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  1. Application of new therapies in Graves' disease and thyroid-associated ophthalmopathy: animal models and translation to human clinical trialsTumor necrosis factor-alpha binding capacity and anti-infliximab antibodies measured by fluid-phase radioimmunoassays as predictors of clinical efficacy

    DEFF Research Database (Denmark)

    Banga, J.P.; Gilbert, J.A.; El, Fassi D.

    2008-01-01

    Most current approaches for treating Graves' disease are based essentially upon regimes developed nearly 50 years ago. Moreover, therapeutic approaches for complications such as thyroid-associated ophthalmopathy (TAO) and dermopathy are singularly dependent on conventional approaches of nonspecif...

  2. 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

  3. 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.

  4. 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.

  5. 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 ...

  6. 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 ...

  7. 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.

  8. Clinical Relevance of KRAS in Human Cancers

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    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.

  9. 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.

  10. 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

  11. 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

  12. 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

  13. 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.

  14. [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.

  15. 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

  16. 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.

  17. 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

  18. 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)

  19. 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.

  20. 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.

  1. 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.

  2. 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)

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. 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

  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. 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.

  16. [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.

  17. 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...

  18. 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

  19. 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

  20. 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)

  1. 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.

  2. 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

  3. 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...

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. 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

  10. 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...

  11. 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.

  12. [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".

  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. 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.

  15. 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.

  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. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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

  7. 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

  8. 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.

  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. 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.

  11. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  13. 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....

  14. 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.

  15. 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.

  16. 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.

  17. [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.

  18. 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

  19. [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.

  20. 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...

  1. 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

  2. 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.

  3. 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.

  4. 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...

  5. 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...

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  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. 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.

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. "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.

  1. 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.

  2. 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...

  3. 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.

  4. 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.

  5. 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...

  6. 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.

  7. 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).

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

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

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    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.

  17. 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.

  18. 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

  19. 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.

  20. 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

  1. Human iPS Cell-Derived Germ Cells: Current Status and Clinical Potential

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    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.

  2. 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.

  3. 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.

  4. 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.

  5. Radio sterilized human ligaments and their clinical application;Ligamentos humanos radioesterilizados y su aplicacion clinica

    Energy Technology Data Exchange (ETDEWEB)

    Luna Z, D.; Reyes F, M. L. [ININ, Carretera Mexico-Toluca s/n, 52750 Ocoyoacac, Estado de Mexico (Mexico); Diaz M, I.; Hernandez R, G., E-mail: daniel.luna@inin.gob.m [Centro Estatal de Trasplantes del Estado de Mexico, Pablo Sidar No. 602, Col. Universidad, 50130 Toluca, Estado de Mexico (Mexico)

    2009-10-15

    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 {sup 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 {sup 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)

  6. A highly invasive human glioblastoma pre-clinical model for testing therapeutics

    Directory of Open Access Journals (Sweden)

    Cao Brian

    2008-12-01

    Full Text Available Abstract Animal models greatly facilitate understanding of cancer and importantly, serve pre-clinically for evaluating potential anti-cancer therapies. We developed an invasive orthotopic human glioblastoma multiforme (GBM mouse model that enables real-time tumor ultrasound imaging and pre-clinical evaluation of anti-neoplastic drugs such as 17-(allylamino-17-demethoxy geldanamycin (17AAG. Clinically, GBM metastasis rarely happen, but unexpectedly most human GBM tumor cell lines intrinsically possess metastatic potential. We used an experimental lung metastasis assay (ELM to enrich for metastatic cells and three of four commonly used GBM lines were highly metastatic after repeated ELM selection (M2. These GBM-M2 lines grew more aggressively orthotopically and all showed dramatic multifold increases in IL6, IL8, MCP-1 and GM-CSF expression, cytokines and factors that are associated with GBM and poor prognosis. DBM2 cells, which were derived from the DBTRG-05MG cell line were used to test the efficacy of 17AAG for treatment of intracranial tumors. The DMB2 orthotopic xenografts form highly invasive tumors with areas of central necrosis, vascular hyperplasia and intracranial dissemination. In addition, the orthotopic tumors caused osteolysis and the skull opening correlated to the tumor size, permitting the use of real-time ultrasound imaging to evaluate antitumor drug activity. We show that 17AAG significantly inhibits DBM2 tumor growth with significant drug responses in subcutaneous, lung and orthotopic tumor locations. This model has multiple unique features for investigating the pathobiology of intracranial tumor growth and for monitoring systemic and intracranial responses to antitumor agents.

  7. Adenocarcinoma in situ and associated human papillomavirus type distribution observed in two clinical trials of a quadrivalent human papillomavirus vaccine

    DEFF Research Database (Denmark)

    Ault, Kevin A; Joura, Elmar A; Kjaer, Susanne K

    2011-01-01

    , we include all women who had at least one follow-up visit postenrollment. Healthy women (17,622) aged 15-26 with no history of HPV disease and a lifetime number of less than five sex partners (average follow-up of 3.6 years) were randomized (1:1) to receive vaccine or placebo at day 1, months 2......The primary objective of this report is to describe the detection of adenocarcinoma in situ (AIS) and associated human papillomavirus (HPV) type distribution that was observed in the context of two phase 3 clinical trials of a quadrivalent HPV6/11/16/18 vaccine. In this intention-to-treat analysis......, and 6. Women underwent colposcopy and biopsy according to a Papanicolaou triage algorithm. All tissue specimens were tested for 14 HPV types and were adjudicated by a pathology panel. During the trials, 22 women were diagnosed with AIS (six vaccine and 16 placebo). There were 25 AIS lesions in total...

  8. Science, humanism, judgement, ethics: person-centered medicine as an emergent model of modern clinical practice.

    Science.gov (United States)

    Miles, Andrew

    2013-01-01

    The Medical University of Plovdiv (MUP) has as its motto 'Committed to humanity". But what does humanity in modern medicine mean? Is it possible to practise a form of medicine that is without humanity? In the current article, it is argued that modern medicine is increasingly being practised in a de-personalised fashion, where the patient is understood not as a unique human individual, a person, but rather as a subject or an object and more in the manner of a complex biological machine. Medicine has, it is contended, become distracted from its duty to care, comfort and console as well as to ameliorate, attenuate and cure and that the rapid development of medicine's scientific knowledge is, paradoxically, principally causative. Signal occurrences in the 'patient as a person' movement are reviewed, together with the emergence of the evidence-based medicine (EBM) and patient-centered care (PCC) movements. The characteristics of a model of medicine evolving in response to medicine's current deficiencies--person-centered healthcare (PCH)--are noted and described. In seeking to apply science with humanism, via clinical judgement, within an ethical framework, it is contended that PCH will prove to be far more responsive to the needs of the individual patient and his/her personal circumstances than current models of practice, so that neither a reductive anatomico-pathological, disease-centric model of illness (EBM), nor an aggressive patient-directed, consumerist form of care (PCC) is allowed continued dominance within modern healthcare systems. In conclusion, it is argued that PCH will enable affordable advances in biomedicine and technology to be delivered to patients within a humanistic framework of clinical practice that recognises the patient as a person and which takes full account of his/her stories, values, preferences, goals, aspirations, fears, worries, hopes, cultural context and which responds to his/her psychological, emotional, spiritual and social necessities

  9. Clinical implication of elevated human cervical cancer oncogene-1 expression in esophageal squamous cell carcinoma.

    Science.gov (United States)

    Liu, Ying; Li, Ke; Ren, Zhonghai; Li, Shenglei; Zhang, Hongyan; Fan, Qingxia

    2012-07-01

    The human cervical cancer oncogene 1 (HCCR-1), a novel human oncoprotein, has been shown to be upregulated in various human tumors and plays a critical role in tumorigenesis and tumor progression. Here, the authors investigated HCCR-1 level in esophageal squamous cell carcinoma (ESCC) tissues and assessed the correlation between HCCR-1 level and prognosis of the patients with ESCC. HCCR-1 levels were investigated by immunohistochemistry, in situ hybridization, real-time quantitative RT-PCR and Western blotting methods; Kaplan-Meier curve was used to evaluate the prognostic value of HCCR-1 level in patients with ESCC using log-rank test. HCCR-1 displayed high levels in ESCC tissues compared to squamous dysplasia tissues and normal esophageal epithelial tissues. No significant correlation was observed between the levels of HCCR-1 mRNA and protein and gender and age (all p>0.05) but obviously related to histological grade, clinical stage, and lymph node metastasis (all p<0.001). Moreover, the survival rate of the patients with low HCCR-1 levels was higher than that of the patients with high HCCR-1 levels (both p<0.05). These data demonstrate that HCCR-1 may be used as a novel predictor for the prognosis of the patients with ESCC.

  10. 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.

  11. 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.

  12. Biomedical optics centers: forty years of multidisciplinary clinical translation for improving human health

    Science.gov (United States)

    Tromberg, Bruce J.; Anderson, R. Rox; Birngruber, Reginald; Brinkmann, Ralf; Berns, Michael W.; Parrish, John A.; Apiou-Sbirlea, Gabriela

    2016-12-01

    Despite widespread government and public interest, there are significant barriers to translating basic science discoveries into clinical practice. Biophotonics and biomedical optics technologies can be used to overcome many of these hurdles, due, in part, to offering new portable, bedside, and accessible devices. The current JBO special issue highlights promising activities and examples of translational biophotonics from leading laboratories around the world. We identify common essential features of successful clinical translation by examining the origins and activities of three major international academic affiliated centers with beginnings traceable to the mid-late 1970s: The Wellman Center for Photomedicine (Mass General Hospital, USA), the Beckman Laser Institute and Medical Clinic (University of California, Irvine, USA), and the Medical Laser Center Lübeck at the University of Lübeck, Germany. Major factors driving the success of these programs include visionary founders and leadership, multidisciplinary research and training activities in light-based therapies and diagnostics, diverse funding portfolios, and a thriving entrepreneurial culture that tolerates risk. We provide a brief review of how these three programs emerged and highlight critical phases and lessons learned. Based on these observations, we identify pathways for encouraging the growth and formation of similar programs in order to more rapidly and effectively expand the impact of biophotonics and biomedical optics on human health.

  13. 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.

  14. 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.

  15. Clinical Tolerogenic Dendritic Cells: Exploring Therapeutic Impact on Human Autoimmune Disease

    Directory of Open Access Journals (Sweden)

    Brett Eugene Phillips

    2017-10-01

    Full Text Available Tolerogenic dendritic cell (tDC-based clinical trials for the treatment of autoimmune diseases are now a reality. Clinical trials are currently exploring the effectiveness of tDC to treat autoimmune diseases of type 1 diabetes mellitus, rheumatoid arthritis, multiple sclerosis (MS, and Crohn’s disease. This review will address tDC employed in current clinical trials, focusing on cell characteristics, mechanisms of action, and clinical findings. To date, the publicly reported human trials using tDC indicate that regulatory lymphocytes (largely Foxp3+ T-regulatory cell and, in one trial, B-regulatory cells are, for the most part, increased in frequency in the circulation. Other than this observation, there are significant differences in the major phenotypes of the tDC. These differences may affect the outcome in efficacy of recently launched and impending phase II trials. Recent efforts to establish a catalog listing where tDC converge and diverge in phenotype and functional outcome are an important first step toward understanding core mechanisms of action and critical “musts” for tDC to be therapeutically successful. In our view, the most critical parameter to efficacy is in vivo stability of the tolerogenic activity over phenotype. As such, methods that generate tDC that can induce and stably maintain immune hyporesponsiveness to allo- or disease-specific autoantigens in the presence of powerful pro-inflammatory signals are those that will fare better in primary endpoints in phase II clinical trials (e.g., disease improvement, preservation of autoimmunity-targeted tissue, allograft survival. We propose that pre-treatment phenotypes of tDC in the absence of functional stability are of secondary value especially as such phenotypes can dramatically change following administration, especially under dynamic changes in the inflammatory state of the patient. Furthermore, understanding the outcomes of different methods of cell delivery and sites

  16. [Clinical characteristics of human recombination activating gene 1 mutations in 8 immunodeficiency patients with diverse phenotypes].

    Science.gov (United States)

    Yu, G; Wang, W J; Liu, D R; Tao, Z F; Hui, X Y; Hou, J; Sun, J Q; Wang, X C

    2018-03-02

    Objective: To investigate the clinical characteristics of 8 immunodeficiency cases caused by human recombination activating gene 1 (RAG1) mutations, and to explore the relationship among genotypes, clinical manifestations and immunophenotypes. Methods: Clinical data were collected and analyzed from patients with RAG1 mutations who visited the Department of Clinical Immunology, Children's Hospital of Fudan University between October 2013 and June 2017. The data included clinical manifestations, immunophenotypes and genotypes. Results: A total of 8 patients were diagnosed with RAG1 deficiency (6 boys and 2 girls). The minimum age of onset was 2 months, and the maximum age was 4 months. The minimum age of diagnosis was 2 months, and the maximum age was 13 years. Four patients had a family history of infant death due to severe infections. Two cases were born to the same consanguineous parents. All cases had recurrent infections, including involvement of respiratory tract (8 cases), digestive tract (6 cases), urinary tract (1 case), and central nervous system (1 case). The pathogens of infection included bacteria, viruses and fungi. Rotavirus was found in 3 cases, cytomegalovirus (CMV) in 5 cases, bacillus Calmette-Guérin adverse reaction in 2 cases (1 of whom had a positive acid-fast smear from lymph node puncture fluid), fungal infection in 3 cases. One case had multiple nodular space-occupying lesions in lungs and abdominal cavity complicated with multiple bone destruction. The peripheral blood lymphocyte counts of all patients ranged between 0.1 ×10(9)/L and 3.3×10(9)/L (median, 0.65×10(9)/L). Eosinophilia was found in 3 cases (range, (0.48-1.69) ×10(9)/L). The patients were classified according to immunophenotype as severe combined immunodeficiency phenotype (4 cases), leaky severe combined immunodeficiency (2 cases), Omenn syndrome (1 case) and combined immunodeficiency (1 case) . Decreased serum IgG levels were found in 3 cases, increased serum IgM levels in

  17. 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.

  18. 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)

  19. 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)

  20. Economic efficiency of countries' clinical review processes and competitiveness on the market of human experimentation.

    Science.gov (United States)

    Ippoliti, Roberto

    2013-01-01

    Clinical research is a specific phase of pharmaceutical industry's production process in which companies test candidate drugs on patients to collect clinical evidence about safety and effectiveness. Information is essential to obtain manufacturing authorization from the national drug agency and, in this way, make profits on the market. Considering this activity, however, the public stakeholder has to face a conflict of interests. On the one side, there is society's necessity to make advances in medicine and, of course, to promote pharmaceutical companies' investments in this specific phase (new generation). On the other side, there is the duty to protect patients involved in these experimental treatments (old generation). To abide by this moral duty, a protection system was developed through the years, based on two legal institutions: informed consent and institutional review board. How should an efficient protection system that would take human experimentation into account be shaped? Would it be possible for the national protection system of patients' rights to affect the choice of whether to develop a clinical trial in a given country or not? Looking at Europe and considering a protection system that is shaped around institutional review boards, this article is an empirical work that tries to give answers to these open questions. It shows how a protection system that can minimize the time necessary to start a trial can positively affect pharmaceutical clinical research, that is, the choice of pharmaceutical companies to start innovative medical treatments in a given country. Copyright © 2013 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  1. 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

  2. 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

  3. The human simulation lab-dissecting sex in the simulator lab: the clinical lacuna of transsexed embodiment.

    Science.gov (United States)

    Singer, Ben

    2013-06-01

    This article begins with an ethnographically documented incident whereby nursing students dissected a medical human simulator model and rearranged it so that the "male" head and torso was attached to the "female" lower half. They then joked about the embodiment of the model, thus staging a scene of anti-trans ridicule. The students' lack of ability, or purposeful refusal, to recognize morphological biodiversity in medical settings indicates a lacuna in clinical imaginaries. Even as trans-identified and gender nonconforming people increasingly access care in the clinic, the lacuna of transsex-as a proxy term for non-binary embodiment-persists at the heart of clinical practice. This article concludes that we might engage in more ethical clinical practice if we recognize and affirm the trace of multiple forms of human being in the non-human simulator.

  4. Manufacturing human mesenchymal stem cells at clinical scale: process and regulatory challenges.

    Science.gov (United States)

    Jossen, Valentin; van den Bos, Christian; Eibl, Regine; Eibl, Dieter

    2018-05-01

    Human mesenchymal stem cell (hMSC)-based therapies are of increasing interest in the field of regenerative medicine. As economic considerations have shown, allogeneic therapy seems to be the most cost-effective method. Standardized procedures based on instrumented single-use bioreactors have been shown to provide billion of cells with consistent product quality and to be superior to traditional expansions in planar cultivation systems. Furthermore, under consideration of the complex nature and requirements of allogeneic hMSC-therapeutics, a new equipment for downstream processing (DSP) was successfully evaluated. This mini-review summarizes both the current state of the hMSC production process and the challenges which have to be taken into account when efficiently producing hMSCs for the clinical scale. Special emphasis is placed on the upstream processing (USP) and DSP operations which cover expansion, harvesting, detachment, separation, washing and concentration steps, and the regulatory demands.

  5. Awareness of human papillomavirus among women attending a well woman clinic.

    Science.gov (United States)

    Waller, J; McCaffery, K; Forrest, S; Szarewski, A; Cadman, L; Wardle, J

    2003-08-01

    To assess the level and accuracy of public understanding of human papillomavirus (HPV) in the United Kingdom. Women attending a well woman clinic were asked to complete a questionnaire assessing HPV awareness and specific knowledge about the virus. Questionnaires were completed by 1032 women, of whom 30% had heard of HPV. Older women, non-smokers, and those with a history of candida, genital warts, or an abnormal smear result were more likely to have heard of HPV. Even among those who had heard of HPV, knowledge was generally poor, and fewer than half were aware of the link with cervical cancer. There was also confusion about whether condoms or oral contraceptives could protect against HPV infection. In this relatively well educated sample, awareness and knowledge of HPV were poor. Public education is urgently needed so that women participating in cervical cancer screening are fully informed about the meaning of their results, especially if HPV testing is soon to be introduced.

  6. 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 ...

  7. 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.

  8. Characterization of plasmids in a human clinical strain of Lactococcus garvieae.

    Directory of Open Access Journals (Sweden)

    Mónica Aguado-Urda

    Full Text Available The present work describes the molecular characterization of five circular plasmids found in the human clinical strain Lactococcus garvieae 21881. The plasmids were designated pGL1-pGL5, with molecular sizes of 4,536 bp, 4,572 bp, 12,948 bp, 14,006 bp and 68,798 bp, respectively. Based on detailed sequence analysis, some of these plasmids appear to be mosaics composed of DNA obtained by modular exchange between different species of lactic acid bacteria. Based on sequence data and the derived presence of certain genes and proteins, the plasmid pGL2 appears to replicate via a rolling-circle mechanism, while the other four plasmids appear to belong to the group of lactococcal theta-type replicons. The plasmids pGL1, pGL2 and pGL5 encode putative proteins related with bacteriocin synthesis and bacteriocin secretion and immunity. The plasmid pGL5 harbors genes (txn, orf5 and orf25 encoding proteins that could be considered putative virulence factors. The gene txn encodes a protein with an enzymatic domain corresponding to the family actin-ADP-ribosyltransferases toxins, which are known to play a key role in pathogenesis of a variety of bacterial pathogens. The genes orf5 and orf25 encode two putative surface proteins containing the cell wall-sorting motif LPXTG, with mucin-binding and collagen-binding protein domains, respectively. These proteins could be involved in the adherence of L. garvieae to mucus from the intestine, facilitating further interaction with intestinal epithelial cells and to collagenous tissues such as the collagen-rich heart valves. To our knowledge, this is the first report on the characterization of plasmids in a human clinical strain of this pathogen.

  9. Increased endothelial apoptotic cell density in human diabetic erectile tissue--comparison with clinical data.

    Science.gov (United States)

    Costa, Carla; Soares, Raquel; Castela, Angela; Adães, Sara; Hastert, Véronique; Vendeira, Pedro; Virag, Ronald

    2009-03-01

    Erectile dysfunction (ED) is a common complication of diabetes. Endothelial cell (EC) dysfunction is one of the main mechanisms of diabetic ED. However, loss of EC integrity has never been assessed in human diabetic corpus cavernosum. To identify and quantify apoptotic cells in human diabetic and normal erectile tissue and to compare these results with each patient's clinical data and erection status. Eighteen cavernosal samples were collected, 13 from diabetics with ED and 5 from nondiabetic individuals. Cavernosal structure and cell proliferation status were evaluated by immunohistochemistry. Tissue integrity was assessed by terminal transferase dUTP nick end labeling assay, an index of apoptotic cell density (ACD) established and compared with each patient age, type of diabetes, arterial risk factors number, arterial/veno-occlusive disease, response to intracavernous vasoactive injections (ICI), and penile nitric oxide release test (PNORT). Establish an index of ACD and correlate those results with patient clinical data. Nondiabetic samples presented few scattered cells in apoptosis and an ACD of 7.15 +/- 0.44 (mean apoptotic cells/tissue area mm(2) +/- standard error). The diabetic group showed an increased ACD of 23.82 +/- 1.53, and apoptotic cells were located specifically at vascular sites. Rehabilitation of these endothelial lesions seemed impaired, as no evidence of EC proliferation was observed. Furthermore, higher ACD in diabetic individuals correlated to poor response to PNORT and to ICI. We provided evidence for the first time that loss of cavernosal EC integrity is a crucial event involved in diabetic ED. Furthermore, we were able to establish a threshold between ACD values and cavernosal tissue functionality, as assessed by PNORT and vasoactive ICI.

  10. Epidemiological and clinical features of human rabies cases in Bali 2008-2010

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    Susilawathi Ni M

    2012-04-01

    Full Text Available Abstract Background Previously thought to be rabies free, Bali experienced an outbreak of animal and human rabies cases in November 2008. We describe the epidemiological and clinical data of human rabies cases occurring in the first two years of the outbreak. Methods We analysed the patient records of all rabies cases from the Sanglah General Hospital in Denpasar, and district hospitals in Buleleng and Tabanan. A conventional reverse transcriptase polymerase chain reaction was developed to detect the rabies virus genome in saliva, corneal swabs, and ante- and post-mortem cerebrospinal fluid (CSF. Results There were 104 human rabies cases in Bali during November 2008-November 2010. Patients' mean age was 36.6 years (range 3-84 years; SD 20.7, most were male (56.7%, and originated from rural districts. Almost all (92% cases had a history of dog bite. Only 5.8% had their wounds treated and received an anti-rabies vaccine (ARV after the bite incident. No patients received rabies immunoglobulin (RIG. The estimated time from dog bite to the onset of signs and symptoms was 110.4 days (range 12-720 days; SD 118.2. The mean length of medical care until death was 21.8 hours (range 1-220 hours; SD 32.6. Less than 50% of patients had prodromal symptoms. The most frequent prodromal symptom was pain or paraesthesia at the bite site (37.6%. The two most common central nervous system infection signs were agitation (89.2% and confusion (83.3%. Signs of autonomic nervous system dysfunction included hydrophobia (93.1%, hypersalivation (88.2%, and dyspnea (74.4%. On admission, 22 of 102 patients (21.6% showed paralytic manifestations, while the rest (78.4% showed furious rabies manifestations. The case-fatality rate was 100%. The rabies virus genome was detected in 50 of 101 patients (49.5% with the highest detection rate from post-mortem CSF samples. Conclusions Rabies is a major public health problem in Bali. Human fatalities occur because of a lack of knowledge

  11. Epidemiological and clinical features of human rabies cases in Bali 2008-2010

    Science.gov (United States)

    2012-01-01

    Background Previously thought to be rabies free, Bali experienced an outbreak of animal and human rabies cases in November 2008. We describe the epidemiological and clinical data of human rabies cases occurring in the first two years of the outbreak. Methods We analysed the patient records of all rabies cases from the Sanglah General Hospital in Denpasar, and district hospitals in Buleleng and Tabanan. A conventional reverse transcriptase polymerase chain reaction was developed to detect the rabies virus genome in saliva, corneal swabs, and ante- and post-mortem cerebrospinal fluid (CSF). Results There were 104 human rabies cases in Bali during November 2008-November 2010. Patients' mean age was 36.6 years (range 3-84 years; SD 20.7), most were male (56.7%), and originated from rural districts. Almost all (92%) cases had a history of dog bite. Only 5.8% had their wounds treated and received an anti-rabies vaccine (ARV) after the bite incident. No patients received rabies immunoglobulin (RIG). The estimated time from dog bite to the onset of signs and symptoms was 110.4 days (range 12-720 days; SD 118.2). The mean length of medical care until death was 21.8 hours (range 1-220 hours; SD 32.6). Less than 50% of patients had prodromal symptoms. The most frequent prodromal symptom was pain or paraesthesia at the bite site (37.6%). The two most common central nervous system infection signs were agitation (89.2%) and confusion (83.3%). Signs of autonomic nervous system dysfunction included hydrophobia (93.1%), hypersalivation (88.2%), and dyspnea (74.4%). On admission, 22 of 102 patients (21.6%) showed paralytic manifestations, while the rest (78.4%) showed furious rabies manifestations. The case-fatality rate was 100%. The rabies virus genome was detected in 50 of 101 patients (49.5%) with the highest detection rate from post-mortem CSF samples. Conclusions Rabies is a major public health problem in Bali. Human fatalities occur because of a lack of knowledge regarding

  12. 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.

  13. [Human plague and pneumonic plague : pathogenicity, epidemiology, clinical presentations and therapy].

    Science.gov (United States)

    Riehm, Julia M; Löscher, Thomas

    2015-07-01

    Yersinia pestis is a highly pathogenic gram-negative bacterium and the causative agent of human plague. In the last 1500 years and during three dreaded pandemics, millions of people became victims of Justinian's plague, the Black Death, or modern plague. Today, Y. pestis is endemic in natural foci of Asian, African and American countries. Due to its broad dissemination in mammal species and fleas, eradication of the pathogen will not be possible in the near future. In fact, plague is currently classified as a "re-emerging disease". Infection may occur after the bite of an infected flea, but also after oral ingestion or inhalation of the pathogen. The clinical presentations comprise the bubonic and pneumonic form, septicemia, rarely pharyngitis, and meningitis. Most human cases can successfully be treated with antibiotics. However, the high transmission rate and lethality of pneumonic plague require international and mandatory case notification and quarantine of patients. Rapid diagnosis, therapy and barrier nursing are not only crucial for the individual patient but also for the prevention of further spread of the pathogen or of epidemics. Therefore, WHO emergency schedules demand the isolation of cases, identification and surveillance of contacts as well as control of zoonotic reservoir animals and vectors. These sanctions and effective antibiotic treatment usually allow a rapid containment of outbreaks. However, multiple antibiotic resistant strains of Y. pestis have been isolated from patients in the past. So far, no outbreaks with such strains have been reported.

  14. 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.

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

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    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.

  16. Clinical cancer chemoprevention: From the hepatitis B virus (HBV vaccine to the human papillomavirus (HPV vaccine

    Directory of Open Access Journals (Sweden)

    Horng-Jyh Tsai

    2015-04-01

    Full Text Available Approximately 2 million new cancer cases are attributed to infectious agents each year worldwide. Vaccines for the hepatitis B virus (HBV, a risk factor of hepatocellular cancer, and human papillomavirus (HPV, a risk factor of cervical cancer, are considered major successes in clinical chemoprevention of cancer. In Taiwan, the first evidence of cancer prevention through vaccinations was provided by HBV vaccination data in infants. The Taiwanese HBV vaccination program has since become a model immunization schedule for newborns worldwide. Persistent infection with high-risk HPV is generally accepted as prerequisite for cervical cancer diagnosis; however, cervical cancer is a rare complication of HPV infections. This is due to the fact that such infections tend to be transient. The safety and efficacy of both available HPV quadrivalent vaccine and bivalent vaccine are not in doubt at the present time. Until a human cytomegalovirus (CMV vaccine becomes available, simple hygienic practices, such as hand washing, can prevent CMV infection both before and during pregnancy. Each country should establish her official guidelines regarding which vaccines should be used to treat various conditions, the target population (i.e., universal or limited to a selected population, and the immunization schedules. After a vaccine is recommended, decisions regarding reimbursement by the public health care fund are evaluated. The guidelines become part of the immunization schedule, which is updated annually and published in the official bulletin. In conclusion, both HBV and HPV vaccines are considered major successes in the chemoprevention of cancer.

  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. Clinical uses of radiosterilized freeze-dried human bone: its application in buccomaxillary surgery

    International Nuclear Information System (INIS)

    Wolfsohn, B.; Taramasso, F.; Godoy, J.; Wodowoz, O.; Saldias, M.; Silva, W.; Machin, D.; Sanchez, G.; Alvarez, I.

    2008-01-01

    Full text: The objective of this paper is to evaluate the uses of different human bone tissue allografts in bucomaxillary surgery between 2005 and 2007. Presentation of our experience using single freeze dried bone allografts and associated to bovine collagen membranes (commercial registered). Twenty patients were treated with cortical struts, cancellous chips, morsellized and morsellized demineralized bone. All the grafts were processed at the INDT multi tissue bank from cardiac arrest and brain death cadaveric donors. All the tissues were radiosterilized by Gamma radiation. Bone allografts were used: 1) to optimize bone support increasing maxillar or mandible bone before implant surgery. 2) in dehiscences and fissures during the implant surgery. 3) to stimulate bone regeneration in alveolar cavity, post-apicectomies, and cystectomies as well as for bone defects. The patients were periodically evaluated using standardized protocols. All the cases were successful showing clinic and radiologically osseointegration after 6 and 12 months. Results were evaluated considering surgical technique and patients bucomaxillary rehabilitation. Clinical uses of bone allografts confirm in our experience, as scientific literature outcomes shows, are useful in patients that refuses autografts ablation. (Author)

  19. The bitter pill: clinical drugs that activate the human bitter taste receptor TAS2R14.

    Science.gov (United States)

    Levit, Anat; Nowak, Stefanie; Peters, Maximilian; Wiener, Ayana; Meyerhof, Wolfgang; Behrens, Maik; Niv, Masha Y

    2014-03-01

    Bitter taste receptors (TAS2Rs) mediate aversive response to toxic food, which is often bitter. These G-protein-coupled receptors are also expressed in extraoral tissues, and emerge as novel targets for therapeutic indications such as asthma and infection. Our goal was to identify ligands of the broadly tuned TAS2R14 among clinical drugs. Molecular properties of known human bitter taste receptor TAS2R14 agonists were incorporated into pharmacophore- and shape-based models and used to computationally predict additional ligands. Predictions were tested by calcium imaging of TAS2R14-transfected HEK293 cells. In vitro testing of the virtual screening predictions resulted in 30-80% success rates, and 15 clinical drugs were found to activate the TAS2R14. hERG potassium channel, which is predominantly expressed in the heart, emerged as a common off-target of bitter drugs. Despite immense chemical diversity of known TAS2R14 ligands, novel ligands and previously unknown polypharmacology of drugs were unraveled by in vitro screening of computational predictions. This enables rational repurposing of traditional and standard drugs for bitter taste signaling modulation for therapeutic indications.

  20. Effect of human papilloma virus expression on clinical course of laryngeal papilloma.

    Science.gov (United States)

    Kim, Kwang Moon; Cho, Nam Hoon; Choi, Hong Shik; Kim, Young Ho; Byeon, Hyung Kwon; Min, Hyun Jin; Kim, Se-Heon

    2008-10-01

    Our observations suggest that human papilloma virus (HPV) 6/11 is the main causative agent of laryngeal papilloma and that detection of active HPV DNA expression may be helpful in identifying patients with aggressive recurrent laryngeal papilloma. HPV is assumed to be the main causative agent of this disease. We investigated the expression of the entire genotype of HPV in cases of laryngeal papilloma and correlated their expression with the clinical course of the disease. Seventy cases of laryngeal papilloma were evaluated for the presence of the HPV genome by in situ hybridization (ISH) using wide-spectrum HPV DNA probe. Specific types of HPV infection were determined by DNA ISH using type-specific HPV DNA probes (HPV 6, 11, 16, 18, 31, 33). Separate analyses were conducted comparing viral types, frequency of recurrences and duration of disease-free periods. We detected HPV DNA in 40 of the 70 laryngeal papilloma cases (57%). In particular, HPV DNA was detected in 75% of the juvenile types. There were significant associations between HPV and laryngeal papilloma (p<0.01). Among the HPV-positive cases, major specific types were HPV 6/11 (97%). Significant associations were also noted between viral expression and clinical course.

  1. UL146 variability among clinical isolates of Human Cytomegalovirus from Japan

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    Francisco Aguayo

    2010-01-01

    Full Text Available Human Cytomegalovirus (HCMV is a herpesvirus associated with serious diseases in immunocompromised subjects. The region between ORF UL133 and UL151 from HCMV, named ULb' is frequently deleted in attenuated AD169 and in highly passaged laboratory strains. However, this region is conserved in low-passaged and more virulent HCMV, like the Toledo strain. The UL146 gene, which is located in the ULb' region, encodes a CXC-chemokine analogue. The diversity of UL146 gene was evaluated among fifty-six clinical isolates of HCMV from Japan. Results show that UL146 gene was successfully amplified by the polymerase chain reaction (PCR in only 17/56 strains (30%, while the success rate for UL145/UL147 gene was 18/56 strains (32%. After DNA sequencing, the 35 amplified strains were classified into 8 groups. When compared, variability of UL146 ranged from 25.1% to 52.9% at the DNA level and from 34.5% to 67% at the amino acid level. Seven groups had the interleukin-8 (IL-8 motif ERL (Glu-Leu-Arg CXC and one group had only the CXC motif, suggesting the absence of the IL-8 function of UL146. In conclusion, we found that UL146 gene of HCMV is hyper-variable in clinical strains from Japan suggesting the possibility of a different function in each sequence group.

  2. 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.

  3. X-ray dark field imaging of human articular cartilage: Possible clinical application to orthopedic surgery

    International Nuclear Information System (INIS)

    Kunisada, Toshiyuki; Shimao, Daisuke; Sugiyama, Hiroshi; Takeda, Ken; Ozaki, Toshifumi; Ando, Masami

    2008-01-01

    Despite its convenience and non-invasiveness on daily clinical use, standard X-ray radiography cannot show articular cartilage. We developed a novel type of X-ray dark field imaging (DFI), which forms images only by a refracted beam with very low background illumination. We examined a disarticulated distal femur and a shoulder joint with surrounding soft tissue and skin, both excised from a human cadaver at the BL20B2 synchrotron beamline at SPring-8. The field was 90 mm wide and 90 mm high. Articular cartilage of the disarticulated distal femur was obvious on DFI, but not on standard X-ray images. Furthermore, DFI allowed visualization in situ of articular cartilage of the shoulder while covered with soft tissue and skin. The gross appearance of the articular cartilage on the dissected section of the proximal humerus was identical to the cartilage shown on the DFI image. These results suggested that DFI could provide a clinically accurate method of assessing articular cartilage. Hence, DFI would be a useful imaging tool for diagnosing joint disease such as osteoarthritis

  4. X-ray dark field imaging of human articular cartilage: Possible clinical application to orthopedic surgery

    Energy Technology Data Exchange (ETDEWEB)

    Kunisada, Toshiyuki [Department of Medical Materials for Musculoskeletal Reconstruction, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 700-8558 (Japan); Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 700-8558 (Japan)], E-mail: toshi-kunisada@umin.ac.jp; Shimao, Daisuke [Department of Radiological Sciences, Ibaraki Prefectural University of Health Sciences, Ibaraki 300-2394 (Japan); Sugiyama, Hiroshi [Photon Factory, Institute of Materials Structure Science, High Energy Accelerator Research Organization (KEK), Ibaraki 305-0801 (Japan); Takeda, Ken; Ozaki, Toshifumi [Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 700-8558 (Japan); Ando, Masami [Research Institute for Science and Technology, Tokyo University of Science, Chiba 278-8510 (Japan)

    2008-12-15

    Despite its convenience and non-invasiveness on daily clinical use, standard X-ray radiography cannot show articular cartilage. We developed a novel type of X-ray dark field imaging (DFI), which forms images only by a refracted beam with very low background illumination. We examined a disarticulated distal femur and a shoulder joint with surrounding soft tissue and skin, both excised from a human cadaver at the BL20B2 synchrotron beamline at SPring-8. The field was 90 mm wide and 90 mm high. Articular cartilage of the disarticulated distal femur was obvious on DFI, but not on standard X-ray images. Furthermore, DFI allowed visualization in situ of articular cartilage of the shoulder while covered with soft tissue and skin. The gross appearance of the articular cartilage on the dissected section of the proximal humerus was identical to the cartilage shown on the DFI image. These results suggested that DFI could provide a clinically accurate method of assessing articular cartilage. Hence, DFI would be a useful imaging tool for diagnosing joint disease such as osteoarthritis.

