is being made. These are foodstuffs with balanced composition, low calorie, sugar and fat content, high content of healthy ingredients for functional and therapeutic purposes. Taking into account that bread is one of the principal foodstuffs, the task of reducing caloric content of baked goods and enriching them with dietary fibers, vitamins and mineral substances is important and urgent. One of the main tasks of the food industry in Ukraine today is the search for new types of additives that contain a complex of functional ingredients and can give therapeutic and prophylactic properties for food products. The article presents the results of a clinical study of dietary additive "Rapamid" and flour products using this additive for the human body. The authors studied radioprotective properties of dietary additive "Rapamid" and flour products with it. Also it was investigated the influence of these additives and products with it on the general clinical condition of the children who receive high doses of radiation. The obtained results show that additional appointment to the normal diet and the basic treatment of dietary аdditive "Rapamid" and flour products with the use of this additive promotes children's immunity, disease prevention with stress and physical stress. Dietary additive "Rapamid" and flour products using this have antioxidant, anti-allergic and radioprotective properties, have positively influences on the cardio - vascular and hematopoietic systems, displays the body of toxic elements and radionuclides.

  20. Evaluation of Ion Torrent sequencing technology for rapid clinical human leucocyte antigen typing.

    Science.gov (United States)

    Guerra, Sandra G; Chong, Winnie; Brown, Colin J; Navarrete, Cristina V

    2018-06-05

    The development of techniques to define the human leucocyte antigen (HLA) region has proven to be challenging due to its high level of polymorphism. Within a clinical laboratory, a technique for high-resolution HLA typing, which is rapid and cost effective is essential. NGS has provided a rapid, high-resolution HLA typing solution, which has reduced the number of HLA ambiguities seen with other typing methods. In this study, the One Lambda NXType NGS kit was tested on the Ion Torrent PGM platform. A total of 362 registry donors from four ethnic populations (Europeans, South Asians, Africans and Chinese) were NGS HLA typed across 9-loci (HLA-A, -B, -C, -DRB1,-DRB345 -DQB1 and -DPB1). Concordance rates of 91%-98% were obtained (for HLA-A, -B, -C, -DRB1, -DQB1 and -DPB1) when compared to historical PCR-SSO HLA types, and the identification of uncommon alleles such as A*24:07:01 and C*04:82 were observed. A turnaround time of four days was achieved for typing 44 samples. However, some limitations were observed; primer locations did not allow all ambiguities to be resolved for HLA Class II where Exon I and IV amplification are needed (HLA-DRB1*04:07:01/04:92, HLA-DRB1*09:01:02/*09:21 and HLA-DRB1*12:01:01/*12:10). This study has demonstrated high-resolution typing by NGS can be achieved in an acceptable turnaround time for a clinical laboratory; however, the Ion Torrent workflow has some technical limitations that should be addressed. © 2018 John Wiley & Sons Ltd.

  1. GLAUCOMA IN PSEUDOEXFOLIATION- CLINICAL PROSPECTIVE STUDY

    Directory of Open Access Journals (Sweden)

    Balasubramanian M. Manickavelu

    2018-01-01

    Full Text Available BACKGROUND Pseudoexfoliation is one of the common cause of secondary open-angle glaucoma worldwide with a mean progression rate higher than primary open-angle glaucoma. In India, prevalence rate of pseudoexfoliation is around 2% (Hiller et al. In South India, the prevalence rate is 6% in >40 years of age as per Krishnadas et al in 2003. The aim of the study is to study the demographic aspects of pseudoexfoliation, the frequency of glaucoma in patients with pseudoexfoliation syndrome and to assess the treatment response in pseudoexfoliation syndrome. MATERIALS AND METHODS The study was conducted among 96 patients with pseudoexfoliation who attended OP Department of Ophthalmology, Government Tiruvannamalai Medical College and Hospital, Tiruvannamalai, from January 2017 to June 2017. Complete ocular examination with visual acuity, anterior segment examination, intraocular pressure, gonioscopy, fundus examination, central corneal thickness, visual field, ultrasound B scan and ultrasound biomicroscopy was done. RESULTS Incidence of glaucoma is more common in pseudoexfoliation and most of them have open angles. All patients with pseudoexfoliation should undergo complete glaucoma evaluation for early detection. Further ophthalmologist should focus on detection of pseudoexfoliation, since it is related to high risk of operative complication. CONCLUSION Incidence of glaucoma is more in pseudoexfoliation with most common bilateral presentation with open angles with recalcitrant intraocular pressure. Severity of optic nerve damage and with progression of field defects appeared to be more compared to primary open-angle glaucoma. Better response to combination drug therapy and surgical therapy than primary open-angle glaucoma.

  2. Implementing genomics and pharmacogenomics in the clinic: The National Human Genome Research Institute's genomic medicine portfolio.

    Science.gov (United States)

    Manolio, Teri A

    2016-10-01

    Increasing knowledge about the influence of genetic variation on human health and growing availability of reliable, cost-effective genetic testing have spurred the implementation of genomic medicine in the clinic. As defined by the National Human Genome Research Institute (NHGRI), genomic medicine uses an individual's genetic information in his or her clinical care, and has begun to be applied effectively in areas such as cancer genomics, pharmacogenomics, and rare and undiagnosed diseases. In 2011 NHGRI published its strategic vision for the future of genomic research, including an ambitious research agenda to facilitate and promote the implementation of genomic medicine. To realize this agenda, NHGRI is consulting and facilitating collaborations with the external research community through a series of "Genomic Medicine Meetings," under the guidance and leadership of the National Advisory Council on Human Genome Research. These meetings have identified and begun to address significant obstacles to implementation, such as lack of evidence of efficacy, limited availability of genomics expertise and testing, lack of standards, and difficulties in integrating genomic results into electronic medical records. The six research and dissemination initiatives comprising NHGRI's genomic research portfolio are designed to speed the evaluation and incorporation, where appropriate, of genomic technologies and findings into routine clinical care. Actual adoption of successful approaches in clinical care will depend upon the willingness, interest, and energy of professional societies, practitioners, patients, and payers to promote their responsible use and share their experiences in doing so. Published by Elsevier Ireland Ltd.

  3. Humane studies of octopuses get a boost

    Science.gov (United States)

    Staaf, Danna

    2018-04-01

    Because of their complex brains, cephalopods enjoy the same protections as vertebrate animals in laboratory experiments in the European Union, New Zealand, and some Australian states. As a result, researchers have to use anesthesia in cephalopod studies that can cause pain. Most use either ethanol or magnesium chloride for this purpose because they immobilize cephalopods quickly and the animals soon recover without lasting effects. But until now it was unclear whether these compounds actually take away pain or just paralyze the animals. Now, a new study in three species suggests that both ethanol and magnesium chloride suppress pain signals in cephalopods, reassuring researchers they are compliant with the law and treating their subjects humanely.

  4. Study of the trial subjects’ protection aspects in Phase I clinical trials and bioequivalence studies

    Directory of Open Access Journals (Sweden)

    K. O. Zupanets

    2016-03-01

    Full Text Available Protection of rights, health and well-being of persons who are taking the drug during the trial (trial subjects is one of the basic principles of clinical trials (CT management. Aim. In order to study key aspects of volunteer protection, determine factors that influence these indicators and estimate the importance of ensuring their proper implementation on the clinical site (CS three survey of 135 trial subjects were carried out to evaluate the importance of assessing the impact of factors such as the procedure of signing the informed consent (IC at the CS and testing procedures for HIV / AIDS, hepatitis and others. Assessment of the quality of life of trial subjects as indirect indicator of the quality of clinical trials that ensures the proper protection of their life was the subject of the third survey. Methods and results. The general model of the relationship between the key aspects of the trial subjects protection and the factors which are providing them during the clinical trials of drugs management was substantiated, which included the main aspects of the trial subjects’ protection, protective factors and basic CT management procedures, the impact of the above factors on the possibility of providing protection aspects depends on their implementation quality. It was found that trial subjects’ protection improvement can be achieved during the IC signing process. It is necessary to ensure a higher level of volunteers understanding of the terms that could be used in the IC form. Regarding the procedure of compulsory testing for HIV/AIDS in the course of screening, we can conclude that the majority of the trial subjects believe that this procedure is an additional factor in their health protection and do not consider it as an excessive psychological pressure on them. Conclusion. Assessing the quality of life during the bioequivalence study at the CS makes possible to reach a conclusion on general well-being and satisfaction with those

  5. CLINICAL

    African Journals Online (AJOL)

    laborative Study (HPMCS), representing the combined data of 3 941 HIV-infected infants and children ... antibody-positive infants with severe disease before confirmation by HIV DNA polymerase chain .... human immunodeficiency virus infection in children less than 13 years of age. MMWR Morb Mortal Wkly Rep 1994; 43: ...

  6. Safety testing of monoclonal antibodies in non-human primates: Case studies highlighting their impact on human risk assessment.

    Science.gov (United States)

    Brennan, Frank R; Cavagnaro, Joy; McKeever, Kathleen; Ryan, Patricia C; Schutten, Melissa M; Vahle, John; Weinbauer, Gerhard F; Marrer-Berger, Estelle; Black, Lauren E

    2018-01-01

    Monoclonal antibodies (mAbs) are improving the quality of life for patients suffering from serious diseases due to their high specificity for their target and low potential for off-target toxicity. The toxicity of mAbs is primarily driven by their pharmacological activity, and therefore safety testing of these drugs prior to clinical testing is performed in species in which the mAb binds and engages the target to a similar extent to that anticipated in humans. For highly human-specific mAbs, this testing often requires the use of non-human primates (NHPs) as relevant species. It has been argued that the value of these NHP studies is limited because most of the adverse events can be predicted from the knowledge of the target, data from transgenic rodents or target-deficient humans, and other sources. However, many of the mAbs currently in development target novel pathways and may comprise novel scaffolds with multi-functional domains; hence, the pharmacological effects and potential safety risks are less predictable. Here, we present a total of 18 case studies, including some of these novel mAbs, with the aim of interrogating the value of NHP safety studies in human risk assessment. These studies have identified mAb candidate molecules and pharmacological pathways with severe safety risks, leading to candidate or target program termination, as well as highlighting that some pathways with theoretical safety concerns are amenable to safe modulation by mAbs. NHP studies have also informed the rational design of safer drug candidates suitable for human testing and informed human clinical trial design (route, dose and regimen, patient inclusion and exclusion criteria and safety monitoring), further protecting the safety of clinical trial participants.

  7. Classified study and clinical value of the phase imaging features

    International Nuclear Information System (INIS)

    Dang Yaping; Ma Aiqun; Zheng Xiaopu; Yang Aimin; Xiao Jiang; Gao Xinyao

    2000-01-01

    445 patients with various heart diseases were examined by the gated cardiac blood pool imaging, and the phase was classified. The relationship between the seven types with left ventricular function index, clinical heart function, different heart diseases as well as electrocardiograph was studied. The results showed that the phase image classification could match with the clinical heart function. It can visually, directly and accurately indicate clinical heart function and can be used to identify diagnosis of heart disease

  8. Effects of intermittent fasting on body composition and clinical health markers in humans.

    Science.gov (United States)

    Tinsley, Grant M; La Bounty, Paul M

    2015-10-01

    Intermittent fasting is a broad term that encompasses a variety of programs that manipulate the timing of eating occasions by utilizing short-term fasts in order to improve body composition and overall health. This review examines studies conducted on intermittent fasting programs to determine if they are effective at improving body composition and clinical health markers associated with disease. Intermittent fasting protocols can be grouped into alternate-day fasting, whole-day fasting, and time-restricted feeding. Alternate-day fasting trials of 3 to 12 weeks in duration appear to be effective at reducing body weight (≈3%-7%), body fat (≈3-5.5 kg), total cholesterol (≈10%-21%), and triglycerides (≈14%-42%) in normal-weight, overweight, and obese humans. Whole-day fasting trials lasting 12 to 24 weeks also reduce body weight (≈3%-9%) and body fat, and favorably improve blood lipids (≈5%-20% reduction in total cholesterol and ≈17%-50% reduction in triglycerides). Research on time-restricted feeding is limited, and clear conclusions cannot be made at present. Future studies should examine long-term effects of intermittent fasting and the potential synergistic effects of combining intermittent fasting with exercise. © The Author(s) 2015. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  9. Clinical and scientific impact of human papillomavirus on head and neck cancer.

    Science.gov (United States)

    Friedman, Jeffrey M; Stavas, Mark J; Cmelak, Anthony J

    2014-10-10

    Head and neck cancer (HNC) arises from the skull base to the clavicles and is the fifth most common cancer in the world by incidence. Historically, in the developed world HNC was associated with tobacco use and alcohol consumption, and the combination of the two produced a synergistic increase in risk. However, beginning in 1983, investigators have found a significant and growing proportion of HNC patients with human papillomavirus-positive (HPV) tumors who neither drank nor used tobacco. Since that time, there has been increased interest in the molecular biology of HPV-positive HNC. Multiple studies now show that HPV has shifted the epidemiological landscape and prognosis of head and neck squamous cell carcinoma (HNSCC). These studies provide strong evidence for improved survival outcomes in patients with HPV-positive HNSCC compared to those with HPV-negative HNSCC. In many reports, HPV status is the strongest predictor of locoregional control, disease specific survival and overall survival. In response to these findings, there has been significant interest in the best management of HPV-positive disease. Discussions within major cooperative groups consider new trials designed to maintain the current strong survival outcomes while reducing the long-term treatment-related toxicities. This review will highlight the epidemiological, clinical and molecular discoveries surrounding HPV-related HNSCC over the recent decades and we conclude by suggesting how these findings may guide future treatment approaches.

  10. Generation of clinical-grade human induced pluripotent stem cells in Xeno-free conditions.

    Science.gov (United States)

    Wang, Juan; Hao, Jie; Bai, Donghui; Gu, Qi; Han, Weifang; Wang, Lei; Tan, Yuanqing; Li, Xia; Xue, Ke; Han, Pencheng; Liu, Zhengxin; Jia, Yundan; Wu, Jun; Liu, Lei; Wang, Liu; Li, Wei; Liu, Zhonghua; Zhou, Qi

    2015-11-12

    Human induced pluripotent stem cells (hiPSCs) are considered as one of the most promising seed cell sources in regenerative medicine. Now hiPSC-based clinical trials are underway. To ensure clinical safety, cells used in clinical trials or therapies should be generated under GMP conditions, and with Xeno-free culture media to avoid possible side effects like immune rejection that induced by the Xeno reagents. However, up to now there are no reports for hiPSC lines developed completely under GMP conditions using Xeno-free reagents. Clinical-grade human foreskin fibroblast (HFF) cells used as feeder cells and parental cells of the clinical-grade hiPSCs were isolated from human foreskin tissues and cultured in Xeno-free media. Clinical-grade hiPSCs were derived by integration-free Sendai virus-based reprogramming kit in Xeno-free pluriton™ reprogramming medium or X medium. Neural cells and cardiomyocytes differentiation were conducted following a series of spatial and temporal specific signals induction according to the corresponding lineage development signals. Biological safety evaluation of the clinical-grade HFF cells and hiPSCs were conducted following the guidance of the "Pharmacopoeia of the People's Republic of China, Edition 2010, Volume III". We have successfully derived several integration-free clinical-grade hiPSC lines under GMP-controlled conditions and with Xeno-free reagents culture media in line with the current guidance of international and national evaluation criteria. As for the source of hiPSCs and feeder cells, biological safety evaluation of the HFF cells have been strictly reviewed by the National Institutes for Food and Drug Control (NIFDC). The hiPSC lines are pluripotent and have passed the safety evaluation. Moreover, one of the randomly selected hiPSC lines was capable of differentiating into functional neural cells and cardiomyocytes in Xeno-free culture media. The clinical-grade hiPSC lines therefore could be valuable sources for

  11. [Human body meridian spatial decision support system for clinical treatment and teaching of acupuncture and moxibustion].