  5. [Consensus statement on the clinical management of human immunodeficiency virus-associated neurocognitive disorders].

    Science.gov (United States)

    Podzamczer Palter, Daniel; Muñoz-Moreno, José A; Alcolea Rodríguez, Daniel; Alonso Villaverde, Carlos; Antela López, Antonio; Blanch Andreu, Jordi; Casado Osorio, José Luis; Galindo Puerto, M José; Garolera i Freixa, Maite; Locutura Rupérez, Jaime; Lleó Bisa, Albert; Prats París, Anna; Pérez-Valero, Ignacio; Portilla Sogorb, Joaquín; Rovira Cañellas, Alex; Téllez Molina, M Jesús; Tiraboschi, Juan Manuel; Vergara Moragues, Esperanza; Arribas López, José Ramón; Goenaga Sánchez, Miguel Ángel; de León-Naranjo, Fernando Lozano; Martínez Chamorro, Esteban; Polo Rodríguez, Rosa; Muñoz-Moreno, José A; Podzamczer, Daniel

    2014-01-01

    To develop a consensus document containing clinical recommendations for the management of human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND). We assembled a panel of experts appointed by GeSIDA and the Secretariat of the National AIDS Plan (PNS), including internal medicine physicians with expertise in the field of HIV, neuropsychologists, neurologists and neuroradiologists. Scientific information was reviewed to October 2012 in publications and conference papers. In support of the recommendations using two levels of evidence: the strength of the recommendation in the opinion of the experts (A, B, C) and the level of empirical evidence (I, II, III), two levels based on the criteria of the Infectious Disease Society of America, already used in previous documents GeSIDA/SPNS. Multiple recommendations for the clinical management of these disorders are provided, including two graphics algorithms, considering both the diagnostic and possible therapeutic strategies. Neurocognitive disorders associated with HIV infection is currently highly prevalent, are associated with a decreased quality of life and daily activities, and given the possibility of occurrence of an increase in the coming years, there is a need to adequately manage these disorders, from a diagnostic as well as therapeutic point of view, and always from a multidisciplinary perspective. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  6. Clinical Implications of Human Population Differences in Genome-wide Rates of Functional Genotypes

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    Ali eTorkamani

    2012-11-01

    Full Text Available There have been a number of recent successes in the use of whole genome sequencing and sophisticated bioinformatics techniques to identify pathogenic DNA sequence variants responsible for individual idiopathic congenital conditions. However, the success of this identification process is heavily influenced by the ancestry or genetic background of a patient with an idiopathic condition. This is so because potential pathogenic variants in a patient’s genome must be contrasted with variants in a reference set of genomes made up of other individuals’ genomes of the same ancestry as the patient. We explored the effect of ignoring the ancestries of both an individual patient and the individuals used to construct reference genomes. We pursued this exploration in two major steps. We first considered variation in the per-genome number and rates likely functional derived (i.e., non-ancestral, based on the chimp genome single nucleotide variants and small indels in 52 individual whole human genomes sampled from 10 different global populations. We took advantage of a suite of computational and bioinformatics techniques to predict the functional effect of over 24 million genomic variants, both coding and non-coding, across these genomes. We found that the typical human genome harbors ~5.5-6.1 million total derived variants, of which ~12,000 are likely to have a functional effect (~5000 coding and ~7000 non-coding. We also found that the rates of functional genotypes per the total number of genotypes in individual whole genomes differ dramatically between human populations. We then created tables showing how the use of comparator or reference genome panels comprised of genomes from individuals that do not have the same ancestral background as a patient can negatively impact pathogenic variant identification. Our results have important implications for clinical sequencing initiatives.

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

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    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

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

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    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

  9. Toxin Gene Analysis of a Variant Strain of Clostridium difficile That Causes Human Clinical Disease

    Science.gov (United States)

    Sambol, Susan P.; Merrigan, Michelle M.; Lyerly, David; Gerding, Dale N.; Johnson, Stuart

    2000-01-01

    A toxin variant strain of Clostridium difficile was isolated from two patients with C. difficile-associated disease (CDAD), one of whom died from extensive pseudomembranous colitis. This strain, identified by restriction endonuclease analysis (REA) as type CF2, was not detected by an immunoassay for C. difficile toxin A. Culture supernatants of CF2 failed to elicit significant enterotoxic activity in the rabbit ileal loop assay but did produce atypical cytopathic effects in cell culture assay. Southern hybridization, PCR amplification, and DNA sequence analyses were performed on the toxin A (tcdA) and toxin B (tcdB) genes of type CF2 isolate 5340. Type CF2 5340 tcdA exhibited a 1,821-bp truncation, due to three deletions in the 3′ end of the gene, and a point mutation in the 5′ end of the gene, resulting in a premature stop codon at tcdA position 139. Type CF2 5340 tcdB exhibited multiple nucleotide base substitutions in the 5′ end of the gene compared to tcdB of the standard toxigenic strain VPI 10463. Type CF2 5340 toxin gene nucleotide sequences and deduced amino acid sequences showed a strong resemblance to those of the previously described variant C. difficile strain 1470, a strain reported to have reduced pathogenicity and no association with clinical illness in humans. REA of strain 1470 identified this strain as a distinct type (CF1) within the same REA group as the closely related type CF2. A review of our clinical-isolate collection identified five additional patients infected with type CF2, three of whom had documented CDAD. PCR amplification of the 3′ end of tcdA demonstrated identical 1.8-kb deletions in all seven type CF2 isolates. REA type CF2 is a toxin variant strain of C. difficile that retains the ability to cause disease in humans but is not detected in clinical immunoassays for toxin A. PMID:10992443

  10. 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

  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. Expression of hsa_circ_PVT1 in human hepatocellular carcinoma and its clinical significance

    Directory of Open Access Journals (Sweden)

    Yuan-xin ZHU

    2018-03-01

    Full Text Available Objective To determine the expression and clinical significance of circ-PVT1 in human hepatocellular carcinoma (HCC and its effect on HCC cell proliferation. Methods The expressions of circ-PVT1 in hepatocellular carcinoma and the matched tumor-adjacent tissues were detected by RT-qPCR and the relationship between pathological indexes and the expression level was analyzed in 46 patients. The expressions of circ-PVT1 in human normal liver cell line (L02 and hepatocellular carcinoma cell lines (HepG2, SMMC-7721, MHCC-97H, MHCC-97L, HCC-LM3 were detected by RT-qPCR and were compared thereafter. With knocking down the expression of circ-PVT1, si-circPVT1 was transfected into HepG2 and SMMC-7721 cells by using lipofectamine technique in vitro, with the si-NC being taken as negative control. After interfering the expression of circ-PVT1, the effect on the proliferation of hepatocellular carcinoma cells was detected by CCK-8 and EDU experiments and flow cytometry was conducted to observe the effect of circ-PVT1 on cell cycle. Results The expression level of circ-PVT1 was significantly higher in HCC tissues than in adjacent tissues (P<0.01, and its high expression level was significantly correlated with tumor size, TNM stage and differentiation degree. Similarly, in human hepatocellular carcinoma cell lines (HepG2, SMMC-7721, MHCC-97H, MHCC-97L, HCC-LM3, the expression level of circ-PVT1 was also higher than that in human normal liver cell line L02 (P<0.05. Compared with the negative control group, silencing of circ-PVT1 resulted in remarkable reduction in cell proliferation of HepG2 and SMMC-7721. Conclusion circ-PVT1 may act as a potential biomarker for HCC diagnosis and may become a novel proliferation factor. DOI: 10.11855/j.issn.0577-7402.2018.03.06

  13. 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.

  14. New clinically relevant, orthotopic mouse models of human chondrosarcoma with spontaneous metastasis

    Directory of Open Access Journals (Sweden)

    Dass Crispin R

    2010-06-01

    Full Text Available Abstract Background Chondrosarcoma responds poorly to adjuvant therapy and new, clinically relevant animal models are required to test targeted therapy. Methods Two human chondrosarcoma cell lines, JJ012 and FS090, were evaluated for proliferation, colony formation, invasion, angiogenesis and osteoclastogenesis. Cell lines were also investigated for VEGF, MMP-2, MMP-9, and RECK expression. JJ012 and FS090 were injected separately into the mouse tibia intramedullary canal or tibial periosteum. Animal limbs were measured, and x-rayed for evidence of tumour take and progression. Tibias and lungs were harvested to determine the presence of tumour and lung metastases. Results JJ012 demonstrated significantly higher proliferative capacity, invasion, and colony formation in collagen I gel. JJ012 conditioned medium stimulated endothelial tube formation and osteoclastogenesis with a greater potency than FS090 conditioned medium, perhaps related to the effects of VEGF and MMP-9. In vivo, tumours formed in intratibial and periosteal groups injected with JJ012, however no mice injected with FS090 developed tumours. JJ012 periosteal tumours grew to 3 times the non-injected limb size by 7 weeks, whereas intratibial injected limbs required 10 weeks to achieve a similar tumour size. Sectioned tumour tissue demonstrated features of grade III chondrosarcoma. All JJ012 periosteal tumours (5/5 resulted in lung micro-metastases, while only 2/4 JJ012 intratibial tumours demonstrated metastases. Conclusions The established JJ012 models replicate the site, morphology, and many behavioural characteristics of human chondrosarcoma. Local tumour invasion of bone and spontaneous lung metastasis offer valuable assessment tools to test the potential of novel agents for future chondrosarcoma therapy.

  15. 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

  16. 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.

  17. 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.

  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. 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.

  20. 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.

  1. 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: ...

  2. 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

  3. 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.

  4. Clinical system for non-invasive in situ monitoring of gases in the human paranasal sinuses.

    Science.gov (United States)

    Lewander, Märta; Guan, Zuguang; Svanberg, Katarina; Svanberg, Sune; Svensson, Tomas

    2009-06-22

    We present a portable system for non-invasive, simultaneous sensing of molecular oxygen (O(2)) and water vapor (H(2)O) in the human paranasal cavities. The system is based on high-resolution tunable diode laser spectroscopy (TDLAS) and digital wavelength modulation spectroscopy (dWMS). Since optical interference and non-ideal tuning of the diode lasers render signal processing complex, we focus on Fourier analysis of dWMS signals and procedures for removal of background signals. Clinical data are presented, and exhibit a significant improvement in signal-to-noise with respect to earlier work. The in situ detection limit, in terms of absorption fraction, is about 5x10(-5) for oxygen and 5x10(-4) for water vapor, but varies between patients due to differences in light attenuation. In addition, we discuss the use of water vapor as a reference in quantification of in situ oxygen concentration in detail. In particular, light propagation aspects are investigated by employing photon time-of-flight spectroscopy.

  5. 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.)

  6. 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.

  7. 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.

  8. Chemoprevention of Lung Cancer: Prospects and Disappointments in Human Clinical Trials

    Directory of Open Access Journals (Sweden)

    William N. Rom

    2013-01-01

    Full Text Available Decreasing the risk of lung cancer, or preventing its development in high-risk individuals, would have a huge impact on public health. The most effective means to decrease lung cancer incidence is to eliminate exposure to carcinogens. However, with recent advances in the understanding of pulmonary carcinogenesis and the identification of intermediate biomarkers, the prospects for the field of chemoprevention research have improved dramatically. Here we review the most recent research in lung cancer chemoprevention—focusing on those agents that have been investigated in human clinical trials. These agents fall into three major categories. First, oxidative stress plays an important role in pulmonary carcinogenesis; and therefore, antioxidants (including vitamins, selenium, green tea extracts, and isothiocyanates may be particularly effective in preventing the development of lung cancer. Second, inflammation is increasingly accepted as a crucial factor in carcinogenesis, and many investigators have focused on anti-inflammatory agents, such as glucocorticoids, NSAIDs, statins, and PPARγ agonists. Finally, the PI3K/AKT/mTOR pathway is recognized to play a central role in tobacco-induced carcinogenesis, and inhibitors of this pathway, including myoinositol and metformin, are promising agents for lung cancer prevention. Successful chemoprevention will likely require targeting of multiple pathways to carcinogenesis—both to minimize toxicity and maximize efficacy.

  9. 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.

  10. 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.

  11. The Impact of Humanities-Based Teaching and Learning Strategies on Critical Thinking and Clinical Reasoning Development among BSN Students

    Science.gov (United States)

    Brodhead, Josette

    2016-01-01

    The ability to function effectively in a dynamic, culturally diverse healthcare environment requires both critical thinking and clinical reasoning skills. The American Association of Colleges of Nursing (AACN, 2008) recognizes the importance of humanities in the baccalaureate nursing curriculum. This quasi-experimental, nonrandomized…

  12. Human papilloma virus DNA and p53 mutation analysis on bladder washes in relation to clinical outcome of bladder cancer.

    NARCIS (Netherlands)

    Moonen, P.M.J.; Bakkers, J.M.J.E.; Kiemeney, L.A.L.M.; Schalken, J.A.; Melchers, W.J.G.; Witjes, J.A.

    2007-01-01

    OBJECTIVES: High-risk human papilloma virus (HPV) types stimulate degradation and deactivation of protein associated with the p53 tumour suppressor gene via the ubiquitin-dependent pathway. For a long time, changes of the p53 tumour suppressor gene have been correlated with poor clinical outcome in

  13. Clinical Trials

    Medline Plus

    Full Text Available ... medical strategy, treatment, or device is safe and effective for humans. What Are Clinical Trials? Clinical trials ... and Centers sponsor clinical trials. Many other groups, companies, and organizations also sponsor clinical trials. Examples include ...

  14. 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.

  15. 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)

  16. 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

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

    Science.gov (United States)

    Manolio, Teri A.

    2016-01-01

    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 diffficulties 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. PMID:27612677

  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. 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.

  20. Intramacrophage survival of uropathogenic Escherichia coli: Differences between diverse clinical isolates and between mouse and human macrophages

    DEFF Research Database (Denmark)

    Bokil, Nilesh J.; Totsika, Makrina; Carey, Alison J.

    2011-01-01

    assays, CFT073 was able to survive within primary mouse bone marrow-derived macrophages (BMM) up to 24h post-infection. Three additional well-characterized clinical UPEC isolates associated with distinct UTI symptomatologies displayed variable long-term survival within BMM. UPEC strains UTI89 and VR50...... or initial uptake of bacteria. E. coli UTI89 localized to a Lamp1+ vesicular compartment within BMM. In contrast to survival within mouse BMM, intracellular bacterial loads of VR50 were low in both human monocyte-derived macrophages (HMDM) and in human T24 bladder epithelial cells. Collectively, these data...

  1. Clinical Implication of Elevated Human Cervical Cancer Oncogene-1 Expression in Esophageal Squamous Cell Carcinoma

    OpenAIRE

    Liu, Ying; Li, Ke; Ren, Zhonghai; Li, Shenglei; Zhang, Hongyan; Fan, Qingxia

    2012-01-01

    The human cervical cancer oncogene 1 (HCCR-1), a novel human oncoprotein, has been shown to be upregulated in various human tumors and plays a critical role in tumorigenesis and tumor progression. Here, the authors investigated HCCR-1 level in esophageal squamous cell carcinoma (ESCC) tissues and assessed the correlation between HCCR-1 level and prognosis of the patients with ESCC. HCCR-1 levels were investigated by immunohistochemistry, in situ hybridization, real-time quantit...

  2. Markers of stem cells in human ovarian granulosa cells: is there a clinical significance in ART?

    Directory of Open Access Journals (Sweden)

    Varras Michail

    2012-11-01

    Full Text Available Abstract Background The purpose of the study was to determine the incidence of gene expression of Oct-4 and DAZL, which are typical markers for stem cells, in human granulosa cells during ovarian stimulation in women with normal FSH levels undergoing IVF or ICSI and to discover any clinical significance of such expression in ART. Methods Twenty one women underwent ovulation induction for IVF or ICSI and ET with standard GnRH analogue-recombinant FSH protocol. Infertility causes were male and tubal factor. Cumulus–mature oocyte complexes were denuded separately and granulosa cells were analyzed for each patient separately using quantitative reverse-transcription–polymerase chain reaction analysis for Oct-4 and DAZL gene expression with G6PD gene as internal standard. Results G6PD and Oct-4 mRNA was detected in the granulosa cells in 47.6% (10/21. The median of Oct-4 mRNA/G6PD mRNA was 1.75 with intra-quarteral range from 0.10 to 98.21. The OCT-4 mRNA expression was statistically significantly correlated with the number of oocytes retrieved; when the Oct-4 mRNA expression was higher, then more than six oocytes were retrieved (p=0.037, Wilcoxon rank-sum. No detection of DAZL mRNA was found in granulosa cells. There was no additional statistically significant correlation between the levels of Oct-4 expression and FSH basal levels or estradiol peak levels or dosage of FSH for ovulation induction. No association was found between the presence or absence of Oct-4 mRNA expression in granulosa cells and ovarian response to gonadotropin stimulation. Also, no influence on pregnancy was observed between the presence or absence of Oct-4 mRNA expression in granulosa cells or to its expression levels accordingly. Conclusions Expression of OCT-4 mRNA, which is a typical stem cell marker and absence of expression of DAZL mRNA, which is a typical germ cell marker, suggest that a subpopulation of luteinized granulosa cells in healthy ovarian follicles (47

  3. The clinical significance of thymidylate synthase expression in human papillomavirus-related oropharyngeal squamous carcinoma

    International Nuclear Information System (INIS)

    Kato, Hisayuki; Yui, Takehiro; Okada, Tatsuyoshi; Urano, Makoto; Sakurai, Kazuo; Naito, Kensei; Yamamoto, Naoki

    2012-01-01

    The focus of human papilloma virus (HPV), particulary HPV 16 is on the role of carcinogenic and prognostic factors on oropharyngeal squamous carcinoma (OSCC). However, it remains unclear why patients with HPV-positive tumors have better outcomes than those with HPV-negative tumors. Thymidylate synthase (TS) is one of the initial key enzymes in the 5-fluouracil (5-FU) metabolic pathway. Clinical studies showed that intratumoural TS level was related to the response to 5-FU-based chemotherapy in patients with several types of cancer such as gastroenterological and head and neck cancers. We investigated the prevalence of HPV infection and TS expression in the patients with OSCC and evaluated the prognostic implications according to the HPV status and TS expression. We evaluated for high-risk HPV types (HPV 16, 18, 31, 33, 51, 52, 58) using a real-time polymerase chain reaction (RT-PCR) assay on archival biopsies from 54 patients with OSCC. Immunohistochemical assessments for TS were also performed. HPV was positive in 22 (40.7%) of 54 samples. Of these positive cases, 21 (95%) carried HPV 16 and only 1 (5%) HPV58 sequences. TS was overexpressed in 25 (46.3%) of 54 samples. Of these, 19 (76.0%) had an HPV-negative status and 21 (84.0%) were heavy smokers. TS overexpression was associated with the patients with HPV-negative tumors (P=0.02) and heavy smokers (p=0.012). Univariate analysis revealed that HPV positive status (77.3% vs. 29.0%; p=0.006) significantly improved overall survival. Conversely, no remarkable prognostic difference was observed on immunohistochemical analysis of TS expression. A multivariate analysis using Cox's proportional hazard model showed that early T stage (T1-2), early N stage (N0-1), and positive HPV status were significantly independent predictors for superior overall survival. Our studies suggested that positive HPV status was most strongly associated with a favorable prognosis in the patients with OSCC. TS expression has an unusual aspect

  4. Correlation between endogenous polyamines in human cardiac tissues and clinical parameters in patients with heart failure.

    Science.gov (United States)

    Meana, Clara; Rubín, José Manuel; Bordallo, Carmen; Suárez, Lorena; Bordallo, Javier; Sánchez, Manuel

    2016-02-01

    Polyamines contribute to several physiological and pathological processes, including cardiac hypertrophy in experimental animals. This involves an increase in ornithine decarboxylase (ODC) activity and intracellular polyamines associated with cyclic adenosine monophosphate (cAMP) increases. The aim of the study was to establish the role of these in the human heart in living patients. For this, polyamines (by high performance liquid chromatography) and the activity of ODC and N(1)-acetylpolyamine oxidases (APAO) were determined in the right atrial appendage of 17 patients undergoing extracorporeal circulation to correlate with clinical parameters. There existed enzymatic activity associated with the homeostasis of polyamines. Left atria size was positively associated with ODC (r = 0.661, P = 0.027) and negatively with APAO-N(1) -acetylspermine (r = -0.769, P = 0.026), suggesting that increased levels of polyamines are associated with left atrial hemodynamic overload. Left ventricular ejection fraction (LVEF) and heart rate were positively associated with spermidine (r = 0.690, P = 0.003; r = 0.590, P = 0.021) and negatively with N(1)-acetylspermidine (r = -0.554, P = 0.032; r = -0.644, P = 0.018). LVEF was negatively correlated with cAMP levels (r = -0.835, P = 0.001) and with cAMP/ODC (r = -0.794, P = 0.011), cAMP/spermidine (r = -0.813, P = 0.001) and cAMP/spermine (r = -0.747, P = 0.003) ratios. Abnormal LVEF patients showed decreased ODC activity and spermidine, and increased N(1) -acetylspermidine, and cAMP. Spermine decreased in congestive heart failure patients. The trace amine isoamylamine negatively correlated with septal wall thickness (r = -0.634, P = 0.008) and was increased in cardiac heart failure. The results indicated that modifications in polyamine homeostasis might be associated with cardiac function and remodelling. Increased cAMP might have a deleterious effect on function. Further studies should confirm these findings and the involvement of

  5. VTEC O157 subtypes associated with the most severe clinical symptoms in humans constitute a minor part of VTEC 0157 isolates from Danish Cattle

    DEFF Research Database (Denmark)

    Roldgaard, Bemt Bjørn; Scheutz, Flemming; Boel, Jeppe

    2004-01-01

    -positive VTEC 0 157 isolates (63 of bovine origin and 86 from human clinical cases) isolated between 1987 and 2001. All were analysed by vtx-PCR-RFLP and phage typing. The vtx-PCR-RFLP showed that isolates carrying the vtx2 gene was more than four times as prevalent among the human clinical isolates (55...

  6. 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 ...

  7. 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 ...

  8. Clinical Trials

    Medline Plus

    Full Text Available ... treatment, or device is safe and effective for humans. What Are Clinical Trials? Clinical trials are research ... are required to have an IRB. Office for Human Research Protections The U.S. Department of Health and ...

  9. 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.

  10. Human In Silico Drug Trials Demonstrate Higher Accuracy than Animal Models in Predicting Clinical Pro-Arrhythmic Cardiotoxicity

    Directory of Open Access Journals (Sweden)

    Elisa Passini

    2017-09-01

    Full Text Available Early prediction of cardiotoxicity is critical for drug development. Current animal models raise ethical and translational questions, and have limited accuracy in clinical risk prediction. Human-based computer models constitute a fast, cheap and potentially effective alternative to experimental assays, also facilitating translation to human. Key challenges include consideration of inter-cellular variability in drug responses and integration of computational and experimental methods in safety pharmacology. Our aim is to evaluate the ability of in silico drug trials in populations of human action potential (AP models to predict clinical risk of drug-induced arrhythmias based on ion channel information, and to compare simulation results against experimental assays commonly used for drug testing. A control population of 1,213 human ventricular AP models in agreement with experimental recordings was constructed. In silico drug trials were performed for 62 reference compounds at multiple concentrations, using pore-block drug models (IC50/Hill coefficient. Drug-induced changes in AP biomarkers were quantified, together with occurrence of repolarization/depolarization abnormalities. Simulation results were used to predict clinical risk based on reports of Torsade de Pointes arrhythmias, and further evaluated in a subset of compounds through comparison with electrocardiograms from rabbit wedge preparations and Ca2+-transient recordings in human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs. Drug-induced changes in silico vary in magnitude depending on the specific ionic profile of each model in the population, thus allowing to identify cell sub-populations at higher risk of developing abnormal AP phenotypes. Models with low repolarization reserve (increased Ca2+/late Na+ currents and Na+/Ca2+-exchanger, reduced Na+/K+-pump are highly vulnerable to drug-induced repolarization abnormalities, while those with reduced inward current density

  11. Human In Silico Drug Trials Demonstrate Higher Accuracy than Animal Models in Predicting Clinical Pro-Arrhythmic Cardiotoxicity.

    Science.gov (United States)

    Passini, Elisa; Britton, Oliver J; Lu, Hua Rong; Rohrbacher, Jutta; Hermans, An N; Gallacher, David J; Greig, Robert J H; Bueno-Orovio, Alfonso; Rodriguez, Blanca

    2017-01-01

    Early prediction of cardiotoxicity is critical for drug development. Current animal models raise ethical and translational questions, and have limited accuracy in clinical risk prediction. Human-based computer models constitute a fast, cheap and potentially effective alternative to experimental assays, also facilitating translation to human. Key challenges include consideration of inter-cellular variability in drug responses and integration of computational and experimental methods in safety pharmacology. Our aim is to evaluate the ability of in silico drug trials in populations of human action potential (AP) models to predict clinical risk of drug-induced arrhythmias based on ion channel information, and to compare simulation results against experimental assays commonly used for drug testing. A control population of 1,213 human ventricular AP models in agreement with experimental recordings was constructed. In silico drug trials were performed for 62 reference compounds at multiple concentrations, using pore-block drug models (IC 50 /Hill coefficient). Drug-induced changes in AP biomarkers were quantified, together with occurrence of repolarization/depolarization abnormalities. Simulation results were used to predict clinical risk based on reports of Torsade de Pointes arrhythmias, and further evaluated in a subset of compounds through comparison with electrocardiograms from rabbit wedge preparations and Ca 2+ -transient recordings in human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs). Drug-induced changes in silico vary in magnitude depending on the specific ionic profile of each model in the population, thus allowing to identify cell sub-populations at higher risk of developing abnormal AP phenotypes. Models with low repolarization reserve (increased Ca 2+ /late Na + currents and Na + /Ca 2+ -exchanger, reduced Na + /K + -pump) are highly vulnerable to drug-induced repolarization abnormalities, while those with reduced inward current density

  12. Ethical and social implications of microdosing clinical trial (3). Radiological protection of human subjects in research

    International Nuclear Information System (INIS)

    Kurihara, Chieko

    2008-01-01

    Internal irradiation of human subjects in research is discussed. Radiological protection of human subjects in medical research in a framework of radiation protection is surveyed from a viewpoint of general life-ethics and research-ethics. A workshop 'On the internal irradiation of human subjects' to summarize special and systematic knowledge was organized by Research Center for Radiation Protection, National Institute of Radiological Sciences in the beginning of 2008. Activities of this workshop are introduced. Discussion covers also (1) Research ethics and radiation protection, (2) Fundamentals and applications of risk-benefit assessment, (3) Human subjects risk assessment in ICRP recommendation, (4) Mechanism of human subjects internal irradiation assessment, and (5) Present status and future prospects in Japan. (K.Y.)

  13. A clinical decision support system for integrating tuberculosis and HIV care in Kenya: a human-centered design approach.

    Science.gov (United States)

    Catalani, Caricia; Green, Eric; Owiti, Philip; Keny, Aggrey; Diero, Lameck; Yeung, Ada; Israelski, Dennis; Biondich, Paul

    2014-01-01

    With the aim of integrating HIV and tuberculosis care in rural Kenya, a team of researchers, clinicians, and technologists used the human-centered design approach to facilitate design, development, and deployment processes of new patient-specific TB clinical decision support system for medical providers. In Kenya, approximately 1.6 million people are living with HIV and have a 20-times higher risk of dying of tuberculosis. Although tuberculosis prevention and treatment medication is widely available, proven to save lives, and prioritized by the World Health Organization, ensuring that it reaches the most vulnerable communities remains challenging. Human-centered design, used in the fields of industrial design and information technology for decades, is an approach to improving the effectiveness and impact of innovations that has been scarcely used in the health field. Using this approach, our team followed a 3-step process, involving mixed methods assessment to (1) understand the situation through the collection and analysis of site observation sessions and key informant interviews; (2) develop a new clinical decision support system through iterative prototyping, end-user engagement, and usability testing; and, (3) implement and evaluate the system across 24 clinics in rural West Kenya. Through the application of this approach, we found that human-centered design facilitated the process of digital innovation in a complex and resource-constrained context.

  14. A clinical decision support system for integrating tuberculosis and HIV care in Kenya: a human-centered design approach.

    Directory of Open Access Journals (Sweden)

    Caricia Catalani

    Full Text Available With the aim of integrating HIV and tuberculosis care in rural Kenya, a team of researchers, clinicians, and technologists used the human-centered design approach to facilitate design, development, and deployment processes of new patient-specific TB clinical decision support system for medical providers. In Kenya, approximately 1.6 million people are living with HIV and have a 20-times higher risk of dying of tuberculosis. Although tuberculosis prevention and treatment medication is widely available, proven to save lives, and prioritized by the World Health Organization, ensuring that it reaches the most vulnerable communities remains challenging. Human-centered design, used in the fields of industrial design and information technology for decades, is an approach to improving the effectiveness and impact of innovations that has been scarcely used in the health field. Using this approach, our team followed a 3-step process, involving mixed methods assessment to (1 understand the situation through the collection and analysis of site observation sessions and key informant interviews; (2 develop a new clinical decision support system through iterative prototyping, end-user engagement, and usability testing; and, (3 implement and evaluate the system across 24 clinics in rural West Kenya. Through the application of this approach, we found that human-centered design facilitated the process of digital innovation in a complex and resource-constrained context.

  15. 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.

  16. 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

  17. Do clinical data and human papilloma virus genotype influence spontaneous regression in grade I cervical intraepithelial neoplasia?

    Science.gov (United States)

    Cortés-Alaguero, Caterina; González-Mirasol, Esteban; Morales-Roselló, José; Poblet-Martinez, Enrique

    2017-03-15

    To determine whether medical history, clinical examination and human papilloma virus (HPV) genotype influence spontaneous regression in cervical intraepithelial neoplasia grade I (CIN-I). We retrospectively evaluated 232 women who were histologically diagnosed as have CIN-I by means of Kaplan-Meier curves, the pattern of spontaneous regression according to the medical history, clinical examination, and HPV genotype. Spontaneous regression occurred in most patients and was influenced by the presence of multiple HPV genotypes but not by the HPV genotype itself. In addition, regression frequency was diminished when more than 50% of the cervix surface was affected or when an abnormal cytology was present at the beginning of follow-up. The frequency of regression in CIN-I is high, making long-term follow-up and conservative management advisable. Data from clinical examination and HPV genotyping might help to anticipate which lesions will regress.

  18. Pink-pigmented non-fermentative gram-negative rods associated with human infections: a clinical and diagnostic challenge.

    Science.gov (United States)

    Hogue, R; Graves, M; Moler, S; Janda, J M

    2007-06-01

    Over the past several decades, the appearance of pink-pigmented bacteria in clinical specimens has gone from being a microbiologic curiosity in the clinical laboratory to the recognition of these aerobic microorganisms as etiologic agents of human disease, most notably bloodstream infections. Advances in the fields of molecular taxonomy and phylogenetics indicate that at least four distinct genera and eight different species are associated with clinical infections in susceptible patient populations. However, these bacteria are slow growing and present multiple diagnostic challenges to the microbiology laboratory including culture, isolation, and identification to species rank. This article provides a current review of these unusual non-fermentative chromogenic bacteria including their disease spectrum, taxonomy, and laboratory identification. The review also highlights the pitfalls or shortcomings we currently have in our knowledge of these microbes and their disease-producing capabilities.

  19. 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.

  20. 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.

  1. 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.

  2. Degenerated human articular cartilage at autopsy represents preclinical osteoarthritic cartilage: comparison with clinically defined osteoarthritic cartilage

    NARCIS (Netherlands)

    van Valburg, A. A.; Wenting, M. J.; Beekman, B.; te Koppele, J. M.; Lafeber, F. P.; Bijlsma, J. W.

    1997-01-01

    To investigate whether macroscopically fibrillated human articular knee cartilage observed at autopsy can be considered an early, preclinical phase of osteoarthritis (OA). Histological and biochemical characteristics of 3 types of articular knee cartilage were compared: macroscopically degenerated

  3. Clinical Trials

    Medline Plus

    Full Text Available ... clinical trials are required to have an IRB. Office for Human Research Protections The U.S. Department of Health and Human Services’ (HHS’) Office for Human Research Protections (OHRP) oversees all research ...

  4. Volume of the human hippocampus and clinical response following electroconvulsive therapy

    DEFF Research Database (Denmark)

    Oltedal, Leif; Narr, Katherine L.; Abbott, Christopher

    2018-01-01

    Background: Hippocampal enlargements are commonly reported following electroconvulsive therapy (ECT). To clarify mechanisms, we examined if ECT induced hippocampal volume change relates to dose (number of ECT sessions and electrode placement) and acts as a biomarker of clinical outcome. Methods...

  5. [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.

  6. 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, ...

  7. Clinical solid waste management practices and its impact on human health and environment - A review

    International Nuclear Information System (INIS)

    Hossain, Md. Sohrab; Santhanam, Amutha; Nik Norulaini, N.A.; Omar, A.K. Mohd

    2011-01-01

    Research highlights: → Appropriate waste management technology for safe handling and disposal of clinical solid waste. → Infectious risk assessment on unsafe handling of clinical solid waste. → Recycling-reuse program of clinical solid waste materials. → Effective sterilization technology to reduce exposure of infectious risk. - Abstract: The management of clinical solid waste (CSW) continues to be a major challenge, particularly, in most healthcare facilities of the developing world. Poor conduct and inappropriate disposal methods exercised during handling and disposal of CSW is increasing significant health hazards and environmental pollution due to the infectious nature of the waste. This article summarises a literature review into existing CSW management practices in the healthcare centers. The information gathered in this paper has been derived from the desk study of open literature survey. Numerous researches have been conducted on the management of CSW. Although, significant steps have been taken on matters related to safe handling and disposal of the clinical waste, but improper management practice is evident from the point of initial collection to the final disposal. In most cases, the main reasons of the mismanagement of CSW are the lack of appropriate legislation, lack of specialized clinical staffs, lack of awareness and effective control. Furthermore, most of the healthcare centers of the developing world have faced financial difficulties and therefore looking for cost effective disposal methods of clinical waste. This paper emphasizes to continue the recycle-reuse program of CSW materials after sterilization by using supercritical fluid carbon dioxide (SF-CO2) sterilization technology at the point of initial collection. Emphasis is on the priority to inactivate the infectious micro-organisms in CSW. In that case, waste would not pose any threat to healthcare workers. The recycling-reuse program would be carried out successfully with the non

  8. PHARMACOLOGICAL IN VITRO MODELS IN PRE-CLINICAL DRUG TESTING - EXAMPLE OF hSERT TRANSFECTED HUMAN EMBRYONIC KIDNEY CELLS

    Directory of Open Access Journals (Sweden)

    Mihajlo Jakovljević

    2012-06-01

    Full Text Available Preclinical drug testing should be considered an important stage during examinations of its efficiency and safety in any likely indication observed. Purpose of the process is acquisition of substantial amount of particular drug-related data before approaching clinical trials in humans. Historical preclinical testing relied on available testing in microbe cultures and animal models. During recent decades laboratory techniques of human cell lines cultivation have been developed and improved. These provide unique possibility of drug acting mechanism testing in a simplified environment lacking basic homeostatic mechanisms. Some examples of these are measuring drug impact to biochemical transport, signaling or anabolic processes. Humane cell lines of embrional kidney 293 are an example of easy-to-grow and disseminate and quite endurable cell line. This methodological article notices some of the details of HEK293 cells cultivation and breading. We took transfection as an example of in vitro model creation for drug testing. Transfection refers to gene introduction into HEK293 cellular genome in order to achieve membrane expression of coded protein. In our case it would be human serotonin transporter. Article contains description of one particular methodological approach in measuring human serotonin transporter expression. The role and importance of serotonin pump in affective disorders genesis was already widely recognized. Aim of the paper was to emphasize feasibility of cell cultivation and its advantages in comparison with alternative traditional methods.

  9. 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.

  10. 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.

  11. Maximum recovery potential of human tumor cells may predict clinical outcome in radiotherapy

    International Nuclear Information System (INIS)

    Weichselbaum, R.R.; Beckett, M.

    1987-01-01

    We studied inherent radiosensitivity/resistance (D0), ability to accumulate sublethal damage (n) and repair of potentially lethal damage (PLDR) in established human tumor cell lines as well as early passage human tumor cell lines derived from patients with known outcome following radiotherapy. Survival 24 hrs after treatment of human tumor cells with X rays in plateau phase cultures is a function of initial damage (D0, n), as well as recovery over 24 hrs (PLDR). A surviving fraction greater than .1 24 hrs following treatment with 7 Gy in plateau phase cultures is associated with tumor cell types (melanoma, osteosarcoma) with a high probability of radiotherapy failure or tumor cells derived from patients who actually failed radiotherapy. Therefore, total cellular recovery following radiation may be an important determinant of radiocurability. Accurate assays of radiotherapy outcome may need to account for all these radiobiological parameters

  12. Clinical Aspects of Trace Elements: Zinc in Human Nutrition – Zinc Deficiency and Toxicity

    Directory of Open Access Journals (Sweden)

    Michelle M Pluhator

    1996-01-01

    Full Text Available Available evidence suggests that trace elements, such as zinc, once thought to have no nutritional relevance, are possibly deficient in large sections of the human population. Conditioned deficiencies have been reported to result from malabsorption syndromes, acrodermatitis enteropathica, alcoholism, gastrointestinal disease, thermal injury, chronic diseases (eg, diabetes, sickle cell anemia, and in total parenteral nutrition therapy. Awareness that patients with these problems are at risk has led health professionals to focus increasingly on the importance of zinc therapy in the prevention and treatment of deficiency. More recently zinc toxicity and its role in human nutrition and well-being have come under investigation. Reports have focused on the role of zinc toxicity in causes of copper deficiency, changes in the immune system and alterations in blood lipids. As the numerous challenges presented by the study of zinc in human nutrition are met, more appropriate recommendations for dietary and therapeutic zinc intake are being made.

  13. Clinical management of canine leishmaniosis versus human leishmaniasis due to Leishmania infantum: Putting "One Health" principles into practice.

    Science.gov (United States)

    Miró, Guadalupe; López-Vélez, Rogelio

    2018-04-30

    The initiative One World, "One Health" tries to rapidly detect emerging or reemerging human and animal infectious diseases and prevent epidemiological situations such as deforestation, some agricultural practices or the appearance of new foci of leishmaniosis due to Leishmania infantum with alternative reservoirs. With this objective in mind, we here consider leishmaniosis in the Mediterranean basin and compare its current clinical management from two perspectives: that of a veterinarian specialized in infectious and parasitic diseases, and that of a physician specialized in infectious tropical diseases. We thus prepared a list of 10 key questions from epidemiology to control of the disease in both species: dogs and humans. This issue requires a concise and clear response to help animal and human health clinicians to improve their clinical management and understanding of this important zoonosis. Our ultimate aim is to update and bring together the information available backed by sound scientific evidence. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  14. Terbium to Quantum Dot FRET Bioconjugates for Clinical Diagnostics: Influence of Human Plasma on Optical and Assembly Properties

    Directory of Open Access Journals (Sweden)

    Niko Hildebrandt

    2011-10-01

    Full Text Available Förster resonance energy transfer (FRET from luminescent terbium complexes (LTC as donors to semiconductor quantum dots (QDs as acceptors allows extraordinary large FRET efficiencies due to the long Förster distances afforded. Moreover, time-gated detection permits an efficient suppression of autofluorescent background leading to sub-picomolar detection limits even within multiplexed detection formats. These characteristics make FRET-systems with LTC and QDs excellent candidates for clinical diagnostics. So far, such proofs of principle for highly sensitive multiplexed biosensing have only been performed under optimized buffer conditions and interactions between real-life clinical media such as human serum or plasma and LTC-QD-FRET-systems have not yet been taken into account. Here we present an extensive spectroscopic analysis of absorption, excitation and emission spectra along with the luminescence decay times of both the single components as well as the assembled FRET-systems in TRIS-buffer, TRIS-buffer with 2% bovine serum albumin, and fresh human plasma. Moreover, we evaluated homogeneous LTC-QD FRET assays in QD conjugates assembled with either the well-known, specific biotin-streptavidin biological interaction or, alternatively, the metal-affinity coordination of histidine to zinc. In the case of conjugates assembled with biotin-streptavidin no significant interference with the optical and binding properties occurs whereas the histidine-zinc system appears to be affected by human plasma.

  15. 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.

  16. 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.

  17. 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.

  18. Thinking about thinking and emotion: the metacognitive approach to the medical humanities that integrates the humanities with the basic and clinical sciences.

    Science.gov (United States)

    Eichbaum, Quentin G

    2014-01-01

    Medical knowledge in recent decades has grown prodigiously and has outstripped the capacity of the human brain to absorb and understand it all. This burgeoning of knowledge has created a dilemma for medical educators. We can no longer expect students to continue memorizing this large body of increasingly complex knowledge. Instead, our efforts should be redirected at developing in students a competency as flexible thinkers and agile learners so they can adeptly deal with new knowledge, complexity, and uncertainty in a rapidly changing world. Such a competency would entail not only cognitive but also emotional skills essential for the holistic development of their professional identity. This article will argue that metacognition--“thinking about thinking (and emotion)”--offers the most viable path toward developing this competency. The overwhelming volume of medical knowledge has driven some medical schools to reduce the time allocated in their curricula to the “soft-option” humanities as they tend to consider them an expendable “luxury.” Vanderbilt University School of Medicine, Nashville, TN, has moved away from the traditional conception of the medical humanities as “the arts,” composed of art, music, and literature, toward an approach that integrates the humanities with the basic and clinical sciences, based on metacognition. This metacognitive approach to the humanities, described in this article, has three goals: 1) to develop students as flexible thinkers and agile learners and to provide them with essential cognitive and emotional skills for navigating medical complexity and uncertainty; 2) to elicit in students empathy and tolerance by making them aware of the immense diversity in human cognition (and emotion); and 3) to integrate the humanities with the basic and clinical sciences. Through this metacognitive approach, students come to understand their patterns of cognition and emotions, and in the group setting, they learn to mindfully

  19. 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

  20. Type-specific human papillomavirus infections among young heterosexual male and female STI clinic attendees

    NARCIS (Netherlands)

    Vriend, Henrike J; Boot, Hein J; van der Sande, Marianne A B; Rossen, John

    BACKGROUND: Baseline genotype-specific human papillomavirus (HPV) prevalence rates and associated risk factors per gender enable future assessment of the impact of vaccination on HPV dynamics. METHODS: Before the start of national HPV vaccination for girls, data were collected cross-sectionally in

  1. Posterior extensions of the human compact atrioventricular node: a neglected anatomic feature of potential clinical significance

    NARCIS (Netherlands)

    Inoue, S.; Becker, A. E.

    1998-01-01

    Catheter ablation procedures have revived interest in the detailed anatomy of the specialized atrioventricular (AV) septal junctional area. The compact AV node usually is considered to have a blunt posterior end. The objective of this study was to reconstruct the human compact AV node in relation to

  2. 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...

  3. The role of the microbiome for human health : from basic science to clinical applications

    NARCIS (Netherlands)

    Mohajeri, M Hasan; Brummer, Robert J M; Rastall, Robert A; Weersma, Rinse K; Harmsen, Hermie J M; Faas, Marijke; Eggersdorfer, Manfred

    The 2017 annual symposium organized by the University Medical Center Groningen in The Netherlands focused on the role of the gut microbiome in human health and disease. Experts from academia and industry examined interactions of prebiotics, probiotics, or vitamins with the gut microbiome in health

  4. Rapid detection of human parechoviruses in clinical samples by real-time PCR

    NARCIS (Netherlands)

    Benschop, Kimberley; Molenkamp, Richard; van der Ham, Alwin; Wolthers, Katja; Beld, Marcel

    2008-01-01

    BACKGROUND: Human parechoviruses (HPeVs) have been associated with severe conditions such as neonatal sepsis and meningitis in young children. Rapid identification of an infectious agent in such serious conditions in these patients is essential for adequate decision making regarding treatment and

  5. The first complete genome sequences of clinical isolates of human coronavirus 229E

    NARCIS (Netherlands)

    Farsani, Seyed Mohammad Jazaeri; Dijkman, Ronald; Jebbink, Maarten F.; Goossens, Herman; Ieven, Margareta; Deijs, Martin; Molenkamp, Richard; van der Hoek, Lia

    2012-01-01

    Human coronavirus 229E has been identified in the mid-1960s, yet still only one full-genome sequence is available. This full-length sequence has been determined from the cDNA-clone Inf-1 that is based on the lab-adapted strain VR-740. Lab-adaptation might have resulted in genomic changes, due to

  6. A draft map of the human ovarian proteome for tissue engineering and clinical applications.

    Science.gov (United States)

    Ouni, Emna; Vertommen, Didier; Chiti, Maria Costanza; Dolmans, Marie-Madeleine; Amorim, Christiani Andrade

    2018-02-23

    Fertility preservation research in women today is increasingly taking advantage of bioengineering techniques to develop new biomimetic materials and solutions to safeguard ovarian cell function and microenvironment in vitro and in vivo. However, available data on the human ovary are limited and fundamental differences between animal models and humans are hampering researchers in their quest for more extensive knowledge of human ovarian physiology and key reproductive proteins that need to be preserved. We therefore turned to multi-dimensional label-free mass spectrometry to analyze human ovarian cortex, as it is a high-throughput and conclusive technique providing information on the proteomic composition of complex tissues like the ovary. In-depth proteomic profiling through two-dimensional liquid chromatography-mass spectrometry, western blot, histological and immunohistochemical analyses, and data mining helped us to confidently identify 1,508 proteins. Moreover, our method allowed us to chart the most complete representation so far of the ovarian matrisome, defined as the ensemble of extracellular matrix proteins and associated factors, including more than 80 proteins. In conclusion, this study will provide a better understanding of ovarian proteomics, with a detailed characterization of the ovarian follicle microenvironment, in order to enable bioengineers to create biomimetic scaffolds for transplantation and three-dimensional in vitro culture. By publishing our proteomic data, we also hope to contribute to accelerating biomedical research into ovarian health and disease in general. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

  7. The local lymph node assay compared with the human maximization test as an indicator of allergic potency in humans using patch test clinic populations.

    Science.gov (United States)

    Zaghi, Danny; Maibach, Howard I

    2009-01-01

    The human maximization test (HMT) is a method to evaluate potency in humans, while the local lymph node assay (LLNA) is a test method that allows for the measuring of the allergic potency of a substance in a rodent. It has been proposed that an EC3 value (the value obtained by the LLNA test, ie, the concentration of an allergen leading to a 3-fold increase of baseline proliferation rate) would be a reliable indicator for a compound's allergic potency in humans. This paper compares the correlation between the EC3 value of a compound and its allergic occurrence in the general population with the correlation between the HMT of the compound and its allergic occurrence in the general population, to determine the relationship to potency. The correlation values when outliers were removed from the sample were -0.56 and -0.71 for LLNA and HMT, respectively, suggesting that there is a possible 20% error margin in LLNA's ability to predict potency. The data also suggest that other factors (such as exposure) could play up to a 30% role in the determination of allergic occurrence in the general population. The potency assays might be made more clinically relevant for predicting allergic frequencies by including a frequency factor and other factors in its dermatotoxicological interpretation.

  8. Alterations in lipoprotein homeostasis during human experimental endotoxemia and clinical sepsis

    NARCIS (Netherlands)

    Levels, Johannes H. M.; Pajkrt, Dasja; Schultz, Marcus; Hoek, Frans J.; van Tol, Arie; Meijers, Joost C. M.; van Deventer, Sander J. H.

    2007-01-01

    Cell wall constituents of bacteria are potent endotoxins initiating inflammatory responses which may cause dramatic changes in lipid metabolism during the acute phase response. In this study, the sequential changes in lipoprotein composition and lipid transfer and binding proteins during clinical

  9. Evaluation of the clinical utility of a rapid blood test for human leptospirosis

    NARCIS (Netherlands)

    Eapen, C. K.; Sugathan, Sheela; Kuriakose, Mariamma; Abdoel, Theresia; Smits, Henk L.

    2002-01-01

    A rapid assay device for the detection of Leptospira-specific immunoglobulin M (IgM) antibodies was applied on whole blood samples collected from a group of consecutive patients admitted with clinical suspicion of leptospirosis to a district hospital in Kerala, India. The hospital is located in an

  10. Characterization of clinical and environmental Mycobacterium avium spp. isolates and their interaction with human macrophages

    Science.gov (United States)

    Members of the Mycobacterium avium complex (MAC) are naturally occurring bacteria in the environment. A link has been suggested between M. avium strains in drinking water and clinical isolates from infected individuals. There is a need to develop new screening methodologies tha...

  11. Human Genome Editing in the Clinic: New Challenges in Regulatory Benefit-Risk Assessment.

    Science.gov (United States)

    Abou-El-Enein, Mohamed; Cathomen, Toni; Ivics, Zoltán; June, Carl H; Renner, Matthias; Schneider, Christian K; Bauer, Gerhard

    2017-10-05

    As genome editing rapidly progresses toward the realization of its clinical promise, assessing the suitability of current tools and processes used for its benefit-risk assessment is critical. Although current regulations may initially provide an adequate regulatory framework, improvements are recommended to overcome several existing technology-based safety and efficacy issues. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Radio-pharmaceuticals for human use: the legal framework and the clinical indications authorised in Spain

    International Nuclear Information System (INIS)

    Cortes-Blanco, A.; Esteban Gomez, J

    2003-01-01

    The inclusion of radio-pharmaceuticals in the health legislation represented a significant change because of the obligation, for the first time, to undergo a registration process to enable them to be marketed. It also served to regulate clinical investigation using these drugs, and the prior evaluation they must undergo in other to obtain official health clearance. (Author) 27 refs

  13. Human adipose-derived stromal cells in a clinically applicable injectable alginate hydrogel

    DEFF Research Database (Denmark)

    Larsen, Bjarke Follin; Juhl, Morten; Cohen, Smadar

    2015-01-01

    BACKGROUND AIMS: Clinical trials have documented beneficial effects of mesenchymal stromal cells from bone marrow and adipose tissue (ASCs) as treatment in patients with ischemic heart disease. However, retention of transplanted cells is poor. One potential way to increase cell retention is to in...

  14. Clinical and molecular features of one case of human infection with Anaplasma phagocytophilum from Podlaskie Province in eastern Poland

    Directory of Open Access Journals (Sweden)

    Renata Welc-Falęciak

    2015-09-01

    Full Text Available The article focuses on the clinical and laboratory diagnosis of human granulocytic anaplasmosis (HGA caused by Anaplasma phagocytophilum infection in one of 28 patients (3.6%; n=1/28 tested samples with early Lyme borreliosis. The clinical and laboratory results of a 42-year-old patient fulfilled criteria of confirm anaplasmosis and suggest an acute stage of illness. The described case provides strong presumptive evidence that infection in this patient was acquired with a pathogenic strain of A. phagocytophilum through a tick bite. A positive DNA with PCR for A. phagocytophilum infection was sequenced and analyzed phylogenetically. Physicians should consider the possibility of anaplasmosis in patients with early Lyme borreliosis, and A. phagocytophilum should be considered as a differential diagnosis in all patients from an endemic region of potential high risk factors for tick-borne diseases.

  15. Human resources requirements for diabetic patients healthcare in primary care clinics of the Mexican Institute of Social Security

    Directory of Open Access Journals (Sweden)

    Svetlana V Doubova

    2013-11-01

    Full Text Available Objective. To estimate the requirements of human resources (HR of two models of care for diabetes patients: conventional and specific, also called DiabetIMSS, which are provided in primary care clinics of the Mexican Institute of Social Security (IMSS. Materials and methods. An evaluative research was conducted. An expert group identified the HR activities and time required to provide healthcare consistent with the best clinical practices for diabetic patients. HR were estimated by using the evidence-based adjusted service target approach for health workforce planning; then, comparisons between existing and estimated HRs were made. Results. To provide healthcare in accordance with the patients’ metabolic control, the conventional model required increasing the number of family doctors (1.2 times nutritionists (4.2 times and social workers (4.1 times. The DiabetIMSS model requires greater increase than the conventional model. Conclusions. Increasing HR is required to provide evidence-based healthcare to diabetes patients.

  16. 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 ...

  17. 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

  18. 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.

  19. 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.

  20. Review of the Clinical and Biologic Aspects of Human Papillomavirus-Positive Squamous Cell Carcinomas of the Head and Neck

    International Nuclear Information System (INIS)

    Blitzer, Grace C.; Smith, Molly A.; Harris, Stephen L.; Kimple, Randall J.

    2014-01-01

    Human papillomavirus (HPV), a known etiology of a subset of head-and-neck squamous cell carcinomas (HNCs), causes numerous alterations in normal cellular functions. This article reviews the biology, detection, and treatment of HPV-positive HNC. The role of HPV oncoproteins in tumor development, the natural history of HPV infection, and risk factors for and prevention of transmission of oral HPV are considered. Commonly used methods for detecting HPV infection, including limitations of these methods, are discussed to aid the practicing clinician in using these tests in their clinical practice. Clinical characteristics of HPV-positive HNC, including potential explanations for the improved outcomes seen in patients with HPV-positive HNC, are assessed. Ongoing clinical trials specific for patients with HPV-positive HNC are described, and areas in need of additional research are summarized. Until the results of ongoing trials are known, treatment of HPV-positive HNC should not differ in clinical practice from treatment of similar non-HPV related cancers

  1. Review of the Clinical and Biologic Aspects of Human Papillomavirus-Positive Squamous Cell Carcinomas of the Head and Neck

    Energy Technology Data Exchange (ETDEWEB)

    Blitzer, Grace C.; Smith, Molly A. [Department of Human Oncology, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin (United States); Harris, Stephen L. [Radiation Oncology Associates, Manchester, New Hampshire (United States); Kimple, Randall J., E-mail: rkimple@humonc.wisc.edu [Department of Human Oncology, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin (United States); University of Wisconsin Carbone Cancer Center, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin (United States)

    2014-03-15

    Human papillomavirus (HPV), a known etiology of a subset of head-and-neck squamous cell carcinomas (HNCs), causes numerous alterations in normal cellular functions. This article reviews the biology, detection, and treatment of HPV-positive HNC. The role of HPV oncoproteins in tumor development, the natural history of HPV infection, and risk factors for and prevention of transmission of oral HPV are considered. Commonly used methods for detecting HPV infection, including limitations of these methods, are discussed to aid the practicing clinician in using these tests in their clinical practice. Clinical characteristics of HPV-positive HNC, including potential explanations for the improved outcomes seen in patients with HPV-positive HNC, are assessed. Ongoing clinical trials specific for patients with HPV-positive HNC are described, and areas in need of additional research are summarized. Until the results of ongoing trials are known, treatment of HPV-positive HNC should not differ in clinical practice from treatment of similar non-HPV related cancers.

  2. 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.

  3. 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.

  4. 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.

  5. Evaluation of Nucleic Acid Isothermal Amplification Methods for Human Clinical Microbial Infection Detection

    Directory of Open Access Journals (Sweden)

    Brett E. Etchebarne

    2017-12-01

    Full Text Available Battling infection is a major healthcare objective. Untreated infections can rapidly evolve toward the condition of sepsis in which the body begins to fail and resuscitation becomes critical and tenuous. Identification of infection followed by rapid antimicrobial treatment are primary goals of medical care, but precise identification of offending organisms by current methods is slow and broad spectrum empirical therapy is employed to cover most potential pathogens. Current methods for identification of bacterial pathogens in a clinical setting typically require days of time, or a 4- to 8-h growth phase followed by DNA extraction, purification and PCR-based amplification. We demonstrate rapid (70–120 min genetic diagnostics methods utilizing loop-mediated isothermal amplification (LAMP to test for 15 common infection pathogen targets, called the Infection Diagnosis Panel (In-Dx. The method utilizes filtration to rapidly concentrate bacteria in sample matrices with lower bacterial loads and direct LAMP amplification without DNA purification from clinical blood, urine, wound, sputum and stool samples. The In-Dx panel was tested using two methods of detection: (1 real-time thermocycler fluorescent detection of LAMP amplification and (2 visual discrimination of color change in the presence of Eriochrome Black T (EBT dye following amplification. In total, 239 duplicate samples were collected (31 blood, 122 urine, 73 mucocutaneous wound/swab, 11 sputum and two stool from 229 prospectively enrolled hospital patients with suspected clinical infection and analyzed both at the hospital and by In-Dx. Sensitivity (Se of the In-Dx panel targets pathogens from urine samples by In-Dx was 91.1% and specificity (Sp was 97.3%, with a positive predictive value (PPV of 53.7% and a negative predictive value (NPV of 99.7% as compared to clinical microbial detection methods. Sensitivity of detection of the In-Dx panel from mucocutaneous swab samples was 65.5% with a

  6. 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

  7. 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.

  8. 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.

  9. Enigmatic human tails: A review of their history, embryology, classification, and clinical manifestations.

    Science.gov (United States)

    Tubbs, R Shane; Malefant, Jason; Loukas, Marios; Jerry Oakes, W; Oskouian, Rod J; Fries, Fabian N

    2016-05-01

    The presence of a human tail is a rare and intriguing phenomenon. While cases have been reported in the literature, confusion remains with respect to the proper classification, definition, and treatment methods. We review the literature concerning this anatomical derailment. We also consider the importance of excluding underlying congenital anomalies in these patients to prevent neurological deficits and other abnormal manifestations. © 2016 Wiley Periodicals, Inc.

  10. 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.

  11. State-of-the-art measurements in human body composition: A moving frontier of clinical importance

    Science.gov (United States)

    Gallagher, D.; Shaheen, I.; Zafar, K.

    2010-01-01

    The measurement of human body composition allows for the estimation of body tissues, organs, and their distributions in living persons without inflicting harm. From a nutritional perspective, the interest in body composition has increased multi-fold with the global increase in the prevalence of obesity and its complications. The latter has driven in part the need for improved measurement methods with greater sensitivity and precision. There is no single gold standard for body-composition measurements in-vivo. All methods incorporate assumptions that do not apply in all individuals and the more accurate models are derived by using a combination of measurements, thereby reducing the importance of each assumption. This review will discuss why the measurement of body composition or human phenotyping is important; discuss new areas where the measurement of body composition (human phenotyping) is recognized as having important application; and will summarize recent advances made in new methodology. Reference will also be made to areas we cannot yet measure due to the lack of appropriate measurement methodologies, most especially measurements methods that provide information on kinetic states (not just static state) and metabolic function. PMID:21234275

  12. 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.

  13. 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

  14. Randomized clinical trial of human interleukin-11 in dengue fever-associated thrombocytopenia

    International Nuclear Information System (INIS)

    Suliman, M.I.; Qayum, I.

    2014-01-01

    Objective: To assess the effectiveness of recombinant human (rh) IL-11 to increase platelets count in patients suffering from Dengue fever (DF). Study Design: Randomized double blind placebo control study. Place and Duration of Study: Farooq Hospital, Lahore, from July to October 2011. Methodology: Forty hospitalized patients suffering from Dengue fever having platelets count A 30000 per micro liter were randomly categorized into two groups, rhIL-11 (test) and distilled water (placebo) groups. The efficacy outcomes (as indicated by step up in platelets count at 48 hours) for the treatment group were compared with the outcomes for the placebo group. Results: The data revealed that the increase in platelet response with recombinant human interleukin 11, 1.5 mg subcutaneously is significantly more brisk than the placebo group. The platelets response in patients with severe thrombocytopenia was greater in the treatment group (50%) at 48 hours as compared to the placebo group (20%) (p=0.047). Response rate was slightly greater among males (6/10, 60%) than females (8/16, 50%); moreover, three-fourth (75%) female responders were in the placebo group, compared to half (50%) male responders in the treatment group. Conclusion: Results of the study suggest that treatment of severe thrombocytopenia accompanying DF with recombinant human interleukin 11 may be a useful therapeutic option. (author)

  15. Enhancement of human adipose-derived stem cell expansion and stability for clinical use

    OpenAIRE

    Krähenbühl, S. M.

    2016-01-01

    Co-culture techniques associating both dermal fibroblasts and epidermal keratinocytes have shown to have better clinical outcome than keratinocyte culture alone for the treatment of severe burns. Since fat grafting has been shown to improve scar remodelling, new techniques such as cell-therapy-assisted surgical reconstruction with isolated and expanded autologous adipose-derived stem cells (ASCs) would be of benefit to increase graft acceptation. Therefore, integrating ASCs into s...

  16. Clinical and Molecular Characteristics of Human Rotavirus G8P[8] Outbreak Strain, Japan, 2014.

    Science.gov (United States)

    Kondo, Kenji; Tsugawa, Takeshi; Ono, Mayumi; Ohara, Toshio; Fujibayashi, Shinsuke; Tahara, Yasuo; Kubo, Noriaki; Nakata, Shuji; Higashidate, Yoshihito; Fujii, Yoshiki; Katayama, Kazuhiko; Yoto, Yuko; Tsutsumi, Hiroyuki

    2017-06-01

    During March-July 2014, rotavirus G8P[8] emerged as the predominant cause of rotavirus gastroenteritis among children in Hokkaido Prefecture, Japan. Clinical characteristics were similar for infections caused by G8 and non-G8 strains. Sequence and phylogenetic analyses suggest the strains were generated by multiple reassortment events between DS-1-like P[8] strains and bovine strains from Asia.

  17. Manufacturing of Human Extracellular Vesicle-Based Therapeutics for Clinical Use

    Directory of Open Access Journals (Sweden)

    Mario Gimona

    2017-06-01

    Full Text Available Extracellular vesicles (EVs derived from stem and progenitor cells may have therapeutic effects comparable to their parental cells and are considered promising agents for the treatment of a variety of diseases. To this end, strategies must be designed to successfully translate EV research and to develop safe and efficacious therapies, whilst taking into account the applicable regulations. Here, we discuss the requirements for manufacturing, safety, and efficacy testing of EVs along their path from the laboratory to the patient. Development of EV-therapeutics is influenced by the source cell types and the target diseases. In this article, we express our view based on our experience in manufacturing biological therapeutics for routine use or clinical testing, and focus on strategies for advancing mesenchymal stromal cell (MSC-derived EV-based therapies. We also discuss the rationale for testing MSC-EVs in selected diseases with an unmet clinical need such as critical size bone defects, epidermolysis bullosa and spinal cord injury. While the scientific community, pharmaceutical companies and clinicians are at the point of entering into clinical trials for testing the therapeutic potential of various EV-based products, the identification of the mode of action underlying the suggested potency in each therapeutic approach remains a major challenge to the translational path.

  18. Maintaining clinical tissue archives and supporting human research: challenges and solutions.

    Science.gov (United States)

    Giannini, Caterina; Oelkers, Michael M; Edwards, William D; Aubry, Marie Christine; Muncil, Maureen M; Mohamud, Koshin H; Sandleback, Sara G; Nowak, John M; Bridgeman, Andrew; Brown, Marie E; Cheville, John C

    2011-03-01

    The increasing number of requests for use of clinically archived tissue in translational research poses unique challenges. Conflicts may arise between pathologists who are responsible for overseeing and preserving the tissues and investigators who need these materials for research purposes. To evaluate the status of our institution's Tissue Registry Archive and to develop updated written policies and procedures to support a new modern and robust tracking system with features of a library loan system. An observational study was performed. We found the existing process for managing loans of tissue (slides and paraffin blocks) to be insufficient for the complexity and volume of this task. After extensive customization, a new tracking system was implemented in January 2008. Analysis of the first year of the system's use (2008) showed that of the 206,330 slides and 51,416 blocks loaned out in 2008, 92% and 94%, respectively, were returned by the due date. These rates were markedly improved from those before the new system: 61% and 47%, respectively, in 2005. Material permanently "lost" in 2008 represented only 0.02% of slides and 0.05% of blocks, none of which was the only diagnostic material for the case. With expanding needs for archived tissues for clinical care and growing demands for translational research, it is essential that pathology departments at institutions with large tissue-based research endeavors have a tracking and management system in place to meet clinical, educational, and research needs, as well as legal requirements.

  19. Molecular Characterization and Clinical Relevance of Metabolic Expression Subtypes in Human Cancers

    Directory of Open Access Journals (Sweden)

    Xinxin Peng

    2018-04-01

    Full Text Available Summary: Metabolic reprogramming provides critical information for clinical oncology. Using molecular data of 9,125 patient samples from The Cancer Genome Atlas, we identified tumor subtypes in 33 cancer types based on mRNA expression patterns of seven major metabolic processes and assessed their clinical relevance. Our metabolic expression subtypes correlated extensively with clinical outcome: subtypes with upregulated carbohydrate, nucleotide, and vitamin/cofactor metabolism most consistently correlated with worse prognosis, whereas subtypes with upregulated lipid metabolism showed the opposite. Metabolic subtypes correlated with diverse somatic drivers but exhibited effects convergent on cancer hallmark pathways and were modulated by highly recurrent master regulators across cancer types. As a proof-of-concept example, we demonstrated that knockdown of SNAI1 or RUNX1—master regulators of carbohydrate metabolic subtypes—modulates metabolic activity and drug sensitivity. Our study provides a system-level view of metabolic heterogeneity within and across cancer types and identifies pathway cross-talk, suggesting related prognostic, therapeutic, and predictive utility. : Peng et al. analyze a cohort of 9,125 TCGA samples across 33 cancer types to characterize tumor subtypes based on the expression of seven metabolic pathways. They find metabolic expression subtypes are associated with patient survivals and suggest the therapeutic and predictive relevance of subtype-related master regulators. Keywords: The Cancer Genome Atlas, tumor subtypes, prognostic markers, somatic drivers, master regulator, therapeutic targets, drug sensitivity, carbohydrate metabolism

  20. 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.

  1. Derivation of the clinical grade human embryonic stem cell line RCe016-A (RC-12

    Directory of Open Access Journals (Sweden)

    P.A. De Sousa

    2016-05-01

    Full Text Available The human embryonic stem cell line RCe016-A (RC-12 was derived under quality assured compliance with UK regulations, EU Directives and International guidance for tissue procurement, processing and storage according to good manufacturing practice (GMP standards. The cell line was derived from a cryopreserved blastocyst stage embryo voluntarily donated as surplus to fertility requirements following informed consent. RCe016-A (RC-12 shows normal pluripotency marker expression and differentiation to three germ layers in vitro. Karyology revealed a mixed male karyotype at early passage (P15, which resolved as normal 46XY by passage 33. Microsatellite PCR identity, HLA and blood group typing data is available.

  2. New Developments in Human Neurocognition: Clinical, Genetic and Brain Imaging Correlates of Impulsivity and Compulsivity

    Science.gov (United States)

    Fineberg, Naomi A.; Chamberlain, Samuel R.; Goudriaan, Anna E.; Stein, Dan J.; Vanderschuren, Louk J.M.J.; Gillan, Claire M.; Shekar, Sameer; Gorwood, Philip A.P.M.; Voon, Valerie; Morein-Zamir, Sharon; Denys, Damiaan; Sahakian, Barbara J.; Moeller, F. Gerard; Robbins, Trevor W.; Potenza, Marc N.

    2014-01-01

    Impulsivity and compulsivity represent useful conceptualizations that involve dissociable cognitive functions, mediated by neuroanatomically and neurochemically distinct components of cortico-subcortical circuitry. The constructs were historically viewed as diametrically opposed, with impulsivity being associated with risk-seeking and compulsivity with harm-avoidance. However, they are increasingly recognized to be linked by shared neuropsychological mechanisms involving dysfunctional inhibition of thoughts and behaviors. In this paper, we selectively review new developments in the investigation of the neurocognition of impulsivity and compulsivity in humans, in order to advance our understanding of the pathophysiology of impulsive, compulsive and addictive disorders and indicate new directions for research. PMID:24512640

  3. Radioimmunoassay of an early plasmin degradation product of human fibrinogen, 'fragment A', and its clinical application

    Energy Technology Data Exchange (ETDEWEB)

    Takagi, K; Kawai, T [Jichi Medical School, Kawachi, Tochigi (Japan)

    1978-02-01

    Upon the plasmin digestion of human fibrinogen, an early cleavage product, which has been designated as fragment A, was isolated, and to study the action of plasmin in the circulation, radioimmunoassay for fragment A was carried out. This assay used rabbit immune serum obtained by injection of fragment A mixed with complete Freund's adjuvant, and fragment A was labelled with /sup 125/I using the Chloramin-T method. In 20 normal healthy donors its serum level was 3.57 +- 1.62..mu..g/ml (mean+-SD), and it was increased significantly in certain diseases, such as acute leukemias, candiovascular disorders, malignancies, renal failure, systemic lupus erythematosus and sepsis.

  4. Best practices in nursing homes. Clinical supervision, management, and human resource practices.

    Science.gov (United States)

    Dellefield, Mary Ellen

    2008-07-01

    Human resource practices including supervision and management are associated with organizational performance. Evidence supportive of such an association in nursing homes is found in the results of numerous research studies conducted during the past 17 years. In this article, best practices related to this topic have been culled from descriptive, explanatory, and intervention studies in a range of interdisciplinary research journals published between 1990 and 2007. Identified best practices include implementation of training programs on supervision and management for licensed nurses, certified nursing assistant job enrichment programs, implementation of consistent nursing assignments, and the use of electronic documentation. Organizational barriers and facilitators of these best practices are described. Copyright 2009, SLACK Incorporated.

  5. Clinical reactivations of herpes simplex virus type 2 infection and human immunodeficiency virus disease progression markers.

    Directory of Open Access Journals (Sweden)

    Bulbulgul Aumakhan

    Full Text Available BACKGROUND: The natural history of HSV-2 infection and role of HSV-2 reactivations in HIV disease progression are unclear. METHODS: Clinical symptoms of active HSV-2 infection were used to classify 1,938 HIV/HSV-2 co-infected participants of the Women's Interagency HIV Study (WIHS into groups of varying degree of HSV-2 clinical activity. Differences in plasma HIV RNA and CD4+ T cell counts between groups were explored longitudinally across three study visits and cross-sectionally at the last study visit. RESULTS: A dose dependent association between markers of HIV disease progression and degree of HSV-2 clinical activity was observed. In multivariate analyses after adjusting for baseline CD4+ T cell levels, active HSV-2 infection with frequent symptomatic reactivations was associated with 21% to 32% increase in the probability of detectable plasma HIV RNA (trend p = 0.004, an average of 0.27 to 0.29 log10 copies/ml higher plasma HIV RNA on a continuous scale (trend p<0.001 and 51 to 101 reduced CD4+ T cells/mm(3 over time compared to asymptomatic HSV-2 infection (trend p<0.001. CONCLUSIONS: HIV induced CD4+ T cell loss was associated with frequent symptomatic HSV-2 reactivations. However, effect of HSV-2 reactivations on HIV disease progression markers in this population was modest and appears to be dependent on the frequency and severity of reactivations. Further studies will be necessary to determine whether HSV-2 reactivations contribute to acceleration of HIV disease progression.

  6. /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

  7. 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.

  8. /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.