    Science.gov (United States)

    Wu, Dehua

    2016-01-01

    The spatial position and distribution of human body meridian are expressed limitedly in the decision support system (DSS) of acupuncture and moxibustion at present, which leads to the failure to give the effective quantitative analysis on the spatial range and the difficulty for the decision-maker to provide a realistic spatial decision environment. Focusing on the limit spatial expression in DSS of acupuncture and moxibustion, it was proposed that on the basis of the geographic information system, in association of DSS technology, the design idea was developed on the human body meridian spatial DSS. With the 4-layer service-oriented architecture adopted, the data center integrated development platform was taken as the system development environment. The hierarchical organization was done for the spatial data of human body meridian via the directory tree. The structured query language (SQL) server was used to achieve the unified management of spatial data and attribute data. The technologies of architecture, configuration and plug-in development model were integrated to achieve the data inquiry, buffer analysis and program evaluation of the human body meridian spatial DSS. The research results show that the human body meridian spatial DSS could reflect realistically the spatial characteristics of the spatial position and distribution of human body meridian and met the constantly changeable demand of users. It has the powerful spatial analysis function and assists with the scientific decision in clinical treatment and teaching of acupuncture and moxibustion. It is the new attempt to the informatization research of human body meridian.

  12. 9.4 T small animal MRI using clinical components for direct translational studies.

    Science.gov (United States)

    Felder, Jörg; Celik, A Avdo; Choi, Chang-Hoon; Schwan, Stefan; Shah, N Jon

    2017-12-28

    Magnetic resonance is a major preclinical and clinical imaging modality ideally suited for longitudinal studies, e.g. in pharmacological developments. The lack of a proven platform that maintains an identical imaging protocol between preclinical and clinical platforms is solved with the construction of an animal scanner based on clinical hard- and software. A small animal magnet and gradient system were connected to a clinical MR system. Several hardware components were either modified or built in-house to achieve compatibility. The clinical software was modified to account for the different field-of-view of a preclinical MR system. The established scanner was evaluated using clinical QA protocols, and platform compatibility for translational research was verified against clinical scanners of different field strength. The constructed animal scanner operates with the majority of clinical imaging sequences. Translational research is greatly facilitated as protocols can be shared between preclinical and clinical platforms. Hence, when maintaining sequences parameters, maximum similarity between pulses played out on a human or an animal system is maintained. Coupling of a small animal magnet with a clinical MR system is a flexible, easy to use way to establish and advance translational imaging capability. It provides cost and labor efficient translational capability as no tedious sequence reprogramming between moieties is required and cross-platform compatibility of sequences facilitates multi-center studies.

  13. Human-centred automation: an explorative study

    International Nuclear Information System (INIS)

    Hollnagel, Erik; Miberg, Ann Britt

    1999-05-01

    The purpose of the programme activity on human-centred automation at the HRP is to develop knowledge (in the form of models and theories) and tools (in the form of techniques and simulators) to support design of automation that ensures effective human performance and comprehension. This report presents the work done on both the analytical and experimental side of this project. The analytical work has surveyed common definitions of automation and traditional design principles. A general finding is that human-centred automation usually is defined in terms of what it is not. This is partly due to a lack of adequate models and of human-automation interaction. Another result is a clarification of the consequences of automation, in particular with regard to situation awareness and workload. The experimental work has taken place as an explorative experiment in HAMMLAB in collaboration with IPSN (France). The purpose of this experiment was to increase the understanding of how automation influences operator performance in NPP control rooms. Two different types of automation (extensive and limited) were considered in scenarios having two different degrees of complexity (high and low), and involving diagnostic and procedural tasks. Six licensed NPP crews from the NPP at Loviisa, Finland, participated in the experiment. The dependent variables applied were plant performance, operator performance, self-rated crew performance, situation awareness, workload, and operator trust in the automation. The results from the diagnostic scenarios indicated that operators' judgement of crew efficiency was related to their level of trust in the automation, and further that operators trusted automation least and rated crew performance lowest in situations where crew performance was efficient and vice versa. The results from procedural scenarios indicated that extensive automation efficiently supported operators' performance, and further that operator' judgement of crew performance efficiency

  14. Translation of Human-Induced Pluripotent Stem Cells: From Clinical Trial in a Dish to Precision Medicine.

    Science.gov (United States)

    Sayed, Nazish; Liu, Chun; Wu, Joseph C

    2016-05-10

    The prospect of changing the plasticity of terminally differentiated cells toward pluripotency has completely altered the outlook for biomedical research. Human-induced pluripotent stem cells (iPSCs) provide a new source of therapeutic cells free from the ethical issues or immune barriers of human embryonic stem cells. iPSCs also confer considerable advantages over conventional methods of studying human diseases. Since its advent, iPSC technology has expanded with 3 major applications: disease modeling, regenerative therapy, and drug discovery. Here we discuss, in a comprehensive manner, the recent advances in iPSC technology in relation to basic, clinical, and population health. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  15. MIH: epidemiologic clinic study in paediatric patient.

    Science.gov (United States)

    Condò, R; Perugia, C; Maturo, P; Docimo, R

    2012-04-01

    The Molar Incisor Hypomineralization (MIH) is a qualitative and quantitative defect of the enamel structure of the first permanent molars, which may vary from 1 to 4 with involvement of maxillary and jaw permanent incisors. AIM.: Aim of this study is that to evaluate, among 1500 paediatric patients chosen at random aged between 0 and 14 years, afferent by the Paediatric Dentistry of the Azienda Ospedialiera Policlinico Tor Vergata of Rome from 1996 to 2011, the incidents and the prevalence of the MIH distribution, and furthermore to ascertain the possible relationship with the data described in the literature. RESULTS AND DISCUSSION.: From the sample of 1500 paediatric patients, the number of those affections from MIH has turned out to be pairs to 110 (7.3%) aged between 4 and 15 years, and an average age equal to 9.7. The incidence of the hypoplastic defects is greater in the elements of the permanents series in which the functional class mainly interested is that of the first molars, with a percentage of 39.8%. Regarding the elements of the deciduous series affections from hypoplasia, they turn out to be in all in number of 20 represented in 80% of the cases from the seconds molars while in the remaining 20% of the cases the items involved are the central incisors. About the percentage of elements involved in the MIH: the molars, involved with a frequency of 56%, turn out to be more hit regarding incisors (44%). As reported in the literature, it can be asserted that the MIH can hit in equal measure both the male sex that feminine one. CONCLUSIONS.: MIH represents a condition quite frequent in the paediatric population. In managing this anomaly takes an essential role in the early diagnosis and in the differential one. The study done underlined the importance of a correct application of the therapeutic protocol which, starting from a careful diagnosis and articulating themselves in the execution of preventive treatments and in severe cases restorative and

  16. Clinical study on transient ischemic attack

    International Nuclear Information System (INIS)

    Takusagawa, Yoshihiko; Fujiwara, Yasuhiro; Ichiki, Ken; Suga, Takeshi; Nishigaki, Shinichi

    1986-01-01

    The purpose of this study was to neuroradiologically elucidate the mechanism by which transient ischemic attack (TIA) occurs. A total of 65 patients with TIA, including 52 with TIA in the internal carotid artery (Group I) and 13 with TIA in the vertebrobasilar artery (Group II), underwent computed tomography (CT) and cerebral angiography (CAG). In Group I, CAG revealed normal findings in 25 patients, extracranial lesions in 14, intracranial lesions in 11, and mixed extra- and intra-cranial lesions in 2; and the corresponding figures for Group II were 8, 4, 1 and 0, respectively. CT findings in Groups I and II included: normal findings in 27 and 9 patients, atrophied cerebrum and dilated cerebral ventricle in 7 and 2, TIA-unrelated infarction in 5 and one, and TIA-related infarction in 15 and one, respectively. In the 15 patients with TIA-related infarction in Group I, 10 had infarction in the basal cell nucleolus and the other 5 had widespread infarction extending to the area under the cortex. The latter 5 patients had cerebral infarction, and showed recanalization of the vessels. This finding may support the theory of ''microembolus'' as a possible cause of TIA. (Namekawa, K.)

  17. Pigment dispersion syndrome: a clinical study.

    Science.gov (United States)

    Scheie, H G; Cameron, J D

    1981-01-01

    This study involved a group of 407 patients (799 eyes) with pigment dispersion syndrome gathered from a glaucoma population of 9200 patients. The sex distribution was equal. The majority (65%) of patients were myopic. The incidence of retinal detachment was 6.4%. No patients were black, but 5 were mulatto. Approximately one-quarter of the patients wih pigment dispersion syndrome (31% of the men, 19% of the women) had glaucoma. The average age of onset of glaucoma was 15 years less than in control patients with chronic simple glaucoma. When both eyes were affected by glaucoma, the glaucoma was consistently more severe in the eye with the more heavily pigmented angle. The degree of iris transillumination was found to be of no importance in predicting the presence of glaucoma or the severity of trabecular pigmentation. The pressure in 66% of the eyes with pigmentary glaucoma was controlled medically. A higher percentage of patients with pigmentary glaucoma required surgery than patients in the control group with chronic simple glaucoma. Men with pigmentary glaucoma required surgery at a much earlier age than women with pigmentary glaucoma. PMID:7236571

  18. Anatomical-clinical investigations of variations of the human coronary arteries

    OpenAIRE

    Aida Hasanović; Faruk Dilberović; Fehim Ovčina

    2003-01-01

    Variations of the human coronary arteries have always attracted the attention of many researchers. A review of the literature shows that variations can cause ischemic heart disease or sudden cardiac death. The aim of the investigations was to examine the existence and clinical significance of variations of the human coronary arteries. Special attention has been focused on myocardial bridging of the coronary arteries and coronary arteriovenous fistula. Our investigations were carried out on th...

  19. Consolidated Human Activity Database (CHAD) for use in human exposure and health studies and predictive models

    Science.gov (United States)

    EPA scientists have compiled detailed data on human behavior from 22 separate exposure and time-use studies into CHAD. The database includes more than 54,000 individual study days of detailed human behavior.

  20. Application of objective clinical human reliability analysis (OCHRA) in assessment of technical performance in laparoscopic rectal cancer surgery.

    Science.gov (United States)

    Foster, J D; Miskovic, D; Allison, A S; Conti, J A; Ockrim, J; Cooper, E J; Hanna, G B; Francis, N K

    2016-06-01

    Laparoscopic rectal resection is technically challenging, with outcomes dependent upon technical performance. No robust objective assessment tool exists for laparoscopic rectal resection surgery. This study aimed to investigate the application of the objective clinical human reliability analysis (OCHRA) technique for assessing technical performance of laparoscopic rectal surgery and explore the validity and reliability of this technique. Laparoscopic rectal cancer resection operations were described in the format of a hierarchical task analysis. Potential technical errors were defined. The OCHRA technique was used to identify technical errors enacted in videos of twenty consecutive laparoscopic rectal cancer resection operations from a single site. The procedural task, spatial location, and circumstances of all identified errors were logged. Clinical validity was assessed through correlation with clinical outcomes; reliability was assessed by test-retest. A total of 335 execution errors identified, with a median 15 per operation. More errors were observed during pelvic tasks compared with abdominal tasks (p technical performance of laparoscopic rectal surgery.

  1. Phytosomal curcumin: A review of pharmacokinetic, experimental and clinical studies.

    Science.gov (United States)

    Mirzaei, Hamed; Shakeri, Abolfazl; Rashidi, Bahman; Jalili, Amin; Banikazemi, Zarrin; Sahebkar, Amirhossein

    2017-01-01

    Curcumin, a hydrophobic polyphenol, is the principal constituent extracted from dried rhizomes of Curcuma longa L. (turmeric). Curcumin is known as a strong anti-oxidant and anti-inflammatory agent that has different pharmacological effects. In addition, several studies have demonstrated that curcumin is safe even at dosages as high as 8g per day; however, instability at physiological pH, low solubility in water and rapid metabolism results in a low oral bioavailability of curcumin. The phytosomal formulation of curcumin (a complex of curcumin with phosphatidylcholine) has been shown to improve curcumin bioavailability. Existence of phospholipids in phytosomes leads to specific physicochemical properties such as amphiphilic nature that allows dispersion in both hydrophilic and lipophilic media. The efficacy and safety of curcumin phytosomes have been shown against several human diseases including cancer, osteoarthritis, diabetic microangiopathy and retinopathy, and inflammatory diseases. This review focuses on the pharmacokinetics as well as pharmacological and clinical effects of phytosomal curcumin. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  2. Clinical significance of serum anti-human papillomavirus 16 and 18 antibodies in cervical neoplasia.

    Science.gov (United States)

    Chay, Doo Byung; Cho, Hanbyoul; Kim, Bo Wook; Kang, Eun Suk; Song, Eunseop; Kim, Jae-Hoon

    2013-02-01

    To estimate the clinical significance of serum anti-human papillomavirus (HPV) antibodies and high-risk cervical HPV DNA in cervical neoplasia. The study population comprised patients who were histopathologically diagnosed with cervical intraepithelial neoplasia (CIN) 1 (n=64), CIN 2 and 3 (n=241), cervical cancer (n=170), and normal control participants (n=975). Cervical HPV DNA tests were performed through nucleic acid hybridization assay tests, and serum anti-HPV 16 and 18 antibodies were measured by competitive immunoassay. The associations of HPV DNA and anti-HPV antibodies were evaluated with demographic characteristics and compared according to the levels of disease severity. Anti-HPV antibodies were also investigated with clinicopathologic parameters, including survival data. Among various demographic characteristics, factors involving sexual behavior had a higher tendency of HPV DNA positivity and HPV seropositivity. Human papillomavirus DNA mean titer and positivity were both increased in patients with cervical neoplasia compared with those with normal control participants, but there was no statistical difference among types of cervical neoplasia. Serum anti-HPV 16 antibodies were also able to differentiate cervical neoplasia from a normal control participant and furthermore distinguished CIN 1 from CIN 2 and 3 (odd ratio 2.87 [1.43-5.78], P=.002). In cervical cancer, HPV 16 seropositivity was associated with prolonged disease-free survival according to the univariable analysis (hazard ratio=0.12 [0.01-0.94], P=.044). Serum anti-HPV 16 antibodies can distinguish cervical neoplasia from a normal control and has the advantage of identifying high-grade CIN. Moreover, in cervical cancer, HPV 16 seropositivity may be associated with a more favorable prognosis. II.

  3. Applying human factors and ergonomics to the misuse of nonsterile clinical gloves in acute care.

    Science.gov (United States)

    Wilson, Jennie; Bak, Aggie; Loveday, Heather P

    2017-07-01

    Health care workers (HCWs) are recommended to wear nonsterile clinical gloves (NSCG) for direct contact with blood and body fluids. However, there is evidence of extensive inappropriate NSCG use. A mixed-methods study comprising observation of NSCG use in 2 acute hospitals and semistructured HCW interviews. Qualitative data were categorized using thematic analysis. Findings were mapped to the Systems Engineering Initiative for Patient Safety model and used to develop a strategy for improving NSCG use. Two hundred seventy-eight procedures performed in 178 episodes of care involved the use of NSCG. NSCG were inappropriate for 59% of procedures (165 out of 278). Risk of cross-contamination occurred in 49% (87 out of 178) episodes. Twenty-six HCWs were interviewed; emotion and socialization were key factors influencing decisions to use NSCG. Data from observation and thematic analysis were mapped to 6 interacting components of the Systems Engineering Initiative for Patient Safety work system. Interventions targeting each component informed quality improvement strategies CONCLUSIONS: Despite intense promotion of hand hygiene as the key measure to protect patients from health care-associated infection, NSCG dominate routine clinical practice and potential cross-contamination occurs in 50% of care episodes. Such practice is associated with significant environmental and financial costs and adversely affects patient safety. The application of human factors and ergonomics to the complex drivers of inappropriate NSCG behavior may be more effective than conventional approaches of education and policy in achieving the goal of preventing health care-associated infection and improving patient safety. Copyright © 2017 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

  4. Clinical and molecular epidemiology of human rhinovirus infections in patients with hematologic malignancy.

    Science.gov (United States)

    Jacobs, Samantha E; Lamson, Daryl M; Soave, Rosemary; Guzman, Brigitte Huertas; Shore, Tsiporah B; Ritchie, Ellen K; Zappetti, Dana; Satlin, Michael J; Leonard, John P; van Besien, Koen; Schuetz, Audrey N; Jenkins, Stephen G; George, Kirsten St; Walsh, Thomas J