  9. Effects of Direct-to-Consumer Advertising and Clinical Guidelines on Appropriate Use of Human Papillomavirus DNA Tests

    Science.gov (United States)

    2011-01-01

    Background Both clinical guidelines and direct-to-consumer (DTC) advertising influence 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 two strategies. Objective To evaluate the effects of clinical guidelines and a targeted DTC advertising campaign on overall and appropriate use of human papillomavirus (HPV) DNA tests. Research Design Quasi-experimental study using difference-in-differences analysis. Data were MarketScan private insurance claims for 500,000 women ages 21 to 64 enrolled at least 12 consecutive months from January 2001 through December 2005. Results 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 two groups of DTC cities (+5.57 percent, padvertising 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 co-sponsored panel, were associated with greater increases in HPV DNA tests for appropriate primary screening than for inappropriate primary screening (β=0.3347, padvertising was associated with increased overall use of a cervical cancer screening test, while 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. PMID:21150798

  10. A proteomic network approach across the ALS-FTD disease spectrum resolves clinical phenotypes and genetic vulnerability in human brain.

    Science.gov (United States)

    Umoh, Mfon E; Dammer, Eric B; Dai, Jingting; Duong, Duc M; Lah, James J; Levey, Allan I; Gearing, Marla; Glass, Jonathan D; Seyfried, Nicholas T

    2018-01-01

    Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative diseases with overlap in clinical presentation, neuropathology, and genetic underpinnings. The molecular basis for the overlap of these disorders is not well established. We performed a comparative unbiased mass spectrometry-based proteomic analysis of frontal cortical tissues from postmortem cases clinically defined as ALS, FTD, ALS and FTD (ALS/FTD), and controls. We also included a subset of patients with the C9orf72 expansion mutation, the most common genetic cause of both ALS and FTD Our systems-level analysis of the brain proteome integrated both differential expression and co-expression approaches to assess the relationship of these differences to clinical and pathological phenotypes. Weighted co-expression network analysis revealed 15 modules of co-expressed proteins, eight of which were significantly different across the ALS-FTD disease spectrum. These included modules associated with RNA binding proteins, synaptic transmission, and inflammation with cell-type specificity that showed correlation with TDP-43 pathology and cognitive dysfunction. Modules were also examined for their overlap with TDP-43 protein-protein interactions, revealing one module enriched with RNA-binding proteins and other causal ALS genes that increased in FTD/ALS and FTD cases. A module enriched with astrocyte and microglia proteins was significantly increased in ALS cases carrying the C9orf72 mutation compared to sporadic ALS cases, suggesting that the genetic expansion is associated with inflammation in the brain even without clinical evidence of dementia. Together, these findings highlight the utility of integrative systems-level proteomic approaches to resolve clinical phenotypes and genetic mechanisms underlying the ALS-FTD disease spectrum in human brain. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

  11. Bringing human resources to the table: utilization of an HR balanced scorecard at Mayo Clinic.

    Science.gov (United States)

    Fottler, Myron D; Erickson, Eric; Rivers, Patrick A

    2006-01-01

    Rather than viewing HR as a critical driver of organizational strategy and outcomes, most health care organizations see HR as a drain on the organization's bottom line. Only by aligning HR with the organizational strategy will HR leaders truly get a seat at the leadership table. HR professionals can overcome impediments and gain a seat at the table by learning the language of business and the ways in which organizational leaders use data to drive their decisions. This article shows how Mayo Clinic uses the popular Balanced Scorecard approach to align its measures of HR performance to the organization's strategic plan.

  12. Quality Control Assays for Clinical-Grade Human Mesenchymal Stromal Cells: Validation Strategy.

    Science.gov (United States)

    Radrizzani, Marina; Soncin, Sabrina; Bolis, Sara; Lo Cicero, Viviana; Andriolo, Gabriella; Turchetto, Lucia

    2016-01-01

    The present chapter focuses on the validation of the following analytical methods for the control of mesenchymal stromal cells (MSC) for cell therapy clinical trials: Microbiological control for cellular product Endotoxin assay Mycoplasma assay Cell count and viability Immunophenotype Clonogenic potential (CFU-F assay) In our lab, these methods are in use for product release, process control or control of the biological starting materials. They are described in detail in the accompanying Chapter 19.For each method, validation goals and strategy are presented, and a detailed experimental scheme is proposed.

  13. Histological evaluation of the human testis--approaches to optimizing the clinical value of the assessment

    DEFF Research Database (Denmark)

    McLachlan, R I; Rajpert-De Meyts, E; Hoei-Hansen, C E

    2007-01-01

    on genotype-phenotype relationships. The rising incidence of testis cancer and carcinoma in situ (CIS), especially in infertile populations, requires that every effort be made for its early detection. We provide a systematic approach to the histological classification of spermatogenic disorders and detection...... within the hypospermatogenesis classification, that helps account for reported success of TESE. We propose a new diagnosis code for testicular biopsies that addresses the needs of ART clinicians and allows data storage and retrieval of value in clinical practice and research....

  14. First clinical evaluation of radioimmunoimaging using anti-human lung cancer monoclonal antibodies

    International Nuclear Information System (INIS)

    Zhou Qian

    1991-01-01

    Anti-human large cell lung cancer monoclonal antibodies (McAb) 2E3 and 6D1 were produced in the laboratory. Immunohistochemical studies and radiobinding assay showed these antibodies possessed high specificity against lung cancer cells. 28 patients with lung masses were investigated with 131 I-labeled McAb 6D1 and/or 2E3 scintigraphy. 19 of them were histologically proven and 13 were diagnosed primary lung carcinoma. Radioimmunoimaging visualized 10/13 of the primary lung cancers with a detection rate of 77%. Only 1 case of the non-cancer patients and a false localization, giving a true negative rate of 83%. Pathologically the squamous cell lung carcinoma had the highest localization and the small cell lung carcinoma next, but the detection rate was 100% for both. The adenocarcinoma of lung was less sensitive to these McAbs, with a detection rate of only 33% (1 of 3 cases). We conclude that radioimmunoimaging with anti-human large cell lung cancer McAbs is more specific and effective in detecting primary lung cancers and differentiating lung masses than with antibodies against other tumor associated antigens

  15. Human-Induced Pluripotent Stem Cell Technology and Cardiomyocyte Generation: Progress and Clinical Applications

    Directory of Open Access Journals (Sweden)

    Angela Di Baldassarre

    2018-05-01

    Full Text Available Human-induced pluripotent stem cells (hiPSCs are reprogrammed cells that have hallmarks similar to embryonic stem cells including the capacity of self-renewal and differentiation into cardiac myocytes. The improvements in reprogramming and differentiating methods achieved in the past 10 years widened the use of hiPSCs, especially in cardiac research. hiPSC-derived cardiac myocytes (CMs recapitulate phenotypic differences caused by genetic variations, making them attractive human disease models and useful tools for drug discovery and toxicology testing. In addition, hiPSCs can be used as sources of cells for cardiac regeneration in animal models. Here, we review the advances in the genetic and epigenetic control of cardiomyogenesis that underlies the significant improvement of the induced reprogramming of somatic cells to CMs; the methods used to improve scalability of throughput assays for functional screening and drug testing in vitro; the phenotypic characteristics of hiPSCs-derived CMs and their ability to rescue injured CMs through paracrine effects; we also cover the novel approaches in tissue engineering for hiPSC-derived cardiac tissue generation, and finally, their immunological features and the potential use in biomedical applications.

  16. Human-Induced Pluripotent Stem Cell Technology and Cardiomyocyte Generation: Progress and Clinical Applications.

    Science.gov (United States)

    Di Baldassarre, Angela; Cimetta, Elisa; Bollini, Sveva; Gaggi, Giulia; Ghinassi, Barbara

    2018-05-25

    Human-induced pluripotent stem cells (hiPSCs) are reprogrammed cells that have hallmarks similar to embryonic stem cells including the capacity of self-renewal and differentiation into cardiac myocytes. The improvements in reprogramming and differentiating methods achieved in the past 10 years widened the use of hiPSCs, especially in cardiac research. hiPSC-derived cardiac myocytes (CMs) recapitulate phenotypic differences caused by genetic variations, making them attractive human disease models and useful tools for drug discovery and toxicology testing. In addition, hiPSCs can be used as sources of cells for cardiac regeneration in animal models. Here, we review the advances in the genetic and epigenetic control of cardiomyogenesis that underlies the significant improvement of the induced reprogramming of somatic cells to CMs; the methods used to improve scalability of throughput assays for functional screening and drug testing in vitro; the phenotypic characteristics of hiPSCs-derived CMs and their ability to rescue injured CMs through paracrine effects; we also cover the novel approaches in tissue engineering for hiPSC-derived cardiac tissue generation, and finally, their immunological features and the potential use in biomedical applications.

  17. Comparison of clinical and parasitological data from controlled human malaria infection trials.

    Directory of Open Access Journals (Sweden)

    Meta Roestenberg

    Full Text Available Exposing healthy human volunteers to Plasmodium falciparum-infected mosquitoes is an accepted tool to evaluate preliminary efficacy of malaria vaccines. To accommodate the demand of the malaria vaccine pipeline, controlled infections are carried out in an increasing number of centers worldwide. We assessed their safety and reproducibility.We reviewed safety and parasitological data from 128 malaria-naïve subjects participating in controlled malaria infection trials conducted at the University of Oxford, UK, and the Radboud University Nijmegen Medical Center, The Netherlands. Results were compared to a report from the US Military Malaria Vaccine Program.We show that controlled human malaria infection trials are safe and demonstrate a consistent safety profile with minor differences in the frequencies of arthralgia, fatigue, chills and fever between institutions. But prepatent periods show significant variation. Detailed analysis of Q-PCR data reveals highly synchronous blood stage parasite growth and multiplication rates.Procedural differences can lead to some variation in safety profile and parasite kinetics between institutions. Further harmonization and standardization of protocols will be useful for wider adoption of these cost-effective small-scale efficacy trials. Nevertheless, parasite growth rates are highly reproducible, illustrating the robustness of controlled infections as a valid tool for malaria vaccine development.

  18. Methylenetetrahydrofolate reductase and transcobalamin genetic polymorphisms in human spontaneous abortion: biological and clinical implications

    Directory of Open Access Journals (Sweden)

    Zetterberg Henrik

    2004-02-01

    Full Text Available Abstract The pathogenesis of human spontaneous abortion involves a complex interaction of several genetic and environmental factors. The firm association between increased homocysteine concentration and neural tube defects (NTD has led to the hypothesis that high concentrations of homocysteine might be embryotoxic and lead to decreased fetal viability. There are several genetic polymorphisms that are associated with defects in folate- and vitamin B12-dependent homocysteine metabolism. The methylenetetrahydrofolate reductase (MTHFR 677C>T and 1298A>C polymorphisms cause elevated homocysteine concentration and are associated with an increased risk of NTD. Additionally, low concentration of vitamin B12 (cobalamin or transcobalamin that delivers vitamin B12 to the cells of the body leads to hyperhomocysteinemia and is associated with NTD. This effect involves the transcobalamin (TC 776C>G polymorphism. Importantly, the biochemical consequences of these polymorphisms can be modified by folate and vitamin B12 supplementation. In this review, I focus on recent studies on the role of hyperhomocysteinemia-associated polymorphisms in the pathogenesis of human spontaneous abortion and discuss the possibility that periconceptional supplementation with folate and vitamin B12 might lower the incidence of miscarriage in women planning a pregnancy.

  19. New sensitive direct radioimmunoassay for human plasma renin and its clinical application

    International Nuclear Information System (INIS)

    Higaki, J.; Ogihara, T.; Imai, N.; Kumahara, Y.; Hontani, S.; Nishiura, M.; Ogawa, H.; Hirose, S.; Murakami, K.

    1984-01-01

    A new sensitive direct radioimmunoassay for human plasma renin has been developed. Renin was purified from Haas' preparation utilizing a pepstatin-C 6 -Sepharose affinity chromatography. Antiserum, prepared by immunizing rabbits with the purified renin, was used for the direct radioimmunoassay at a final dilution of 1:30,000. The antibody was specific for human renal and plasma renin, but did not cross-react with cathepsin D, trypsin, or renins of mouse, dog, and rat. Radioimmunoassay was performed by the double antibody technique using the delayed tracer addition method. In this method, a standard curve was obtained over a range from 0.2 to 8.0 ng/ml. The values from this assay correlated well with total renin activity measured as the generation rate of angiotensin I after trypsin activation, but correlated weakly with active renin activity. This finding disclosed that both active and inactive renin were detected by this method. In normal participants, plasma renin concentration determined by direct radioimmunoassay was increased by standing and furosemide injection. The plasma renin concentration determined by direct radioimmunoassay of patients with essential hypertension was not significantly different from values in normal controls. The values were higher in patients with renovascular hypertension, malignant hypertension and Bartter's syndrome, but lower in patients with primary aldosteronism than in normal controls. 20 references, 7 figures

  20. Viral phenotype, antiretroviral resistance and clinical evolution in human immunodeficiency virus-infected children.

    Science.gov (United States)

    Mellado, M J; Cilleruelo, M J; Ortiz, M; Villota, J; García, M; Perez-Jurado, M L; Barreiro, G; Martín-Fontelos, P; Bernal, A

    1997-11-01

    The syncytium-inducing (SI) viral phenotype and the emergence of viral strains resistant to zidovudine have been described in persons infected with HIV, and in some cases they have been associated with poor prognosis. HIV isolates obtained from 37 HIV-infected children were analyzed to determine whether the SI viral phenotype and the mutation on the 215 position of the reverse transcriptase (M215) could be used as markers of disease progression. We performed peripheral blood coculture mononuclear cells, and we analyzed the induction of syncytia using the MT-2 cell line. The emergence of mutations on the 215 position was determined by PCR. We found a statistically significant association (P < 0.05) between SI viral phenotype and (1) recurrent serious bacterial infections, (2) absolute CD4+ cell counts <2 SD, (3) progression to AIDS and (4) death. Sixty percent of the children treated with zidovudine developed 215 mutant viral strains without statistically significant association with clinical or immunologic findings. The SI viral phenotype was statistically associated with the presence of the 215 mutation (P < 0.05). SI viral phenotype is a marker associated with a poor clinical and immunologic progression of the disease and it may facilitate the emergence of mutant strains in children treated with zidovudine.

  1. [Recombinant human erythropoietin in neonates: guidelines for clinical practice from the French Society of Neonatology].

    Science.gov (United States)

    Lopez, E; Beuchée, A; Truffert, P; Pouvreau, N; Patkai, J; Baud, O; Boubred, F; Flamant, C; Jarreau, P-H

    2015-10-01

    1/To assess the effectiveness and safety of EPO in reducing red blood cell (RBC) transfusions in preterm infants. 2/To provide guidelines for clinical practice in France. 1/This systematic evidence review is based on PubMed search, Cochrane library. 2/Using French National Authority for Health methods concerning guidelines for clinical practice. Early EPO reduced the risk of RBC transfusions, donor exposure, and the number of transfusions in very preterm infants (LE2). Late EPO reduced the risk of RBC transfusions and the number of transfusions in very preterm infants (LE2). There is no difference between the effectiveness of early and late EPO (LE2). There is no difference between high-dose and low-dose EPO (LE2). The level of evidence is too low to recommend the intravenous route. EPO has no impact on the rate of bronchopulmonary dysplasia, necrotizing enterocolitis (LE3), and retinopathy of prematurity (LE2). The level of evidence is too low to recommend EPO for neuroprotection in very preterm or term infants. EPO to reduce RBC transfusion in very preterm infants is recommended (Level A). The optimal time to start therapy is unknown (Level B). The recommended dose is 750IU/kg/week via three subcutaneous injections for 6weeks (Level B). Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  2. Cool and menthol receptor TRPM8 in human urinary bladder disorders and clinical correlations

    Directory of Open Access Journals (Sweden)

    Benham Christopher D

    2006-03-01

    Full Text Available Abstract Background The recent identification of the cold-menthol sensory receptor (TRPM8; CMR1, provides us with an opportunity to advance our understanding of its role in the pathophysiology of bladder dysfunction, and its potential mediation of the bladder cooling reflex. In this study, we report the distribution of the cool and menthol receptor TRPM8 in the urinary bladder in patients with overactive and painful bladder syndromes, and its relationship with clinical symptoms. Methods Bladder specimens obtained from patients with painful bladder syndrome (PBS, n = 16, idiopathic detrusor overactivity (IDO, n = 14, and asymptomatic microscopic hematuria (controls, n = 17, were immunostained using specific antibodies to TRPM8; nerve fibre and urothelial immunostaining were analysed using fibre counts and computerized image analysis respectively. The results of immunohistochemistry were compared between the groups and correlated with the Pain, Frequency and Urgency scores. Results TRPM8-immunoreactive staining was observed in the urothelium and nerve fibres scattered in the suburothelium. The nerve fibre staining was seen in fine-calibre axons and thick (myelinated fibres. There was marked increase of TRPM8-immunoreactive nerve fibres in IDO (P = 0.0249 and PBS (P Conclusion This study demonstrates increased TRPM8 in nerve fibres of overactive and painful bladders, and its relationship with clinical symptoms. TRPM8 may play a role in the symptomatology and pathophysiology of these disorders, and may provide an additional target for future overactive and painful bladder pharmacotherapy.

  3. Standardization of clinical enzyme analysis using frozen human serum pools with values assigned by the International Federation of Clinical Chemistry and Laboratory Medicine reference measurement procedures.

    Science.gov (United States)

    Tong, Qing; Chen, Baorong; Zhang, Rui; Zuo, Chang

    Variation in clinical enzyme analysis, particularly across different measuring systems and laboratories, represents a critical but long-lasting problem in diagnosis. Calibrators with traceability and commutability are imminently needed to harmonize analysis in laboratory medicine. Fresh frozen human serum pools were assigned values for alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), creatine kinase (CK) and lactate dehydrogenase (LDH) by six laboratories with established International Federation of Clinical Chemistry and Laboratory Medicine reference measurement procedures. These serum pools were then used across 76 laboratories as a calibrator in the analysis of five enzymes. Bias and imprecision in the measurement of the five enzymes tested were significantly reduced by using the value-assigned serum in analytical systems with open and single-point calibration. The median (interquartile range) of the relative biases of ALT, AST, GGT, CK and LDH were 2.0% (0.6-3.4%), 0.8% (-0.8-2.3%), 1.0% (-0.5-2.0%), 0.2% (-0.3-1.0%) and 0.2% (-0.9-1.1%), respectively. Before calibration, the interlaboratory coefficients of variation (CVs) in the analysis of patient serum samples were 8.0-8.2%, 7.3-8.5%, 8.1-8.7%, 5.1-5.9% and 5.8-6.4% for ALT, AST, GGT, CK and LDH, respectively; after calibration, the CVs decreased to 2.7-3.3%, 3.0-3.6%, 1.6-2.1%, 1.8-1.9% and 3.3-3.5%, respectively. The results suggest that the use of fresh frozen serum pools significantly improved the comparability of test results in analytical systems with open and single-point calibration.

  4. Future requirements. Clinical investigations

    DEFF Research Database (Denmark)

    Qvist, V.

    2002-01-01

    Biocompatability, Cariology, Clinical trials, Dental materials, Helath services research, Human, Pedodontics......Biocompatability, Cariology, Clinical trials, Dental materials, Helath services research, Human, Pedodontics...

  5. 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…

  6. Distinguishing molecular features and clinical characteristics of a putative new rhinovirus species, human rhinovirus C (HRV C.

    Directory of Open Access Journals (Sweden)

    Peter McErlean

    Full Text Available BACKGROUND: Human rhinoviruses (HRVs are the most frequently detected pathogens in acute respiratory tract infections (ARTIs and yet little is known about the prevalence, recurrence, structure and clinical impact of individual members. During 2007, the complete coding sequences of six previously unknown and highly divergent HRV strains were reported. To catalogue the molecular and clinical features distinguishing the divergent HRV strains, we undertook, for the first time, in silico analyses of all available polyprotein sequences and performed retrospective reviews of the medical records of cases in which variants of the prototype strain, HRV-QPM, had been detected. METHODOLOGY/PRINCIPLE FINDINGS: Genomic analyses revealed that the six divergent strains, residing within a clade we previously called HRV A2, had the shortest polyprotein of all picornaviruses investigated. Structure-based amino acid alignments identified conserved motifs shared among members of the genus Rhinovirus as well as substantive deletions and insertions unique to the divergent strains. Deletions mostly affected regions encoding proteins traditionally involved in antigenicity and serving as HRV and HEV receptor footprints. Because the HRV A2 strains cannot yet be cultured, we created homology models of predicted HRV-QPM structural proteins. In silico comparisons confirmed that HRV-QPM was most closely related to the major group HRVs. HRV-QPM was most frequently detected in infants with expiratory wheezing or persistent cough who had been admitted to hospital and required supplemental oxygen. It was the only virus detected in 65% of positive individuals. These observations contributed to an objective clinical impact ranging from mild to severe. CONCLUSIONS: The divergent strains did not meet classification requirements for any existing species of the genus Rhinovirus or Enterovirus. HRV A2 strains should be partitioned into at least one new species, putatively called Human

  7. 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.

  8. The Biological Function and Clinical Utilization of CD147 in Human Diseases: A Review of the Current Scientific Literature

    Science.gov (United States)

    Xiong, Lijuan; Edwards, Carl K.; Zhou, Lijun

    2014-01-01

    CD147 or EMMPRIN is a member of the immunoglobulin superfamily in humans. It is widely expressed in human tumors and plays a central role in the progression of many cancers by stimulating the secretion of matrix metalloproteinases (MMPs) and cytokines. CD147 regulates cell proliferation, apoptosis, and tumor cell migration, metastasis and differentiation, especially under hypoxic conditions. CD147 is also important to many organ systems. This review will provide a detailed overview of the discovery, characterization, molecular structure, diverse biological functions and regulatory mechanisms of CD147 in human physiological and pathological processes. In particular, recent studies have demonstrated the potential application of CD147 not only as a phenotypic marker of activated regulatory T cells but also as a potential diagnostic marker for early-stage disease. Moreover, CD147 is recognized as an effective therapeutic target for hepatocellular carcinoma (HCC) and other cancers, and exciting clinical progress has been made in HCC treatment using CD147-directed monoclonal antibodies. PMID:25268615

  9. Biodiversity, the Human Microbiome and Mental Health: Moving toward a New Clinical Ecology for the 21st Century?

    Directory of Open Access Journals (Sweden)

    Susan L. Prescott

    2016-01-01

    Full Text Available Advances in research concerning the brain-related influences of the microbiome have been paradigm shifting, although at an early stage, clinical research involving beneficial microbes lends credence to the notion that the microbiome may be an important target in supporting mental health (defined here along the continuum between quality of life and the criteria for specific disorders. Through metagenomics, proteomics, metabolomics, and systems biology, a new emphasis to personalized medicine is on the horizon. Humans can now be viewed as multispecies organisms operating within an ecological theatre; it is important that clinicians increasingly see their patients in this context. Historically marginalized ecological aspects of health are destined to become an important consideration in the new frontiers of practicing medicine with the microbiome in mind. Emerging evidence indicates that macrobiodiversity in the external environment can influence mental well-being. Local biodiversity may also drive differences in human-associated microbiota; microbial diversity as a product of external biodiversity may have far-reaching effects on immune function and mood. With a focus on the microbiome as it pertains to mental health, we define environmental “grey space” and emphasize a new frontier involving bio-eco-psychological medicine. Within this concept the ecological terrain can link dysbiotic lifestyles and biodiversity on the grand scale to the local human-associated microbial ecosystems that might otherwise seem far removed from one another.

  10. The Biological Function and Clinical Utilization of CD147 in Human Diseases: A Review of the Current Scientific Literature

    Directory of Open Access Journals (Sweden)

    Lijuan Xiong

    2014-09-01

    Full Text Available CD147 or EMMPRIN is a member of the immunoglobulin superfamily in humans. It is widely expressed in human tumors and plays a central role in the progression of many cancers by stimulating the secretion of matrix metalloproteinases (MMPs and cytokines. CD147 regulates cell proliferation, apoptosis, and tumor cell migration, metastasis and differentiation, especially under hypoxic conditions. CD147 is also important to many organ systems. This review will provide a detailed overview of the discovery, characterization, molecular structure, diverse biological functions and regulatory mechanisms of CD147 in human physiological and pathological processes. In particular, recent studies have demonstrated the potential application of CD147 not only as a phenotypic marker of activated regulatory T cells but also as a potential diagnostic marker for early-stage disease. Moreover, CD147 is recognized as an effective therapeutic target for hepatocellular carcinoma (HCC and other cancers, and exciting clinical progress has been made in HCC treatment using CD147-directed monoclonal antibodies.

  11. Comparing Efficacy and Costs of Four Facial Fillers in Human Immunodeficiency Virus-Associated Lipodystrophy: A Clinical Trial.

    Science.gov (United States)

    Vallejo, Alfonso; Garcia-Ruano, Angela A; Pinilla, Carmen; Castellano, Michele; Deleyto, Esther; Perez-Cano, Rosa

    2018-03-01

    The objective of this study was to evaluate and compare the safety and effectiveness of four different dermal fillers in the treatment of facial lipoatrophy secondary to human immunodeficiency virus. The authors conducted a clinical trial including 147 patients suffering from human immunodeficiency virus-induced lipoatrophy treated with Sculptra (poly-L-lactic acid), Radiesse (calcium hydroxylapatite), Aquamid (polyacrylamide), or autologous fat. Objective and subjective changes were evaluated during a 24-month follow-up. Number of sessions, total volume injected, and overall costs of treatment were also analyzed. A comparative cost-effectiveness analysis of the treatment options was performed. Objective improvement in facial lipoatrophy, assessed by the surgeon in terms of changes from baseline using the published classification of Fontdevila, was reported in 53 percent of the cases. Patient self-evaluation showed a general improvement after the use of facial fillers. Patients reported being satisfied with the treatment and with the reduced impact of lipodystrophy on their quality of life. Despite the nonsignificant differences observed in the number of sessions and volume, autologous fat showed significantly lower costs than all synthetic fillers (p < 0.05). Surgical treatment of human immunodeficiency virus-associated facial lipoatrophy using dermal fillers is a safe and effective procedure that improves the aesthetic appearance and the quality of life of patients. Permanent fillers and autologous fat achieve the most consistent results over time, with lipofilling being the most cost-effective procedure.

  12. Metabolomic approach to human brain spectroscopy identifies associations between clinical features and the frontal lobe metabolome in multiple sclerosis

    Science.gov (United States)

    Vingara, Lisa K.; Yu, Hui Jing; Wagshul, Mark E.; Serafin, Dana; Christodoulou, Christopher; Pelczer, István; Krupp, Lauren B.; Maletić-Savatić, Mirjana

    2013-01-01

    Proton magnetic resonance spectroscopy (1H-MRS) is capable of noninvasively detecting metabolic changes that occur in the brain tissue in vivo. Its clinical utility has been limited so far, however, by analytic methods that focus on independently evaluated metabolites and require prior knowledge about which metabolites to examine. Here, we applied advanced computational methodologies from the field of metabolomics, specifically partial least squares discriminant analysis and orthogonal partial least squares, to in vivo 1H-MRS from frontal lobe white matter of 27 patients with relapsing–remitting multiple sclerosis (RRMS) and 14 healthy controls. We chose RRMS, a chronic demyelinating disorder of the central nervous system, because its complex pathology and variable disease course make the need for reliable biomarkers of disease progression more pressing. We show that in vivo MRS data, when analyzed by multivariate statistical methods, can provide reliable, distinct profiles of MRS-detectable metabolites in different patient populations. Specifically, we find that brain tissue in RRMS patients deviates significantly in its metabolic profile from that of healthy controls, even though it appears normal by standard MRI techniques. We also identify, using statistical means, the metabolic signatures of certain clinical features common in RRMS, such as disability score, cognitive impairments, and response to stress. This approach to human in vivo MRS data should promote understanding of the specific metabolic changes accompanying disease pathogenesis, and could provide biomarkers of disease progression that would be useful in clinical trials. PMID:23751863

  13. New clinical and histological patterns of acute disseminated histoplasmosis in human immunodeficiency virus-positive patients with acquired immunodeficiency syndrome.

    Science.gov (United States)

    Ollague Sierra, Jose E; Ollague Torres, Jose M

    2013-04-01

    Histoplasmosis has attained increasing relevance in the past 3 decades because of the appearance of the human immunodeficiency virus (HIV). In most immunocompetent persons, the infection is asymptomatic or can produce a respiratory condition with symptoms and radiological images similar to those observed in pulmonary tuberculosis; in non-HIV+ immunocompromised patients, it can cause respiratory symptoms or evolve into a disseminated infection. The same can occur in acquired immunodeficiency syndrome (AIDS) patients. We have observed a series of HIV+ patients with AIDS who presented with cutaneous histoplasmosis and in whom the clinical and histopathological features were highly unusual, including variable mucocutaneous lesions that were difficult to diagnose clinically. These patients displayed unusual, previously undescribed, histological patterns, including lichenoid pattern, nodular pseudomyxoid pattern, pyogenic granuloma-like pattern, perifollicular pattern, and superficial (S), mid (M), and deep perivascular dermatitis; and more commonly encountered patterns, such as histiocytic lobular panniculitis and focal nodular dermatitis. The novel histopathological patterns of cutaneous involvement by histoplasmosis seen in these patients resembled other common inflammatory and infectious conditions and required a high level of suspicion and the application of special stains for organisms for confirmation. These new, clinical, and histological findings do not seem to be commonly encountered in HIV- patients infected with the fungus but seem to be displayed most prominently in HIV+ patients with AIDS.

  14. 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.

  15. Assessment by human research ethics committees of potential conflicts of interest arising from pharmaceutical sponsorship of clinical research.

    Science.gov (United States)

    Newcombe, J P; Kerridge, I H

    2007-01-01

    Conflicts of interest arising from pharmaceutical industry sponsorship of clinical research have the potential to bias research outcomes and ultimately prejudice patient care. It is unknown how Australian Human Research Ethics Committees (HREC) assess and manage such conflicts of interest. We aimed to gain an understanding of how HREC approach the problem of potential conflicts of interest arising from pharmaceutical sponsorship of clinical research. We conducted a survey of HREC chairpersons in New South Wales. HREC vary widely in their approaches to conflicts of interest, including in their use of National Health and Medical Research Council guidelines, which were often misinterpreted or overlooked. Many committees rely primarily on researchers disclosing potential conflicts of interest, whereas a majority of HREC use disclosure to research participants as the primary tool for preventing and managing conflicts of interest. Almost no HREC place limitations on researcher relationships with pharmaceutical companies. These findings suggest reluctance on the part of HREC to regulate many potential conflicts of interest between researchers and pharmaceutical sponsors, which may arise from uncertainty regarding the meaning or significance of conflicts of interest in research, from ambiguity surrounding the role of HREC in assessing and managing conflicts of interest in research or from misinterpretation or ignorance of current National Health and Medical Research Council guidelines. Further review of policies and practices in this important area may prove beneficial in safeguarding clinical research and patient care while promoting continuing constructive engagement with the pharmaceutical industry.

  16. Reflections on Ethics and Humanity in Pediatric Neurology: the Value of Recognizing Ethical Issues in Common Clinical Practice.

    Science.gov (United States)

    Ronen, Gabriel M; Rosenbaum, Peter L

    2017-05-01

    Our goals in this reflection are to (i) identify the ethical dimensions inherent in any clinical encounter and (ii) bring to the forefront of our pediatric neurology practice the myriad of opportunities to explore and learn from these ethical questions. We highlight specifically Beauchamp and Childress's principles of biomedical ethics. We use the terms ethics in common clinical practice and an ethical lens to remind people of the ubiquity of ethical situations and the usefulness of using existing ethical principles to analyze and resolve difficult situations in clinical practice. We start with a few common situations with which many of us tend to struggle. We describe what we understand as ethics and how and why developments in technology, novel potential interventions, policies, and societal perspectives challenge us to think about and debate ethical issues. Individual patients are not a singular population; each patient has their own unique life situations, culture, goals, and expectations that need to be considered with a good dose of humanity and humility. We believe that using an ethical lens-by which we mean making an explicit effort to identify and consider these issues openly-will help us to achieve this goal in practice, education, and research.

  17. Human enterovirus D68 in clinical and sewage samples in Israel.

    Science.gov (United States)

    Weil, Merav; Mandelboim, Michal; Mendelson, Ella; Manor, Yossi; Shulman, Lester; Ram, Daniela; Barkai, Galia; Shemer, Yonat; Wolf, Dana; Kra-Oz, Zipi; Weiss, Leah; Pando, Rakefet; Hindiyeh, Musa; Sofer, Danit

    2017-01-01

    Since mid-August 2014, North America experienced a wide outbreak of Enterovirus D68 (EV-D68) associated with severe respiratory illness in children. Several other countries also reported cases of EV-D68 in 2014. The aim of this study was to determine whether EV-D68 circulated in Israel in 2014, caused severe respiratory illness in children and was the causative agent of Acute Flaccid Paralysis. Archived clinical respiratory samples from a cohort of 710 hospitalized pediatric patient's (<10years old) with respiratory illness were screened for clade B specific EV-D68 by real-time PCR. The patients were seen at four medical centers covering the entire country between August and November 2014. We also evaluated 49 patient stool samples from 26 AFP cases during 2014 for presence of EV-D68. In addition, RNA from sewage samples collected throughout Israel during the same study period was also tested for EV-D68. Partial VP1 sequencing was performed on all positive samples. Of the 710 clinical samples evaluated, 7 (1%) were positive for EV-D68. Two patients were from the central part of Israel, while the rest was from the southern part. The majority of the patients did not have any underlying disease. Not only that, but, none of the 26 suspected AFP cases had EV-D68 nucleic acid in their stool samples. EV-D68 RNA was detected in 9 out of 93 sewage samples, mainly from Southern Israel. Sequence analysis of EV-D68 VP1 gene from both sewage and clinical samples indicated that the Israeli EV-D68 RNA belonged to Clade B which was genetically similar to 2014 circulating European and North American EV-D68 virus. EV-D68 circulated in Israel during the 2014 summer-fall season and caused hospitalization of a small percent of the patients with respiratory illness. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Modeling sound transmission of human middle ear and its clinical applications using finite element analysis

    Directory of Open Access Journals (Sweden)

    Shou-I Chen

    2013-03-01

    Full Text Available We have developed a new finite element (FE model of human right ear, including the accurate geometry of middle ear ossicles, external ear canal, tympanic cavity, and mastoid cavity. The FE model would be suitable to study the dynamic behaviors of pathological middle ear conditions, including changes of stapedial ligament stiffness, tensor tympani ligament (TTL, and tympanic membrane (TM stiffness and thickness. Increasing stiffness of stapedial ligament has substantial effect on stapes footplate movement, especially at low frequencies, but less effect on umbo movement. Softer TTL will result in increasing umbo and stapes footplate displacement, especially at low frequencies (f1500 Hz. As (TM thickness was increased, the umbo displacement was reduced, especially at very low frequencies (f<600 Hz. Otherwise, the stapes displacement was reduced at all frequencies.

  19. Improved method and its clinical application of a radioimmunoassay of arginine vasopressin in human serum

    International Nuclear Information System (INIS)

    Wagner, H.; Maier, V.; Franz, H.W.; Ulm Univ.; Ulm Univ.

    1977-01-01

    A sensitive and specific double-antibody radioimmunoassay for measuring circulating levels of arginine vasopressin in human serum is described. It is possible to detect arginine vasopressin levels of 1 μU/ml serum without extraction procedure. Normal subjects were found to have 5.7 +- 4.4 μU/ml after a dehydration period of 12 hours. Water loading diminished arginine vasopressin concentrations while dehydration incrased it. Application of furosemide over a period of 14 days brought forth constant but not significant decreases. Subjects suffering from psychogenic polydipsia showed normal levels in spite of drinking 8-12 liters of water per day. Patients suffering from liver cirrhosis with ascites showed significantly higher arginine vasopressin levels, approaching normal values when ascites was under control. (orig.) [de

  20. Clinical manifestation and pathophysiology of Crimean-Congo hemorrhagic fever on human

    Directory of Open Access Journals (Sweden)

    Siavash Hamzehpour

    2017-10-01

    Full Text Available The Crimean-Congo hemorrhagic fever is a febrile and acute viral disease, and it is sporadic and epidemic in human societies, although it is special for animals (1. The disease was first identified in the Crimean Peninsula in the years 1945-1944 and was called the Crimean Hemorrhagic Fever. In 1956, the epidemic of the disease in the Congo also occurred, and due to the similarity of the disease agent, the combination of names of these two regions was used for naming the disease (2. The cause of this disease is a single-stranded viraemia virus from the genus Neurovirus and the Bunyaviridae family (3. One of the ways to transmit the disease is tick bites, and the hyaloma ticks are the most important constituent of the Crimean-Congo fever vein and the reservoir. In addition to transmitting the disease to vertebrates, due to a vertical and horizontal transmission, they transmit it to the next generation (4. Also, human contact with meat, blood and contaminated secretions of livestock in a livestock eradication period causes the transmission of the disease (5. Human to human transmission, which is more often seen as a hospital infection, is also a means of transmitting the disease (6. The incubation period after a tick bite is 1 to 3 days and a maximum of 9 days, and is slightly longer after contact with contaminated blood or tissue about 5-6 days, and finally 14 days (7. In the early stages of the disease, symptoms are sudden which include severe headaches, fever, chills, muscle pain, especially the back and leg muscles, neck stiffness, dizziness, reddening of the eyes, fear of light, nausea, vomiting and diarrhea. Then, a severe generalized muscle pain appears, mostly at the back and hamstring, and the patient complains of back pain and epigastric pain (8. In the examination of patients, facial flushing and chest thigtness, hyperemia of throat mucusand petechialsare common symptoms which draw attention. Hemorrhagic phenomena include melena

  1. Human Behaviour and Responses Challenge towards Emergence of Infectious Diseases: E.coli clinical isolate

    Directory of Open Access Journals (Sweden)

    Ummi Mohlisi Mohd Asmawi

    2016-01-01

    Full Text Available Consumption of undercooked ground beef is the most common route of transmission of verotoxin-producing E.coli. It is estimated that non-O157 verotoxigenic E.coli (VTEC can cause diarrhea.The sample was isolated from Universiti Malaya Medical Centre. All the isolates were identified using agarose gel electrophoresis method. This study aims to detect the verotoxin genes and detect the link or involvement of plasmids with these verotoxin genes. Therefore, this study will contribute to shed new light on resolving the significant and global problem of diarrheal disease caused by this particular pathogenic organism and help in improvising novel therapeutic approaches to improve human healthcare.

  2. Improved method and its clinical application of a radioimmunoassay of arginine vasopressin in human serum

    Energy Technology Data Exchange (ETDEWEB)

    Wagner, H; Maier, V; Franz, H W [Ulm Univ. (Germany, F.R.). Abt. Endokrinologie und Stoffwechsel; Ulm Univ. (Germany, F.R.). Zentrum fuer Innere Medizin und Kinderheilkunde; Ulm Univ. (Germany, F.R.). Sektion Nephrologie)

    1977-05-01

    A sensitive and specific double-antibody radioimmunoassay for measuring circulating levels of arginine vasopressin in human serum is described. It is possible to detect arginine vasopressin levels of 1 ..mu..U/ml serum without extraction procedure. Normal subjects were found to have 5.7 +- 4.4 ..mu..U/ml after a dehydration period of 12 hours. Water loading diminished arginine vasopressin concentrations while dehydration incrased it. Application of furosemide over a period of 14 days brought forth constant but not significant decreases. Subjects suffering from psychogenic polydipsia showed normal levels in spite of drinking 8-12 liters of water per day. Patients suffering from liver cirrhosis with ascites showed significantly higher arginine vasopressin levels, approaching normal values when ascites was under control.

  3. 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.

  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. Quality Control Assays for Clinical-Grade Human Mesenchymal Stromal Cells: Methods for ATMP Release.

    Science.gov (United States)

    Radrizzani, Marina; Soncin, Sabrina; Lo Cicero, Viviana; Andriolo, Gabriella; Bolis, Sara; Turchetto, Lucia

    2016-01-01

    Mesenchymal stromal/stem cells (MSC) are promising candidates for the development of cell-based therapies for various diseases and are currently being evaluated in a number of clinical trials (Sharma et al., Transfusion 54:1418-1437, 2014; Ikebe and Suzuki, Biomed Res Int 2014:951512, 2014). MSC for therapeutic applications are classified as advanced therapy medicinal products (ATMP) (Regulation (EC) No 1394/2007 of the European Parliament and of the Council of 13 November 2007 on advanced therapy medicinal products and amending Directive 2001/83/EC and Regulation (EC) No 726/2004) and must be prepared according to good manufacturing practices ( http://ec.europa.eu/health/documents/eudralex/vol-4 ). They may be derived from different starting materials (mainly bone marrow (BM), adipose tissue, or cord blood) and applied as fresh or cryopreserved products, in the autologous as well as an allogeneic context (Sharma et al., Transfusion 54:1418-1437, 2014; Ikebe and Suzuki, Biomed Res Int 2014:951512, 2014; Sensebé and Bourin, Transplantation 87(9 Suppl):S49-S53, 2009). In any case, they require an approved and well-defined panel of assays in order to be released for clinical use.This chapter describes analytical methods implemented and performed in our cell factory as part of the release strategy for an ATMP consisting of frozen autologous BM-derived MSC. Such methods are designed to assess the safety (sterility, endotoxin, and mycoplasma assays) and identity/potency (cell count and viability, immunophenotype and clonogenic assay) of the final product. Some assays are also applied to the biological starting material (sterility) or carried out as in-process controls (sterility, cell count and viability, immunophenotype, clonogenic assay).The validation strategy for each analytical method is described in the accompanying Chapter 20 .

  7. 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

  8. Human Amniotic Membrane-Derived Products in Sports Medicine: Basic Science, Early Results, and Potential Clinical Applications.

    Science.gov (United States)

    Riboh, Jonathan C; Saltzman, Bryan M; Yanke, Adam B; Cole, Brian J

    2016-09-01

    Amniotic membrane (AM)-derived products have been successfully used in ophthalmology, plastic surgery, and wound care, but little is known about their potential applications in orthopaedic sports medicine. To provide an updated review of the basic science and preclinical and clinical data supporting the use of AM-derived products and to review their current applications in sports medicine. Systematic review. A systematic search of the literature was conducted using the Medline, EMBASE, and Cochrane databases. The search term amniotic membrane was used alone and in conjunction with stem cell, orthopaedic, tissue engineering, scaffold, and sports medicine. The search identified 6870 articles, 80 of which, after screening of the titles and abstracts, were considered relevant to this study. Fifty-five articles described the anatomy, basic science, and nonorthopaedic applications of AM-derived products. Twenty-five articles described preclinical and clinical trials of AM-derived products for orthopaedic sports medicine. Because the level of evidence obtained from this search was not adequate for systematic review or meta-analysis, a current concepts review on the anatomy, physiology, and clinical uses of AM-derived products is presented. Amniotic membranes have many promising applications in sports medicine. They are a source of pluripotent cells, highly organized collagen, antifibrotic and anti-inflammatory cytokines, immunomodulators, and matrix proteins. These properties may make it beneficial when applied as tissue engineering scaffolds, improving tissue organization in healing, and treatment of the arthritic joint. The current body of evidence in sports medicine is heavily biased toward in vitro and animal studies, with little to no human clinical data. Nonetheless, 14 companies or distributors offer commercial AM products. The preparation and formulation of these products alter their biological and mechanical properties, and a thorough understanding of these

  9. Clinical assessment of bone quality of human extraction sockets after conversion with growth factors.

    Science.gov (United States)

    Ntounis, Athanasios; Geurs, Nico; Vassilopoulos, Philip; Reddy, Michael

    2015-01-01

    The study was conducted to evaluate the effect of mineralized freeze-dried bone allograft (FDBA), alone or in combination with growth factors in extraction sockets, on subjective assessment of bone quality during implant placement. Forty-one patients whose treatment plan involved extraction of anterior or premolar teeth were randomized into four groups: Group 1, collagen plug (control); Group 2, FDBA/β-tricalcium phosphate (β-TCP)/collagen plug; Group 3, FDBA/β-TCP/platelet-rich plasma (PRP)/collagen plug; Group 4, FDBA/β-TCP/recombinant human platelet-derived growth factor BB (rhPDGF-BB)/collagen plug. After 8 weeks of healing, implants were placed. The clinicians assessed bone quality according to the Misch classification. A benchtop calibration exercise test was conducted to evaluate agreement and accuracy of operators in recognizing different bone qualities. Differences were analyzed using one-way analysis of variance (ANOVA) or chi-square tests for continuous and categorical data. Pairwise comparisons were tested using least squares means (LS means). Spearman correlation coefficients were used to evaluate the relationship of bone growth with potential confounders. P .05). Inclusion of bone grafting is associated with a shift from D4 quality to D3 quality bone. Inclusion of PRP in bone grafting eliminates the incidence of D4 bone, establishing D3 and D2 quality bone as prevalent (56% vs. 42%, respectively). Inclusion of rhPDGF-BB and β-TCP in combination with the bone grafting has the same effect, although D2 quality is less prevalent. When compared to sockets grafted with FDBA/β-TCP/collagen plug alone, the sockets with growth factors demonstrated fewer residual bone graft particles. (1) Inclusion of bone grafting enhanced bone quality as assessed during implant placement. (2) Overall inclusion of PRP and rhPDGF-BB enhanced subjective bone quality, eliminating incidence of D4 quality in human extraction sockets. (3) The use of PRP or rhPDGF-BB may

  10. Standardization and clinical application of human serum somotomedin B radioimmunoassay. Development of the enzimatic radioiodination

    International Nuclear Information System (INIS)

    Silva Gomes, E.N.D. da.

    1979-01-01

    The various steps that are necessary for the setting up of Somatomedin B radioimunoassay are presented. Radioiodination was carried out through the enzimatic method of Lactoperoxidase while the purification of the labelled was performed first of Sephadex G-25 fine and then on Sephadex G-75. It was found that a preparation of 125 I labelled Somatomedin B presented a radiochemical purity of 99,8%, a mean specific activity determined by the self-displacement method of 54.1 +-3.6μCi/μg and a binding of 98% in the presence of antibody excess. It was also shown that the high stability of this preparation allows its use for up to one month after labelling, if it is stored in refrigerator at + 4 0 C. The separation between the free and the bound antigen was achieved through the method of the second antibody after a period of incubation of 4 days at 4 0 C. The statistic analysis of the method showed also its specificity, which is proved through a study of the dilution effect on human seruns where endogenous Somatomedin B is determined. The sensitivity of the method determined by discrete analysis of the first values on the standard curve was of 0.31 ng/ml. Finally are presented the serum levels of Somatomedin B that have been found in normal subjects and in individuals with alteration HGH secretion [pt

  11. From Human Papillomavirus (HPV) Detection to Cervical Cancer Prevention in Clinical Practice

    International Nuclear Information System (INIS)

    Lee, Sin Hang; Vigliotti, Jessica S.; Vigliotti, Veronica S.; Jones, William

    2014-01-01

    The newly gained knowledge of the viral etiology in cervical carcinogenesis has prompted industrial interests in developing virology-based tools for cervical cancer prevention. Due to the long incubation period from viral infection to developing an invasive cancer, a process whose outcome is influenced by numerous life-style and genetic factors, the true efficacy of the genotype-specific human papillomavirus (HPV) vaccines in cervical cancer prevention cannot be determined for another 30 years. Most HPV DNA test kits designed to replace the traditional Papanicolaou (Pap) smears for precancer detection lack the analytical sensitivity and specificity to comprehensively detect all potentially carcinogenic HPVs and to perform reliable genotyping. The authors implemented the classic nested PCR and Sanger DNA-sequencing technology for routine HPV testing. The results showed a true negative HPV PCR invariably indicates the absence of precancerous cells in the cytology samples. However, 80.5% of single positive HPV-16 tests and 97.3% of single positive HPV-18 tests were associated with a negative or a largely self-reversible Pap cytology. Routine sensitive and reliable HPV type-specific or perhaps even variant-specific methods are needed to address the issues of persistence of HPV infection if a virology-based primary cervical screen is used to replace the Pap cytology screening paradigm

  12. From Human Papillomavirus (HPV) Detection to Cervical Cancer Prevention in Clinical Practice

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sin Hang, E-mail: shlee01@snet.net; Vigliotti, Jessica S.; Vigliotti, Veronica S.; Jones, William [Department of Pathology, Milford Hospital, 300 Seaside Ave., Milford, CT 06460 (United States)

    2014-10-02

    The newly gained knowledge of the viral etiology in cervical carcinogenesis has prompted industrial interests in developing virology-based tools for cervical cancer prevention. Due to the long incubation period from viral infection to developing an invasive cancer, a process whose outcome is influenced by numerous life-style and genetic factors, the true efficacy of the genotype-specific human papillomavirus (HPV) vaccines in cervical cancer prevention cannot be determined for another 30 years. Most HPV DNA test kits designed to replace the traditional Papanicolaou (Pap) smears for precancer detection lack the analytical sensitivity and specificity to comprehensively detect all potentially carcinogenic HPVs and to perform reliable genotyping. The authors implemented the classic nested PCR and Sanger DNA-sequencing technology for routine HPV testing. The results showed a true negative HPV PCR invariably indicates the absence of precancerous cells in the cytology samples. However, 80.5% of single positive HPV-16 tests and 97.3% of single positive HPV-18 tests were associated with a negative or a largely self-reversible Pap cytology. Routine sensitive and reliable HPV type-specific or perhaps even variant-specific methods are needed to address the issues of persistence of HPV infection if a virology-based primary cervical screen is used to replace the Pap cytology screening paradigm.

  13. Synthesis of nano-cuboidal gold particles for effective antimicrobial property against clinical human pathogens.

    Science.gov (United States)

    Murphin Kumar, Paskalis Sahaya; MubarakAli, Davoodbasha; Saratale, Rijuta Ganesh; Saratale, Ganesh Dattatraya; Pugazhendhi, Arivalagan; Gopalakrishnan, Kumar; Thajuddin, Nooruddin

    2017-12-01

    Algae could offer a potential source of fine chemicals, pharmaceuticals and biofuels. In this study, a green synthesis of dispersed cuboidal gold nanoparticles (AuNPs) was achieved using red algae, Gelidium amansii reacted with HAuCl 4 . It was found to be 4-7 nm sized cubical nanoparticles with aspect ratio of 1.4 were synthesized using 0.5 mM of HAuCl 4 by HRSEM analysis. The crystalline planes (111), (200), (220), (311) and elemental signal of gold was observed by XRD and EDS respectively. The major constitutes, galactose and 3,6-anhydrogalactose in the alga played a critical role in the synthesis of crystalline AuNPs with cubical dimension. Further, the antibacterial potential of synthesized AuNPs was tested against human pathogens, Escherichia coli and Staphylococcus aureus. The synthesized AuNPs found biocompatible up to 100 ppm and high concentration showed an inhibition against cancer cell. This novel report could be helped to exploration of bioresources to material synthesis for the application of biosensor and biomedical application. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Radioimmunoassay of arginine-vasopressin in human plasma: Development and clinical application

    International Nuclear Information System (INIS)

    Hummerich, W.; Konrads, A.; Roesch, R.; Sofroniew, M.

    1983-01-01

    A sensitive and specific radioimmunoassay for the measurement of arg-vasopressin (AVP) in human plasma is described. Recovery of added AVP from plasma was about 65-70%. An acetone extraction step was necessary to prevent unspecific blank effects. Sensitivity of the assay in 0.5 pg AVP/ml plasma. In normally hydrated subjects AVP-concentration ranged from 0.7 pg/ml to 5.8 pg/ml and showed a good correlation with plasma osmolality. In patients with complete diabetes insipidus (D.i.) AVP-values were below the sensitivity limit of the method and they were subnormal when D.i. was incomplete. There was no increase of AVP-concentration during fluid restriction in patients with complete or incomplete D.i. In subjects with psychogenic polydipsia AVP-values were normal and dehydration produced adequate rises of plasma AVP. In patients with SIADH (Schwartz-Bartter-syndrome) AVP-values were greatly enhanced (> 10 pg/ml) when correlated to plasma osmolality ( 2 O). (orig.)

  15. Radioimmunoassay of arginine-vasopressin in human plasma: Development and clinical application

    Energy Technology Data Exchange (ETDEWEB)

    Hummerich, W.; Konrads, A.; Roesch, R.; Sofroniew, M.

    1983-02-15

    A sensitive and specific radioimmunoassay for the measurement of arg-vasopressin (AVP) in human plasma is described. Recovery of added AVP from plasma was about 65-70%. An acetone extraction step was necessary to prevent unspecific blank effects. Sensitivity of the assay in 0.5 pg AVP/ml plasma. In normally hydrated subjects AVP-concentration ranged from 0.7 pg/ml to 5.8 pg/ml and showed a good correlation with plasma osmolality. In patients with complete diabetes insipidus (D.i.) AVP-values were below the sensitivity limit of the method and they were subnormal when D.i. was incomplete. There was no increase of AVP-concentration during fluid restriction in patients with complete or incomplete D.i. In subjects with psychogenic polydipsia AVP-values were normal and dehydration produced adequate rises of plasma AVP. In patients with SIADH (Schwartz-Bartter-syndrome) AVP-values were greatly enhanced (> 10 pg/ml) when correlated to plasma osmolality (< 170 mosmol/kg H/sub 2/O).

  16. The clinical application of fluorescent-enzyme immunoassay to detect human thyroid peroxidase autoantibody quantitatively

    International Nuclear Information System (INIS)

    Chai Jinyan; Fang Peihua; Li Ning; Zhang Yanli

    2010-01-01

    Objective: To establish a fluorescent-enzyme immunoassay (FEIA) with recombinant human thyroid peroxidase (hTPO) as the antigen. Methods: Sera of 326 healthy people, 119 cases of Hashimoto's thyroiditis (HT), 116 cases of Graves disease (untreated), 28 cases of nodular goiter, 10 ca-ses of subacute thyroiditis and 6 cases of simple goiter were measured by the FEIA with recombinant hTPO as the antigen. Rrank sum test and χ 2 -test were used in inter-groups. Results: (1) Concentration above 4000 U/L was considered to be positive. (2) The intra-assay coefficient of variation (CV) and the inter-as-say CV were 4.59% ∼ 6.52% and 17.37% ∼ 17.45%. (3) The values measured by the FEIA were positively correlated with the values measured by hTPO antibody (hTPOAb) commercial kit (r=0.80, P 2 = 53.45, 39.30, 15.41 and 21.74, all P < 0.01). Conclusions: The method can be applied in the serum measurement of thyroid disease. HT presented the highest positive rate, therefore, the FEIA was an effective method in diagnosing HT. (authors)

  17. Genetic, anatomic, and clinical determinants of human serum sterol and vitamin D levels.

    Science.gov (United States)

    Stiles, Ashlee R; Kozlitina, Julia; Thompson, Bonne M; McDonald, Jeffrey G; King, Kevin S; Russell, David W

    2014-09-23

    An unknown fraction of the genome participates in the metabolism of sterols and vitamin D, two classes of lipids with diverse physiological and pathophysiological roles. Here, we used mass spectrometry to measure the abundance of >60 sterol and vitamin D derivatives in 3,230 serum samples from a well-phenotyped patient population. Twenty-nine of these lipids were detected in a majority of samples at levels that varied over thousands of fold in different individuals. Pairwise correlations between sterol and vitamin D levels revealed evidence for shared metabolic pathways, additional substrates for known enzymes, and transcriptional regulatory networks. Serum levels of multiple sterols and vitamin D metabolites varied significantly by sex, ethnicity, and age. A genome-wide association study identified 16 loci that were associated with levels of 19 sterols and 25-hydroxylated derivatives of vitamin D (P < 10(-7)). Resequencing, expression analysis, and biochemical experiments focused on one such locus (CYP39A1), revealed multiple loss-of-function alleles with additive effects on serum levels of the oxysterol, 24S-hydroxycholesterol, a substrate of the encoded enzyme. Body mass index, serum lipid levels, and hematocrit were strong phenotypic correlates of interindividual variation in multiple sterols and vitamin D metabolites. We conclude that correlating population-based analytical measurements with genotype and phenotype provides productive insight into human intermediary metabolism.

  18. Prevalence and clinical utility of human papilloma virus genotyping in patients with cervical lesions.

    Science.gov (United States)

    Kaur, Parminder; Aggarwal, Aruna; Nagpal, Madhu; Oberoi, Loveena; Sharma, Swati

    2014-08-01

    Cervical cancer is the commonest cancer among Indian women. High-risk human papilloma virus (HPV) detection holds the potential to be used as a tool to identify women, at risk of subsequent development of cervical cancer. There is a pressing need to identify prevalence of asymptomatic cervical HPV infection in local population. In our study, we explored the prevalence of HPV genotypes and their distribution in women with cervical lesions. Scrape specimens were obtained from 100 women (study group) with cervical abnormalities. HPV was detected with amplicor HPV tests, and the individual genotypes in these specimens were identified by Hybribio Genoarray test kit. Fifty specimens were also collected from females with healthy cervix (control group). The present study also aimed to determine the status of HPV prevalence and its association with different sociodemographic factors. Out of the total number of 100 samples, 10 (10 %) women tested positive for HPV DNA. Among them, HPV 18 was observed in 6, HPV 16 in 2, HPV 52 and HPV 39 in one each. Fifty specimens collected from patients with healthy cervix were not infected with any of the HPV genotype. Our study generates data of HPV prevalence in patients with cervical lesions visiting tertiary care institute. The data generated will be useful for laying guidelines for mass screening of HPV detection, treatment, and prophylaxis.

  19. Micro-polarimetry for pre-clinical diagnostics of pathological changes in human tissues

    Science.gov (United States)

    Golnik, Andrzej; Golnik, Natalia; Pałko, Tadeusz; Sołtysiński, Tomasz

    2008-05-01

    The paper presents a practical study of several methods of image analysis applied to polarimetric images of regular and malignant human tissues. The images of physiological and pathologically changed tissues from body and cervix of uterus, intestine, kidneys and breast were recorded in transmitted light of different polarization state. The set up of the conventional optical microscope with CCD camera and rotating polarizer's were used for analysis of the polarization state of the light transmitted through the tissue slice for each pixel of the camera image. The set of images corresponding to the different coefficients of the Stockes vectors, a 3×3 subset of the Mueller matrix as well as the maps of the magnitude and in-plane direction of the birefringent components in the sample were calculated. Then, the statistical analysis and the Fourier transform as well as the autocorrelation methods were used to analyze spatial distribution of birefringent elements in the tissue samples. For better recognition of tissue state we proposed a novel method that takes advantage of multiscale image data decomposition The results were used for selection of the optical characteristics with significantly different values for regular and malignant tissues.

  20. Clinical guideline representation in a CDS: a human information processing method.

    Science.gov (United States)

    Kilsdonk, Ellen; Riezebos, Rinke; Kremer, Leontien; Peute, Linda; Jaspers, Monique

    2012-01-01

    The Dutch Childhood Oncology Group (DCOG) has developed evidence-based guidelines for screening childhood cancer survivors for possible late complications of treatment. These paper-based guidelines appeared to not suit clinicians' information retrieval strategies; it was thus decided to communicate the guidelines through a Computerized Decision Support (CDS) tool. To ensure high usability of this tool, an analysis of clinicians' cognitive strategies in retrieving information from the paper-based guidelines was used as requirements elicitation method. An information processing model was developed through an analysis of think aloud protocols and used as input for the design of the CDS user interface. Usability analysis of the user interface showed that the navigational structure of the CDS tool fitted well with the clinicians' mental strategies employed in deciding on survivors screening protocols. Clinicians were more efficient and more complete in deciding on patient-tailored screening procedures when supported by the CDS tool than by the paper-based guideline booklet. The think-aloud method provided detailed insight into users' clinical work patterns that supported the design of a highly usable CDS system.

  1. A Clinical Indications Prediction Scale Based on TWIST1 for Human Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    Siddaraju V. Boregowda

    2016-02-01

    Full Text Available In addition to their stem/progenitor properties, mesenchymal stem cells (MSCs also exhibit potent effector (angiogenic, antiinflammatory, immuno-modulatory functions that are largely paracrine in nature. It is widely believed that effector functions underlie most of the therapeutic potential of MSCs and are independent of their stem/progenitor properties. Here we demonstrate that stem/progenitor and effector functions are coordinately regulated at the cellular level by the transcription factor Twist1 and specified within populations according to a hierarchical model. We further show that manipulation of Twist1 levels by genetic approaches or by exposure to widely used culture supplements including fibroblast growth factor 2 (Ffg2 and interferon gamma (IFN-gamma alters MSC efficacy in cell-based and in vivo assays in a predictable manner. Thus, by mechanistically linking stem/progenitor and effector functions our studies provide a unifying framework in the form of an MSC hierarchy that models the functional complexity of populations. Using this framework, we developed a CLinical Indications Prediction (CLIP scale that predicts how donor-to-donor heterogeneity and culture conditions impact the therapeutic efficacy of MSC populations for different disease indications.

  2. Clinical and Molecular Epidemiology of Human Parainfluenza Viruses 1-4 in Children from Viet Nam.

    Science.gov (United States)

    Linster, Martin; Do, Lien Anh Ha; Minh, Ngo Ngoc Quang; Chen, Yihui; Zhe, Zhu; Tuan, Tran Anh; Tuan, Ha Manh; Su, Yvonne C F; van Doorn, H Rogier; Moorthy, Mahesh; Smith, Gavin J D

    2018-05-01

    HPIVs are serologically and genetically grouped into four species that account for up to 10% of all hospitalizations due to acute respiratory infection in children under the age of five. Genetic and epidemiological data for the four HPIVs derived from two pediatric cohorts in Viet Nam are presented. Respiratory samples were screened for HPIV1-4 by real-time PCR. Demographic and clinical data of patients infected with different HPIV were compared. We used a hemi-nested PCR approach to generate viral genome sequences from HPIV-positive samples and conducted a comprehensive phylogenetic analysis. In total, 170 samples tested positive for HPIV. HPIV3 was most commonly detected in our cohort and 80 co-detections of HPIV with other respiratory viruses were found. Phylogenetic analyses suggest local endemic circulation as well as punctuated introductions of new HPIV lineages. Viral gene flow analysis revealed that Viet Nam is a net importer of viral genetic diversity. Epidemiological analyses imply similar disease severity for all HPIV species. HPIV sequences from Viet Nam formed local clusters and were interspersed with sequences from diverse geographic regions. Combined, this new knowledge will help to investigate global HPIV circulation patterns in more detail and ultimately define more suitable vaccine strains.

  3. Insight into the cellular fate and toxicity of aluminium adjuvants used in clinically approved human vaccinations.

    Science.gov (United States)

    Mold, Matthew; Shardlow, Emma; Exley, Christopher

    2016-08-12

    Aluminium adjuvants remain the most widely used and effective adjuvants in vaccination and immunotherapy. Herein, the particle size distribution (PSD) of aluminium oxyhydroxide and aluminium hydroxyphosphate adjuvants was elucidated in attempt to correlate these properties with the biological responses observed post vaccination. Heightened solubility and potentially the generation of Al(3+) in the lysosomal environment were positively correlated with an increase in cell mortality in vitro, potentially generating a greater inflammatory response at the site of simulated injection. The cellular uptake of aluminium based adjuvants (ABAs) used in clinically approved vaccinations are compared to a commonly used experimental ABA, in an in vitro THP-1 cell model. Using lumogallion as a direct-fluorescent molecular probe for aluminium, complemented with transmission electron microscopy provides further insight into the morphology of internalised particulates, driven by the physicochemical variations of the ABAs investigated. We demonstrate that not all aluminium adjuvants are equal neither in terms of their physical properties nor their biological reactivity and potential toxicities both at the injection site and beyond. High loading of aluminium oxyhydroxide in the cytoplasm of THP-1 cells without immediate cytotoxicity might predispose this form of aluminium adjuvant to its subsequent transport throughout the body including access to the brain.

  4. Radioimmunoassay of thyrotropin releasing hormone in human serum and its clinical application

    International Nuclear Information System (INIS)

    Zhao Zhiying; Liu Shizhen

    1995-01-01

    The study was aimed at investigating the relationship between the TRH level in peripheral blood and the physiological, pathophysiological variation of the hypothalamic-pituitary-thyroid axis, especially at studying the relationship between TRH level and various thyroid function states as well as its clinical significance. A highly sensitive, specific radioimmunoassay of the thyrotropin releasing hormone (TRH) has been developed in the laboratory using 125 I labeled anti-TRH antibodies. Blood samples were collected in tubes containing a mixture of 8-hydroxyquinoline sulfur, Tween 20 and EDTA-2NA(E). The sensitivity was 8.3% pmol/L, and the intra- and inter-assay coefficients of variation were 2.5%∼4.9% and 8.9%∼10.0% respectively. The recovery rate ranged from 92%∼105%. The TRH levels in sera of 80 normals and 324 patients with pituitary thyroid diseases were measured with this assay. The results show a significant decrease of TRH levels in hyperthyroid patients and increase in hypothyroid subjects. The TRH levels in patients with nodular goiter and cold nodules, pituitary dwarfism and pituitary tumours were not significantly different from those of the normal group. The results demonstrated that measurement of TRH level in peripheral blood is useful in investigating the physiological and pathophysiological status of the hypothalamic-pituitary-thyroid axis function and the change in TRH levels has close relations with the thyroid function

  5. 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

  6. Zinc in human serum. Biochemical and clinical aspects. Zink i humant serum. Biokemiske og kliniske aspekter

    Energy Technology Data Exchange (ETDEWEB)

    Kiilerich, S

    1987-01-01

    The zinc ion is essential for the living organism. Many pathological conditions have been described as a consequence of zinc deficiency. As zinc constitutes less than 0.01 percent of the body weight, it conventionally belongs to the group of trace elements. The method of atomic absorption spectrophotometry is used to measure the concentration of zinc in serum and urine from healthy persons. The assumptions of the method is discussed. The importance of protein binding, diet and the diurnal variation of serum zinc concentration is presented. Serum versus plasma zinc concentration is discussed. Reference serum zinc values from 104 normal subjects are given. Zinc in serum is almost entirely bound to proteins. A preliminary model for the estimation of the distribution of zinc between serum albumin and ..cap alpha../sub 2/-macroglobulin is set up. This estimate has been examined by an ultracentrufugation method. The binding of zinc to a ..cap alpha../sup 2/-macroglobulin in normal persons is appoximately 7 percent, in patients with cirrhosis of the liver of alcoholic origin approximately 6 percent, in patients with insulin dependent diabetes mellitus approximately 5 percent, and in patients with chronic renal failure approximately 2 percent. It is concluded, therefore, that for clinical purposes it is sufficient to use the concentration of total serum zinc corrected for the concentration of serum albumin.

  7. Clinical Trials

    Medline Plus

    Full Text Available ... Entire Site NHLBI Entire Site Health Topics News & Resources Intramural Research ... or device is safe and effective for humans. What Are Clinical Trials? Clinical trials are research ...

  8. Clinical Trials

    Medline Plus

    Full Text Available ... to main content U.S. Department of Health & Human ... of people. Clinical trials produce the best data available for health care decisionmaking. The purpose of clinical trials is research, ...

  9. 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 ...

  10. Distribution and pharmacokinetics of methamphetamine in the human body: clinical implications

    International Nuclear Information System (INIS)

    Volkow, N.D.; Fowler, J.S.; Wang, G.-J.; Shumay, E.; Telang, F.; Thanos, P.; Alexoff, D.

    2010-01-01

    Methamphetamine is one of the most toxic of the drugs of abuse, which may reflect its distribution and accumulation in the body. However no studies have measured methamphetamine's organ distribution in the human body. Positron Emission Tomography (PET) was used in conjunction with ( 11 C)d-methamphetamine to measure its whole-body distribution and bioavailability as assessed by peak uptake (% Dose/cc), rate of clearance (time to reach 50% peak-clearance) and accumulation (area under the curve) in healthy participants (9 Caucasians and 10 African Americans). Methamphetamine distributed through most organs. Highest uptake (whole organ) occurred in lungs (22% Dose; weight ∼1246 g), liver (23%; weight ∼1677 g) and intermediate in brain (10%; weight ∼1600 g). Kidneys also showed high uptake (per/cc basis) (7%; weight 305 g). Methamphetamine's clearance was fastest in heart and lungs (7-16 minutes), slowest in brain, liver and stomach (>75 minutes), and intermediate in kidneys, spleen and pancreas (22-50 minutes). Lung accumulation of ( 11 C)d-methamphetamine was 30% higher for African Americans than Caucasians (p < 0.05) but did not differ in other organs. The high accumulation of methamphetamine, a potent stimulant drug, in most body organs is likely to contribute to the medical complications associated with methamphetamine abuse. In particular, we speculate that methamphetamine's high pulmonary uptake could render this organ vulnerable to infections (tuberculosis) and pathology (pulmonary hypertension). Our preliminary findings of a higher lung accumulation of methamphetamine in African Americans than Caucasians merits further investigation and questions whether it could contribute to the infrequent use of methamphetamine among African Americans.

  11. Clinical Effect of Human Papillomavirus Genotypes in Patients With Cervical Cancer Undergoing Primary Radiotherapy

    International Nuclear Information System (INIS)

    Wang, Chun-Chieh; Lai, Chyong-Huey; Huang, Huei-Jean; Chao, Angel; Chang, Chee-Jen; Chang, Ting-Chang; Chou, Hung-Hsueh; Hong, Ji-Hong

    2010-01-01

    Purpose: To study the prognostic value of the human papillomavirus (HPV) genotypes in cervical cancer patients undergoing radiotherapy. Patients and Methods: A total of 1,010 patients with cervical cancer after radiotherapy between 1993 and 2000 were eligible for this study. The HPV genotypes were determined by a genechip, which detects 38 types of HPV. The patient characteristics and treatment outcomes were analyzed using the Cox regression hazard model and classification and regression tree decision tree method. Results: A total of 25 genotypes of HPV were detected in 992 specimens (98.2%). The leading 8 types were HPV16, 58, 18, 33, 52, 39, 31, and 45. These types belong to two high-risk HPV species: alpha-7 (HPV18, 39, 45) and alpha-9 (HPV16, 31, 33, 52, 58). Three HPV-based risk groups, which were independent of established prognostic factors, such as International Federation of Gynecology and Obstetrics stage, age, pathologic features, squamous cell carcinoma antigen, and lymph node metastasis, were associated with the survival outcomes. The high-risk group consisted of the patients without HPV infection or the ones infected with the alpha-7 species only. Patients co-infected with the alpha-7 and alpha-9 species belonged to the medium-risk group, and the others were included in the low-risk group. Conclusion: The results of the present study have confirmed the prognostic value of HPV genotypes in cervical cancer treated with radiotherapy. The different effect of the alpha-7 and alpha-9 species on the radiation response deserves additional exploration.

  12. Standardization of the radioimmunoassay technique for the determination of human gastrin and its clinical application

    International Nuclear Information System (INIS)

    Peig Ginabredra, M.G.