    2015-10-01

    Human rhinoviruses (HRVs) are common causes of upper respiratory tract infection (URTI) in hematologic malignancy (HM) patients. Predictors of lower respiratory tract infection (LRTI) including the impact of HRV species and types are poorly understood. This study aims to describe the clinical and molecular epidemiology of HRV infections among HM patients. From April 2012-March 2013, HRV-positive respiratory specimens from symptomatic HM patients were molecularly characterized by analysis of partial viral protein 1 (VP1) or VP4 gene sequence. HRV LRTI risk-factors and outcomes were analyzed using multivariable logistic regression. One hundred and ten HM patients presented with HRV URTI (n=78) and HRV LRTI (n=32). Hypoalbuminemia (OR 3.0; 95% CI, 1.0-9.2; p=0.05) was independently associated with LRTI, but other clinical and laboratory markers of host immunity did not differ between patients with URTI versus LRTI. Detection of bacterial co-pathogens was common in LRTI cases (25%). Among 92 typeable respiratory specimens, there were 58 (64%) HRV-As, 12 (13%) HRV-Bs, and 21 (23%) HRV-Cs, and one Enterovirus 68. LRTI rates among HRV-A (29%), HRV-B (17%), and HRV-C (29%) were similar. HRV-A infections occurred year-round while HRV-B and HRV-C infections clustered in the late fall and winter. HRVs are associated with LRTI in HM patients. Illness severity is not attributable to specific HRV species or types. The frequent detection of bacterial co-pathogens in HRV LRTIs further substantiates the hypothesis that HRVs predispose to bacterial superinfection of the lower airways, similar to that of other community-acquired respiratory viruses. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Computational challenges and human factors influencing the design and use of clinical research participant eligibility pre-screening tools

    Directory of Open Access Journals (Sweden)

    Pressler Taylor R

    2012-05-01

    Full Text Available Abstract Background Clinical trials are the primary mechanism for advancing clinical care and evidenced-based practice, yet challenges with the recruitment of participants for such trials are widely recognized as a major barrier to these types of studies. Data warehouses (DW store large amounts of heterogenous clinical data that can be used to enhance recruitment practices, but multiple challenges exist when using a data warehouse for such activities, due to the manner of collection, management, integration, analysis, and dissemination of the data. A critical step in leveraging the DW for recruitment purposes is being able to match trial eligibility criteria to discrete and semi-structured data types in the data warehouse, though trial eligibility criteria tend to be written without concern for their computability. We present the multi-modal evaluation of a web-based tool that can be used for pre-screening patients for clinical trial eligibility and assess the ability of this tool to be practically used for clinical research pre-screening and recruitment. Methods The study used a validation study, usability testing, and a heuristic evaluation to evaluate and characterize the operational characteristics of the software as well as human factors affecting its use. Results Clinical trials from the Division of Cardiology and the Department of Family Medicine were used for this multi-modal evaluation, which included a validation study, usability study, and a heuristic evaluation. From the results of the validation study, the software demonstrated a positive predictive value (PPV of 54.12% and 0.7%, respectively, and a negative predictive value (NPV of 73.3% and 87.5%, respectively, for two types of clinical trials. Heuristic principles concerning error prevention and documentation were characterized as the major usability issues during the heuristic evaluation. Conclusions This software is intended to provide an initial list of eligible patients to a

  6. Regional enteritis and gluten-free diet. A clinical study

    NARCIS (Netherlands)

    Merwe, Christiaan Frederik van der

    1974-01-01

    The purpose of this clinical study was to determine whether the use of a gluten-free diet influenced the course and prognosis of regional enteritis. Following a few clinical communications in the Dutch medical literature reporting favourable results obtained with the gluten-free diet in the

  7. Dutch transmural nurse clinics for chronic patients: a descriptive study.

    NARCIS (Netherlands)

    Temmink, D.; Francke, A.L.; Kerkstra, A.; Huyer Abu-Saad, H.

    2000-01-01

    'Transmural care' can be defined as patient-tailored care provided on the basis of close collaboration and joint responsibility between hospitals and home care organizations. One form of transmural care is transmural nurse clinics for chronically ill. This study describes 62 transmural nurse clinics

  8. Rethinking clinical governance : Healthcare professionals' views: a Delphi study

    NARCIS (Netherlands)

    Veenstra, Gepke L.; Ahaus, Kees; Welker, Gera A.; Heineman, Erik; van der Laan, Maarten J.; Muntinghe, Friso L. H.

    OBJECTIVE: Although the guiding principle of clinical governance states that healthcare professionals are the leading contributors to quality and safety in healthcare, little is known about what healthcare professionals perceive as important for clinical governance. The aim of this study is to

  9. Establishment and clinical application of immunoradiometric assay for human growth hormone in serum

    International Nuclear Information System (INIS)

    Ji Jinfeng; Wu Congyuan; Niu Zhanpo; Zhang Kui; Song Ailing; Deng Jieying; Shi Mifan

    1992-01-01

    An immunoradiometric assay (IRMA) for human growth hormone (hGH) in serum is developed based on two high specific monoclonal antibodies against hGh. It can specifically detect the levels of serum bioactive hGh and had no cross-reaction with human prolactin (hPRL) and hGh oligmeric forms. The sensitivity was 0.2 ng/ml and the recovery for different concentrations of hGh was 92.0% ∼ 103.2%. The coefficients of variation for intra and inter-assay were<9.1% and <14.2%, respectively. Integral analysis of the results of RIA and IRMA with the patients' clinical manifestations revealed that hGh IRMA is better than hGh RIA in reflecting the clinical states of different acromegalic patients

  10. [Study of the relationship between human quality and reliability].

    Science.gov (United States)

    Long, S; Wang, C; Wang, L i; Yuan, J; Liu, H; Jiao, X

    1997-02-01

    To clarify the relationship between human quality and reliability, 1925 experiments in 20 subjects were carried out to study the relationship between disposition character, digital memory, graphic memory, multi-reaction time and education level and simulated aircraft operation. Meanwhile, effects of task difficulty and enviromental factor on human reliability were also studied. The results showed that human quality can be predicted and evaluated through experimental methods. The better the human quality, the higher the human reliability.

  11. Molecular characterization of rotavirus strains detected during a clinical trial of a human rotavirus vaccine in Blantyre, Malawi

    Science.gov (United States)

    Nakagomi, Toyoko; Nakagomi, Osamu; Dove, Winifred; Doan, Yen Hai; Witte, Desiree; Ngwira, Bagrey; Todd, Stacy; Steele, A Duncan; Neuzil, Kathleen M; Cunliffe, Nigel A

    2014-01-01

    The human, G1P[8] rotavirus vaccine (Rotarix) significantly reduced severe rotavirus gastroenteritis episodes in a clinical trial in South Africa and Malawi, but vaccine efficacy was lower in Malawi (49.5%) than reported in South Africa (76.9%) and elsewhere. The aim of this study was to examine the molecular relationships of circulating wild-type rotaviruses detected during the clinical trial in Malawi to RIX4414 (the strain contained in Rotarix) and to common human rotavirus strains. Of 88 rotavirus-positive, diarrhoeal stool specimens, 43 rotaviruses exhibited identifiable RNA migration patterns when examined by polyacrylamide gel electrophoresis. The genes encoding VP7, VP4, VP6 and NSP4 of 5 representative strains possessing genotypes G12P[6], G1P[8], G9P[8], and G8P[4] were sequenced. While their VP7 (G) and VP4 (P) genotype designations were confirmed, the VP6 (I) and NSP4 (E) genotypes were either I1E1 or I2E2, indicating that they were of human rotavirus origin. RNA-RNA hybridization using 21 culture-adapted strains showed that Malawian rotaviruses had a genomic RNA constellation common to either the Wa-like or DS-1 like human rotaviruses. Overall, the Malawi strains appear similar in their genetic make-up to rotaviruses described in countries where vaccine efficacy is greater, suggesting that the lower efficacy in Malawi is unlikely to be explained by the diversity of circulating strains. PMID:22520123

  12. How valid are claims for synergy in published clinical studies?

    Science.gov (United States)

    Ocana, A; Amir, E; Yeung, C; Seruga, B; Tannock, I F

    2012-08-01

    Clinical trials evaluating drug combinations are often stimulated by claims of synergistic interactions in preclinical models. Overuse or misuse of the term synergy could lead to poorly designed clinical studies. We searched PubMed using the terms 'synergy' or 'synergistic' and 'cancer' to select articles published between 2006 and 2010. Eligible studies were those that referred to synergy in preclinical studies to justify a drug combination evaluated in a clinical trial. Eighty-six clinical articles met eligibility criteria and 132 preclinical articles were cited in them. Most of the clinical studies were phase I (43%) or phase II trials (56%). Appropriate methods to evaluate synergy in preclinical studies included isobologram analysis in 18 studies (13.6%) and median effect in 10 studies (7.6%). Only 26 studies using animal models (39%) attempted to evaluate therapeutic index. There was no association between the result of the clinical trial and the use of an appropriate method to evaluate synergy (P=0.25, chi-squared test). Synergy is cited frequently in phase I and phase II studies to justify the evaluation of a specific drug combination. Inappropriate methods for evaluation of synergy and poor assessment of therapeutic index have been used in most preclinical articles.

  13. Identification of Clinical Staphylococcal Isolates from Humans by Internal Transcribed Spacer PCR

    Science.gov (United States)

    Couto, Isabel; Pereira, Sandro; Miragaia, Maria; Sanches, Ilda Santos; de Lencastre, Hermínia

    2001-01-01

    The emergence of coagulase-negative staphylococci not only as human pathogens but also as reservoirs of antibiotic resistance determinants requires the deployment and development of methods for their rapid and reliable identification. Internal transcribed spacer-PCR (ITS-PCR) was used to identify a collection of 617 clinical staphylococcal isolates. The amplicons were resolved in high-resolution agarose gels and visually compared with the patterns obtained for the control strains of 29 staphylococcal species. Of the 617 isolates studied, 592 (95.95%) were identified by ITS-PCR and included 11 species: 302 isolates of Staphylococcus epidermidis, 157 of S. haemolyticus, 79 of S. aureus, 21 of S. hominis, 14 of S. saprophyticus, 8 of S. warneri, 6 of S. simulans, 2 of S. lugdunensis, and 1 each of S. caprae, S. carnosus, and S. cohnii. All species analyzed had unique ITS-PCR patterns, although some were very similar, namely, the group S. saprophyticus, S. cohnii, S. gallinarum, S. xylosus, S. lentus, S. equorum, and S. chromogenes, the pair S. schleiferi and S. vitulus, and the pair S. piscifermentans and S. carnosus. Four species, S. aureus, S. caprae, S. haemolyticus, and S. lugdunensis, showed polymorphisms on their ITS-PCR patterns. ITS-PCR proved to be a valuable alternative for the identification of staphylococci, offering, within the same response time and at lower cost, higher reliability than the currently available commercial systems. PMID:11526135

  14. Identification of clinical staphylococcal isolates from humans by internal transcribed spacer PCR.

    Science.gov (United States)

    Couto, I; Pereira, S; Miragaia, M; Sanches, I S; de Lencastre, H

    2001-09-01

    The emergence of coagulase-negative staphylococci not only as human pathogens but also as reservoirs of antibiotic resistance determinants requires the deployment and development of methods for their rapid and reliable identification. Internal transcribed spacer-PCR (ITS-PCR) was used to identify a collection of 617 clinical staphylococcal isolates. The amplicons were resolved in high-resolution agarose gels and visually compared with the patterns obtained for the control strains of 29 staphylococcal species. Of the 617 isolates studied, 592 (95.95%) were identified by ITS-PCR and included 11 species: 302 isolates of Staphylococcus epidermidis, 157 of S. haemolyticus, 79 of S. aureus, 21 of S. hominis, 14 of S. saprophyticus, 8 of S. warneri, 6 of S. simulans, 2 of S. lugdunensis, and 1 each of S. caprae, S. carnosus, and S. cohnii. All species analyzed had unique ITS-PCR patterns, although some were very similar, namely, the group S. saprophyticus, S. cohnii, S. gallinarum, S. xylosus, S. lentus, S. equorum, and S. chromogenes, the pair S. schleiferi and S. vitulus, and the pair S. piscifermentans and S. carnosus. Four species, S. aureus, S. caprae, S. haemolyticus, and S. lugdunensis, showed polymorphisms on their ITS-PCR patterns. ITS-PCR proved to be a valuable alternative for the identification of staphylococci, offering, within the same response time and at lower cost, higher reliability than the currently available commercial systems.

  15. Fluorescence properties of human teeth and dental calculus for clinical applications

    Science.gov (United States)

    Lee, Yong-Keun

    2015-04-01

    Fluorescent emission of human teeth and dental calculus is important for the esthetic rehabilitation of teeth, diagnosis of dental caries, and detection of dental calculus. The purposes of this review were to summarize the fluorescence and phosphorescence of human teeth by ambient ultraviolet (UV) light, to investigate the clinically relevant fluorescence measurement methods in dentistry, and to review the fluorescence of teeth and dental calculus by specific wavelength light. Dentine was three times more phosphorescent than enamel. When exposed to light sources containing UV components, the fluorescence of human teeth gives them the quality of vitality, and fluorescent emission with a peak of 440 nm is observed. Esthetic restorative materials should have fluorescence properties similar to those of natural teeth. Based on the fluorescence of teeth and restorative materials as determined with a spectrophotometer, a fluorescence parameter was defined. As to the fluorescence spectra by a specific wavelength, varied wavelengths were investigated for clinical applications, and several methods for the diagnosis of dental caries and the detection of dental calculus were developed. Since fluorescent properties of dental hard tissues have been used and would be expanded in diverse fields of clinical practice, these properties should be investigated further, embracing newly developed optical techniques.

  16. A review of human factors principles for the design and implementation of medication safety alerts in clinical information systems

    OpenAIRE

    Phansalkar, Shobha; Edworthy, Judy; Hellier, Elizabeth; Seger, Diane L; Schedlbauer, Angela; Avery, Anthony J; Bates, David W

    2010-01-01

    The objective of this review is to describe the implementation of human factors principles for the design of alerts in clinical information systems. First, we conduct a review of alarm systems to identify human factors principles that are employed in the design and implementation of alerts. Second, we review the medical informatics literature to provide examples of the implementation of human factors principles in current clinical information systems using alerts to provide medication decisio...

  17. MORPHOLOGICAL STUDY OF THE HUMAN OVARY IN DIFFERENT AGE GROUPS

    Directory of Open Access Journals (Sweden)

    Ritu Saloi

    2017-02-01

    Full Text Available BACKGROUND Ovarian pathology can manifest in various ways, e.g. menstrual abnormalities, cystic disease, infertility, benign and malignant tumours of the ovary, etc. Ovarian cancer is one of the leading cancers in Indian women. The aim was undertaken to observe the age-related changes in the human ovary and to study if there is any difference between the right and left ovaries with respect to length, breadth, thickness and weight and compare it with the established findings of previous workers, which will help the clinicians to adopt appropriate diagnosis and treatment of the various clinical conditions associated with the ovaries. MATERIALS AND METHODS A study on human ovary was conducted in the Department of Anatomy, Gauhati Medical College, Guwahati. The morphological characteristics of 42 pairs of normal human ovaries of different age groups were studied (14 pairs in each age group. The ovaries were divided into three groups, viz. Group A or pre-reproductive, Group B or reproductive and Group C or postmenopausal. The results were statistically analysed and ‘t’ test was done to find out the significant difference of mean value. RESULTS The morphology of the ovary including the length, breadth, thickness and weight of the three groups were measured and the findings were compared with each other and also with the findings of studies done by previous workers. CONCLUSION The study showed that there were certain differences in the morphology of ovary in the three groups. The study also revealed that the weight of the right ovary was more than the left ovary in all the three age groups. The results were statistically analysed and compared with the findings of previous workers.

  18. In Vitro Maturation of a Humanized Shark VNAR Domain to Improve Its Biophysical Properties to Facilitate Clinical Development

    Directory of Open Access Journals (Sweden)

    John Steven

    2017-10-01

    Full Text Available Molecular engineering to increase the percentage identity to common human immunoglobulin sequences of non-human therapeutic antibodies and scaffolds has become standard practice. This strategy is often used to reduce undesirable immunogenic responses, accelerating the clinical development of candidate domains. The first humanized shark variable domain (VNAR was reported by Kovalenko and colleagues and used the anti-human serum albumin (HSA domain, clone E06, as a model to construct a number of humanized versions including huE06v1.10. This study extends this work by using huE06v1.10 as a template to isolate domains with improved biophysical properties and reduced antigenicity. Random mutagenesis was conducted on huE06v1.10 followed by refinement of clones through an off-rate ranking-based selection on target antigen. Many of these next-generation binders retained high affinity for target, together with good species cross-reactivity. Lead domains were assessed for any tendency to dimerize, tolerance to N- and C-terminal fusions, affinity, stability, and relative antigenicity in human dendritic cell assays. Functionality of candidate clones was verified in vivo through the extension of serum half-life in a typical drug format. From these analyses the domain, BA11, exhibited negligible antigenicity, high stability and high affinity for mouse, rat, and HSA. When these attributes were combined with demonstrable functionality in a rat model of PK, the BA11 clone was established as our clinical candidate.