    1989-01-01

    It was developed and standardized a system of radioimmunoassay for the determination of gastrin, employing synthetic human gastrin for radioiodination and preparation of standard as well as specific antibody raised rabbits. The hormone was labeled with 125 I by the Cloramine T techique and purified by anion exchange chromatography in QAE-Sephadex A-25, being determined its specific activity. The tracer thus obtained was submitted to analysis of purity by poliacrilamide gel eletrophoresis and precipitation of proteins by trichloroacetic acid. Its stability evaluated according to the time of storage, being its purity and adequation for the use in radioimmunoassay also compared to a tracer obtained from a commercial diagnosis kit. The assays were performed by incubation of radioiodinated gastrin, standard gastrin prepared in plasma free from this hormone (from zero to 500 pmol/l) or samples to be assayed with the antiserum for 4 days at 4 0 C. The separation between the free gastrin and the gastrin bound to the antibody was carried out by adsorption of the free hormone to the charcoal, whose ideal concentration was previously determined. Plasma free from gastrin was obtained from time-expired blood bank plasma submitted to extraction with charcoal. When performed the quality control, this radioimmunoassay was shown specific, accurate, precise and sensitive, allowing the performance of valid assays. Its validation was even confirmed by clear discrimination not only of the gastrin concentration in subjects with very low levels (gastrectomized) and extremely high levels (Zollinger-Ellison syndrome) as well as gastrin concentrations in subjects with other diseases, such as Chagas disease, pernicious anemia and chronic renal failure. (author) [pt

  13. 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)

  14. Catalytic antibodies in clinical and experimental pathology: human and mouse models.

    Science.gov (United States)

    Ponomarenko, Natalya A; Durova, Oxana M; Vorobiev, Ivan I; Aleksandrova, Elena S; Telegin, Georgy B; Chamborant, Olga G; Sidorik, Lyudmila L; Suchkov, Sergei V; Alekberova, Zemfira S; Gnuchev, Nikolay V; Gabibov, Alexander G

    2002-11-01

    Most of the data accumulated through studies on natural catalytic autoantibodies indicate that production scales up markedly in pathological abnormalities. We have previously described an increased level of DNA-hydrolyzing autoantibodies in the sera of patients with various autoimmune disorders [systemic lupus erythematosus (SLE), rheumatoid arthritis, scleroderma], HIV infection and lymphoproliferative diseases accompanied by autoimmune manifestations. In the present study, we show that an increased level of catalytic activity of autoantibodies can be observed in the sera of autoimmune mice, thus providing a fundamental insight into the medical relevance of abzymes. Polyclonal autoantibodies purified from sera of NZB/W, MRL-lpr/lpr and SJL/J mice show proteolytic and DNA-hydrolyzing activities, as opposed to those harvested from non-autoimmune BALB/c mice. The expressiveness of the catalytic activity was strongly dependent on the age of the animal. The highest levels of catalytic activity were found in the sera of mice aged between 8 and 12 months; the lowest level was typical of younger animals whose age ranged from 6 to 8 weeks. Specific inhibition assays of the catalytic activities were performed to throw light on the nature of the abzyme activity. Within a cohort of aging animals, a strong correlation between marked autoimmune abnormalities and levels of catalytic activities has been established. Nonimmunized SJL/J mice revealed specific immune responses to myelin basic protein (MBP), skeletal muscle myosin (skMyo) and cardiac myosin (Myo), and highly purified antibodies from their serum show specific proteolytic attack against the target antigens. This finding prompted us to undertake a more detailed study of specific antibody-mediated proteolysis in diseased humans. A targeted catalytic response was originally demonstrated against MBP and Myo in multiple sclerosis and myocarditis patients, respectively.

  15. First-in-Human Clinical Trial of Oral ONC201 in Patients with Refractory Solid Tumors.

    Science.gov (United States)

    Stein, Mark N; Bertino, Joseph R; Kaufman, Howard L; Mayer, Tina; Moss, Rebecca; Silk, Ann; Chan, Nancy; Malhotra, Jyoti; Rodriguez, Lorna; Aisner, Joseph; Aiken, Robert D; Haffty, Bruce G; DiPaola, Robert S; Saunders, Tracie; Zloza, Andrew; Damare, Sherri; Beckett, Yasmeen; Yu, Bangning; Najmi, Saltanat; Gabel, Christian; Dickerson, Siobhan; Zheng, Ling; El-Deiry, Wafik S; Allen, Joshua E; Stogniew, Martin; Oster, Wolfgang; Mehnert, Janice M

    2017-08-01

    Purpose: ONC201 is a small-molecule selective antagonist of the G protein-coupled receptor DRD2 that is the founding member of the imipridone class of compounds. A first-in-human phase I study of ONC201 was conducted to determine its recommended phase II dose (RP2D). Experimental Design: This open-label study treated 10 patients during dose escalation with histologically confirmed advanced solid tumors. Patients received ONC201 orally once every 3 weeks, defined as one cycle, at doses from 125 to 625 mg using an accelerated titration design. An additional 18 patients were treated at the RP2D in an expansion phase to collect additional safety, pharmacokinetic, and pharmacodynamic information. Results: No grade >1 drug-related adverse events occurred, and the RP2D was defined as 625 mg. Pharmacokinetic analysis revealed a C max of 1.5 to 7.5 μg/mL (∼3.9-19.4 μmol/L), mean half-life of 11.3 hours, and mean AUC of 37.7 h·μg/L. Pharmacodynamic assays demonstrated induction of caspase-cleaved keratin 18 and prolactin as serum biomarkers of apoptosis and DRD2 antagonism, respectively. No objective responses by RECIST were achieved; however, radiographic regression of several individual metastatic lesions was observed along with prolonged stable disease (>9 cycles) in prostate and endometrial cancer patients. Conclusions: ONC201 is a selective DRD2 antagonist that is well tolerated, achieves micromolar plasma concentrations, and is biologically active in advanced cancer patients when orally administered at 625 mg every 3 weeks. Clin Cancer Res; 23(15); 4163-9. ©2017 AACR . ©2017 American Association for Cancer Research.

  16. Distribution and pharmacokinetics of methamphetamine in the human body: clinical implications

    Energy Technology Data Exchange (ETDEWEB)

    Volkow, N.D.; Fowler, J.; Volkow, N.D.; Fowler, J.S.; Wang, G.-J.; Shumay, E.; Telang, F.; Thanos, P.; Alexoff, D.

    2010-12-01

    Methamphetamine is one of the most toxic of the drugs of abuse, which may reflect its distribution and accumulation in the body. However no studies have measured methamphetamine's organ distribution in the human body. Positron Emission Tomography (PET) was used in conjunction with [{sup 11}C]d-methamphetamine to measure its whole-body distribution and bioavailability as assessed by peak uptake (% Dose/cc), rate of clearance (time to reach 50% peak-clearance) and accumulation (area under the curve) in healthy participants (9 Caucasians and 10 African Americans). Methamphetamine distributed through most organs. Highest uptake (whole organ) occurred in lungs (22% Dose; weight {approx}1246 g), liver (23%; weight {approx}1677 g) and intermediate in brain (10%; weight {approx}1600 g). Kidneys also showed high uptake (per/cc basis) (7%; weight 305 g). Methamphetamine's clearance was fastest in heart and lungs (7-16 minutes), slowest in brain, liver and stomach (>75 minutes), and intermediate in kidneys, spleen and pancreas (22-50 minutes). Lung accumulation of [{sup 11}C]d-methamphetamine was 30% higher for African Americans than Caucasians (p < 0.05) but did not differ in other organs. The high accumulation of methamphetamine, a potent stimulant drug, in most body organs is likely to contribute to the medical complications associated with methamphetamine abuse. In particular, we speculate that methamphetamine's high pulmonary uptake could render this organ vulnerable to infections (tuberculosis) and pathology (pulmonary hypertension). Our preliminary findings of a higher lung accumulation of methamphetamine in African Americans than Caucasians merits further investigation and questions whether it could contribute to the infrequent use of methamphetamine among African Americans.

  17. Relationship of periodontal clinical parameters with bacterial composition in human dental plaque.

    Science.gov (United States)

    Fujinaka, Hidetake; Takeshita, Toru; Sato, Hirayuki; Yamamoto, Tetsuji; Nakamura, Junji; Hase, Tadashi; Yamashita, Yoshihisa

    2013-06-01

    More than 600 bacterial species have been identified in the oral cavity, but only a limited number of species show a strong association with periodontitis. The purpose of the present study was to provide a comprehensive outline of the microbiota in dental plaque related to periodontal status. Dental plaque from 90 subjects was sampled, and the subjects were clustered based on bacterial composition using the terminal restriction fragment length polymorphism of 16S rRNA genes. Here, we evaluated (1) periodontal clinical parameters between clusters; (2) the correlation of subgingival bacterial composition with supragingival bacterial composition; and (3) the association between bacterial interspecies in dental plaque using a graphical Gaussian model. Cluster 1 (C1) having high prevalence of pathogenic bacteria in subgingival plaque showed increasing values of the parameters. The values of the parameters in Cluster 2a (C2a) having high prevalence of non-pathogenic bacteria were markedly lower than those in C1. A cluster having low prevalence of non-pathogenic bacteria in supragingival plaque showed increasing values of the parameters. The bacterial patterns between subgingival plaque and supragingival plaque were significantly correlated. Chief pathogens, such as Porphyromonas gingivalis, formed a network with other pathogenic species in C1, whereas a network of non-pathogenic species, such as Rothia sp. and Lautropia sp., tended to compete with a network of pathogenic species in C2a. Periodontal status relates to non-pathogenic species as well as to pathogenic species, suggesting that the bacterial interspecies connection affects dental plaque virulence.

  18. Clinical identification of bacteria in human chronic wound infections: culturing vs. 16S ribosomal DNA sequencing

    Directory of Open Access Journals (Sweden)

    Rhoads Daniel D

    2012-11-01

    Full Text Available Abstract Background Chronic wounds affect millions of people and cost billions of dollars in the United States each year. These wounds harbor polymicrobial biofilm communities, which can be difficult to elucidate using culturing methods. Clinical molecular microbiological methods are increasingly being employed to investigate the microbiota of chronic infections, including wounds, as part of standard patient care. However, molecular testing is more sensitive than culturing, which results in markedly different results being reported to clinicians. This study compares the results of aerobic culturing and molecular testing (culture-free 16S ribosomal DNA sequencing, and it examines the relative abundance score that is generated by the molecular test and the usefulness of the relative abundance score in predicting the likelihood that the same organism would be detected by culture. Methods Parallel samples from 51 chronic wounds were studied using aerobic culturing and 16S DNA sequencing for the identification of bacteria. Results One hundred forty-five (145 unique genera were identified using molecular methods, and 68 of these genera were aerotolerant. Fourteen (14 unique genera were identified using aerobic culture methods. One-third (31/92 of the cultures were determined to be Staphylococcus aureus, Pseudomonas aeruginosa, and Enterococcus faecalis with higher relative abundance scores were more likely to be detected by culture as demonstrated with regression modeling. Conclusion Discordance between molecular and culture testing is often observed. However, culture-free 16S ribosomal DNA sequencing and its relative abundance score can provide clinicians with insight into which bacteria are most abundant in a sample and which are most likely to be detected by culture.

  19. Swift Acetate Glial Assay (SAGA): an accelerated human ¹³C MRS brain exam for clinical diagnostic use.

    Science.gov (United States)

    Sailasuta, Napapon; Tran, Thao T; Harris, Kent C; Ross, B D

    2010-12-01

    We demonstrate a robust procedure for the quantitative characterization of glial metabolism in human brain. In the past, the slope of the uptake and production of enriched label at steady state were used to determine metabolic rates, requiring the patient to be in the magnet for 120-160 min. In the present method, (13)C cerebral metabolite profiles were acquired at steady state alone on a routine clinical MR scanner in 25.6 min. Results obtained from the new short method (SAGA) were comparable to those achieved in a conventional, long method and effective for determination of glial metabolic rate in posterior-parietal and frontal brain regions. Copyright © 2010 Elsevier Inc. All rights reserved.

  20. Human immunodeficiency virus type 1 quantitative cell microculture as a measure of antiviral efficacy in a multicenter clinical trial.

    Science.gov (United States)

    Fiscus, S A; DeGruttola, V; Gupta, P; Katzenstein, D A; Meyer, W A; LoFaro, M L; Katzman, M; Ragni, M V; Reichelderfer, P S; Coombs, R W

    1995-02-01

    A quantitative cell microculture assay (QMC) was used to measure the human immunodeficiency virus type 1 (HIV-1) peripheral blood mononuclear cell (PBMC)-associated titer in 109 subjects rolled in an open-label phase I/II study of didanosine monotherapy or combination therapy with zidovudine. The titer was inversely correlated with CD4+ cell count at baseline (r = .37, P = .001). After 12 weeks of therapy, subjects showed a significant decreases in virus titer and those with the highest baseline virus titers had the greatest increase in CD4+ cell number (r = .430, P = .002). The QMC assay was more sensitive (98%) for assessing the antiretroviral effect of therapy than was immune complex-dissociated HIV p24 antigen (32%) or plasma culture (3.4%). Estimated sample sizes for phase I/II clinical trials were derived using the within-subject QMC SD of .72 log10 infectious units per 10(6) PMBC.

  1. Human leukocyte antigen genetics and clinical features of self-treated patients on a gluten-free diet.

    Science.gov (United States)

    Coburn, John A; Vande Voort, Jennifer L; Lahr, Brian D; Van Dyke, Carol T; Kroning, Cynthia M; Wu, Tsung-Teh; Gandhi, Manish J; Murray, Joseph A

    2013-01-01

    Increasingly, people start a gluten-free diet (GFD) without a clear celiac disease (CD) diagnosis. Human leukocyte antigen (HLA) genotyping is useful in ruling out CD in patients with equivocal results of serologic testing or small-bowel biopsy (SBB), but its utility and the clinical features of patients on self-treated GFD (ST-GFD) are largely unknown. Retrospective study of single tertiary care center cohort compared 137 patients on ST-GFD and 443 patients with well-defined CD. We compared HLA genotype, symptoms, serologic and SBB results, and response to GFD between the 2 groups. Analysis used univariate logistic regression modeling, adjusted for age and sex. Patients with ST-GFD presented more often with diarrhea (Pgluten sensitivity may play a role.

  2. [Human trypanosomiasis focus of Vavoua (Ivory Coast). A clinical, parasitological and sero-immunological survey (author's transl)].

    Science.gov (United States)

    Duvallet, G; Stanghellini, A; Saccharin, C; Vivant, J F

    1979-01-01

    Vavoua human trypanosomiasis focus, located 60 km north of Daloa (Ivory Coast Republic) is facing a period of hyperactivity. A medical survey has been conducted in 9 villages of this focus: 7.424 persons have been examined and 128 new cases diagnosed in the field after clinical and parasitological examinations. Indirect Fluorescence Antibody Test applied to dried blood blots, in the laboratory, revealed 266 immunological suspects to be reexamined. 185 suspects were reexamined, 104 of whom were diagnosed after tyrpanosomes had been found in blood or/and in gland juice. The microhaematocrit centrifuge technique gave good results. Most of the 232 new cases were in the classical first period (unaltered CSF). Authors are insisting on the importance of survey prospections allowing an early diagnosis of sleeping sickness and on the interest of an immunodiagnostic test in addition to classical techniques to diagnose asymptomatical forms.

  3. An integrative clinical database and diagnostics platform for biomarker identification and analysis in ion mobility spectra of human exhaled air

    DEFF Research Database (Denmark)

    Schneider, Till; Hauschild, Anne-Christin; Baumbach, Jörg Ingo

    2013-01-01

    data integration and semi-automated data analysis, in particular with regard to the rapid data accumulation, emerging from the high-throughput nature of the MCC/IMS technology. Here, we present a comprehensive database application and analysis platform, which combines metabolic maps with heterogeneous...... biomedical data in a well-structured manner. The design of the database is based on a hybrid of the entity-attribute-value (EAV) model and the EAV-CR, which incorporates the concepts of classes and relationships. Additionally it offers an intuitive user interface that provides easy and quick access...... to have a clear understanding of the detailed composition of human breath. Therefore, in addition to the clinical studies, there is a need for a flexible and comprehensive centralized data repository, which is capable of gathering all kinds of related information. Moreover, there is a demand for automated...

  4. The ethics of withdrawal: the case of follow-up from first-in-human clinical trials.

    Science.gov (United States)

    Hug, Kristina; Johansson, Mats

    2017-01-01

    This paper aims to analyze whether patients should be allowed to veto research-related use of medical data collected during routine follow-ups after their withdrawal from first-in-human clinical trials. Forms of withdrawal are identified and it is argued that the right to withdraw might be limited to some of these. The paper concludes that if veto right is denied, then: the research participant should be informed about the potential use of his/her follow-up data in case of his/her withdrawal and consent to it; follow-up should not be initiated for research purposes; compulsory use of follow-up data should imply the use of data anyway collected, requiring no additional effort from the patient; and before deciding about the veto right, investigation of concerned patients' value preferences is needed.

  5. Clinical high-resolution mapping of the proteoglycan-bound water fraction in articular cartilage of the human knee joint.

    Science.gov (United States)

    Bouhrara, Mustapha; Reiter, David A; Sexton, Kyle W; Bergeron, Christopher M; Zukley, Linda M; Spencer, Richard G

    2017-11-01

    We applied our recently introduced Bayesian analytic method to achieve clinically-feasible in-vivo mapping of the proteoglycan water fraction (PgWF) of human knee cartilage with improved spatial resolution and stability as compared to existing methods. Multicomponent driven equilibrium single-pulse observation of T 1 and T 2 (mcDESPOT) datasets were acquired from the knees of two healthy young subjects and one older subject with previous knee injury. Each dataset was processed using Bayesian Monte Carlo (BMC) analysis incorporating a two-component tissue model. We assessed the performance and reproducibility of BMC and of the conventional analysis of stochastic region contraction (SRC) in the estimation of PgWF. Stability of the BMC analysis of PgWF was tested by comparing independent high-resolution (HR) datasets from each of the two young subjects. Unlike SRC, the BMC-derived maps from the two HR datasets were essentially identical. Furthermore, SRC maps showed substantial random variation in estimated PgWF, and mean values that differed from those obtained using BMC. In addition, PgWF maps derived from conventional low-resolution (LR) datasets exhibited partial volume and magnetic susceptibility effects. These artifacts were absent in HR PgWF images. Finally, our analysis showed regional variation in PgWF estimates, and substantially higher values in the younger subjects as compared to the older subject. BMC-mcDESPOT permits HR in-vivo mapping of PgWF in human knee cartilage in a clinically-feasible acquisition time. HR mapping reduces the impact of partial volume and magnetic susceptibility artifacts compared to LR mapping. Finally, BMC-mcDESPOT demonstrated excellent reproducibility in the determination of PgWF. Published by Elsevier Inc.

  6. Autoreactive T Cells in Human Smokers Is Predictive of Clinical Outcome

    Directory of Open Access Journals (Sweden)

    Chuang eXu

    2012-08-01

    Full Text Available Cross-sectional studies have suggested a role for activation of adaptive immunity in smokers with emphysema, but the clinical application of these findings has not been explored. Here we examined the utility of detecting autoreactive T cells as a screening tool for emphysema in an at-risk population of smokers. We followed 156 former and current (ever-smokers for two years to assess whether peripheral blood CD4 T cell cytokine responses to lung elastin fragments (EFs could discriminate between those with and without emphysema, and to evaluate the relevance of autoreactive T cells to predict changes during follow-up in lung physiological parameters. Volunteers underwent baseline complete phenotypic assessment with pulmonary function tests, quantitative chest CT, yearly six minutes walk distance (6MWD testing, and annual measurement of CD4 T cell cytokine responses to EFs. The areas under the receiver operating characteristic curve to predict emphysema for interferon gamma (IFN-γ, and interleukin 6 (IL-6 responses to EFs were 0.81 (95% CI of 0.74 to 0.88 and 0.79 (95% CI of 0.72 to 0.86 respectively. We developed a dual cytokine enzyme-linked immunocell spot assay, the γ-6 Spot, using CD4 T cell IFN-γ and IL-6 responses and found that it discriminated emphysema with 90% sensitivity. After adjusting for potential confounders, the presence of autoreactive T cells was predictive of a decrease in 6MWD over two years (decline in 6MWD, -19 meters (m per fold change in IFN-γ; P=0.026, and -26 m per fold change in IL-6; P=0.003. These findings collectively suggest that the EF specific autoreactive CD4 T cell assay, γ-6 Spot, could provide a non-invasive diagnostic tool with potential application to large-scale screening to discriminate emphysema in ever-smokers, and predict early relevant physiological outcomes in those at risk.

  7. [Clinical effect of three dimensional human body scanning system BurnCalc in the evaluation of burn wound area].

    Science.gov (United States)

    Lu, J; Wang, L; Zhang, Y C; Tang, H T; Xia, Z F

    2017-10-20

    Objective: To validate the clinical effect of three dimensional human body scanning system BurnCalc developed by our research team in the evaluation of burn wound area. Methods: A total of 48 burn patients treated in the outpatient department of our unit from January to June 2015, conforming to the study criteria, were enrolled in. For the first 12 patients, one wound on the limbs or torso was selected from each patient. The stability of the system was tested by 3 attending physicians using three dimensional human body scanning system BurnCalc to measure the area of wounds individually. For the following 36 patients, one wound was selected from each patient, including 12 wounds on limbs, front torso, and side torso, respectively. The area of wounds was measured by the same attending physician using transparency tracing method, National Institutes of Health (NIH) Image J method, and three dimensional human body scanning system BurnCalc, respectively. The time for getting information of 36 wounds by three methods was recorded by stopwatch. The stability among the testers was evaluated by the intra-class correlation coefficient (ICC). Data were processed with randomized blocks analysis of variance and Bonferroni test. Results: (1) Wound area of patients measured by three physicians using three dimensional human body scanning system BurnCalc was (122±95), (121±95), and (123±96) cm(2,) respectively, and there was no statistically significant difference among them ( F =1.55, P >0.05). The ICC among 3 physicians was 0.999. (2) The wound area of limbs of patients measured by transparency tracing method, NIH Image J method, and three dimensional human body scanning system BurnCalc was (84±50), (76±46), and (84±49) cm(2,) respectively. There was no statistically significant difference in the wound area of limbs of patients measured by transparency tracing method and three dimensional human body scanning system BurnCalc ( P >0.05). The wound area of limbs of patients

  8. Human-Mouse Dosimetry in Clinical Radioimmunotherapy - Special Emphasis on Pediatric Applications

    International Nuclear Information System (INIS)

    Kairemo, K.J.A.; Pyyry, J.; Heiskanen, T.; Flux, G.; Fisher, D.R.

    2009-01-01

    Monoclonal antibody ('MAB') has been developed for targeting secretory alpha-fetoprotein in hepatic tissue. We have used these MABs for radioimmunotherapy and dose planning of recurrent hepatoblastoma, a rare childhood malignancy This MAB has been labelled with In- 111 and Y-90 for clinical purposes, and can be applied for diagnosis and therapy of liver neoplasms. Physiology based pharmacokinetic (PBPK) modeling and simulation is a useful method for prediction of biodistribution of macromolecules, it can enhance our understanding of the underlying mechanisms and hence may help in rational design of diagnostic and therapeutic agents. Here we also discuss PBPK modeling and simulation of this MAB in mice without tumor and in a pediatric patient. In the clinical study, radiopharmacokinetic parameters for this MAB ( 111 In-DOTA-hAFP31 IgG) were calculated after serial quantitative whole body scans in a child with hepatoblastoma. A 3-D dose planning computer program was used to calculate tumor doses for In-111 and Y-90, the active tumor was delineated on PET/CT images and tumor dose calculation was done based on the In-111-MAB SPECT data using dose point kernel approach both for In-111 and Y-90. The results were compared with MIRD doses obtained for organs in SPECT imaging field, i.e. bone marrow, heart, kidneys, liver, spleen, lungs. The simulated results were fitted to experimental time series data by varying parameters which were not fixed a priori. From quantitative serial imaging based on 8 whole body images at 0-168 hrs using In-111- MAB, the half-lives of spleen, lungs, kidneys and whole body were 502 hrs, 230 hrs, 193 hrs and 490 hrs, respectively. The measured blood half-life was 132 hrs, after a total MAB dose of 50 mg and In-111 activity of 105 MBq. The presumed Y-90 dose based on this kinetic behavior was 43 MBq which should had given 0.3Gy bone marrow dose with assumption of bone marrow: blood ratio 0.4 for IgG. The calculated MIRD Y-90 doses were for

  9. [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

  10. Clinically Detectable Dental Identifiers Observed in Intra-oral Photographs and Extra-oral Radiographs, Validated for Human Identification Purposes.

    Science.gov (United States)

    Angelakopoulos, Nikolaos; Franco, Ademir; Willems, Guy; Fieuws, Steffen; Thevissen, Patrick

    2017-07-01

    Screening the prevalence and pattern of dental identifiers contributes toward the process of human identification. This research investigated the uniqueness of clinical dental identifiers in photographs and radiographs. Panoramic and lateral cephalometric radiographs and five intra-oral photographs of 1727 subjects were used. In a target set, two observers examined different subjects. In a subset, both observers examined the same subjects (source set). The distance between source and target subjects was quantified for each identifier. The percentage of subjects in the target set being at least as close as the correct subject was assessed. The number of molars (34.6%), missing teeth (42%), and displaced teeth (59.9%) were the most unique identifiers in photographs and panoramic and lateral cephalometric radiographs, respectively. The pattern of rotated teeth (14.9%) was the most unique in photographs, while displaced teeth was in panoramic (37.6%) and lateral cephalometric (54.8%) radiographs. Morphological identifiers were the most unique, highlighting their importance for human identifications. © 2016 American Academy of Forensic Sciences.

  11. Clinical pathophysiology of human T-lymphotropic virus-type1-associated myelopathy/tropical spastic paraparesis

    Directory of Open Access Journals (Sweden)

    Yoshihisa eYamano

    2012-11-01

    Full Text Available Human T-lymphotropic virus type 1 (HTLV-1, a human retrovirus, is the causative agent of a progressive neurological disease termed HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP. HAM/TSP is a chronic inflammatory disease of the central nervous system and is characterized by unremitting myelopathic symptoms such as spastic paraparesis, lower limb sensory disturbance, and bladder/bowel dysfunction. Approximately 0.25%–3.8% of HTLV-1-infected individuals develop HAM/TSP, which is more common in women than in men. Since the discovery of HAM/TSP, significant advances have been made with respect to elucidating the virological, molecular, and immunopathological mechanisms underlying this disease. These findings suggest that spinal cord invasion by HTLV-1-infected T cells triggers a strong virus-specific immune response and increases proinflammatory cytokine and chemokine production, leading to chronic lymphocytic inflammation and tissue damage in spinal cord lesions. However, little progress has been made in the development of an optimal treatment for HAM/TSP, more specifically in the identification of biomarkers for predicting disease progression and of molecular targets for novel therapeutic strategies targeting the underlying pathological mechanisms. This review summarizes current clinical and pathophysiological knowledge on HAM/TSP and discusses future focus areas for research on this disease.

  12. Quantitative Clinical Diagnostic Analysis of Acetone in Human Blood by HPLC: A Metabolomic Search for Acetone as Indicator

    Directory of Open Access Journals (Sweden)

    Esin Akgul Kalkan

    2016-01-01

    Full Text Available Using high-performance liquid chromatography (HPLC and 2,4-dinitrophenylhydrazine (2,4-DNPH as a derivatizing reagent, an analytical method was developed for the quantitative determination of acetone in human blood. The determination was carried out at 365 nm using an ultraviolet-visible (UV-Vis diode array detector (DAD. For acetone as its 2,4-dinitrophenylhydrazone derivative, a good separation was achieved with a ThermoAcclaim C18 column (15 cm × 4.6 mm × 3 μm at retention time (tR 12.10 min and flowrate of 1 mL min−1 using a (methanol/acetonitrile water elution gradient. The methodology is simple, rapid, sensitive, and of low cost, exhibits good reproducibility, and allows the analysis of acetone in biological fluids. A calibration curve was obtained for acetone using its standard solutions in acetonitrile. Quantitative analysis of acetone in human blood was successfully carried out using this calibration graph. The applied method was validated in parameters of linearity, limit of detection and quantification, accuracy, and precision. We also present acetone as a useful tool for the HPLC-based metabolomic investigation of endogenous metabolism and quantitative clinical diagnostic analysis.

  13. Derivation of xeno-free and GMP-grade human embryonic stem cells--platforms for future clinical applications.

    Directory of Open Access Journals (Sweden)

    Shelly E Tannenbaum

    Full Text Available Clinically compliant human embryonic stem cells (hESCs should be developed in adherence to ethical standards, without risk of contamination by adventitious agents. Here we developed for the first time animal-component free and good manufacturing practice (GMP-compliant hESCs. After vendor and raw material qualification, we derived xeno-free, GMP-grade feeders from umbilical cord tissue, and utilized them within a novel, xeno-free hESC culture system. We derived and characterized three hESC lines in adherence to regulations for embryo procurement, and good tissue, manufacturing and laboratory practices. To minimize freezing and thawing, we continuously expanded the lines from initial outgrowths and samples were cryopreserved as early stocks and banks. Batch release criteria included DNA-fingerprinting and HLA-typing for identity, characterization of pluripotency-associated marker expression, proliferation, karyotyping and differentiation in-vitro and in-vivo. These hESCs may be valuable for regenerative therapy. The ethical, scientific and regulatory methodology presented here may serve for development of additional clinical-grade hESCs.

  14. Serum Cytokine Responses over the Entire Clinical-Immunological Spectrum of Human Leishmania (L. infantum chagasi Infection

    Directory of Open Access Journals (Sweden)

    Patrícia Karla Ramos

    2016-01-01

    Full Text Available The clinical-immunological spectrum of human Leishmania (L. infantum chagasi infection in Amazonian Brazil was recently reviewed based on clinical, DTH, and IFAT (IgG evaluations that identified five profiles: three asymptomatic (asymptomatic infection, AI; subclinical resistant infection, SRI; and indeterminate initial infection, III and two symptomatic (symptomatic infection, SI; American visceral leishmaniasis, AVL; and subclinical oligosymptomatic infection, SOI. TNF-α, IL-4, IL-6, and IL-10 serum cytokines were analyzed using multiplexed Cytometric Bead Array in 161 samples from endemic areas in the Brazilian Amazon: SI [AVL] (21 cases, III (49, SRI (19, SOI (12, AI (36, and a control group [CG] (24. The highest IL-6 serum levels were observed in the SI profile (AVL; higher IL-10 serum levels were observed in SI than in SOI or CG and in AI and III than in SOI; higher TNF-α serum levels were seen in SI than in CG. Positive correlations were found between IL-6 and IL-10 serum levels in the SI and III profiles and between IL-6 and TNF-α and between IL-4 and TNF-α in the III profile. These results provide strong evidence for associating IL-6 and IL-10 with the immunopathogenesis of AVL and help clarify the role of these cytokines in the infection spectrum.

  15. Human serum and platelet lysate are appropriate xeno-free alternatives for clinical-grade production of human MuStem cell batches.

    Science.gov (United States)

    Saury, Charlotte; Lardenois, Aurélie; Schleder, Cindy; Leroux, Isabelle; Lieubeau, Blandine; David, Laurent; Charrier, Marine; Guével, Laëtitia; Viau, Sabrina; Delorme, Bruno; Rouger, Karl

    2018-05-02

    Canine MuStem cells have demonstrated regenerative efficacy in a dog model of muscular dystrophy, and the recent characterization of human counterparts (hMuStem) has highlighted the therapeutic potential of this muscle-derived stem cell population. To date, these cells have only been generated in research-grade conditions. However, evaluation of the clinical efficacy of any such therapy will require the production of hMuStem cells in compliance with good manufacturing practices (GMPs). Because the current use of fetal bovine serum (FBS) to isolate and expand hMuStem cells raises several ethical, safety, and supply concerns, we assessed the use of two alternative xeno-free blood derivatives: human serum (HS) and a human platelet lysate (hPL). hMuStem cells were isolated and expanded in vitro in either HS-supplemented or hPL-supplemented media and the proliferation rate, clonogenicity, myogenic commitment potential, and oligopotency compared with that observed in FBS-supplemented medium. Flow cytometry and high-throughput 3'-digital gene expression RNA sequencing were used to characterize the phenotype and global gene expression pattern of hMuStem cells cultured with HS or hPL. HS-supplemented and hPL-supplemented media both supported the isolation and long-term proliferation of hMuStem cells. Compared with FBS-based medium, both supplements enhanced clonogenicity and allowed for a reduction in growth factor supplementation. Neither supplement altered the cell lineage pattern of hMuStem cells. In vitro differentiation assays revealed a decrease in myogenic commitment and in the fusion ability of hMuStem cells when cultured with hPL. In return, this reduction of myogenic potential in hPL-supplemented cultures was rapidly reversed by substitution of hPL with HS or fibrinogen-depleted hPL. Moreover, culture of hMuStem cells in hPL hydrogel and fibrinogen-depleted hPL demonstrated that myogenic differentiation potential is maintained in heparin-free hPL derivatives. Our

  16. An Integrative Clinical Database and Diagnostics Platform for Biomarker Identification and Analysis in Ion Mobility Spectra of Human Exhaled Air

    Directory of Open Access Journals (Sweden)

    Schneider Till

    2013-06-01

    Full Text Available Over the last decade the evaluation of odors and vapors in human breath has gained more and more attention, particularly in the diagnostics of pulmonary diseases. Ion mobility spectrometry coupled with multi-capillary columns (MCC/IMS, is a well known technology for detecting volatile organic compounds (VOCs in air. It is a comparatively inexpensive, non-invasive, high-throughput method, which is able to handle the moisture that comes with human exhaled air, and allows for characterizing of VOCs in very low concentrations. To identify discriminating compounds as biomarkers, it is necessary to have a clear understanding of the detailed composition of human breath. Therefore, in addition to the clinical studies, there is a need for a flexible and comprehensive centralized data repository, which is capable of gathering all kinds of related information. Moreover, there is a demand for automated data integration and semi-automated data analysis, in particular with regard to the rapid data accumulation, emerging from the high-throughput nature of the MCC/IMS technology. Here, we present a comprehensive database application and analysis platform, which combines metabolic maps with heterogeneous biomedical data in a well-structured manner. The design of the database is based on a hybrid of the entity-attribute- value (EAV model and the EAV-CR, which incorporates the concepts of classes and relationships. Additionally it offers an intuitive user interface that provides easy and quick access to the platform’s functionality: automated data integration and integrity validation, versioning and roll-back strategy, data retrieval as well as semi-automatic data mining and machine learning capabilities. The platform will support MCC/IMS-based biomarker identification and validation. The software, schemata, data sets and further information is publicly available at http://imsdb.mpi-inf.mpg.de.

  17. Crestal Sinus Augmentation with Recombinant Human Bone Morphogenetic Protein 2: Clinical and Radiographic Outcomes of 2-Year Pilot Trial.

    Science.gov (United States)

    Kuchler, Ulrike; Rudelstorfer, Claudia M; Barth, Barbara; Tepper, Gabor; Lidinsky, Dominika; Heimel, Patrick; Watzek, Georg; Gruber, Reinhard

    Recombinant human bone morphogenetic protein 2 (rhBMP-2) together with an absorbable collagen carrier (ACS) was approved for augmentation of the maxillary sinus prior to implant placement. The original registration trial was based on a lateral window approach. Clinical outcomes of crestal sinus augmentation with rhBMP-2 have not been reported so far. An uncontrolled pilot trial in which seven patients with a residual maxillary height below 5 mm were enrolled to receive crestal sinus augmentation with rhBMP-2/ACS was conducted. Elevation of the sinus mucosa was performed by gel pressure. Primary endpoints were the gain in augmentation height and volume measured by computed tomography after 6 months. Evaluation of bone quality at the time of implant placement was based on histology. Secondary endpoints were the clinical and radiologic evaluation of the implants and patient satisfaction by visual analog scale (VAS) at the 2-year follow-up. Median gain in augmentation height was 7.2 mm (range 0.0 to 17.5 mm). Five patients gained at least 5 mm of bone height. Two patients with a perforation of the sinus mucosa failed to respond to rhBMP-2/ACS and underwent lateral window augmentation. The median gain in augmentation volume of the five patients was 781.3 mm³ (range 426.9 to 1,242.8 mm³). Biopsy specimens showed a cancellous network consisting of primary plexiform bone with little secondary lamellar bone. After 2 years, implants were in function with no signs of inflammation or peri-implant bone loss. Patients were satisfied with the esthetic outcomes and chewing function. This pilot clinical trial supports the original concept that rhBMP-2/ACS supports bone formation, also in crestal sinus augmentation, and emphasizes the relevance of the integrity of the sinus mucosa to predict the bone gain.