  19. Inter-observer reliability assessments in time motion studies: the foundation for meaningful clinical workflow analysis.

    Science.gov (United States)

    Lopetegui, Marcelo A; Bai, Shasha; Yen, Po-Yin; Lai, Albert; Embi, Peter; Payne, Philip R O

    2013-01-01

    Understanding clinical workflow is critical for researchers and healthcare decision makers. Current workflow studies tend to oversimplify and underrepresent the complexity of clinical workflow. Continuous observation time motion studies (TMS) could enhance clinical workflow studies by providing rich quantitative data required for in-depth workflow analyses. However, methodological inconsistencies have been reported in continuous observation TMS, potentially reducing the validity of TMS' data and limiting their contribution to the general state of knowledge. We believe that a cornerstone in standardizing TMS is to ensure the reliability of the human observers. In this manuscript we review the approaches for inter-observer reliability assessment (IORA) in a representative sample of TMS focusing on clinical workflow. We found that IORA is an uncommon practice, inconsistently reported, and often uses methods that provide partial and overestimated measures of agreement. Since a comprehensive approach to IORA is yet to be proposed and validated, we provide initial recommendations for IORA reporting in continuous observation TMS.

  20. Clinical waste incinerators in Cameroon--a case study

    DEFF Research Database (Denmark)

    Mochungong, Peter Ikome Kuwoh; Gulis, Gabriel; Sodemann, Morten

    2012-01-01

    Incinerators are widely used to treat clinical waste in Cameroon's Northwest Region. These incinerators cause public apprehension owing to purported risks to operators, communities and the environment. This article aims to summarize findings from an April 2008 case study....

  1. Facilitating Case Studies in Massage Therapy Clinical Education

    Science.gov (United States)

    Baskwill, Amanda

    2013-01-01

    The integration of evidence into reflective health care practice has been on the rise in recent years and is a phenomenon that has affected all health care professions, including massage therapy. Clinical case studies are a research design that follows one patient or subject, making the studies ideal for use in clinical practice. They are valuable for communicating information from clinical practice to the broader community. Case studies have face validity that may be more valuable to individual practitioners than homogeneous randomized controlled trials, as the practitioner may recognize a complex patient in the case report. At Humber College, Student Massage Therapists (SMTs) create, conduct, and communicate results of a clinical case study prior to graduation. This article describes the process and experience. PMID:23730397

  2. Case Study: Caregiver Perception of Pediatric Multidisciplinary Feeding Outpatient Clinic

    Directory of Open Access Journals (Sweden)

    Thomas F. Fisher PhD, OT, FAOTA

    2014-01-01

    Full Text Available This study explores the perception of satisfaction of caregivers who attended a feeding clinic at a large pediatric hospital in the midwest. The clinic is designed for a multidisciplinary team to meet with the child and the caregiver. Thirty-five participants were involved in the study. Results indicated that most participants were satisfied with the clinic experience. However, there were areas of care not covered by the members of the feeding team, which indicates a need. It is suggested that this need could be filled by occupational therapists.

  3. Phase I study of anticolon cancer humanized antibody A33.

    Science.gov (United States)

    Welt, Sydney; Ritter, Gerd; Williams, Clarence; Cohen, Leonard S; John, Mary; Jungbluth, Achim; Richards, Elizabeth A; Old, Lloyd J; Kemeny, Nancy E

    2003-04-01

    Humanized A33 (huA33; IgG1) monoclonal antibody detects a determinant expressed by 95% of colorectal cancers and can activate immune cytolytic mechanisms. The present study was designed to (a) define the toxicities and maximum tolerated dose of huA33 and (b) determine huA33 immunogenicity. Patients (n = 11) with advanced chemotherapy-resistant colorectal cancer received 4-week cycles of huA33 at 10, 25, or 50 mg/m(2)/week. Serum samples were analyzed using biosensor technology for evidence of human antihuman antibody (HAHA) response. Eight of 11 patients developed a HAHA response. Significant toxicity was limited to four patients who developed high HAHA titers. In two of these cases, infusion-related reactions such as fevers, rigors, facial flushing, and changes in blood pressure were observed, whereas in the other two cases, toxicity consisted of skin rash, fever, or myalgia. Of three patients who remained HAHA negative, one achieved a radiographic partial response, with reduction of serum carcinoembryonic antigen from 80 to 3 ng/ml. Four patients had radiographic evidence of stable disease (2, 4, 6, and 12 months), with significant reductions (>25%) in serum carcinoembryonic antigen levels in two cases. The complementarity-determining region-grafted huA33 antibody is immunogenic in the majority of colon cancer patients (73%). HAHA activity can be measured reproducibly and quantitatively by BIACORE analysis. Whereas the huA33 construct tested here may be too immunogenic for further clinical development, the antitumor effects observed in the absence of antibody-mediated toxicity and in this heavily pretreated patient population warrant clinical testing of other IgG1 humanized versions of A33 antibody.

  4. Genome-wide association study of clinical dimensions of schizophrenia

    DEFF Research Database (Denmark)

    Fanous, Ayman H; Zhou, Baiyu; Aggen, Steven H

    2012-01-01

    Multiple sources of evidence suggest that genetic factors influence variation in clinical features of schizophrenia. The authors present the first genome-wide association study (GWAS) of dimensional symptom scores among individuals with schizophrenia.......Multiple sources of evidence suggest that genetic factors influence variation in clinical features of schizophrenia. The authors present the first genome-wide association study (GWAS) of dimensional symptom scores among individuals with schizophrenia....

  5. Clinical Outcomes Used in Clinical Pharmacy Intervention Studies in Secondary Care

    Directory of Open Access Journals (Sweden)

    Lene Juel Kjeldsen

    2017-05-01

    Full Text Available The objective was to investigate type, frequency and result of clinical outcomes used in studies to assess the effect of clinical pharmacy interventions in inpatient care. The literature search using Pubmed.gov was performed for the period up to 2013 using the search phrases: “Intervention(s” and “pharmacist(s” and “controlled” and “outcome(s” or “effect(s”. Primary research studies in English of controlled, clinical pharmacy intervention studies, including outcome evaluation, were selected. Titles, abstracts and full-text papers were assessed individually by two reviewers, and inclusion was determined by consensus. In total, 37 publications were included in the review. The publications presented similar intervention elements but differed in study design. A large variety of outcome measures (135 had been used to evaluate the effect of the interventions; most frequently clinical measures/assessments by physician and health care service use. No apparent pattern was established among primary outcome measures with significant effect in favour of the intervention, but positive effect was most frequently related to studies that included power calculations and sufficient inclusion of patients (73% vs. 25%. This review emphasizes the importance of considering the relevance of outcomes selected to assess clinical pharmacy interventions and the importance of conducting a proper power calculation.

  6. Subjective Quantitative Studies of Human Agency

    Science.gov (United States)

    Alkire, Sabina

    2005-01-01

    Amartya Sen's writings have articulated the importance of human agency, and identified the need for information on agency freedom to inform our evaluation of social arrangements. Many approaches to poverty reduction stress the need for empowerment. This paper reviews "subjective quantitative measures of human agency at the individual level." It…

  7. Platelet-rich plasma in orthopedic therapy: a comparative systematic review of clinical and experimental data in equine and human musculoskeletal lesions.

    Science.gov (United States)

    Brossi, Patrícia M; Moreira, Juliana J; Machado, Thaís S L; Baccarin, Raquel Y A

    2015-04-22

    This systematic review aimed to present and critically appraise the available information on the efficacy of platelet rich plasma (PRP) in equine and human orthopedic therapeutics and to verify the influence of study design and methodology on the assumption of PRP's efficacy. We searched Medline, PubMed, Embase, Bireme and Google Scholar without restrictions until July 2013. Randomized trials, human cohort clinical studies or case series with a control group on the use of PRP in tendons, ligaments or articular lesions were included. Equine clinical studies on the same topics were included independently of their design. Experimental studies relevant to the clarification of PRP's effects and mechanisms of action in tissues of interest, conducted in any animal species, were selected. This review included 123 studies. PRP's beneficial effects were observed in 46.7% of the clinical studies, while the absence of positive effects was observed in 43.3%. Among experimental studies, 73% yielded positive results, and 7.9% yielded negative results. The most frequent flaws in the clinical trials' designs were the lack of a true placebo group, poor product characterization, insufficient blinding, small sampling, short follow-up periods, and adoption of poor outcome measures. The methods employed for PRP preparation and administration and the selected outcome measures varied greatly. Poor study design was a common feature of equine clinical trials. From studies in which PRP had beneficial effects, 67.8% had an overall high risk of bias. From the studies in which PRP failed to exhibit beneficial effects, 67.8% had an overall low risk of bias. Most experimental studies revealed positive effects of PRP. Although the majority of equine clinical studies yielded positive results, the human clinical trials' results failed to corroborate these findings. In both species, beneficial results were more frequently observed in studies with a high risk of bias. The use of PRP in musculoskeletal

  8. Cytological techniques to study human female meiotic prophase.

    Science.gov (United States)

    Roig, Ignasi; Garcia-Caldés, Montserrat

    2009-01-01

    Most of the human aneuploidies have a maternal origin. This feature makes the study of human female meiosis a fundamental topic to understand the reasons leading to this important social problem. Unfortunately, due to sample collection difficulties, not many studies have been performed on human female meiotic prophase. In this chapter we present a comprehensive collection of protocols that allows the study of human female meiotic prophase through different technical approaches using both spread and structurally preserved oocytes.

  9. Microneedle delivery: clinical studies and emerging medical applications.

    Science.gov (United States)

    Pettis, Ronald J; Harvey, Alfred J

    2012-03-01

    The concept of microneedle drug delivery was described three decades ago; however, effective clinical demonstration has only occurred within the past 10-15 years. Substantial progress in microneedle design and fabrication including extensive in vitro, ex vivo, and in vivo preclinical evaluation with various drugs, vaccines and other agents has transpired over the last decade. In contrast with this large volume of preclinical data, there are relatively few published microneedle clinical studies. To date, the clinical investigative focus has included testing to reduce dermal barrier properties and enhance transdermal delivery; evaluation of enhanced vaccine antigenicity, including development of the first commercial microneedle product for intradermal influenza vaccination; evaluation of altered microneedle protein pharmacokinetics and pharmacodynamics, especially for insulin; and evaluation of the pain and other perceptions associated with microneedle usage. This review summarizes the various aspects of microneedle clinical evaluation to date and identifies areas requiring further clinical evaluation.

  10. Prospective assessment of clinical symptoms associated with enterovirus and parechovirus genotypes in a multicenter study in Dutch children

    NARCIS (Netherlands)

    de Crom, S. C. M.; Rossen, J. W. A.; de Moor, R. A.; Veldkamp, E. J. M.; van Furth, A. M.; Obihara, C. C.

    Background: Human non-polio enterovirus (EV) and human parechovirus (HPeV) are important pathogens viral infection and aseptic meningitis in children. The aim of this study is to prospectively compare the incidence, clinical signs, blood and cerebrospinal fluid in EV and HPeV infected children.

  11. Recent Developments in Instrumentation for Pre-Clinical Imaging Studies

    International Nuclear Information System (INIS)

    Meikle, S.R.

    2002-01-01

    Full text: Recent advances in imaging instrumentation have led to a variety of tomograph designs for dedicated pre clinical imaging of laboratory animals. These advances make it possible to image and quantify the kinetics of radiolabelled pharmaceuticals in a wide range of animal models from rodents to non-human primates. Applications include evaluation of promising new radiopharmaceuticals, study of the molecular origins of human disease and evaluation of new forms of therapy. These applications and advances in instrumentation are equally applicable to positron emitters and single photon emitters. This paper provides an overview of recent advances which have led to the current state-of-the-art in pre clinical imaging. The common inorganic scintillators that have been used for SPECT and PET, including some of the promising materials recently studied. The current crystal of choice for SPECT imaging is NaI(Tl) because of its high light output and density which make it well suited to imaging photons in the 100-200 keV range. However, NaI(Tl) has the disadvantage that it must be hermetically sealed to prevent absorption of moisture from the environment. Therefore, investigators have explored a number of alternative inorganic crystals, including CsI(Tl) and cerium-doped yttrium aluminium perovskite (YAP), as well as solid state detectors such as cadmium zinc telluride (CZT). Many of the crystals used in SPECT have also been tried for PET, including NaI(Tl) and YAP. However these crystals have lower stopping power than BGO and NaI(Tl) is also relatively slow. A very promising scintillator for PET is cerium-doped lutetium oxyorthosilicate (LSO) (1) which has similar stopping power to BGO and relatively high light output and fast decay. The first PET scanner to use LSO was the UCLA animal scanner, microPET, which also makes use of a number of other new technologies and unique design features. Recently, improvements in multi-anode and crossed wire position sensitive

  12. Understanding implementation processes of clinical pathways and clinical practice guidelines in pediatric contexts: a study protocol

    Directory of Open Access Journals (Sweden)

    Scott Shannon D

    2011-12-01

    Full Text Available Abstract Background Canada is among the most prosperous nations in the world, yet the health and wellness outcomes of Canadian children are surprisingly poor. There is some evidence to suggest that these poor health outcomes are partly due to clinical practice variation, which can stem from failure to apply the best available research evidence in clinical practice, otherwise known as knowledge translation (KT. Surprisingly, clinical practice variation, even for common acute paediatric conditions, is pervasive. Clinical practice variation results in unnecessary medical treatments, increased suffering, and increased healthcare costs. This study focuses on improving health outcomes for common paediatric acute health concerns by evaluating strategies that improve KT and reduce clinical practice variation. Design/Methods Using a multiple case study design, qualitative and quantitative data will be collected from four emergency departments in western Canada. Data sources will include: pre- and post-implementation focus group data from multidisciplinary healthcare professionals; individual interviews with the local champions, KT intervention providers, and unit/site leaders/managers; Alberta Context Tool (ACT survey data; and aggregated patient outcome data. Qualitative and quantitative data will be systematically triangulated, and matrices will be built to do cross-case comparison. Explanations will be built about the success or lack of success of the clinical practice guidelines (CPG and clinical pathways (CPs uptake based upon the cross-case comparisons. Significance This study will generate new knowledge about the potential causal mechanisms and factors which shape implementation. Future studies will track the impact of the CPG/CPs implementation on children's health outcome, and healthcare costs.

  13. submitter Clinical evaluation of the radiolanthanide terbium-152: first-in-human PET/CT with $^152$Tb-DOTATOC

    CERN Document Server

    Baum, Richard P; Benešová, Martina; Vermeulen, Christiaan; Gnesin, Silvano; Köster, Ulli; Johnston, Karl; Müller, Dirk; Senftleben, Stefan; Kulkarni, Harshad R; Türler, Andreas; Schibli, Roger; Prior, John O; van der Meulen, Nicholas P; Müller, Cristina

    2017-01-01

    The existence of theragnostic pairs of radionuclides allows the preparation of radiopharmaceuticals for diagnostic and therapeutic purposes. Radiolanthanides, such as $^{177}$Lu, are successfully used for therapeutic purposes; however, a perfect diagnostic match is currently not available for clinical use. A unique, multi-disciplinary study was performed using $^{152}$Tb ($T_{1/2}$ = 17.5 h, E$\\beta ^+_{average}$ = 1140 keV, I$β^+$ = 20.3%), which resulted in the first-in-human PET/CT images with this promising radionuclide. For this purpose, $^{152}$Tb was produced via a spallation process followed by mass separation at ISOLDE, CERN. The chemical separation and quality control, performed at PSI, resulted in a pure product in sufficient yields. Clinical PET phantom studies revealed an increased image noise level, because of the smaller $\\beta^+$ branching ratio of $^{152}$Tb as compared to standard PET nuclides at matched activity concentrations; however, the expected recovery would be comparable at matched ...

  14. Effect of cisplatin on the clinically relevant radiosensitivity of human cervical carcinoma cell lines

    International Nuclear Information System (INIS)

    Britten, Richard A.; Evans, Andrew J.; Allalunis-Turner, M. Joan; Pearcey, Robert G.

    1996-01-01

    Purpose: To evaluate the effect of clinically relevant levels of cisplatin on the radiosensitivity of human cervical tumor cells, and to estimate what changes in local control rates might be expected to accrue from the concomitant use of cisplatin during fractionated radiotherapy. Methods and Materials: The effects of concomitant cisplatin (1 μg/ml, a typical intratumor concentration) on the clinically relevant radiosensitivity, i.e., surviving fraction after 2 G (SF 2 ) values, was determined in 19 cloned human cervical tumor cell lines. These early passage cell lines had SF 2 values ranging from 0.26 to 0.87. Results: The concomitant administration of cisplatin reduced the clinically relevant radiosensitivity in the majority (11 out of 19) of the human tumor cell lines investigated. In only 4 out of 19 was any radiosensitization observed, and in 4 out of 19 cell lines there was no significant change in radiosensitivity. However, the sum of the independent cell killing by radiation and cisplatin, was approximately twofold higher than after radiation alone. There was no apparent dependence of the cisplatin-induced changes in SF 2 values upon the level of cell killing by cisplatin. However, there is a suggestion that concomitant cisplatin administration may have a differential effect in inherently radiosensitive and resistant human tumor cell lines. Conclusions: Our data suggest that concomitant cisplatin/radiotherapy regimens may result in a higher level of local tumor control, but primarily through additive toxicity and not through radiosensitization. Future improvements in local tumor control may, thus, be derived by increasing the total dose of cisplatin

  15. [Review of 1,172 clinical cases with human communication disorders].

    Science.gov (United States)

    de Díaz, M R; de Pustilnik, N F; Tortolero, Y

    1976-01-01

    The study comprised 1,172 clinical cases that were classified according to sex, age and speech disorders. A review is made on the most common alterations that they present, the selective treatment in each type and their rehabilitation.

  16. A review on the clinical spectrum and natural history of human influenza.

    Science.gov (United States)

    Punpanich, Warunee; Chotpitayasunondh, Tawee

    2012-10-01

    The objective of this review is to provide updated information on the clinical spectrum and natural history of human influenza, including risk factors for severe disease, and to identify the knowledge gap in this area. We searched the MEDLINE database of the recent literature for the period January 2009 to August 17, 2011 with regard to the abovementioned aspects of human influenza, focusing on A(H1N1)pdm09 and seasonal influenza. The clinical spectrum and outcomes of cases of A(H1N1)pdm09 influenza have been mild and rather indistinguishable from those of seasonal influenza. Sporadic cases covering a wide range of neurological complications have been reported. Underlying predisposing conditions considered to be high-risk for A(H1N1)pdm09 infections are generally similar to those of seasonal influenza, but with two additional risk groups: pregnant women and the morbidly obese. Co-infections with bacteria and D222/N variants or 225G substitution of the viral genome have also been reported to be significant factors associated with the severity of disease. The current knowledge gap includes: (1) a lack of clarification regarding the relatively greater severity of the Mexican A(H1N1)pdm09 influenza outbreak in the early phase of the pandemic; (2) insufficient data on the clinical impact, risk factors, and outcomes of human infections caused by resistant strains of influenza; and (3) insufficient data from less developed countries that would enable them to prioritize strategies for influenza prevention and control. Clinical features and risk factors of A(H1N1)pdm09 are comparable to those of seasonal influenza. Emerging risk factors for severe disease with A(H1N1)pdm09 include morbid obesity, pregnancy, bacterial co-infections, and D222/N variants or 225G substitution of the viral genome. Copyright © 2012 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  17. Effects of direct-to-consumer advertising and clinical guidelines on appropriate use of human papillomavirus DNA tests.

    Science.gov (United States)

    Price, Rebecca Anhang; Frank, Richard G; Cleary, Paul D; Goldie, Sue J

    2011-02-01

    Both clinical guidelines and direct-to-consumer (DTC) advertising influence the use of new health care technologies, but little is known about their relative effects. The introduction of a cervical cancer screening test in 2000 offered a unique opportunity to assess the 2 strategies. To evaluate the effects of clinical guidelines and a targeted DTC advertising campaign on overall and appropriate use of human papillomavirus (HPV) DNA tests. Quasi-experimental study using difference-in-differences analysis. Data were MarketScan private insurance claims for 500,000 women aged 21 to 64 enrolled at least 12 consecutive months from January 2001 through December 2005. Both clinical guidelines and DTC advertising were associated with increases in overall HPV DNA test use. DTC advertising was associated with a statistically significant increase in HPV DNA test use in 2 groups of DTC cities (+5.57%, P advertising was associated with comparable increases in the probability of appropriate and inappropriate use of the HPV DNA test in primary screening. Clinical guideline releases from the American College of Obstetricians and Gynecologists, and by a cosponsored panel, were associated with greater increases in HPV DNA tests for appropriate primary screening than for inappropriate primary screening (β = 0.3347, P advertising was associated with increased overall use of a cervical cancer screening test, whereas clinical guidelines were differentially associated with increased appropriate use. These findings suggest distinct influences of consumer marketing and professional guidelines on the use of health care products and services.

  18. The experience of graduated midwifery students about clinical education: A phenomenological study

    Directory of Open Access Journals (Sweden)

    R. Shahoei

    2013-06-01

    Full Text Available Introduction: Improvement and promotion of the quality of clinical education requires continuous assessment of the current situation, and also identifying the strengths and weaknesses. Students' views and ideas as learner can help future planning. This study aims to identify the experiences of midwifery graduates about factors affecting their clinical learning. Methods: A qualitative study using phenomenology approach was conducted. Ten midwifery graduates were selected based on purposive sampling and then interviewed. Data were analyzed by thematic analysis. Results: The extracted conceptual codes were classified into several main concepts. There were two main themes factors facilitating learning and factors preventing learning, and seven sub themes performance of instructor, pre-clinical training, students satisfaction, lack of peripheral facilities, lack of coordination of educational planning and behaviors of health care personnel. Conclusion: Trained human resources and equipment for midwifery educational planning are needed to provide a supportive learning atmosphere and promote the quality of clinical learning.

  19. Prospective Clinical Study of Precision Oncology in Solid Tumors.

    Science.gov (United States)

    Sohal, Davendra P S; Rini, Brian I; Khorana, Alok A; Dreicer, Robert; Abraham, Jame; Procop, Gary W; Saunthararajah, Yogen; Pennell, Nathan A; Stevenson, James P; Pelley, Robert; Estfan, Bassam; Shepard, Dale; Funchain, Pauline; Elson, Paul; Adelstein, David J; Bolwell, Brian J

    2015-11-09

    Systematic studies evaluating clinical benefit of tumor genomic profiling are lacking. We conducted a prospective study in 250 patients with select solid tumors at the Cleveland Clinic. Eligibility required histopathologic diagnosis, age of 18 years or older, Eastern Cooperative Oncology Group performance status 0-2, and written informed consent. Tumors were sequenced using FoundationOne (Cambridge, MA). Results were reviewed at the Cleveland Clinic Genomics Tumor Board. Outcomes included feasibility and clinical impact. Colorectal (25%), breast (18%), lung (13%), and pancreatobiliary (13%) cancers were the most common diagnoses. Median time from consent to result was 25 days (range = 3-140). Of 223 evaluable samples, 49% (n = 109) of patients were recommended a specific therapy, but only 11% (n = 24) received such therapy: 12 on clinical trials, nine off-label, three on-label. Lack of clinical trial access (n = 49) and clinical deterioration (n = 29) were the most common reasons for nonrecommendation/nonreceipt of genomics-driven therapy. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  20. Understanding Motivation for Study: Human Capital or Human Capability?

    Science.gov (United States)

    Fredman, Nick

    2014-01-01

    Much research into the reasons students undertake tertiary study is at least implicitly based on rational choice theory: students calculate costs in order to maximize direct individual gain. The policy emphasis on pathways has somewhat broader bases including social inclusion as well as economic productivity, but narrowly focuses on institutional…

  1. Human Induced Pluripotent Stem Cells from Basic Research to Potential Clinical Applications in Cancer

    Directory of Open Access Journals (Sweden)

    Teresa de Souza Fernandez

    2013-01-01

    Full Text Available The human induced pluripotent stem cells (hiPSCs are derived from a direct reprogramming of human somatic cells to a pluripotent stage through ectopic expression of specific transcription factors. These cells have two important properties, which are the self-renewal capacity and the ability to differentiate into any cell type of the human body. So, the discovery of hiPSCs opens new opportunities in biomedical sciences, since these cells may be useful for understanding the mechanisms of diseases in the production of new diseases models, in drug development/drug toxicity tests, gene therapies, and cell replacement therapies. However, the hiPSCs technology has limitations including the potential for the development of genetic and epigenetic abnormalities leading to tumorigenicity. Nowadays, basic research in the hiPSCs field has made progress in the application of new strategies with the aim to enable an efficient production of high-quality of hiPSCs for safety and efficacy, necessary to the future application for clinical practice. In this review, we show the recent advances in hiPSCs’ basic research and some potential clinical applications focusing on cancer. We also present the importance of the use of statistical methods to evaluate the possible validation for the hiPSCs for future therapeutic use toward personalized cell therapies.

  2. Recommendations on disease management for patients with advanced human epidermal growth factor receptor 2-positive breast cancer and brain metastases: American Society of Clinical Oncology clinical practice guideline.

    Science.gov (United States)

    Ramakrishna, Naren; Temin, Sarah; Chandarlapaty, Sarat; Crews, Jennie R; Davidson, Nancy E; Esteva, Francisco J; Giordano, Sharon H; Gonzalez-Angulo, Ana M; Kirshner, Jeffrey J; Krop, Ian; Levinson, Jennifer; Modi, Shanu; Patt, Debra A; Perez, Edith A; Perlmutter, Jane; Winer, Eric P; Lin, Nancy U

    2014-07-01

    To provide formal expert consensus-based recommendations to practicing oncologists and others on the management of brain metastases for patients with human epidermal growth factor receptor 2 (HER2) -positive advanced breast cancer. The American Society of Clinical Oncology (ASCO) convened a panel of medical oncology, radiation oncology, guideline implementation, and advocacy experts and conducted a systematic review of the literature. When that failed to yield sufficiently strong quality evidence, the Expert Panel undertook a formal expert consensus-based process to produce these recommendations. ASCO used a modified Delphi process. The panel members drafted recommendations, and a group of other experts joined them for two rounds of formal ratings of the recommendations. No studies or existing guidelines met the systematic review criteria; therefore, ASCO conducted a formal expert consensus-based process. Patients with brain metastases should receive appropriate local therapy and systemic therapy, if indicated. Local therapies include surgery, whole-brain radiotherapy, and stereotactic radiosurgery. Treatments depend on factors such as patient prognosis, presence of symptoms, resectability, number and size of metastases, prior therapy, and whether metastases are diffuse. Other options include systemic therapy, best supportive care, enrollment onto a clinical trial, and/or palliative care. Clinicians should not perform routine magnetic resonance imaging (MRI) to screen for brain metastases, but rather should have a low threshold for MRI of the brain because of the high incidence of brain metastases among patients with HER2-positive advanced breast cancer. © 2014 by American Society of Clinical Oncology.

  3. Characterization of Hospital-Associated Lineages of Ampicillin-Resistant Enterococcus faecium from Clinical Cases in Dogs and Humans

    Directory of Open Access Journals (Sweden)

    Cindy-Love eTremblay

    2013-08-01

    Full Text Available Ampicillin-resistant Enterococcus faecium (ARE has rapidly emerged worldwide and is one of the most important nosocomial pathogens. However, very few reports are available on ARE isolates from canine clinical cases. The objective of this study was to characterize ARE strains of canine clinical origin from a veterinary teaching hospital in Canada and to compare them with human strains. Ten ARE strains from dogs and humans were characterized by multilocus sequence typing (MLST, pulsed field gel electrophoresis (PFGE, antibiotic susceptibility and biofilm activities, presence of rep-families, CRISPR-cas and putative virulence genes. All ARE strains (n = 10 were resistant to ciprofloxacin and lincomycin. Resistances to tetracycline (n = 6, macrolides (n = 6, and to high concentrations of gentamicin, kanamycin and streptomycin (n = 5 were also observed. Canine ARE isolates were found to be susceptible to vancomycin whereas resistance to this antibiotic was observed in human strains. Ampicillin resistance was linked to PBP5 showing mutations at 25 amino acid positions. Fluoroquinolone resistance was attributable to ParC, GyrA, and GyrB mutations. Data demonstrated that all canine ARE were acm (collagen binding protein-positive and that most harbored the efaAfm gene, encoding for a cell wall adhesin. Biofilm formation was observed in two human strains but not in canine strains. Two to five rep-families were observed per strain but no CRISPR sequences were found. A total of six STs (1, 18, 65, 202, 205, and 803 were found with one belonging to a new ST (ST803. These STs were identical or closely related to human hospital-associated lineages. This report describes for the first time the characterization of canine ARE hospital-associated strains in Canada and also supports the importance of prudent antibiotic use in veterinary medicine to avoid zoonotic spread of canine ARE.

  4. Evidenced-based review of clinical studies on periodontics.

    Science.gov (United States)

    2009-08-01

    Periodontal diseases have several implications for the practice of endodontics. First, advanced periodontitis often has direct implications for the long-term prognosis of the case and requires careful evaluation and coordinated treatment of both the periodontic and endodontic diseases. Second, the potential for functional interactions between odontogenic pathoses and marginal periodontitis requires careful collection of clinical observations and monitoring the outcome of various treatments. In this section, we provide an analysis of recent clinical studies in this area.

  5. A human factors needs assessment and planning study

    International Nuclear Information System (INIS)

    Price, H.E.; Van Cott, H.P.

    1982-06-01

    A study was done to assess the need for human factors research, development, and regulatory action in the Atomic Energy Control Board. Further study or development in nine human factors areas is proposed. The urgency, schedule, and resources judged to be necessary for the proposed efforts are estimated. Special emphasis is placed on the need for task analysis information, for the evaluation of control room and maintenance human engineering, and for the development of an improved human error reporting system

  6. The effect of skin-to-skin contact at birth, early versus immediate, on the duration of exclusive human lactancy in full-term newborns treated at the Clínica Universidad de La Sabana: study protocol for a randomized clinical trial.