  18. A HUMANIZED CLINICALLY CALIBRATED QUANTITATIVE SYSTEMS PHARMACOLOGY MODEL FOR HYPOKINETIC MOTOR SYMPTOMS IN PARKINSON’S DISEASE

    Directory of Open Access Journals (Sweden)

    Hugo eGeerts

    2016-02-01

    Full Text Available The current treatment of Parkinson’s disease with dopamine-centric approaches such as L-DOPA and dopamine agonists, although very succesfull, is in need of alternative treatment strategies, both in terms of disease modification and symptom management. Various non-dopaminergic treatment approaches did not result in a clear clinical benefit, despite showing a clear effect in preclinical animal models. In addition, polypharmacy is common, sometimes leading to unintended effects on non-motor symptoms such as in cognitive and psychiatric domains. To explore novel targets for symptomatic treatment and possible synergistic pharmacodynamic effects between different drugs, we developed a Quantitative Systems Pharmacology (QSP platform of the closed cortico-striatal-thalamic-cortical basal ganglia loop of the dorsal motor circuit. This mechanism-based simulation platform is based on the known neuro-anatomy and neurophysiology of the basal ganglia and explicitly incorporates domain expertise in a formalized way. The calculated beta/gamma power ratio of the local field potential in the subthalamic nucleus correlates well (R2=0.71 with clinically observed extra-pyramidal symptoms triggered by antipsychotics during schizophrenia treatment (43 drug-dose combinations. When incorporating Parkinsonian (PD pathology and reported compensatory changes, the computer model suggests a major increase in b/g ratio (corresponding to bradykinesia and rigidity from a dopamine depletion of 70% onwards. The correlation between the outcome of the QSP model and the reported changes in UPDRS III Motor Part for 22 placebo-normalized drug-dose combinations is R2=0.84. The model also correctly recapitulates the lack of clinical benefit for perampanel, MK-0567 and flupirtine and offers a hypothesis for the translational disconnect. Finally, using human PET imaging studies with placebo response, the computer model predicts well the placebo response for chronic treatment, but not

  19. Human Flt3L generates dendritic cells from canine peripheral blood precursors: implications for a dog glioma clinical trial.

    Directory of Open Access Journals (Sweden)

    Weidong Xiong

    2010-06-01

    Full Text Available Glioblastoma multiforme (GBM is the most common primary brain tumor in adults and carries a dismal prognosis. We have developed a conditional cytotoxic/immunotherapeutic approach using adenoviral vectors (Ads encoding the immunostimulatory cytokine, human soluble fms-like tyrosine kinase 3 ligand (hsFlt3L and the conditional cytotoxic molecule, i.e., Herpes Simplex Type 1- thymide kinase (TK. This therapy triggers an anti-tumor immune response that leads to tumor regression and anti-tumor immunological memory in intracranial rodent cancer models. We aim to test the efficacy of this immunotherapy in dogs bearing spontaneous GBM. In view of the controversy regarding the effect of human cytokines on dog immune cells, and considering that the efficacy of this treatment depends on hsFlt3L-stimulated dendritic cells (DCs, in the present work we tested the ability of Ad-encoded hsFlt3L to generate DCs from dog peripheral blood and compared its effects with canine IL-4 and GM-CSF.Our results demonstrate that hsFlT3L expressed form an Ad vector, generated DCs from peripheral blood cultures with very similar morphological and phenotypic characteristics to canine IL-4 and GM-CSF-cultured DCs. These include phagocytic activity and expression of CD11c, MHCII, CD80 and CD14. Maturation of DCs cultured under both conditions resulted in increased secretion of IL-6, TNF-alpha and IFN-gamma. Importantly, hsFlt3L-derived antigen presenting cells showed allostimulatory potential highlighting their ability to present antigen to T cells and elicit their proliferation.These results demonstrate that hsFlt3L induces the proliferation of canine DCs and support its use in upcoming clinical trials for canine GBM. Our data further support the translation of hsFlt3L to be used for dendritic cells' vaccination and gene therapeutic approaches from rodent models to canine patients and its future implementation in human clinical trials.

  20. 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.

  1. [Corynebacterium imitans isolated from blood culture in a patient with suspected bacteremia - the first isolation from human clinical material in the Czech Republic].

    Science.gov (United States)

    JeŽek, Petr; Zavadilová, Jana; Kolínská, Renáta; Švec, Pavel; Guttwirth, Jiří; Petráš, Petr

    2014-09-01

    The current view of the clinical importance of nondiphtherial corynebacteria recovered from human clinical material has changed considerably in recent decades; in many cases, a direct etiological role is assumed or has already been demonstrated. Presented is a case of suspected bacteremia in a hospitalized elderly woman with isolation of the very rare species Corynebacterium imitans from blood culture. However, the etiological significance of the isolated microorganism remains unclear. The aim was not to demonstrate the etiological significance of the isolated C. imitans strain but to report the occurrence of this very rare species which is considered to be the first isolation from humans in the Czech Republic.

  2. Initial clinical trial of epratuzumab (humanized anti-CD22 antibody) for immunotherapy of systemic lupus erythematosus.

    Science.gov (United States)

    Dörner, Thomas; Kaufmann, Joerg; Wegener, William A; Teoh, Nick; Goldenberg, David M; Burmester, Gerd R

    2006-01-01

    B cells play an important role in the pathogenesis of systemic lupus erythematosus (SLE), so the safety and activity of anti-B cell immunotherapy with the humanized anti-CD22 antibody epratuzumab was evaluated in SLE patients. An open-label, single-center study of 14 patients with moderately active SLE (total British Isles Lupus Assessment Group (BILAG) score 6 to 12) was conducted. Patients received 360 mg/m2 epratuzumab intravenously every 2 weeks for 4 doses with analgesic/antihistamine premedication (but no steroids) prior to each dose. Evaluations at 6, 10, 18 and 32 weeks (6 months post-treatment) follow-up included safety, SLE activity (BILAG score), blood levels of epratuzumab, B and T cells, immunoglobulins, and human anti-epratuzumab antibody (HAHA) titers. Total BILAG scores decreased by > or = 50% in all 14 patients at some point during the study (including 77% with a > or = 50% decrease at 6 weeks), with 92% having decreases of various amounts continuing to at least 18 weeks (where 38% showed a >/= 50% decrease). Almost all patients (93%) experienced improvements in at least one BILAG B- or C-level disease activity at 6, 10 and 18 weeks. Additionally, 3 patients with multiple BILAG B involvement at baseline had completely resolved all B-level disease activities by 18 weeks. Epratuzumab was well tolerated, with a median infusion time of 32 minutes. Drug serum levels were measurable for at least 4 weeks post-treatment and detectable in most samples at 18 weeks. B cell levels decreased by an average of 35% at 18 weeks and remained depressed at 6 months post-treatment. Changes in routine safety laboratory tests were infrequent and without any consistent pattern, and there was no evidence of immunogenicity or significant changes in T cells, immunoglobulins, or autoantibody levels. In patients with mild to moderate active lupus, 360 mg/m2 epratuzumab was well tolerated, with evidence of clinical improvement after the first infusion and durable clinical

  3. Intramacrophage survival of uropathogenic Escherichia coli: Differences between diverse clinical isolates and between mouse and human macrophages

    KAUST Repository

    Bokil, Nilesh J.

    2011-11-01

    Uropathogenic E. coli (UPEC) are the primary cause of urinary tract infections. Recent studies have demonstrated that UPEC can invade and replicate within epithelial cells, suggesting that this bacterial pathogen may occupy an intracellular niche within the host. Given that many intracellular pathogens target macrophages, we assessed the interactions between UPEC and macrophages. Colonization of the mouse bladder by UPEC strain CFT073 resulted in increased expression of myeloid-restricted genes, consistent with the recruitment of inflammatory macrophages to the site of infection. In in vitro assays, CFT073 was able to survive within primary mouse bone marrow-derived macrophages (BMM) up to 24h post-infection. Three additional well-characterized clinical UPEC isolates associated with distinct UTI symptomatologies displayed variable long-term survival within BMM. UPEC strains UTI89 and VR50, originally isolated from patients with cystitis and asymptomatic bacteriuria respectively, showed elevated bacterial loads in BMM at 24h post-infection as compared to CFT073 and the asymptomatic bacteriuria strain 83972. These differences did not correlate with differential effects on macrophage survival or initial uptake of bacteria. E. coli UTI89 localized to a Lamp1 + vesicular compartment within BMM. In contrast to survival within mouse BMM, intracellular bacterial loads of VR50 were low in both human monocyte-derived macrophages (HMDM) and in human T24 bladder epithelial cells. Collectively, these data suggest that some UPEC isolates may subvert macrophage anti-microbial pathways, and that host species differences may impact on intracellular UPEC survival. © 2011 Elsevier GmbH.

  4. Randomized, double-blinded clinical trial for human norovirus inactivation in oysters by high hydrostatic pressure processing.

    Science.gov (United States)

    Leon, Juan S; Kingsley, David H; Montes, Julia S; Richards, Gary P; Lyon, G Marshall; Abdulhafid, Gwen M; Seitz, Scot R; Fernandez, Marina L; Teunis, Peter F; Flick, George J; Moe, Christine L

    2011-08-01

    Contamination of oysters with human noroviruses (HuNoV) constitutes a human health risk and may lead to severe economic losses in the shellfish industry. There is a need to identify a technology that can inactivate HuNoV in oysters. In this study, we conducted a randomized, double-blinded clinical trial to assess the effect of high hydrostatic pressure processing (HPP) on Norwalk virus (HuNoV genogroup I.1) inactivation in virus-seeded oysters ingested by subjects. Forty-four healthy, positive-secretor adults were divided into three study phases. Subjects in each phase were randomized into control and intervention groups. Subjects received Norwalk virus (8FIIb, 1.0 × 10(4) genomic equivalent copies) in artificially seeded oysters with or without HPP treatment (400 MPa at 25°C, 600 MPa at 6°C, or 400 MPa at 6°C for 5 min). HPP at 600 MPa, but not 400 MPa (at 6° or 25°C), completely inactivated HuNoV in seeded oysters and resulted in no HuNoV infection among these subjects, as determined by reverse transcription-PCR detection of HuNoV RNA in subjects' stool or vomitus samples. Interestingly, a white blood cell (granulocyte) shift was identified in 92% of the infected subjects and was significantly associated with infection (P = 0.0014). In summary, these data suggest that HPP is effective at inactivating HuNoV in contaminated whole oysters and suggest a potential intervention to inactivate infectious HuNoV in oysters for the commercial shellfish industry.

  5. Clinical, radiographic, and histological observation of a human immature permanent tooth with chronic apical abscess after revitalization treatment.

    Science.gov (United States)

    Shimizu, Emi; Ricucci, Domenico; Albert, Jeffrey; Alobaid, Adel S; Gibbs, Jennifer L; Huang, George T-J; Lin, Louis M

    2013-08-01

    Revitalization procedures have been widely used for the treatment of immature permanent teeth with apical periodontitis. The treatment procedures appear to be capable of encouraging continued root development and thickening of the canal walls. The nature of tissues formed in the canal space and at the root apex after revitalization has been shown histologically in several animal studies; similar studies in humans were recently reported. A 9-year-old boy had a traumatic injury to his upper anterior teeth. Tooth #9 suffered a complicated crown fracture with a pulp exposure, which was restored with a composite resin. The tooth developed a chronic apical abscess. Revitalization procedures were performed on tooth #9 because it was an immature permanent tooth with an open apex and thin canal walls. Twenty-six months after revitalization, the tooth had a horizontal crown fracture at the cervical level and could not be restored. The tooth was extracted and processed for routine histological and immunohistochemical examination to identify the nature of tissues formed in the canal space. Clinically and radiographically, the revitalization of the present case was successful because of the absence of signs and symptoms and the resolution of periapical lesion as well as thickening of the canal walls and continued root development. The tissue formed in the canal was well-mineralized cementum- or bone-like tissue identified by routine histology and immunohistochemistry. No pulp-like tissue characterized by the presence of polarized odontoblast-like cells aligning dentin-like hard tissue was observed. The tissues formed in the canal of revitalized human tooth are similar to cementum- or bone-like tissue and fibrous connective tissue. Copyright © 2013 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  6. An externally head-mounted wireless neural recording device for laboratory animal research and possible human clinical use.

    Science.gov (United States)

    Yin, Ming; Li, Hao; Bull, Christopher; Borton, David A; Aceros, Juan; Larson, Lawrence; Nurmikko, Arto V

    2013-01-01

    In this paper we present a new type of head-mounted wireless neural recording device in a highly compact package, dedicated for untethered laboratory animal research and designed for future mobile human clinical use. The device, which takes its input from an array of intracortical microelectrode arrays (MEA) has ninety-seven broadband parallel neural recording channels and was integrated on to two custom designed printed circuit boards. These house several low power, custom integrated circuits, including a preamplifier ASIC, a controller ASIC, plus two SAR ADCs, a 3-axis accelerometer, a 48MHz clock source, and a Manchester encoder. Another ultralow power RF chip supports an OOK transmitter with the center frequency tunable from 3GHz to 4GHz, mounted on a separate low loss dielectric board together with a 3V LDO, with output fed to a UWB chip antenna. The IC boards were interconnected and packaged in a polyether ether ketone (PEEK) enclosure which is compatible with both animal and human use (e.g. sterilizable). The entire system consumes 17mA from a 1.2Ahr 3.6V Li-SOCl2 1/2AA battery, which operates the device for more than 2 days. The overall system includes a custom RF receiver electronics which are designed to directly interface with any number of commercial (or custom) neural signal processors for multi-channel broadband neural recording. Bench-top measurements and in vivo testing of the device in rhesus macaques are presented to demonstrate the performance of the wireless neural interface.

  7. Suitable reference genes for real-time PCR in human HBV-related hepatocellular carcinoma with different clinical prognoses

    International Nuclear Information System (INIS)

    Fu, Li-Yun; Jia, Hu-Liang; Dong, Qiong-Zhu; Wu, Jin-Cai; Zhao, Yue; Zhou, Hai-Jun; Ren, Ning; Ye, Qin-Hai; Qin, Lun-Xiu

    2009-01-01

    Housekeeping genes are routinely used as endogenous references to account for experimental differences in gene expression assays. However, recent reports show that they could be de-regulated in different diseases, model animals, or even under varied experimental conditions, which may lead to unreliable results and consequently misinterpretations. This study focused on the selection of suitable reference genes for quantitative PCR in human hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) with different clinical outcomes. We evaluated 6 commonly used housekeeping genes' expression levels in 108 HBV-related HCCs' matched tumor and non-tomor tissue samples with different clinical outcomes and 26 normal liver specimens by real-time PCR. The expression stability of the 6 genes was compared using the software programs geNorm and NormFinder. To show the impact of reference genes on data analysis, we took PGK1 as a target gene normalized by each reference gene, and performed one-way ANOVA and the equivalence test. With the geNorm and NormFinder software programs, analysis of TBP and HPRT1 showed the best stability in all tissue samples, while 18s and ACTB were less stable. When 18s or ACTB was used for normalization, no significant difference of PGK1 expression (p > 0.05) was found among HCC tissues with and without metastasis, and normal liver specimens; however, dramatically differences (p < 0.001) were observed when either TBP or the combination of TBP and HPRT1 were selected as reference genes. TBP and HPRT1 are the most reliable reference genes for q-PCR normalization in HBV-related HCC specimens. However, the well-used ACTB and 18S are not suitable, which actually lead to the misinterpretation of the results in gene expression analysis

  8. [Relationship between viral load of human bocavirus and clinical characteristics in children with acute lower respiratory tract infection].

    Science.gov (United States)

    Ding, Xiao-Fang; Zhang, Bing; Zhong, Li-Li; Xie, Le-Yun; Xiao, Ni-Guang

    2017-03-01

    To investigate the prevalence of human bocavirus (HBoV) in children with acute lower respiratory tract infection and to explore the relationship between the viral load of HBoV and the clinical characteristics of acute lower respiratory tract infection in children. A total of 1 554 nasopharyngeal aspirates from children who were hospitalized due to acute lower respiratory tract infection between March 2011 and March 2014 were collected. Quantitative real-time PCR was used to detect 12 RNA and 2 DNA viruses, adenovirus (ADV) and HBoV, and to measure the viral load of HBoV in HBoV-positive children. A comprehensive analysis was performed with reference to clinical symptoms and indicators. In the 1 554 specimens, 1 212 (77.99%) were positive for viruses, and 275 (17.70%) were HBoV-positive. In HBoV-positive cases, 94.9% were aged infection, and 230 (83.64%) had mixed infection. There was no significant difference in viral load between children with single infection and mixed infection (P>0.05). The patients with fever had a significantly higher viral load than those without fever (Pacute lower respiratory tract infection (P>0.05). HBoV is one of the important pathogens of acute lower respiratory tract infection in children. Children with a higher viral load of HBoV are more likely to experience symptoms such as fever and wheezing. However, the severity of disease and mixed infection are not significantly related to viral load.

  9. Absence of Decline of Kidney Function in Human Immunodeficiency Virus-Infected Patients Under Routine Clinical Management.

    Science.gov (United States)

    Boucquemont, Julie; Lawson-Ayayi, Sylvie; Rigothier, Claire; Bonnet, Fabrice; Proust-Lima, Cécile; Neau, Didier; Greib, Carine; Miremont-Salamé, Ghada; Dabis, François; Dupon, Michel; Dauchy, Frédéric-Antoine

    2017-01-01

    Since the introduction of antiretroviral therapy (ART), human immunodeficiency virus (HIV)-infected patients have a drastically improved prognosis but at the same time they are also more affected by non-HIV related complications, such as chronic kidney disease. The objective of our study was to investigate the effect of proteinuria and tenofovir (TDF)-containing ART regimens on the temporal evolution of estimated glomerular filtration rate (eGFR). Between April 2008 and October 2012, we enrolled 395 patients with a complete renal evaluation among patients from the ANRS C03 Aquitaine cohort, a prospective hospital-based cohort of HIV-1-infected patients under routine clinical management in southwestern France. eGFR was estimated at each patient follow-up visit. A linear mixed model was used to analyze eGFR dynamics, accounting for change in TDF by modeling eGFR trajectory according to treatment periods. At inclusion, 56.7% of patients were treated with TDF-containing ART regimens; prevalence of glomerular and tubular proteinuria was 7.9 and 10.8% respectively. A 1-year increase of cumulative exposure to TDF was significantly associated with a mean eGFR decrease of 1.27 mL/min/1.73 m2 (95% CI [-2.14 to -0.41]). Only a urine protein to creatinine ratio >100 mg/mmol and/or a urine albumin to creatinine ratio >70 mg/mmol were associated with eGFR trajectory (mean slope 6.18 mL/min/1.73 m2 per year; 95% CI [2.71 to 9.65]), whereas TDF use was not associated with such eGFR temporal evolution. Decline in kidney function is limited under routine clinical management with monitoring of renal function and interventions including decision to continue or discontinue TDF. © 2017 S. Karger AG, Basel.

  10. Pooled human platelet lysate versus fetal bovine serum—investigating the proliferation rate, chromosome stability and angiogenic potential of human adipose tissue-derived stem cells intended for clinical use

    DEFF Research Database (Denmark)

    Trojahn Kølle, Stig-Frederik; Oliveri, Roberto S; Glovinski, Peter V

    2013-01-01

    Because of an increasing focus on the use of adipose-derived stem cells (ASCs) in clinical trials, the culture conditions for these cells are being optimized. We compared the proliferation rates and chromosomal stability of ASCs that had been cultured in Dulbecco's modified Eagle's Medium (DMEM) ......) supplemented with either pooled human platelet lysate (pHPL) or clinical-grade fetal bovine serum (FBS) (DMEM(pHPL) versus DMEM(FBS))....

  11. [Human enterovirus infection status and clinical characteristics of 274 patients with viral encephalitis in Henan Province, 2011-2012].

    Science.gov (United States)

    Ma, H X; Pan, J J; Li, Y; Kang, K; Huang, X Y; You, A G; Xu, B L

    2017-02-06

    Objective: To investigate human enterovirus (HEV) infection and clinical characteristics of viral encephalitis patients in Pingdingshan, Henan Province. Methods: Cerebrospinal fluid specimens and epidemiological information were collected from 274 viral encephalitis patients in the departments of pediatrics and neurology in hospitals in Pingdingshan, Henan Province, from April 2011 to August 2012. Patients with bacterial infections were excluded from the study. Demographic information was collected by questionnaires and clinical information was mainly obtained from hospital examinations. Viral RNA was extracted using magnetic bead extraction. Real-time RT-PCR was then performed for HEV, CV-A16, and EV-A71 testing. SPSS statistical software was statistical analyses. Significant differences were determined using the chi-squared test ( P15 years old age groups, HEV infections comprised 31.5% (53/168), 52.9% (18/34), 53.0% (35/66), and 16.7% (1/6) (χ(2)=13.10, P= 0.003), respectively. The EV-A71 infection rates were 17.9% (30/168), 23.5% (8/34), 6.1% (4/66), and 0 (χ(2)=8.04, P= 0.045), respectively. The other enterovirus (OEV) infection rates were 12.5% (21/168), 29.4% (10/34), 48.5% (32/66), and 16.7% (1/6) (χ(2)=35.19, P< 0.001), respectively. The rate of vomiting in OEV and EV-A71 infected patients was 73% (44/60) and 26% (11/42), respectively, while the frequency of skin rash in OEV and EV-A71 infected patients was 32% (19/60) and 79% (33/42), respectively. Approximately 95% (99/104) of patients infected with HEV had a fever, and the breathing rhythm change rate was 19% (20/104), which was lower than that of patients without HEV infection (36.8% (60/163)) (χ(2)=9.35, P= 0.002). Conclusion: In Pingdingshan, HEV was a major causative agent of viral encephalitis and the rate of OEV infection was high, especially in children aged 3-15 years old. Fever was a common clinical symptom of patients infected with HEV. Patients infected with OEV primarily exhibited

  12. Comparison of Human Immunodeficiency Virus Type 1 Tropism Profiles in Clinical Samples by the Trofile and MT-2 Assays▿

    Science.gov (United States)

    Coakley, Eoin; Reeves, Jacqueline D.; Huang, Wei; Mangas-Ruiz, Marga; Maurer, Irma; Harskamp, Agnes M.; Gupta, Soumi; Lie, Yolanda; Petropoulos, Christos J.; Schuitemaker, Hanneke; van 't Wout, Angélique B.

    2009-01-01

    The recent availability of CCR5 antagonists as anti-human immunodeficiency virus (anti-HIV) therapeutics has highlighted the need to accurately identify CXCR4-using variants in patient samples when use of this new drug class is considered. The Trofile assay (Monogram Biosciences) has become the method that is the most widely used to define tropism in the clinic prior to the use of a CCR5 antagonist. By comparison, the MT-2 assay has been used since early in the HIV epidemic to define tropism in clinical specimens. Given that there are few data from direct comparisons of these two assays, we evaluated the performance of the plasma-based Trofile assay and the peripheral blood mononuclear cell (PBMC)-based MT-2 assay for the detection of CXCR4 use in defining the tropism of HIV isolates derived from clinical samples. The various samples used for this comparison were derived from participants of the Amsterdam Cohort Studies on HIV infection and AIDS who underwent consecutive MT-2 assay testing of their PBMCs at approximately 3-month intervals. This unique sample set was specifically selected because consecutive MT-2 assays had demonstrated a shift from negative to positive in PBMCs, reflecting the first emergence of CXCR4-using virus in PBMCs above the level of detection of the assay in these individuals. Trofile testing was performed with clonal HIV type 1 (HIV-1) variants (n = 21), MT-2 cell culture-derived cells (n = 20) and supernatants (n = 42), and plasma samples (n = 76). Among the clonal HIV-1 variants and MT-2 cell culture-derived samples, the results of the Trofile and MT-2 assays demonstrated a high degree of concordance (95% to 98%). Among consecutive plasma samples, detection of CXCR4-using virus was at or before the time of first detection by the MT-2 assay in 5/10 patients by the original Trofile assay and in 9/10 patients by the enhanced-sensitivity Trofile assay. Differences in the time to the first detection of CXCR4 use between the MT-2 assay (PBMCs

  13. Comparison of human immunodeficiency virus type 1 tropism profiles in clinical samples by the Trofile and MT-2 assays.

    Science.gov (United States)

    Coakley, Eoin; Reeves, Jacqueline D; Huang, Wei; Mangas-Ruiz, Marga; Maurer, Irma; Harskamp, Agnes M; Gupta, Soumi; Lie, Yolanda; Petropoulos, Christos J; Schuitemaker, Hanneke; van 't Wout, Angélique B

    2009-11-01

    The recent availability of CCR5 antagonists as anti-human immunodeficiency virus (anti-HIV) therapeutics has highlighted the need to accurately identify CXCR4-using variants in patient samples when use of this new drug class is considered. The Trofile assay (Monogram Biosciences) has become the method that is the most widely used to define tropism in the clinic prior to the use of a CCR5 antagonist. By comparison, the MT-2 assay has been used since early in the HIV epidemic to define tropism in clinical specimens. Given that there are few data from direct comparisons of these two assays, we evaluated the performance of the plasma-based Trofile assay and the peripheral blood mononuclear cell (PBMC)-based MT-2 assay for the detection of CXCR4 use in defining the tropism of HIV isolates derived from clinical samples. The various samples used for this comparison were derived from participants of the Amsterdam Cohort Studies on HIV infection and AIDS who underwent consecutive MT-2 assay testing of their PBMCs at approximately 3-month intervals. This unique sample set was specifically selected because consecutive MT-2 assays had demonstrated a shift from negative to positive in PBMCs, reflecting the first emergence of CXCR4-using virus in PBMCs above the level of detection of the assay in these individuals. Trofile testing was performed with clonal HIV type 1 (HIV-1) variants (n = 21), MT-2 cell culture-derived cells (n = 20) and supernatants (n = 42), and plasma samples (n = 76). Among the clonal HIV-1 variants and MT-2 cell culture-derived samples, the results of the Trofile and MT-2 assays demonstrated a high degree of concordance (95% to 98%). Among consecutive plasma samples, detection of CXCR4-using virus was at or before the time of first detection by the MT-2 assay in 5/10 patients by the original Trofile assay and in 9/10 patients by the enhanced-sensitivity Trofile assay. Differences in the time to the first detection of CXCR4 use between the MT-2 assay (PBMCs

  14. Human papillomavirus and its clinical relevance in oesophageal squamous cell carcinoma in a Kurdish population in the west of Iran.

    Science.gov (United States)

    Soheili, Fariborz; Heidary, Nilofar; Rahbar, Mahtab; Nikkho, Bahram; Fotouhi, Omid; Afkhamzadeh, Abdolrahim; Jafari, Hossein; Bagheri, Vahid

    2016-04-01

    Background The aetiological role of Human Papillomavirus (HPV) in oesophageal squamous cell carcinoma (ESCC) was evaluated by assessment of the presence and status of HPV DNA in a Kurdish population in the west of Iran. Methods One hundred and three paraffin-embedded ESCC tissue samples, diagnosed between 2007-2013, were included in the study. DNA was extracted and then HPV presence and genotypes were determined by PCR and INNO-LiPA genotyping, respectively. Results HPV DNA was detected in 11/103 (10.7%) of ESCCs. HPV-18 and HPV-16 genotypes were determined in five and six samples, respectively. Co-infection of HPV-6 was only found with HPV-18 in two cases. There were no statistically significant distinctions between HPV-positive and HPV-negative cases with regard to clinical and pathologic findings. Conclusion The present study indicates that, among a group of Kurdish people in two provinces in the west of Iran, as a low-risk ESCC area, HPV could be one of the risk factors, although in a small proportion of the patients.

  15. High-risk human papilloma virus associated oropharynx squamous cells carcinomas: Clinical, biological implications and therapeutical perspectives

    International Nuclear Information System (INIS)

    Guihard, S.; Noel, G.; Jung, A.C.

    2012-01-01

    The infection of the head and neck epithelium by high-risk human papillomaviruses (HPV) is a risk factor for cancer onset and development. The incidence of HPV-related head and neck squamous cell carcinoma is currently increasing. These lesions display distinct clinical features. HPV positive patients are often younger and have a smaller history of tobacco smoking and alcohol drinking, but have a history of virus-transmitting sex practices. HPV-related tumours are mainly found in the oropharynx, are more associated to a local lymph node invasion and display a poorly differentiated morphology. Despite these more aggressive features, HPV-positive head and neck squamous cell carcinomas correlate with an improved local control, disease-free and global survival. It is thought that HPV-driven specific biologic abnormalities underlie higher tumour sensitivity to chemotherapeutic drugs and ionizing radiations. The expression of the HPV E6 and E7 onco-proteins induce cell transformation by interfering with cell signalling pathways involved in apoptosis, cell cycle, angiogenesis and induce the overexpression of the CDKN2A gene. Therefore, alternative treatments based on therapies targeting these pathways in combination with radiation dose de-escalation could be proposed to HPV-positive patients, if they are properly and reliably identified. (authors)

  16. Clinical and pathological aspects of human African trypanosomiasis (T. b. gambiense) with particular reference to reactive arsenical encephalopathy.

    Science.gov (United States)

    Haller, L; Adams, H; Merouze, F; Dago, A

    1986-01-01

    Fourteen of 330 patients treated with melarsoprol (Mel B) for human African trypanosomiasis (HAT) developed a severe reactive arsenical encephalopathy (RAE). Six of these cases were fatal and postmortem examination was performed on 5 patients. Symptoms of "sleeping sickness" were compared with symptoms after treatment with arsenicals and the subsequent onset of RAE. There are 3 characteristic syndromes of RAE: convulsive status associated with acute cerebral edema, rapidly progressive coma without convulsions, and acute nonlethal mental disturbances without neurological signs. Three subjects revealed hypoxic brain damage with acute cerebral edema, and multiple hemorrhages of brain stem in those comatose. The pathology of the underlying HAT (chronic perivascular inflammation and plasma cytic infiltration of the brain) and the pathology of the RAE (characterized by acute vasculitis) are distinct. RAE occurs in the first as well as in the second stage (CNS involvement) of trypanosomiasis but the reason for this is unclear; an exclusive toxicity of the drug, or a Herxheimer reaction are possible but seem unlikely. Both clinical and laboratory findings point rather to a drug-related, delayed immune response.

  17. An orphan G-protein-coupled receptor causes human gigantism and/or acromegaly: Molecular biology and clinical correlations.

    Science.gov (United States)

    Trivellin, Giampaolo; Hernández-Ramírez, Laura C; Swan, Jeremy; Stratakis, Constantine A

    2018-04-01

    X-linked acrogigantism (X-LAG) is a recently described form of familial or sporadic pituitary gigantism characterized by very early onset GH and IGF-1 excess, accelerated growth velocity, gigantism and/or acromegaloid features. Germline or somatic microduplications of the Xq26.3 chromosomal region, invariably involving the GPR101 gene, constitute the genetic defect leading to X-LAG. GPR101 encodes a class A G protein-coupled receptor that activates the 3',5'-cyclic adenosine monophosphate signaling pathway. Highly expressed in the central nervous system, the main physiological function and ligand of GPR101 remain unknown, but it seems to play a role in the normal development of the GHRH-GH axis. Early recognition of X-LAG cases is imperative because these patients require clinical management that differs from that of other patients with acromegaly or gigantism. Medical treatment with pegvisomant seems to be the best approach, since X-LAG tumors are resistant to the treatment with somatostatin analogues and dopamine agonists; surgical cure requires near-total hypophysectomy. Currently, the efforts of our research focus on the identification of GPR101 ligands; in addition, the long-term follow-up of X-LAG patients is of extreme interest as this is expected to lead to better understanding of GPR101 effects on human pathophysiology. Copyright © 2018. Published by Elsevier Ltd.

  18. Characterization of Human Cytomegalovirus Genome Diversity in Immunocompromised Hosts by Whole-Genome Sequencing Directly From Clinical Specimens.

    Science.gov (United States)

    Hage, Elias; Wilkie, Gavin S; Linnenweber-Held, Silvia; Dhingra, Akshay; Suárez, Nicolás M; Schmidt, Julius J; Kay-Fedorov, Penelope C; Mischak-Weissinger, Eva; Heim, Albert; Schwarz, Anke; Schulz, Thomas F; Davison, Andrew J; Ganzenmueller, Tina

    2017-06-01

    Advances in next-generation sequencing (NGS) technologies allow comprehensive studies of genetic diversity over the entire genome of human cytomegalovirus (HCMV), a significant pathogen for immunocompromised individuals. Next-generation sequencing was performed on target enriched sequence libraries prepared directly from a variety of clinical specimens (blood, urine, breast milk, respiratory samples, biopsies, and vitreous humor) obtained longitudinally or from different anatomical compartments from 20 HCMV-infected patients (renal transplant recipients, stem cell transplant recipients, and congenitally infected children). De novo-assembled HCMV genome sequences were obtained for 57 of 68 sequenced samples. Analysis of longitudinal or compartmental HCMV diversity revealed various patterns: no major differences were detected among longitudinal, intraindividual blood samples from 9 of 15 patients and in most of the patients with compartmental samples, whereas a switch of the major HCMV population was observed in 6 individuals with sequential blood samples and upon compartmental analysis of 1 patient with HCMV retinitis. Variant analysis revealed additional aspects of minor virus population dynamics and antiviral-resistance mutations. In immunosuppressed patients, HCMV can remain relatively stable or undergo drastic genomic changes that are suggestive of the emergence of minor resident strains or de novo infection. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  19. Human c-peptide immunoreactivity (CPR) in blood and urine - evaluation of a radioimmunoassay method and its clinical applications

    Energy Technology Data Exchange (ETDEWEB)

    Kuzuya, T; Matsuda, A; Saito, T; Yoshida, S

    1976-01-01

    A double-antibody radioimmunoassay method, using synthetic human connecting peptide as an immunizing antigen and standard, was evaluated for clinical assay of blood and urine samples. Normal fasting blood connecting peptide immunoreacivity (CPR) was 2.45 +- 0.96 ng/ml, increasing promptly after a 50 g oral glucose load, but somewhat slower than insulin. Molar concentration of CPR exceeded that of insulin. CPR responses to glucose were subnormal in diabetics, very low in juvenile-type cases, and often poor in patients on insulin treatment. Fasting CPR levels were elevated in patients on corticosteroid treatment and with uraemia. A patient with insulin 'auto-antibody' had high serum CPR. A considerable amount of CPR appeared in urine. Normal daily excretion of CPR was 1.52 +- 0.55 ..mu..g/kg or 55.1 +- 18.2 ng/mg creatinine. Urine CPR was very low in juvenile-type diabetics, and elevated in patients on corticosteroid treatment. The results confirm that blood and urine CPR are useful measures of the endocrine pancreatic function.

  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. Under Persistent Assault: Understanding the Factors that Deteriorate Human Skin and Clinical Efficacy of Topical Antioxidants in Treating Aging Skin

    Directory of Open Access Journals (Sweden)

    Patricia K. Farris

    2015-11-01

    Full Text Available Recent studies contend that the skin is subject to far more damage than just ultraviolet (UV light, with infrared radiation and pollution now clearly demonstrated to degrade cutaneous tissue. While consumers continue to strive for new ways to augment the aesthetic appeal and improve the health of their skin, awareness regarding environmental insults and effective ways to protect the skin remains low. New advances in dermatologic science have exponentially increased the available information on the underlying mechanism of cutaneous damage and potential of topical antioxidants to treat aging skin. Combining antioxidants that can work through multiple pathways holds great potential for a cumulative and synergistic way to treat aging skin. Our goal is to provide a comprehensive review on environmental factors that damage human skin, discuss scientifically proven benefits of topical antioxidants, understand challenges of formulating and administering topical antioxidants, evaluate novel mechanisms of antioxidant activity, and suggest practical ways of integrating topical antioxidants with aesthetic procedures to complement clinical outcomes.

  2. 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.

  3. Integrating Positive and Clinical Psychology: Viewing Human Functioning as Continua from Positive to Negative Can Benefit Clinical Assessment, Interventions and Understandings of Resilience

    OpenAIRE

    Johnson, J; Wood, AM

    2017-01-01

    In this review we argue in favour of further integration between the disciplines of positive and clinical psychology. We argue that most of the constructs studied by both positive and clinical psychology exist on continua ranging from positive to negative (e.g., gratitude to ingratitude, anxiety to calmness) and so it is meaningless to speak of one or other field studying the “positive” or the “negative”. However, we highlight historical and cultural factors which have led positive and clinic...