    Science.gov (United States)

    Agudelo, Sergio; Gamboa, Oscar; Rodríguez, Fabio; Cala, Sandra; Gualdrón, Nathalie; Obando, Evelyn; Padrón, María Lucía

    2016-10-26

    Human lactancy is a simple and cost-effective strategy that influences infant and maternal mortality rates. Skin-to-skin contact (SSC) is an immediate postpartum period strategy that has proven to benefit the initiation and continuation of human lactation and to decrease hospitalization during the first week of life. This study aims to determine the effect of SSC initiation at birth (immediate versus early) in healthy, full-term newborns treated at the Universidad de La Sabana Clinic on the duration of exclusive human lactation. A randomized, blind clinical trial will be performed with full-term healthy newborns born at the Universidad de La Sabana Clinic. The blind trial participants will be those persons measuring the results and analyzing the data. The sample size will be calculated for a type I error of 5 %, a two-tailed type II error of 20 %, and an estimated percentage loss of 30 %; 150 infants will be included in each group. Randomization will be performed using permuted, size-6 blocks. Descriptive analysis will be conducted using central tendency and dispersion measurements. A bivariate analysis will be performed to determine which variables are associated with exclusive lactancy at 6 months. For continuous variables, Student's t test will be used for independent samples, and the Wilcoxon rank sum test will be used if the assumptions of normality for the t tests are not fulfilled. The assumption of normality will be evaluated using the Shapiro-Wilk and Kolmogorov-Smirnov tests. Categorical variables in contingency tables will be constructed to assess the independence between variables using the chi-square test, or Fisher's exact test when the assumption of the number of cases is not met by the values in the contingency tables multiplied by two. This will be calculated as a measurement of the effect of relative risk (RR) with confidence intervals; the adjusted measurements will be calculated using a multivariate regression Poisson model. Variables with

  7. Acute radiation proctitis. A clinical, histopathological and histochemical study

    International Nuclear Information System (INIS)

    Hovdenak, Nils

    2004-01-01

    The aim of the study is: 1) A sequential description of the clinical course of acute radiation proctitis during pelvic RT. 2) A sequential description of the rectal mucosal histopathology during pelvic RT as a possible substrate for clinical toxicity. 3) To assess the mucosal protease activity during RT as a possible explanation of the observed tissue changes. 4) To assess the efficacy of prophylactic sucralfate in acute radiation proctitis a randomised study was initiated and carried out together with a meta-analysis of previously available data. 5) Most studies on clinical acute toxicity in pelvic RT use either the RTOG/EORTC score system or focus on diarrhoea/stool frequency. A more differentiated and sensitive recording was developed and tested to pick up symptoms escaping the commonly used scores. 6) Study the relation between histopathological findings and the clinical picture. 4 papers presenting various studies are included. The titles are: 1) Acute radiation proctitis: a sequential clinicopathologic study during pelvic radiotherapy. 2) Clinical significance of increased gelatinolytic activity in the rectal mucosa during external beam radiation therapy of prostate cancer. 3) Profiles and time course of acute radiation toxicity symptoms during conformal radiotherapy for cancer of the prostate. 4) Sucralfate does not ameliorate acute radiation proctitis. Some future prospects are discussed

  8. Acute radiation proctitis. A clinical, histopathological and histochemical study

    Energy Technology Data Exchange (ETDEWEB)

    Hovdenak, Nils

    2004-07-01

    The aim of the study is: 1) A sequential description of the clinical course of acute radiation proctitis during pelvic RT. 2) A sequential description of the rectal mucosal histopathology during pelvic RT as a possible substrate for clinical toxicity. 3) To assess the mucosal protease activity during RT as a possible explanation of the observed tissue changes. 4) To assess the efficacy of prophylactic sucralfate in acute radiation proctitis a randomised study was initiated and carried out together with a meta-analysis of previously available data. 5) Most studies on clinical acute toxicity in pelvic RT use either the RTOG/EORTC score system or focus on diarrhoea/stool frequency. A more differentiated and sensitive recording was developed and tested to pick up symptoms escaping the commonly used scores. 6) Study the relation between histopathological findings and the clinical picture. 4 papers presenting various studies are included. The titles are: 1) Acute radiation proctitis: a sequential clinicopathologic study during pelvic radiotherapy. 2) Clinical significance of increased gelatinolytic activity in the rectal mucosa during external beam radiation therapy of prostate cancer. 3) Profiles and time course of acute radiation toxicity symptoms during conformal radiotherapy for cancer of the prostate. 4) Sucralfate does not ameliorate acute radiation proctitis. Some future prospects are discussed.

  9. Improvement in the performance of external quality assessment in Korean HIV clinical laboratories using unrecalcified human plasma.

    Science.gov (United States)

    Wang, Jin-Sook; Kee, Mee-Kyung; Choi, Byeong-Sun; Kim, Chan-Wha; Kim, Hyon-Suk; Kim, Sung Soon

    2012-01-01

    The external quality assessment schemes (EQAS) organizer provides a suitable program to monitor and improve the quality of human immunodeficiency virus (HIV) testing laboratories with EQAS panels prepared under various conditions. The aim of the current study was to investigate the effects of human plasma samples on the EQAS results of HIV obtained from hospital-based clinical laboratories. From 2007 to 2009, HIV EQAS panels consisted of four to six samples that consisted of undiluted positive and negative samples and were provided to laboratories twice per year. Up until the first half EQAS in 2008, EQAS panel materials were obtained by converting acid citrate dextrose treated plasma to serum via chemical treatment with CaCl2. Beginning with the second EQAS in 2008, all materials were prepared without the defibrination process. Approximately 300 HIV clinical laboratories participated in this program. The overall performance of clinical laboratories was shown to be improved when using unrecalcified plasma panels compared with recalcified panels. Significant differences were observed in EIA analyses of plasma for both positive (plaboratories.

  10. A clinical evaluation of a bioresorbable membrane and porous hydroxyapatite in the treatment of human molar class II furcations

    Directory of Open Access Journals (Sweden)

    K Gita Malathi

    2013-01-01

    Full Text Available Background: The ultimate goal of periodontal therapy is predictable regeneration of a functional attachment apparatus destroyed as a result of periodontitis. Reconstructive procedures have been used with varying success during the past decades to accomplish this goal. Aim: To evaluate whether the use of porous hydroxyapatite alone or a bioresorbable membrane alone would enhance the clinical results in the treatment of class II furcation defects in human lower molars. Materials and Methods: Fifteen patients with chronic periodontitis, aged between 39 and 49 years, with a pair of similar bilateral class II furcation defects (classification of Hamp et al. in mandibular first molars were selected. A split-mouth design was incorporated and the selected 30 furcation defects were assigned to one of the two treatment groups, i.e., Group I treated with a bioresorbable membrane from bovine-derived collagen guided tissue regeneration membrane and Group II treated using porous hydroxyapatite bone graft material on the contralateral sides. Evaluation of clinical parameters, probing depths and attachment levels, and radiographs was done preoperatively and 6 months postoperatively. Results: Both the groups showed statistically significant mean reduction in probing depths and gain in clinical attachment levels and linear bone fill. Comparison between Group I and Group II showed insignificant difference. Conclusion: Within the limits of this study, both the treatment modalities are beneficial for the treatment of human mandibular class II furcation defects.

  11. Characterizing environmental risk factors for West Nile virus in Quebec, Canada, using clinical data in humans and serology in pet dogs.

    Science.gov (United States)

    Rocheleau, J P; Michel, P; Lindsay, L R; Drebot, M; Dibernardo, A; Ogden, N H; Fortin, A; Arsenault, J

    2017-10-01

    The identification of specific environments sustaining emerging arbovirus amplification and transmission to humans is a key component of public health intervention planning. This study aimed at identifying environmental factors associated with West Nile virus (WNV) infections in southern Quebec, Canada, by modelling and jointly interpreting aggregated clinical data in humans and serological data in pet dogs. Environmental risk factors were estimated in humans by negative binomial regression based on a dataset of 191 human WNV clinical cases reported in the study area between 2011 and 2014. Risk factors for infection in dogs were evaluated by logistic and negative binomial models based on a dataset including WNV serological results from 1442 dogs sampled from the same geographical area in 2013. Forested lands were identified as low-risk environments in humans. Agricultural lands represented higher risk environments for dogs. Environments identified as impacting risk in the current study were somewhat different from those identified in other studies conducted in north-eastern USA, which reported higher risk in suburban environments. In the context of the current study, combining human and animal data allowed a more comprehensive and possibly a more accurate view of environmental WNV risk factors to be obtained than by studying aggregated human data alone.

  12. Psychological functioning in adolescents referred to specialist gender identity clinics across Europe: a clinical comparison study between four clinics.

    Science.gov (United States)

    de Graaf, Nastasja M; Cohen-Kettenis, Peggy T; Carmichael, Polly; de Vries, Annelou L C; Dhondt, Karlien; Laridaen, Jolien; Pauli, Dagmar; Ball, Juliane; Steensma, Thomas D

    2018-07-01

    Adolescents seeking professional help with their gender identity development often present with psychological difficulties. Existing literature on psychological functioning of gender diverse young people is limited and mostly bound to national chart reviews. This study examined the prevalence of psychological functioning and peer relationship problems in adolescents across four European specialist gender services (The Netherlands, Belgium, the UK, and Switzerland), using the Child Behavioural Checklist (CBCL) and the Youth Self-Report (YSR). Differences in psychological functioning and peer relationships were found in gender diverse adolescents across Europe. Overall, emotional and behavioural problems and peer relationship problems were most prevalent in adolescents from the UK, followed by Switzerland and Belgium. The least behavioural and emotional problems and peer relationship problems were reported by adolescents from The Netherlands. Across the four clinics, a similar pattern of gender differences was found. Birth-assigned girls showed more behavioural problems and externalising problems in the clinical range, as reported by their parents. According to self-report, internalising problems in the clinical range were more prevalent in adolescent birth-assigned boys. More research is needed to gain a better understanding of the difference in clinical presentations in gender diverse adolescents and to investigate what contextual factors that may contribute to this.

  13. Clinical and Para Clinical Information Needs of Infertility Electronic Health Records in Iran: A Delphi Study.

    Science.gov (United States)

    Farzandipour, Mehrdad; Jeddi, Fateme Rangraz; Gilasi, Hamid Reza; Shirzadi, Diana

    2017-09-01

    infertility is referred to the person's inability to conceive pregnancy after one year of intercourse without using protection. This study paves the ground for creating a complete, united, and coherent source of patients' medical information. this is an applied research of descriptive-cross sectional type which has been carried out through qualitative - quantitative methods. The sample of the present study was 50 specialists in the field of infertility which has been chosen based on purposive sampling method. Designing the questionnaire was done based on library studies and Gathering experts' views was done based on Delphi technique. 261 items from clinical and Para clinical information of infertile patients' electronic health records were subjected to an opinion poll by experts. During this process 223 items were accepted and 38 items have been rejected after two sessions of surveys by infertility experts. Para clinical information section consisted of 57 items that all of them have been accepted by the experts. Also, clinical information section consisted of 242 items from which 204 items were accepted and 38 items were rejected by the experts. existence of a structured electronic record system of infertile patients' information leads to the integration of patients' information, improvement of health care services and a decrease in treatment costs: all working to increase information safety. Furthermore, only essential and relevant information would be provided for the specialists and it will facilitate and direct the future infertility related studies due to the coherence, unity and relevance of the information.

  14. [Clinical stages of patients with Alzheimer disease treated in specialist clinics in Spain. The EACE study].

    Science.gov (United States)

    Alom Poveda, J; Baquero, M; González-Adalid Guerreiro, M

    2013-10-01

    The diagnostic paradigm of Alzheimer disease (AD) is changing; there is a trend toward diagnosing the disease in its early stages, even before the complete syndrome of dementia is apparent. The clinical stage at which AD is usually diagnosed in our area is unknown. Therefore, the purpose of this study is to describe the clinical stages of AD patients at time of diagnosis. Multicentre, observational and cross-sectional study. Patients with probable AD according to NINCDS-ARDRA criteria, attended in specialist clinics in Spain, were included in the study. We recorded the symptom onset to evaluation and symptom onset to diagnosis intervals and clinical status of AD (based on MMSE, NPI questionnaire, and CDR scale). Participants in this study included 437 specialists representing all of Spain's autonomous communities and a total of 1,707 patients, of whom 1,694 were included in the analysis. Mean MMSE score was 17.6±4.8 (95% CI:17.4-17.9). Moderate cognitive impairment (MMSE between 10 and 20) was detected in 64% of the patients, and severe cognitive impairment (MMSEde Neurología. Published by Elsevier Espana. All rights reserved.

  15. Hydroxyurea revisited: a decade of clinical effects studies

    International Nuclear Information System (INIS)

    Sinclair, W.K.

    1981-01-01

    Over a decade ago hydroxyurea was shown to selectively kill cells in the S phase in a proliferating cell population and to block cells at the G 1 -S border. Consequently, blocked cells became sensitized to irradiation and were further sensitized when the drug was present after exposure. In the ensuing decade, many in vivo studies on hydroxyurea have confirmed that the main properties of hydroxyurea identified in the dish are also evident in vivo. During a period of about ten years, a considerable number of clinical studies have been performed, the results of which have been mixed, ranging from indeterminate to encouraging, depending to some extent on the site treated and whether careful randomized studies were done. The question arises whether the clinical studies have represented adequate tests, by laboratory standards, of the likely effectiveness of the drug in clinical circumstances. The clinical studies with hydroxyurea have been examined in this light, since the results might also bear on the use of many other such agents in combination therapy. This examination revealed that no attempts have been made to determine the concentration of hydroxyurea in the tumor and other relevant tissues as a function of time or to assess the cell kinetic features of the tumor and thus estimate the appropriate dose regimen. It would seem that a wide gap still exists between laboratory research and clinical application

  16. Clinical evaluation of lumbar CT assisted discography in comparison with human cadaver

    Energy Technology Data Exchange (ETDEWEB)

    Ito, Shigehiko

    1988-04-01

    In order to estimate the clinical value of lumbar CT assisted discography (CTD), results obtained by this method were compared with histological findings of the cross section of the spine in fresh human cadavera. Based on these findings, preoperative CTD of lumbar disc herniation was investigated. In the discs of human cadavera, the contrast medium mainly invaded the fissures of nucleus pulposus and the ruptures of annulus fibrosus and then diffused to the surrounding tissues. These ruptures were classified into two categories: radial and circumferential. This indentification was possible only in CTD and was obscure in the usual discogram. Not all the ruptures could be dyed in a severe degenerative disc, and a rupture which was not communicated with nucleus pulposus was not dyed in a mild degenerative disc. In the preoperative CTD of lumbar disc herniation, the posterior radial ruptures representing the route of herniated nuclei were characteristic and the circumferential ruptures were found complicated.

  17. Displacement of Drugs from Human Serum Albumin: From Molecular Interactions to Clinical Significance.

    Science.gov (United States)

    Rimac, Hrvoje; Debeljak, Željko; Bojić, Mirza; Miller, Larisa

    2017-01-01

    Human serum albumin (HSA) is the most abundant protein in human serum. It has numerous functions, one of which is transport of small hydrophobic molecules, including drugs, toxins, nutrients, hormones and metabolites. HSA has the ability to interact with a wide variety of structurally different compounds. This promiscuous, nonspecific affinity can lead to sudden changes in concentrations caused by displacement, when two or more compounds compete for binding to the same molecular site. It is important to consider drug combinations and their binding to HSA when defining dosing regimens, as this can directly influence drug's free, active concentration in blood. In present paper we review drug interactions with potential for displacement from HSA, situations in which they are likely to occur and their clinical significance. We also offer guidelines in designing drugs with decreased binding to HSA. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  18. Human Cognitive Limitations. Broad, Consistent, Clinical Application of Physiological Principles Will Require Decision Support.

    Science.gov (United States)

    Morris, Alan H

    2018-02-01

    Our education system seems to fail to enable clinicians to broadly understand core physiological principles. The emphasis on reductionist science, including "omics" branches of research, has likely contributed to this decrease in understanding. Consequently, clinicians cannot be expected to consistently make clinical decisions linked to best physiological evidence. This is a large-scale problem with multiple determinants, within an even larger clinical decision problem: the failure of clinicians to consistently link their decisions to best evidence. Clinicians, like all human decision-makers, suffer from significant cognitive limitations. Detailed context-sensitive computer protocols can generate personalized medicine instructions that are well matched to individual patient needs over time and can partially resolve this problem.

  19. A metabolomic evaluation of the phytochemical composition of tomato juices being used in human clinical trials.

    Science.gov (United States)

    Cichon, Morgan J; Riedl, Ken M; Schwartz, Steven J

    2017-08-01

    Juices from the traditional red tomato and a unique tangerine tomato variety are being investigated as health promoting foods in human clinical trials. However, it is unknown how the tangerine and red tomato juices differ in biologically relevant phytochemicals beyond carotenoids. Here liquid-chromatography high-resolution mass spectrometry metabolomics was used to evaluate broadly the similarities and differences in carotenoids and other phytochemicals between red and tangerine tomato juices intended for clinical interventions. This untargeted approach was successful in the rapid detection and extensive characterization of phytochemicals belonging to various compound classes. The tomato juices were found to differ significantly in a number of phytochemicals, including carotenoids, chlorophylls, neutral lipids, and cinnamic acid derivatives. The largest differences were in carotenoids, including lycopene, phytoene, phytofluene, neurosporene, and ζ-carotene. Smaller, but significant, differences were observed in polar phytochemicals, such as chlorogenic acid, hydroxyferulic acid, phloretin-di-C-glycoside, and isopropylmalic acid. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Health, human rights, and the conduct of clinical research within oppressed populations

    Directory of Open Access Journals (Sweden)

    Mills Edward J

    2007-11-01

    Full Text Available Abstract Background Clinical trials evaluating interventions for infectious diseases require enrolling participants that are vulnerable to infection. As clinical trials are conducted in increasingly vulnerable populations, issues of protection of these populations become challenging. In settings where populations are forseeably oppressed, the conduct of research requires considerations that go beyond common ethical concerns and into issues of international human rights law. Discussion Using examples of HIV prevention trials in Thailand, hepatitis-E prevention trials in Nepal and malaria therapeutic trials in Burma (Myanmar, we address the inadequacies of current ethical guidelines when conducting research within oppressed populations. We review existing legislature in the United States and United Kingdom that may be used against foreign investigators if trial hardships exist. We conclude by making considerations for research conducted within oppressed populations.

  1. Progressing a human embryonic stem-cell-based regenerative medicine therapy towards the clinic.

    Science.gov (United States)

    Whiting, Paul; Kerby, Julie; Coffey, Peter; da Cruz, Lyndon; McKernan, Ruth

    2015-10-19

    Since the first publication of the derivation of human embryonic stem cells in 1998, there has been hope and expectation that this technology will lead to a wave of regenerative medicine therapies with the potential to revolutionize our approach to managing certain diseases. Despite significant resources in this direction, the path to the clinic for an embryonic stem-cell-based regenerative medicine therapy has not proven straightforward, though in the past few years progress has been made. Here, with a focus upon retinal disease, we discuss the current status of the development of such therapies. We also highlight some of our own experiences of progressing a retinal pigment epithelium cell replacement therapy towards the clinic. © 2015 The Author(s).

  2. Clinical audit of COPD in outpatient respiratory clinics in Spain: the EPOCONSUL study

    Directory of Open Access Journals (Sweden)

    Calle Rubio M

    2017-01-01

    Full Text Available Myriam Calle Rubio,1–3 Bernardino Alcázar Navarrete,4 Joan B Soriano,5 Juan J Soler-Cataluña,6 José Miguel Rodríguez González-Moro,7 Manuel E Fuentes Ferrer,2,3,8 José Luis López-Campos9 On behalf of the EPOCONSUL Study 1Pulmonary Department, Hospital Clínico San Carlos, 2Department of Medicine, Faculty of Medicine, University Complutense of Madrid, 3Research Institute of Hospital Clínico San Carlos (IdISSC, Madrid, 4Pulmonary Department, Hospital de Alta Resolución de Noja, Granada, 5Research Institute of Hospital University La Princesa (IISP, University Autónoma of Madrid, 6Pulmonary Department, Hospital de Arnau de Villanova, Valencia, 7Pulmonary Department, Hospital Universitario Principe de Asturias, Alcalá de Henares, Madrid, 8UGC of Preventive Medicine and Research Institute of Hospital Clínico San Carlos, Madrid, 9Pulmonary Department, Hospital University Virgen del Rocio, Institute of Biomedicine of Sevilla (IBiS, Sevilla, Spain Background: Chronic obstructive pulmonary disease (COPD outpatients account for a large burden of usual care by respirologists. EPOCONSUL is the first national clinical audit conducted in Spain on the medical care for COPD patients delivered in outpatient respiratory clinics. We aimed to evaluate the clinical interventions and the degree of adherence to recommendations in outpatients of current COPD clinical practice guidelines.Methodology: This is an observational study with prospective recruitment (May 2014–May 2015 of patients with a COPD diagnosis as seen in outpatient respiratory clinics. The information collected was historical in nature as for the clinical data of the last and previous consultations, and the information concerning hospital resources was concurrent.Results: A total of 17,893 clinical records of COPD patients in outpatient respiratory clinics from 59 Spanish hospitals were evaluated. Of the 5,726 patients selected, 4,508 (78.7% were eligible. Overall, 12.1% of COPD patients

  3. Venomous and poisonous arthropods: identification, clinical manifestations of envenomation, and treatments used in human injuries

    Directory of Open Access Journals (Sweden)

    Vidal Haddad Junior

    2015-12-01

    Full Text Available Abstract This review presents the main species of venomous and poisonous arthropods, with commentary on the clinical manifestations provoked by the toxins and therapeutic measures used to treat human envenomations. The groups of arthopods discussed include the class Arachnida (spiders and scorpions, which are responsible for many injuries reported worldwide, including Brazil; the subphylum Myriapoda, with the classes Chilopoda and Diplopoda (centipedes and millipedes; and the subphylum Hexapoda, with the class Insecta and the orders Coleoptera (beetles, Hemiptera (stink bugs, giant water bugs, and cicadas, Hymenoptera (ants, wasps, and bees, and Lepidoptera (butterflies and moths.

  4. Clinical Features of Human Metapneumovirus Infection in Ambulatory Children Aged 5-13 Years.

    Science.gov (United States)

    Howard, Leigh M; Edwards, Kathryn M; Zhu, Yuwei; Griffin, Marie R; Weinberg, Geoffrey A; Szilagyi, Peter G; Staat, Mary A; Payne, Daniel C; Williams, John V

    2018-05-15

    We detected human metapneumovirus (HMPV) in 54 (5%) of 1055 children aged 5 to 13 years with acute respiratory illness (ARI) identified by outpatient and emergency department surveillance between November and May 2003-2009. Its clinical features were similar to those of HMPV-negative ARI, except a diagnosis of pneumonia was more likely (13% vs 4%, respectively; P = .005) and a diagnosis of pharyngitis (7% vs 24%, respectively; P = .005) was less likely in patients with HMPV- positive ARI than those with HMPV-negative ARI.

  5. Utility of an Equine Clinical Skills Course: A Pilot Study.

    Science.gov (United States)

    Christensen, Bruce W; Danielson, Jared A

    Recent publications have revealed inadequacies in the veterinary training of future equine practitioners. To help address this problem, a 2-week Equine Clinical Skills course was designed and implemented to provide fourth-year veterinary students with opportunities to have hands-on experience with common equine clinical skills using live animals and cadavers. Alumni and employers of alumni were surveyed to determine whether or not students participating in the course were more competent performing clinical skills during their first year post-graduation than those who had not participated in the course. Students who participated in the course were also surveyed before and after completing the course to determine whether or not their self-assessed skills improved during the course. Alumni who had taken the course rated their ability to perform the clinical skills more highly than alumni who had not taken the course. Similarly, students participating in the course indicated that they were significantly more able to perform the clinical skills after the course than when it began. Employers did not indicate a difference between the clinical skills of those who had taken the course and those who had not. Because this study involved a limited number of respondents from one institution, further studies should be conducted to replicate these findings and determine their generalizability.

  6. Microdose clinical trial: quantitative determination of nicardipine and prediction of metabolites in human plasma.

    Science.gov (United States)

    Yamane, Naoe; Takami, Tomonori; Tozuka, Zenzaburo; Sugiyama, Yuichi; Yamazaki, Akira; Kumagai, Yuji

    2009-01-01

    A sample treatment procedure and high-sensitive liquid chromatography/tandem mass spectrometry (LC/MS/MS) method for quantitative determination of nicardipine in human plasma were developed for a microdose clinical trial with nicardipine, a non-radioisotope labeled drug. The calibration curve was linear in the range of 1-500 pg/mL using 1 mL of plasma. Analytical method validation for the clinical dose, for which the calibration curve was linear in the range of 0.2-100 ng/mL using 20 microL of plasma, was also conducted. Each method was successfully applied to making determinations in plasma using LC/MS/MS after administration of a microdose (100 microg) and clinical dose (20 mg) to each of six healthy volunteers. We tested new approaches in the search for metabolites in plasma after microdosing. In vitro metabolites of nicardipine were characterized using linear ion trap-fourier transform ion cyclotron resonance mass spectrometry (LIT-FTICRMS) and the nine metabolites predicted to be in plasma were analyzed using LC/MS/MS. There is a strong possibility that analysis of metabolites by LC/MS/MS may advance to utilization in microdose clinical trials with non-radioisotope labeled drugs.

  7. Diagnosis of human fascioliasis in Arusha region, northern Tanzania by microscopy and clinical manifestations in patients.

    Science.gov (United States)

    Lukambagire, Abdul-Hamid Settenda; Mchaile, Deborah N; Nyindo, Mramba

    2015-12-23

    Human fascioliasis (HF) is a zoonotic disease that has been identified in many countries worldwide. This report concerns the identification and clinical management of cases of human fascioliasis in the suburbs of Arusha city, northern Tanzania in 2013. Fascioliasis is included among the WHO's Neglected Tropical Diseases as a plant transmitted trematode infection. Human fascioliasis has not been described before in the East Africa region, including Tanzania. Patients presenting at a primary healthcare centre in Arusha Region, northern Tanzania provided fresh stool samples for routine ova and parasite screening (saline and iodine preparations). Subsequent stool samples were preserved in 5 % formalin in saline and subjected to ether sedimentation for examination. Out of 1460 patients, 305 (21 %) were diagnosed positive for fascioliasis based on the demonstration of brownish, oval eggs with inconspicuous opercula in stool. Two distinct egg sizes were identified; large 170-212.5 by 115-150 μm (mean 194.5 by 130.5 μm) and smaller eggs 120-150 by 87.5 - 112.5 μm (mean 138.8 by 101 μm). Clinically, patients presented with fever (39 - 40 °C) and abdominal pain. Some patients had pruritis around the mouth and their lips were swollen. 3 patients were treated and cured with single dose Triclabendazole. The remaining 302 patients were treated with Nitazoxanide and 122 (40 %) were cleared of infection with a single course. Snails of the genus Lymnaea were found in the surroundings. This report serves to remind medical professionals in East Africa that HF is a probable differential diagnosis in patients presenting with similar symptoms. It is possible to diagnose fascioliasis by light microscopy although specific antigen tests are required for confirmation. Human fascioliasis however, has not been described or reported in Tanzania before and begs further investigation.

  8. Insulin action in the human brain: evidence from neuroimaging studies.

    Science.gov (United States)

    Kullmann, S; Heni, M; Fritsche, A; Preissl, H

    2015-06-01

    Thus far, little is known about the action of insulin in the human brain. Nonetheless, recent advances in modern neuroimaging techniques, such as functional magnetic resonance imaging (fMRI) or magnetoencephalography (MEG), have made it possible to investigate the action of insulin in the brain in humans, providing new insights into the pathogenesis of brain insulin resistance and obesity. Using MEG, the clinical relevance of the action of insulin in the brain was first identified, linking cerebral insulin resistance with peripheral insulin resistance, genetic predisposition and weight loss success in obese adults. Although MEG is a suitable tool for measuring brain activity mainly in cortical areas, fMRI provides high spatial resolution for cortical as well as subcortical regions. Thus, the action of insulin can be detected within all eating behaviour relevant regions, which include regions deeply located within the brain, such as the hypothalamus, midbrain and brainstem, as well as regions within the striatum. In this review, we outline recent advances in the field of neuroimaging aiming to investigate the action of insulin in the human brain using different routes of insulin administration. fMRI studies have shown a significant insulin-induced attenuation predominantly in the occipital and prefrontal cortical regions and the hypothalamus, successfully localising insulin-sensitive brain regions in healthy, mostly normal-weight individuals. However, further studies are needed to localise brain areas affected by insulin resistance in obese individuals, which is an important prerequisite for selectively targeting brain insulin resistance in obesity. © 2015 British Society for Neuroendocrinology.

  9. Infections in orthopaedic surgery : clinical and experimental studies

    NARCIS (Netherlands)

    Vogely, Henri Charles

    2000-01-01

    The diagnostic difficulties, variability in outcome and the heterogeinity of the problem of orthopaedic infections stimulated the author to a study of the literature, and several clinical and experimental studies. The diagnosis prosthesis-related infection can only be reached with an acceptable

  10. PRELIMINARY CLINICAL STUDY OF KALANCHOE SPATHULATA DC. ON INFLAMMATORY WOUND

    Science.gov (United States)

    Yadav, C. L.; Yadav, C. S.

    1985-01-01

    Here, an attempt is made to study the clinical aspect of Kalanchoe spathulata Dc. It has been observed that would heals rapidly leaving no scar. The study clearly validates the ancient concept of Ayurveda, that without taking the help of surgery, there are several medicinal plants which may cure diseases very well. PMID:22557495

  11. We "Must" Integrate Human Rights into the Social Studies.

    Science.gov (United States)

    O'Brien, Ed

    1999-01-01

    Asserts that educators need to teach about human rights issues, such as social and economic rights, in the social studies curriculum because these issues are disregarded throughout the country. Defines human rights, discusses the importance of the Universal Declaration of Human Rights (UDHR), and provides two lessons. (CMK)

  12. Under-correction of human myopia – Is it myopigenic?: A retrospective analysis of clinical refraction data

    Directory of Open Access Journals (Sweden)

    Balamurali Vasudevan

    2014-07-01

    Conclusion: Under-correction of myopia produced a small but progressively greater degree of myopic progression than did full correction. The present finding is consistent with earlier clinical trials and modeling of human myopia.

  13. Climate change studies and the human sciences

    Science.gov (United States)

    Holm, Poul; Winiwarter, Verena

    2017-09-01

    Policy makers have made repeated calls for integration of human and natural sciences in the field of climate change. Serious multidisciplinary attempts began already in the 1950s. Progress has certainly been made in understanding the role of humans in the planetary system. New perspectives have clarified policy advice, and three insights are singled out in the paper: the critique of historicism, the distinction between benign and wicked problems, and the cultural critique of the 'myths of nature'. Nevertheless, analysis of the IPCC Assessment Reports indicates that integration is skewed towards a particular dimension of human sciences (economics) and major insights from cultural theory and historical analysis have not made it into climate science. A number of relevant disciplines are almost absent in the composition of authorship. Nevertheless, selective assumptions and arguments are made about e.g. historical findings in key documents. In conclusion, we suggest to seek remedies for the lack of historical scholarship in the IPCC reports. More effort at science-policy exchange is needed, and an Integrated Platform to channel humanities and social science expertise for climate change research might be one promising way.

  14. Radioimmunoassay study of neurophysins in human plasma

    International Nuclear Information System (INIS)

    Reinharz, A.C.; Tissot-Berthet, M.-C.; Vallotton, M.B.

    1978-01-01

    Using a homologous system we have developed a specific and sensitive radioimmunoassay for the measurement of one of the human neurophysins in unextracted human plasma. This neurophysin is specifically secreted in response to oestrogen and has therefore been referred to as human oestrogen-stimulated neurophysin (h-OeSN). The plasma concentration was 0.57 plus minus 0.17 ng/ml (SD) in females and 0.88 plus minus 0.76 ng/ml (SD) in males. This difference is not significant. In women on oral contraceptives, plasma h-OeSN was 2.0 plus minus 1.1 ng/ml. During pregnancy h-OeSN increased progressively to 3.7 plus minus 2.9 ng/ml at the end of the first trimester, and 5.2 plus minus 2.8 ng/ml at term. Plasma h-OeSN concentrations increased rapidly and markedly in men treated with ethinyl-oestradiol. We have also demonstrated the presence of h-OeSN in amniotic and cerebrospinal fluids. A second human neurophysin, which is stimulated by nicotine but not by oestrogen, was also measured. This neurophysin was monitored by a heterologous system using antiserum raised against bovine neurophysin II (b-NII), and b-NII as the standard and tracer. (author)

  15. A retrospective longitudinal study of animal and human rabies in Botswana 1989-2006

    OpenAIRE

    K.T. Moagabo; K.B. Monyame; E.K. Baipoledi; M. Letshwenyo; N. Mapitse; J.M.K. Hyera

    2009-01-01

    A longitudinal study of animal and human rabies covering 18 years from 1989 to 2006 was retrospectively conducted in order to highlight the epidemiological features and trends of the disease in Botswana. Over the 18-year period, a total of 4 306 brain specimens collected from various species of animals including human beings with clinical signs consistent with rabies were submitted to the National Veterinary Laboratory in Gaborone for confirmatory diagnosis. Of the samples submitted, 2 ...

  16. Noonan syndrome: a clinical and genetic study of 31 patients

    Directory of Open Access Journals (Sweden)

    Bertola Débora Romeo

    1999-01-01

    Full Text Available Noonan syndrome is a multiple congenital anomaly syndrome, inherited in an autosomal dominant pattern. We studied 31 patients (18 males and 13 females affected by this disorder regarding their clinical and genetic characteristics. The most frequent clinical findings were short stature (71%; craniofacial dysmorphisms, especially hypertelorism, ptosis, downslanting of the palpebral fissures; short or webbed neck (87%; cardiac anomalies (65%, and fetal pads in fingers and toes (70%. After studying the probands' first-degree relatives, we made the diagnosis of Noonan syndrome in more than one family member in three families. Therefore, the majority of our cases were sporadic.

  17. Proteomic Studies on Human and Experimental Cerebral Malaria

    KAUST Repository

    Moussa, Ehab

    2012-07-01

    Cerebral malaria (CM) is a severe neurological complication of malaria infection that results from interrelated pathologies. Despite extensive research efforts, the mechanism of the disease is not completely understood. Clinical studies, postmortem analysis, and animal models have been the main research arenas in CM. In this thesis, shotgun proteomics approach was used to further understand the pathology of human and experimental CM. The mechanism by which CM turns fatal is yet to be identified. A clinical proteomics study was conducted on pooled plasma samples from children with reversible or fatal CM from the Gambia. The results show that depletion of coagulation factors and increased levels of circulating proteasomes are associated with fatal pediatric CM. This data suggests that the ongoing coagulation during CM might be a disseminated intravascular coagulation state that eventually causes depletion of the coagulation factors leading to petechial hemorrhages. In addition, the mechanism(s) by which blood transfusion benefits CM in children was investigated. To that end, the concentration and multimerization pattern of von-willebrand factor, and the concentration of haptoglobin in the plasma of children with CM who received blood transfusions were measured. In addition to clinical studies, experimental cerebral malaria (ECM) in mice has been long used as a model for the disease. A shotgun proteomics workflow was optimized to identify the proteomic signature of the brain tissue of mice with ECM.Because of the utmost importance of membrane proteins in the pathology of the disease, sample fractionation and filter aided sample preparation were used to recover them. The proteomic signature of the brains of mice infected with P. berghei ANKA that developed neurological syndrome, mice infected with P. berghei NK56 that developed severe malaria but without neurological signs, and non-infected mice, were compared to identify CM specific proteins. Among the differentially

  18. Nutritional Risk, Micronutrient Status and Clinical Outcomes: A Prospective Observational Study in an Infectious Disease Clinic

    Directory of Open Access Journals (Sweden)

    Oguzhan Sıtkı Dizdar

    2016-02-01

    Full Text Available Malnutrition has been associated with increased morbidity and mortality. The objective of this study was to determine the nutritional status and micronutrient levels of hospitalized patients in an infectious disease clinic and investigate their association with adverse clinical outcomes. The nutritional status of the study participants was assessed using the Nutritional Risk Screening 2002 (NRS 2002 and micronutrient levels and routine biochemical parameters were tested within the first 24 h of the patient’s admission. The incidence of zinc, selenium, thiamine, vitamin B6, vitamin B12 deficiency were 66.7% (n = 40, 46.6% (n = 29, 39.7% (n = 27, 35.3% (n = 24, 14.1% (n = 9, respectively. Selenium levels were significantly higher in patients with urinary tract infections, but lower in soft tissue infections. Copper levels were significantly higher in patients with soft tissue infections. In the Cox regression models, lower albumin, higher serum lactate dehydrogenase levels and higher NRS-2002 scores were associated with increased death. Thiamine, selenium, zinc and vitamin B6 deficiencies but not chromium deficiencies are common in infectious disease clinics. New associations were found between micronutrient levels and infection type and their adverse clinical outcomes. Hypoalbuminemia and a high NRS-2002 score had the greatest accuracy in predicting death, systemic inflammatory response syndrome and sepsis on admission.

  19. Human iPS Cell-Derived Germ Cells: Current Status and Clinical Potential

    Directory of Open Access Journals (Sweden)

    Tetsuya Ishii

    2014-10-01

    Full Text Available Recently, fertile spermatozoa and oocytes were generated from mouse induced pluripotent (iPS cells using a combined in vitro and in vivo induction system. With regard to germ cell induction from human iPS cells, progress has been made particularly in the male germline, demonstrating in vitro generation of haploid, round spermatids. Although iPS-derived germ cells are expected to be developed to yield a form of assisted reproductive technology (ART that can address unmet reproductive needs, genetic and/or epigenetic instabilities abound in iPS cell generation and germ cell induction. In addition, there is still room to improve the induction protocol in the female germline. However, rapid advances in stem cell research are likely to make such obstacles surmountable, potentially translating induced germ cells into the clinical setting in the immediate future. This review examines the current status of the induction of germ cells from human iPS cells and discusses the clinical potential, as well as future directions.

  20. /sup 99m/Tc-labeled solid-phase meal: a quantitative clinical measurement of human gastric emptying

    International Nuclear Information System (INIS)

    Martin, J.L.; Beck, W.J.; McDonald, A.P.; Carlson, G.M.; Mathias, J.R.

    1983-01-01

    A solid-phase meal labeled with /sup 99m/Tc-sulfur colloid provides an improved clinical test for the quantitative evaluation of human gastric emptying. We studied 12 healthy male controls and five male patients with known gastric stasis secondary to a vagotomy and drainage procedure. All subjects were fasted for 8 hours before the study, and each consumed an unbuttered biscuit and a poached egg white containing 1 mCi of /sup 99m/Tc-sulfur colloid. For 2 hours, 60-second counts were measured every 10 minutes by a Pho Gamma III scintillation camera. The t 1 / 2 for control subjects was 60 minutes, at which time patients with gastric stasis had retained 98% of the test meal. At 120 minutes, control subjects and patients with gastric stasis had 4.7% and 89%, respectively, of the meal remaining in the stomach. The solid-phase test meal labeled with /sup 99m/Tc-sulfur colloid is easy to perform and can be used clinically to quantitatively measure gastric emptying in humans. This test can discriminate between control subjects and patients with known gastric stasis

  1. /sup 99m/Tc-labeled solid-phase meal: a quantitative clinical measurement of human gastric emptying

    Energy Technology Data Exchange (ETDEWEB)

    Martin, J.L.; Beck, W.J.; McDonald, A.P.; Carlson, G.M.; Mathias, J.R.

    1983-08-01

    A solid-phase meal labeled with /sup 99m/Tc-sulfur colloid provides an improved clinical test for the quantitative evaluation of human gastric emptying. We studied 12 healthy male controls and five male patients with known gastric stasis secondary to a vagotomy and drainage procedure. All subjects were fasted for 8 hours before the study, and each consumed an unbuttered biscuit and a poached egg white containing 1 mCi of /sup 99m/Tc-sulfur colloid. For 2 hours, 60-second counts were measured every 10 minutes by a Pho Gamma III scintillation camera. The t/sup 1///sup 2/ for control subjects was 60 minutes, at which time patients with gastric stasis had retained 98% of the test meal. At 120 minutes, control subjects and patients with gastric stasis had 4.7% and 89%, respectively, of the meal remaining in the stomach. The solid-phase test meal labeled with /sup 99m/Tc-sulfur colloid is easy to perform and can be used clinically to quantitatively measure gastric emptying in humans. This test can discriminate between control subjects and patients with known gastric stasis.

  2. Comprehensive safety assessment of a human inactivated diploid enterovirus 71 vaccine based on a phase III clinical trial.

    Science.gov (United States)

    Zhang, Wei; Kong, Yujia; Jiang, Zhiwei; Li, Chanjuan; Wang, Ling; Xia, Jielai

    2016-04-02

    Human enterovirus 71 (EV71) is a causative agent of hand, foot, and mouth disease (HFMD). In a previous phase III trial in children, a human diploid cell-based inactivated EV71 vaccine elicited EV71 specific immune responses and protection against EV71 associated HFMD. This study aimed to assess the factors influencing the severity of adverse events observed in this previous trial. This was a randomized, double-blinded, placebo-controlled, phase III clinical trial of a human diploid vaccine carried out in 12,000 children in Guangxi Zhuang Autonomous Region, China (ClinicalTrials.gov: NCT01569581). Solicited events were recorded for 7 days and unsolicited events were reported for 28 days after each injection. Age trend analysis of adverse reaction was conducted in each treatment group. Multiple logistic regression models were built to identify factors influencing the severity of adverse reactions. Fewer solicited adverse reactions were observed in older participants within the first 7 days after vaccination (P < 0.0001), except local pain and pruritus. More severe adverse reactions were observed after the initial injection than after the booster injection. Serious cold or respiratory tract infections (RTI) were observed more often in children aged 6-36 months than in older children. Only the severity of local swelling was associated with body mass index. Children with throat discomfort before injection had a higher risk of serious cold or RTI. These results indicated that the human diploid cell-based vaccine achieved a satisfactory safety profile.

  3. Molecular characterization of rotavirus strains detected during a clinical trial of a human rotavirus vaccine in Blantyre, Malawi.

    Science.gov (United States)

    Nakagomi, Toyoko; Nakagomi, Osamu; Dove, Winifred; Doan, Yen Hai; Witte, Desiree; Ngwira, Bagrey; Todd, Stacy; Duncan Steele, A; Neuzil, Kathleen M; Cunliffe, Nigel A

    2012-04-27

    The human, G1P[8] rotavirus vaccine (Rotarix™) significantly reduced severe rotavirus gastroenteritis episodes in a clinical trial in South Africa and Malawi, but vaccine efficacy was lower in Malawi (49.5%) than reported in South Africa (76.9%) and elsewhere. The aim of this study was to examine the molecular relationships of circulating wild-type rotaviruses detected during the clinical trial in Malawi to RIX4414 (the strain contained in Rotarix™) and to common human rotavirus strains. Of 88 rotavirus-positive, diarrhoeal stool specimens, 43 rotaviruses exhibited identifiable RNA migration patterns when examined by polyacrylamide gel electrophoresis. The genes encoding VP7, VP4, VP6 and NSP4 of 5 representative strains possessing genotypes G12P[6], G1P[8], G9P[8], and G8P[4] were sequenced. While their VP7 (G) and VP4 (P) genotype designations were confirmed, the VP6 (I) and NSP4 (E) genotypes were either I1E1 or I2E2, indicating that they were of human rotavirus origin. RNA-RNA hybridization using 21 culture-adapted strains showed that Malawian rotaviruses had a genomic RNA constellation common to either the Wa-like or the DS-1 like human rotaviruses. Overall, the Malawi strains appear similar in their genetic make-up to rotaviruses described in countries where vaccine efficacy is greater, suggesting that the lower efficacy in Malawi is unlikely to be explained by the diversity of circulating strains. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. Clinical features of human metapneumovirus genotypes in children with acute lower respiratory tract infection in Changsha, China.

    Science.gov (United States)

    Zeng, Sai-Zhen; Xiao, Ni-Guang; Zhong, Li-Li; Yu, Tian; Zhang, Bing; Duan, Zhao-Jun

    2015-11-01

    To explore the epidemiological and clinical features of different human metapneumovirus (hMPV) genotypes in hospitalized children. Reverse transcription polymerase chain reaction (RT-PCR) or PCR was employed to screen for both hMPV and other common respiratory viruses in 2613 nasopharyngeal aspirate specimens collected from children with lower respiratory tract infections from September 2007 to February 2011 (a period of 3.5 years). The demographics and clinical presentations of patients infected with different genotypes of hMPV were compared. A total of 135 samples were positive for hMPV (positive detection rate: 5.2%). Co-infection with other viruses was observed in 45.9% (62/135) of cases, and human bocavirus was the most common additional respiratory virus. The most common symptoms included cough, fever, and wheezing. The M gene was sequenced for 135 isolates; of these, genotype A was identified in 72.6% (98/135) of patients, and genotype B was identified in 27.4% (37/135) of patients. The predominant genotype of hMPV changed over the 3.5-year study period from genotype A2b to A2b or B1 and then to predominantly B1. Most of clinical features were similar between patients infected with different hMPV genotypes. These results suggested that hMPV is an important viral pathogen in pediatric patients with acute lower respiratory tract infection in Changsha. The hMPV subtypes A2b and B1 were found to co-circulate. The different hMPV genotypes exhibit similar clinical characteristics. © 2015 Wiley Periodicals, Inc.

  5. Clinical and epidemiological features of human rabies cases in the Philippines: a review from 1987 to 2006.

    Science.gov (United States)

    Dimaano, Efren M; Scholand, Stephen J; Alera, Maria Theresa P; Belandres, Domingo B

    2011-07-01

    Rabies viral infection causes a fatal encephalomyelitis. In humans, classic features include hydrophobia, aerophobia, hypersalivation, agitation, and neurological symptoms. In the Philippines, canine rabies contributes to a significant burden of human disease. We retrospectively reviewed the medical records of 1839 patients admitted to San Lazaro Hospital, Manila, Philippines between 1987 and 2006, with a clinical diagnosis of rabies. We used the World Health Organization case definition for clinical rabies, which is defined by the presence of hydrophobia. Male patients outnumbered females by 2.2 to 1 and twice the number of adults were affected compared with children. Most patients were indigent. Dog bites occurred more than cat bites (97.1% vs. 2.9%) and most cases were caused by a single bite (86.2%), compared to multiple bites (8.7%). Bites to the face, head, and neck led to shorter incubation times, yet the incubation period varied, with most cases (42.7%) occurring in the bracket of 91-365 days post-exposure. Clinical symptoms included hydrophobia in all cases, as per our case definition, and aerophobia in 95.5%; only 9.4% had fever, 9.2% exhibited restlessness, and 6.7% exhibited hypersalivation. Localized neurological symptoms included pain (4.1%), numbness (2.6%), and itching (2.3%). None of the patients received appropriate post-exposure prophylaxis (PEP). This study examines the largest cohort of rabies patients reported to-date. Better understanding of clinical disease manifestations may help in salvage efforts to save patients with rabies. Knowledge of epidemiological factors will improve preventative efforts to reduce suffering from rabies. Copyright © 2011 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  6. Driving clinical study efficiency by using a productivity breakdown model: comparative evaluation of a global clinical study and a similar Japanese study.

    Science.gov (United States)

    Takahashi, K; Sengoku, S; Kimura, H

    2011-02-01

    A fundamental management imperative of pharmaceutical companies is to contain surging costs of developing and launching drugs globally. Clinical studies are a research and development (R&D) cost driver. The objective of this study was to develop a productivity breakdown model, or a key performance indicator (KPI) tree, for an entire clinical study and to use it to compare a global clinical study with a similar Japanese study. We, thereby, hope to identify means of improving study productivity. We developed the new clinical study productivity breakdown model, covering operational aspects and cost factors. Elements for improving clinical study productivity were assessed from a management viewpoint by comparing empirical tracking data from a global clinical study with a Japanese study with similar protocols. The following unique and material differences, beyond simple international difference in cost of living, that could affect the efficiency of future clinical trials were identified: (i) more frequent site visits in the Japanese study, (ii) head counts at the Japanese study sites more than double those of the global study and (iii) a shorter enrollment time window of about a third that of the global study at the Japanese study sites. We identified major differences in the performance of the two studies. These findings demonstrate the potential of the KPI tree for improving clinical study productivity. Trade-offs, such as those between reduction in head count at study sites and expansion of the enrollment time window, must be considered carefully. © 2010 Blackwell Publishing Ltd.

  7. Which Obstacles Prevent Us from Recruiting into Clinical Trials: A Survey about the Environment for Clinical Studies at a German University Hospital in a Comprehensive Cancer Center

    Directory of Open Access Journals (Sweden)

    Christoph Straube

    2017-08-01

    Full Text Available BackgroundProspective clinical studies are the most important tool in modern medicine. The standard in good clinical practice in clinical trials has constantly improved leading to more sophisticated protocols. Moreover, translational questions are increasingly addressed in clinical trials. Such trials must follow elaborate rules and regulations. This is accompanied by a significant increase in documentation issues which require substantial manpower. Furthermore, university-based clinical centers are interested in increasing the amount of patients treated within clinical trials, and this number has evolved to be a key quality criterion. The present study was initiated to elucidate the obstacles that limit clinical scientists in screening and recruiting for clinical trials.MethodsA specific questionnaire with 28 questions was developed focusing on all aspects of clinical trial design as well as trial management. This included questions on organizational issues, medical topics as well as potential patients’ preferences and physician’s goals. The questionnaire was established to collect data anonymously on a web-based platform. The survey was conducted within the Klinikum rechts der Isar, Faculty of Medicine, Technical University of Munich; physicians of all levels (Department Chairs, attending physicians, residents, as well as study nurses, and other study-related staff were addressed. The answers were analyzed using the Survio analyzing tool (http://www.survio.com/de/.ResultsWe collected 42 complete sets of answers; in total 28 physicians, 11 study nurses, and 3 persons with positions in administration answered our survey. The study centers reported to participate in a range of 3–160 clinical trials with a recruitment rate of 1–80%. Main obstacles were determined: 31/42 (74% complained about limited human resources and 22/42 (52% reported to have a lack on tec