  4. The value of integrating pre-clinical data to predict nausea and vomiting risk in humans as illustrated by AZD3514, a novel androgen receptor modulator

    Energy Technology Data Exchange (ETDEWEB)

    Grant, Claire, E-mail: claire.grant@astrazeneca.com [Drug Safety and Metabolism, AstraZeneca, Alderley Park, Macclesfield SK10 4TG (United Kingdom); Ewart, Lorna [Drug Safety and Metabolism, AstraZeneca, Da Vinci Building, Melbourn Science Park, Cambridge Road, Melbourn, Royston SG8 6HB (United Kingdom); Muthas, Daniel [Respiratory, Inflammation and Autoimmunity iMED, AstraZeneca, Pepparedsleden 1, 431 83 Mölndal (Sweden); Deavall, Damian [Drug Safety and Metabolism, AstraZeneca, Alderley Park, Macclesfield SK10 4TG (United Kingdom); Smith, Simon A. [Oncology Translational Medicine Unit, Early Clinical Development, AstraZeneca, Da Vinci Building, Melbourn Science Park, Melbourn, Royston SG8 6HB (United Kingdom); Clack, Glen [Translational Medicine Unit, Early Clinical Development, AstraZeneca, Alderley Park, Macclesfield SK10 4TG (United Kingdom); Newham, Pete [Drug Safety and Metabolism, AstraZeneca, Darwin Building, Cambridge Science Park, Milton Road, Cambridge CB4 0WG (United Kingdom)

    2016-04-01

    Nausea and vomiting are components of a complex mechanism that signals food avoidance and protection of the body against the absorption of ingested toxins. This response can also be triggered by pharmaceuticals. Predicting clinical nausea and vomiting liability for pharmaceutical agents based on pre-clinical data can be problematic as no single animal model is a universal predictor. Moreover, efforts to improve models are hampered by the lack of translational animal and human data in the public domain. AZD3514 is a novel, orally-administered compound that inhibits androgen receptor signaling and down-regulates androgen receptor expression. Here we have explored the utility of integrating data from several pre-clinical models to predict nausea and vomiting in the clinic. Single and repeat doses of AZD3514 resulted in emesis, salivation and gastrointestinal disturbances in the dog, and inhibited gastric emptying in rats after a single dose. AZD3514, at clinically relevant exposures, induced dose-responsive “pica” behaviour in rats after single and multiple daily doses, and induced retching and vomiting behaviour in ferrets after a single dose. We compare these data with the clinical manifestation of nausea and vomiting encountered in patients with castration-resistant prostate cancer receiving AZD3514. Our data reveal a striking relationship between the pre-clinical observations described and the experience of nausea and vomiting in the clinic. In conclusion, the emetic nature of AZD3514 was predicted across a range of pre-clinical models, and the approach presented provides a valuable framework for predicition of clinical nausea and vomiting. - Highlights: • Integrated pre-clinical data can be used to predict clinical nausea and vomiting. • Data integrated from standard toxicology studies is sufficient to make a prediction. • The use of the nausea algorithm developed by Parkinson (2012) aids the prediction. • Additional pre-clinical studies can be used

  5. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer

    NARCIS (Netherlands)

    Wolff, Antonio C.; Hammond, M. Elizabeth H.; Schwartz, Jared N.; Hagerty, Karen L.; Allred, D. Craig; Cote, Richard J.; Dowsett, Mitchell; Fitzgibbons, Patrick L.; Hanna, Wedad M.; Langer, Amy; McShane, Lisa M.; Paik, Soonmyung; Pegram, Mark D.; Perez, Edith A.; Press, Michael F.; Rhodes, Anthony; Sturgeon, Catharine; Taube, Sheila E.; Tubbs, Raymond; Vance, Gail H.; van de Vijver, Marc; Wheeler, Thomas M.; Hayes, Daniel F.

    2007-01-01

    PURPOSE: To develop a guideline to improve the accuracy of human epidermal growth factor receptor 2 (HER2) testing in invasive breast cancer and its utility as a predictive marker. METHODS: The American Society of Clinical Oncology and the College of American Pathologists convened an expert panel,

  6. 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

  7. [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.

  8. Genotypic and Phenotypic Characteristics Associated with Biofilm Formation by Human Clinical Escherichia coli Isolates of Different Pathotypes.

    Science.gov (United States)

    Schiebel, Juliane; Böhm, Alexander; Nitschke, Jörg; Burdukiewicz, Michał; Weinreich, Jörg; Ali, Aamir; Roggenbuck, Dirk; Rödiger, Stefan; Schierack, Peter

    2017-12-15

    Bacterial biofilm formation is a widespread phenomenon and a complex process requiring a set of genes facilitating the initial adhesion, maturation, and production of the extracellular polymeric matrix and subsequent dispersal of bacteria. Most studies on Escherichia coli biofilm formation have investigated nonpathogenic E. coli K-12 strains. Due to the extensive focus on laboratory strains in most studies, there is poor information regarding biofilm formation by pathogenic E. coli isolates. In this study, we genotypically and phenotypically characterized 187 human clinical E. coli isolates representing various pathotypes (e.g., uropathogenic, enteropathogenic, and enteroaggregative E. coli ). We investigated the presence of biofilm-associated genes ("genotype") and phenotypically analyzed the isolates for motility and curli and cellulose production ("phenotype"). We developed a new screening method to examine the in vitro biofilm formation ability. In summary, we found a high prevalence of biofilm-associated genes. However, we could not detect a biofilm-associated gene or specific phenotype correlating with the biofilm formation ability. In contrast, we did identify an association of increased biofilm formation with a specific E. coli pathotype. Enteroaggregative E. coli (EAEC) was found to exhibit the highest capacity for biofilm formation. Using our image-based technology for the screening of biofilm formation, we demonstrated the characteristic biofilm formation pattern of EAEC, consisting of thick bacterial aggregates. In summary, our results highlight the fact that biofilm-promoting factors shown to be critical for biofilm formation in nonpathogenic strains do not reflect their impact in clinical isolates and that the ability of biofilm formation is a defined characteristic of EAEC. IMPORTANCE Bacterial biofilms are ubiquitous and consist of sessile bacterial cells surrounded by a self-produced extracellular polymeric matrix. They cause chronic and device

  9. Epidemiology of Human Parechovirus Type1 in Clinical Samples from Children with Gastroenteritis Using RT-PCR

    Directory of Open Access Journals (Sweden)

    Dabirmanesh B

    2011-03-01

    Full Text Available Background and Objectives: Human parechovirus type-1 (HPeV-1 is a genus of picornaviridea with a single stranded positive sense RNA genome. In general it seems to be responsible for more gastrointestinal and respiratory syndromes and less responsible for central nervous system (CNS symptoms. Since there is no accurate information about diagnosis and epidemiology of HPeV-1 in Iran and it is very important to distinguish between viral and bacterial diarrhea to decrease the unnecessary use of antibiotics, this study aimed at rapid detection and epidemiology of HPeV-1 in stool samples from children with gastroenteritis using specific RT-PCR. Methods: Viral RNA was isolated from 472 stool samples from children (under 4 years old with diarrhea; CDNA was prepared and amplified using specific primers from 5′untranslated region (5′ UTR of HPeV-1 genome by nested RT-PCR. Amplified DNA product was electrophoresed on 1% agarose gel and a single band of 265 bp was obtained. Data were analyzed by SPSS software. We also performed a comparison between the cell culture (Vero and RT-PCR method for HPeV1 detection.Results: Out of 472 samples examined during two years, 112 samples were HpeV-1 positive (23.7%. The results showed that the prevalence of this virus was in children under one year (6-12 months old with diarrhea (p=0.036 in spring and autumn (p<0.001. Boys had more positive cases than the girls (p<0.001. Out of 20 samples which were found positive by HPeV1 RT-PCR only three of them showed CPE on Vero Cells after a week.Conclusion: The results revealed that RT-PCR is a more practical and sensitive technique for HPeV-1 detection directly from clinical samples, which is valuable for epidemiology. Also, the rapid detection of HPeV1 by RT-PCR can decrease both the unnecessary use of antibiotics and the costs in clinical practice

  10. Epidemiology of Human Parechovirus Type1 in Clinical Samples from Children with Gastroenteritis Using RT-PCR

    Directory of Open Access Journals (Sweden)

    F Ghazi

    2012-05-01

    Full Text Available

    Background and Objectives: Human parechovirus type-1 (HPeV-1 is a genus of picornaviridea with a single stranded positive sense RNA genome. In general it seems to be responsible for more gastrointestinal and respiratory syndromes and less responsible for central nervous system (CNS symptoms. Since there is no accurate information about diagnosis and epidemiology of HPeV-1 in Iran and it is very important to distinguish between viral and bacterial diarrhea to decrease the unnecessary use of antibiotics, this study aimed at rapid detection and epidemiology of HPeV-1 in stool samples from children with gastroenteritis using specific RT-PCR.

     

    Methods: Viral RNA was isolated from 472 stool samples from children (under 4 years old with diarrhea; CDNA was prepared and amplified using specific primers from 5untranslated region (5 UTR of HPeV-1 genome by nested RT-PCR. Amplified DNA product was electrophoresed on 1% agarose gel and a single band of 265 bp was obtained. Data were analyzed by SPSS software. We also performed a comparison between the cell culture (Vero and RT-PCR method for HPeV1 detection.

     

    Results: Out of 472 samples examined during two years, 112 samples were HpeV-1 positive (23.7%. The results showed that the prevalence of this virus was in children under one year (6-12 months old with diarrhea (p=0.036 in spring and autumn (p<0.001. Boys had more positive cases than the girls (p<0.001. Out of 20 samples which were found positive by HPeV1 RT-PCR only three of them showed CPE on Vero Cells after a week.

     

    Conclusion: The results revealed that RT-PCR is a more practical and sensitive technique for HPeV-1 detection directly from clinical samples, which is valuable for epidemiology. Also, the rapid

  11. Human interleukin-10 delivered intrathecally by self-complementary adeno-associated virus 8 induces xenogeneic transgene immunity without clinical neurotoxicity in swine.

    Science.gov (United States)

    Unger, Mark D; Pleticha, Josef; Heilmann, Lukas F; Newman, Laura K; Maus, Timothy P; Beutler, Andreas S

    2018-05-25

    Intrathecal interleukin-10 delivered by plasmid or viral gene vectors has been proposed for clinical testing because it is effective for chronic pain in rodents, a potential therapeutic for various human diseases, and was found to be non-toxic in dogs, when the human interleukin-10 ortholog was tested. However, recent studies in swine testing porcine interleukin-10 demonstrated fatal neurotoxicity. To deliver vector-encoded human interleukin-10 in swine, measure expression of the transgene in cerebrospinal fluid, and monitor animals for signs of neurotoxicity. Human interleukin-10 levels peaked 2 weeks after vector administration followed by a rapid decline that occurred concomitant with the emergence of anti-human interleukin-10 antibodies in the cerebrospinal fluid and serum. Animals remained neurologically healthy throughout the study period. This study suggests that swine are not idiosyncratically sensitive to intrathecal interleukin-10 because, recapitulating previous reports in dogs, they suffered no clinical neurotoxicity from the human ortholog. These results strongly infer that toxicity of intrathecal interleukin-10 in large animal models was previously overlooked because of a species mismatch between transgene and host. The present study further suggests that swine were protected from interleukin-10 by a humoral immune response against the xenogeneic cytokine. Future safety studies of interleukin-10 or related therapeutics may require syngeneic large animal models. This article is protected by copyright. All rights reserved.

  12. Glycan analysis of Fonsecaea monophora from clinical and environmental origins reveals different structural profile and human antigenic response

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    Juliana Reis Burjack

    2014-10-01

    Full Text Available Dematiaceous fungi constitute a large and heterogeneous group, characterized by having a dark pigment, the dihydroxynaftalen melanin - DHN, inside their cell walls. In nature they are found mainly as soil microbiota or decomposing organic matter, and are spread in tropical and subtropical regions. The fungus Fonsecaea monophora causes chromoblastomycosis in humans, and possesses essential mechanisms that may enhance pathogenicity, proliferation and dissemination inside the host. Glycoconjugates confer important properties to these pathogenic microorganisms. In this work, structural characterization of glycan structures present in two different strains of F. monophora MMHC82 and FE5p4, from clinical and environmental origins, respectively, was performed. Each one were grown on Minimal Medium (MM and Czapeck-Dox (CD medium, and the water soluble cell wall glycoconjugates and exopolysaccharides (EPS were evaluated by NMR, methylation and principal component analysis (PCA. By combining the methylation and 2D NMR analyses, it was possible to visualize the glycosidic profiles of the complex carbohydrate mixtures. Significant differences were observed in β-D-Galf-(1→5 and (1→6 linkages, α- and β-D-Glcp-(1→3, (1→4 and (1→6 units, as well as in α-D-Manp. PCA from 1H-NMR data showed that MMHC82 from CD medium showed a higher variation in the cell wall carbohydrates, mainly related to O-2 substituted β-D-Galf (δ 106.0/5.23 and δ 105.3/5.23 units. In order to investigate the antigenic response of the glycoconjugates, these were screened against serum from chromoblastomycosis patients. The antigen which contained the cell wall of MMHC82 grown in MM had β-D-Manp units that promoted higher antigenic response. The distribution of these fungal species in nature and the knowledge of how cell wall polysaccharides and glycoconjugates structure vary, may contribute to the better understanding and the elucidation of the pathology caused by this

  13. Development and Application of a Clinical Microsystem Simulation Methodology for Human Factors-Based Research of Alarm Fatigue.

    Science.gov (United States)

    Kobayashi, Leo; Gosbee, John W; Merck, Derek L

    2017-07-01

    (1) To develop a clinical microsystem simulation methodology for alarm fatigue research with a human factors engineering (HFE) assessment framework and (2) to explore its application to the comparative examination of different approaches to patient monitoring and provider notification. Problems with the design, implementation, and real-world use of patient monitoring systems result in alarm fatigue. A multidisciplinary team is developing an open-source tool kit to promote bedside informatics research and mitigate alarm fatigue. Simulation, HFE, and computer science experts created a novel simulation methodology to study alarm fatigue. Featuring multiple interconnected simulated patient scenarios with scripted timeline, "distractor" patient care tasks, and triggered true and false alarms, the methodology incorporated objective metrics to assess provider and system performance. Developed materials were implemented during institutional review board-approved study sessions that assessed and compared an experimental multiparametric alerting system with a standard monitor telemetry system for subject response, use characteristics, and end-user feedback. A four-patient simulation setup featuring objective metrics for participant task-related performance and response to alarms was developed along with accompanying structured HFE assessment (questionnaire and interview) for monitor systems use testing. Two pilot and four study sessions with individual nurse subjects elicited true alarm and false alarm responses (including diversion from assigned tasks) as well as nonresponses to true alarms. In-simulation observation and subject questionnaires were used to test the experimental system's approach to suppressing false alarms and alerting providers. A novel investigative methodology applied simulation and HFE techniques to replicate and study alarm fatigue in controlled settings for systems assessment and experimental research purposes.

  14. Color-coding and human factors engineering to improve patient safety characteristics of paper-based emergency department clinical documentation.

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    Kobayashi, Leo; Boss, Robert M; Gibbs, Frantz J; Goldlust, Eric; Hennedy, Michelle M; Monti, James E; Siegel, Nathan A

    2011-01-01

    Investigators studied an emergency department (ED) physical chart system and identified inconsistent, small font labeling; a single-color scheme; and an absence of human factors engineering (HFE) cues. A case study and description of the methodology with which surrogate measures of chart-related patient safety were studied and subsequently used to reduce latent hazards are presented. Medical records present a challenge to patient safety in EDs. Application of HFE can improve specific aspects of existing medical chart organization systems as they pertain to patient safety in acute care environments. During 10 random audits over 5 consecutive days (573 data points), 56 (9.8%) chart binders (range 0.0-23%) were found to be either misplaced or improperly positioned relative to other chart binders; 12 (21%) were in the critical care area. HFE principles were applied to develop an experimental chart binder system with alternating color-based chart groupings, simple and prominent identifiers, and embedded visual cues. Post-intervention audits revealed significant reductions in chart binder location problems overall (p < 0.01), for Urgent Care A and B pods (6.4% to 1.2%; p < 0.05), Fast Track C pod (19.3% to 0.0%; p < 0.05) and Behavioral/Substance Abuse D pod (15.7% to 0.0%; p < 0.05) areas of the ED. The critical care room area did not display an improvement (11.4% to 13.2%; p = 0.40). Application of HFE methods may aid the development, assessment, and modification of acute care clinical environments through evidence-based design methodologies and contribute to safe patient care delivery.

  15. Fluid mechanics of human fetal right ventricles from image-based computational fluid dynamics using 4D clinical ultrasound scans.

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    Wiputra, Hadi; Lai, Chang Quan; Lim, Guat Ling; Heng, Joel Jia Wei; Guo, Lan; Soomar, Sanah Merchant; Leo, Hwa Liang; Biwas, Arijit; Mattar, Citra Nurfarah Zaini; Yap, Choon Hwai

    2016-12-01

    There are 0.6-1.9% of US children who were born with congenital heart malformations. Clinical and animal studies suggest that abnormal blood flow forces might play a role in causing these malformation, highlighting the importance of understanding the fetal cardiovascular fluid mechanics. We performed computational fluid dynamics simulations of the right ventricles, based on four-dimensional ultrasound scans of three 20-wk-old normal human fetuses, to characterize their flow and energy dynamics. Peak intraventricular pressure gradients were found to be 0.2-0.9 mmHg during systole, and 0.1-0.2 mmHg during diastole. Diastolic wall shear stresses were found to be around 1 Pa, which could elevate to 2-4 Pa during systole in the outflow tract. Fetal right ventricles have complex flow patterns featuring two interacting diastolic vortex rings, formed during diastolic E wave and A wave. These rings persisted through the end of systole and elevated wall shear stresses in their proximity. They were observed to conserve ∼25.0% of peak diastolic kinetic energy to be carried over into the subsequent systole. However, this carried-over kinetic energy did not significantly alter the work done by the heart for ejection. Thus, while diastolic vortexes played a significant role in determining spatial patterns and magnitudes of diastolic wall shear stresses, they did not have significant influence on systolic ejection. Our results can serve as a baseline for future comparison with diseased hearts. Copyright © 2016 the American Physiological Society.

  16. Clinical Significance of Cannabinoid Receptors CB1 and CB2 Expression in Human Malignant and Benign Thyroid Lesions

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    Eleftheria Lakiotaki

    2015-01-01

    Full Text Available The endocannabinoid system is comprised of cannabinoid receptors (CB1 and CB2, their endogenous ligands (endocannabinoids, and proteins responsible for their metabolism participate in many different functions indispensable to homeostatic regulation in several tissues, exerting also antitumorigenic effects. The present study aimed to evaluate the clinical significance of CB1 and CB2 expression in human benign and malignant thyroid lesions. CB1 and CB2 proteins’ expression was assessed immunohistochemically on paraffin-embedded thyroid tissues obtained from 87 patients with benign (n=43 and malignant (n=44 lesions and was statistically analyzed with clinicopathological parameters, follicular cells’ proliferative capacity, and risk of recurrence rate estimated according to the American Thyroid Association (ATA staging system. Enhanced CB1 and CB2 expression was significantly more frequently observed in malignant compared to benign thyroid lesions (p=0.0010 and p=0.0005, resp.. Enhanced CB1 and CB2 expression was also significantly more frequently observed in papillary carcinomas compared to hyperplastic nodules (p=0.0097 and p=0.0110, resp.. In malignant thyroid lesions, elevated CB2 expression was significantly associated with the presence of lymph node metastases (p=0.0301. Enhanced CB2 expression was also more frequently observed in malignant thyroid cases with presence of capsular (p=0.1165, lymphatic (p=0.1989, and vascular invasion (p=0.0555, as well as in those with increased risk of recurrence rate (p=0.1165, at a nonsignificant level though, whereas CB1 expression was not associated with any of the clinicopathological parameters examined. Our data suggest that CB receptors may be involved in malignant thyroid transformation and especially CB2 receptor could serve as useful biomarker and potential therapeutic target in thyroid neoplasia.

  17. Pattern of sexually transmitted infections in human immunodeficiency virus positive women attending antenatal clinics in north-central Nigeria

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    Salamat A Isiaka-Lawal

    2014-01-01

    Full Text Available Background: Sexually transmitted infections (STIs are prevalent during pregnancy and may have adverse sequalae in both mother and fetus. Interactions between these infections and human immunodeficiency virus (HIV synergize and may cause adverse pregnancy outcomes and reverse the gains of prevention of mother to child transmission of HIV. Objectives: The objective of this study is to determine the prevalence of candidiasis, trichomoniasis, gonococcal infection, syphilis, and bacterial vaginosis in HIV pregnant women and compare with HIV negative controls. Materials and Methods: A case-control study was conducted during the period from April to December 2010 at the Department of Obstetrics/Gynecology of University of Ilorin Teaching Hospital and three Primary Health Centers in Ilorin. A total of 160 HIV positive pregnant women attending antenatal clinics were recruited, along with the same number of HIV negative matched controls. A structured proforma was used to collect information from patients, vaginal examination was performed and samples were taken from the endocervix and the posterior vaginal fornix with swab sticks. Results: STIs were recovered from 142 women, giving overall prevalence of 44.4%. HIV infected women had a higher prevalence (60% compared to uninfected (28.8%. The most prevalent STI was vaginal candidiasis (29.1%, followed by bacterial vaginosis (9.7%, and trichomoniasis (5.6%. The prevalence of candidiasis, bacterial vaginosis, and trichomoniasis was higher among HIV positive pregnant women compared to HIV negative controls (P < 0.05. No woman had syphilis or gonorrhea. Conclusion: The prevalence of candidiasis, bacterial vaginosis and trichomoniasis was higher in HIV infected pregnant women compared to uninfected. Routine screening of HIV infected pregnant women for these organisms is advocated.

  18. HPLC MS/MS method for quantification of meprobamate in human plasma: application to 24/7 clinical toxicology.

    Science.gov (United States)

    Delavenne, Xavier; Gay-Montchamp, Jean Pierre; Basset, Thierry

    2011-01-15

    We described the development and full validation of rapid and accurate liquid chromatography method, coupled with tandem mass spectrometry detection, for quantification of meprobamate in human plasma with [(13)C-(2)H(3)]-meprobamate as internal standard. Plasma pretreatment involved a one-step protein precipitation with acetonitrile. Separation was performed by reversed-phase chromatography on a Luna MercuryMS C18 (20 mm×4 mm×3 μm) column using a gradient elution mode. The mobile phase was a mix of distilled water containing 0.1% formic acid and acetonitrile containing 0.1% formic acid. The selected reaction monitoring transitions, in electrospray positive ionization, used for quantification were 219.2→158.2 m/z and 223.1→161.1m/z for meprobamate and internal standard, respectively. Qualification transitions were 219.2→97.0 and 223.1→101.1 m/z for meprobamate and internal standard, respectively. The method was linear over the concentration range of 1-300 mg/L. The intra- and inter-day precision values were below 6.4% and accuracy was within 95.3% and 103.6% for all QC levels (5, 75 and 200 mg/L). The lower limit of quantification was 1 mg/L. Total analysis time was reduced to 6 min including sample preparation. The present method is successfully applied to 24/7 clinical toxicology and demonstrated its usefulness to detect meprobamate poisoning. Copyright © 2010 Elsevier B.V. All rights reserved.

  19. Seroprevalence of hepatitis and human immuno-deficiency virus in multitransfused patients from a pediatric hematology clinic

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    Suar Çakı Kılıç

    2008-12-01

    Full Text Available OBJECTIVE: Transfusion transmitted hepatitis has been a severe problem in Turkey in pediatric cancer patients and in chronic congenital anemia. The aim of the present study was to investigate the prevalence of hepatitis B, hepatitis C and human immunodeficiency virus infections in these patients in a University Hospital. METHODS: Multi-transfused 66 children (59 acute leukemia, 6 thalassemia major, 1 severe hereditary spherocytosis diagnosed and followed-up between May, 2000 and December, 2006 were evaluated. Screening of all the patients for HbsAg, anti-HBs, anti-HBc, anti-HCV and anti-HIV was performed at presentation and during the last follow-up. Serologic studies of leukemic patients were also repeated at the end of the chemotherapy. Hepatitis B vaccination was administered to unvaccinated patients with anemia. All blood products were provided by Blood Bank of the Center. RESULTS: No patient was found HBsAg, anti-HCV or anti-HIV positive at diagnosis and at the end of the therapy. There was history of hepatitis B vaccination in only 42% of the patients at diagnosis due to administration of this vaccine to newborns since 1998. At the beginning of the study, 45 % (n=27 of the leukemic patients were immune for hepatitis B, but after completion of the intensive chemotherapy seropositivity persisted in only 28.8 % (n=17. CONCLUSION: Transmission of these viruses is no longer a real problem even in multitransfused immunosuppressed children in Pediatric Hematology Units as a result of the improvements in screening of voluntary blood donors, administration of disposable material in clinics and vaccination by hepatitis B.

  20. Heritability and clinical determinants of serum indoxyl sulfate and p-cresyl sulfate, candidate biomarkers of the human microbiome enterotype.

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    Liesbeth Viaene

    Full Text Available BACKGROUND: Indoxyl sulfate and p-cresyl sulfate are unique microbial co-metabolites. Both co-metabolites have been involved in the pathogenesis of accelerated cardiovascular disease and renal disease progression. Available evidence suggests that indoxyl sulfate and p-cresyl sulfate may be considered candidate biomarkers of the human enterotype and may help to explain the link between diet and cardiovascular disease burden. OBJECTIVE AND DESIGN: Information on clinical determinants and heritability of indoxyl sulfate and p-cresyl sulfate serum is non-existing. To clarify this issue, the authors determined serum levels of indoxyl sulfate and p-cresyl sulfate in 773 individuals, recruited in the frame of the Flemish Study on Environment, Genes and Health Outcomes (FLEMENGHO study. RESULTS: Serum levels of indoxyl sulfate and p-cresyl sulfate amounted to 3.1 (2.4-4.3 and 13.0 (7.4-21.5 μM, respectively. Regression analysis identified renal function, age and sex as independent determinants of both co-metabolites. Both serum indoxyl sulfate (h2 = 0.17 and p-cresyl sulfate (h2 = 0.18 concentrations showed moderate but significant heritability after adjustment for covariables, with significant genetic and environmental correlations for both co-metabolites. LIMITATIONS: Family studies cannot provide conclusive evidence for a genetic contribution, as confounding by shared environmental effects can never be excluded. CONCLUSIONS: The heritability of indoxyl sulfate and p-cresyl sulfate is moderate. Besides genetic host factors and environmental factors, also renal function, sex and age influence the serum levels of these co-metabolites.

  1. Human papilloma virus testing knowledge and attitudes among women attending colposcopy clinic with ASCUS/LGSIL pap smears.

    Science.gov (United States)

    Le, T; Hicks, W; Menard, C; Boyd, D; Hewson, T; Hopkins, L; Kee Fung, M Fung

    2004-09-01

    To study women's knowledge regarding the role of human papilloma virus (HPV) in cervical intraepithelial neoplasia and their attitudes toward the integration of HPV testing as part of routine follow-up of atypical squamous cell of uncertain significance/low-grade squamous intraepithelial lesion (ASCUS/LGSIL) abnormalities. Over a 12-month period, all women attending the University of Ottawa colposcopy clinic for evaluation and follow-up of ASCUS/LGSIL Pap smears were recruited. Demographic data included age, nature of the Pap smear abnormality, gravidity, parity, occupation and education level, smoking history, previous history of abnormal smears, colposcopic examination and treatment, and current method of contraception. The women were asked to rate their level of concern over their Pap smear abnormality, from 0 (not concerned) to 10 (very concerned). Women's knowledge regarding the role of HPV in cervical intraepithelial neoplasia and the rationale behind the use of HPV testing was assessed by the clinic nurse as being minimal, moderate, or good, as defined by pre-specified criteria. Upon explanation by the nurses of the results of the recent ALTS (ASCUS/LGSIL Triage Study) trial, the women were asked to state whether they preferred to continue with regular colposcopic surveillance every 6 months, or to use the results of the HPV test, if negative, to reduce the number of colposcopy examinations to one annually. Descriptive statistics and logistic regression analysis were used to identify significant demographic factors associated with the women's preference for incorporation of HPV testing in their follow-up. All P values less than.10 were considered to be statistically significant, due to the exploratory nature of the study. Of the 100 women who participated in the study, 42% presented with ASCUS. The mean age (+/- SD) of the women was 33.63 +/- 11.25 years (range, 18-75 years); 66% were office workers with at least a community college degree, 86% reported

  2. Phenotypic, Genotypic, and Antimicrobial Characteristics of Streptococcus halichoeri Isolates from Humans, Proposal To Rename Streptococcus halichoeri as Streptococcus halichoeri subsp. halichoeri, and Description of Streptococcus halichoeri subsp. hominis subsp. nov., a Bacterium Associated with Human Clinical Infections.

    Science.gov (United States)

    Shewmaker, P L; Whitney, A M; Humrighouse, B W

    2016-03-01

    Phenotypic, genotypic, and antimicrobial characteristics of six phenotypically distinct human clinical isolates that most closely resembled the type strain of Streptococcus halichoeri isolated from a seal are presented. Sequencing of the 16S rRNA, rpoB, sodA, and recN genes; comparative whole-genome analysis; conventional biochemical and Rapid ID 32 Strep identification methods; and antimicrobial susceptibility testing were performed on the human isolates, the type strain of S. halichoeri, and type strains of closely related species. The six human clinical isolates were biochemically indistinguishable from each other and showed 100% 16S rRNA, rpoB, sodA, and recN gene sequence similarity. Comparative 16S rRNA gene sequencing analysis revealed 98.6% similarity to S. halichoeri CCUG 48324(T), 97.9% similarity to S. canis ATCC 43496(T), and 97.8% similarity to S. ictaluri ATCC BAA-1300(T). A 3,530-bp fragment of the rpoB gene was 98.8% similar to the S. halichoeri type strain, 84.6% to the S. canis type strain, and 83.8% to the S. ictaluri type strain. The S. halichoeri type strain and the human clinical isolates were susceptible to the antimicrobials tested based on CLSI guidelines for Streptococcus species viridans group with the exception of tetracycline and erythromycin. The human isolates were phenotypically distinct from the type strain isolated from a seal; comparative whole-genome sequence analysis confirmed that the human isolates were S. halichoeri. On the basis of these results, a novel subspecies, Streptococcus halichoeri subsp. hominis, is proposed for the human isolates and Streptococcus halichoeri subsp. halichoeri is proposed for the gray seal isolates. The type strain of the novel subspecies is SS1844(T) = CCUG 67100(T) = LMG 28801(T). Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  3. The Human Gene Mutation Database: building a comprehensive mutation repository for clinical and molecular genetics, diagnostic testing and personalized genomic medicine.

    Science.gov (United States)

    Stenson, Peter D; Mort, Matthew; Ball, Edward V; Shaw, Katy; Phillips, Andrew; Cooper, David N

    2014-01-01

    The Human Gene Mutation Database (HGMD®) is a comprehensive collection of germline mutations in nuclear genes that underlie, or are associated with, human inherited disease. By June 2013, the database contained over 141,000 different lesions detected in over 5,700 different genes, with new mutation entries currently accumulating at a rate exceeding 10,000 per annum. HGMD was originally established in 1996 for the scientific study of mutational mechanisms in human genes. However, it has since acquired a much broader utility as a central unified disease-oriented mutation repository utilized by human molecular geneticists, genome scientists, molecular biologists, clinicians and genetic counsellors as well as by those specializing in biopharmaceuticals, bioinformatics and personalized genomics. The public version of HGMD (http://www.hgmd.org) is freely available to registered users from academic institutions/non-profit organizations whilst the subscription version (HGMD Professional) is available to academic, clinical and commercial users under license via BIOBASE GmbH.

  4. How to apply clinical cases and medical literature in the framework of a modified "failure mode and effects analysis" as a clinical reasoning tool--an illustration using the human biliary system.

    Science.gov (United States)

    Wong, Kam Cheong

    2016-04-06

    Clinicians use various clinical reasoning tools such as Ishikawa diagram to enhance their clinical experience and reasoning skills. Failure mode and effects analysis, which is an engineering methodology in origin, can be modified and applied to provide inputs into an Ishikawa diagram. The human biliary system is used to illustrate a modified failure mode and effects analysis. The anatomical and physiological processes of the biliary system are reviewed. Failure is defined as an abnormality caused by infective, inflammatory, obstructive, malignancy, autoimmune and other pathological processes. The potential failures, their effect(s), main clinical features, and investigation that can help a clinician to diagnose at each anatomical part and physiological process are reviewed and documented in a modified failure mode and effects analysis table. Relevant medical and surgical cases are retrieved from the medical literature and weaved into the table. A total of 80 clinical cases which are relevant to the modified failure mode and effects analysis for the human biliary system have been reviewed and weaved into a designated table. The table is the backbone and framework for further expansion. Reviewing and updating the table is an iterative and continual process. The relevant clinical features in the modified failure mode and effects analysis are then extracted and included in the relevant Ishikawa diagram. This article illustrates an application of engineering methodology in medicine, and it sows the seeds of potential cross-pollination between engineering and medicine. Establishing a modified failure mode and effects analysis can be a teamwork project or self-directed learning process, or a mix of both. Modified failure mode and effects analysis can be deployed to obtain inputs for an Ishikawa diagram which in turn can be used to enhance clinical experiences and clinical reasoning skills for clinicians, medical educators, and students.

  5. Cost-effective master cell bank validation of multiple clinical-grade human pluripotent stem cell lines from a single donor.

    Science.gov (United States)

    Devito, Liani; Petrova, Anastasia; Miere, Cristian; Codognotto, Stefano; Blakely, Nicola; Lovatt, Archie; Ogilvie, Caroline; Khalaf, Yacoub; Ilic, Dusko

    2014-10-01

    Standardization guidelines for human pluripotent stem cells are still very broadly defined, despite ongoing clinical trials in the U.S., U.K., and Japan. The requirements for validation of human embryonic (hESCs) and induced pluripotent stem cells (iPSCs) in general follow the regulations for other clinically compliant biologics already in place but without addressing key differences between cell types or final products. In order to realize the full potential of stem cell therapy, validation criteria, methodology, and, most importantly, strategy, should address the shortfalls and efficiency of current approaches; without this, hESC- and, especially, iPSC-based therapy will not be able to compete with other technologies in a cost-efficient way. We addressed the protocols for testing cell lines for human viral pathogens and propose a novel strategy that would significantly reduce costs. It is highly unlikely that the multiple cell lines derived in parallel from a tissue sample taken from one donor would have different profiles of endogenous viral pathogens; we therefore argue that samples from the Master Cell Banks of sibling lines could be safely pooled for validation. We illustrate this approach with tiered validation of two sibling clinical-grade hESC lines, KCL033 and KCL034 (stage 1, sterility; stage 2, specific human pathogens; and stage 3, nonspecific human pathogens). The results of all tests were negative. This cost-effective strategy could also be applied for validation of Master Cell Banks of multiple clinical-grade iPSC lines derived from a single donor. ©AlphaMed Press.

  6. 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

  7. Transmission of methicillin-resistant Staphylococcus pseudintermedius between infected dogs and cats and contact pets, humans and the environment in households and veterinary clinics.

    Science.gov (United States)

    van Duijkeren, E; Kamphuis, M; van der Mije, I C; Laarhoven, L M; Duim, B; Wagenaar, J A; Houwers, D J

    2011-06-02

    The objective of this study was to investigate the prevalence of methicillin-resistant Staphylococcus pseudintermedius (MRSP) in people, pets and the environment in households with a pet with a clinical MRSP-infection within the past year. Personnel and the environment at veterinary clinics were also screened. Nasal swabs (humans), nasal and perineal swabs (pets) and environmental wipes were examined using selective culturing. Twenty households were enrolled; 10/20 index cases still had clinical signs of infection at the start of the study and all were MRSP-positive. Of the remaining 10 index cases five were MRSP-positive in nasal and/or perineal samples. Five of 14 (36%) contact dogs and four of 13 (31%) contact cats were found MRSP-positive. In the households with an index case with clinical signs of infection 6/7 (86%) contact animals were MRSP-positive. MRSP was cultured from 2/45 (4%) human nasal samples. Domestic contamination was widespread as positive samples were found in 70% of the households and 44% of all environmental samples were MRSP-positive. In all but one of these MRSP-positive households the index case was still MRSP positive. Among the personnel in veterinary clinics 4/141 (3%) were MRSP-positive. MRSP was cultured from 31/200 environmental samples in 7/13 clinics at the first sampling and in 3/6 clinics the environment remained MRSP-positive after cleaning and disinfection indicating that current cleaning procedures often were unable to eliminate MRSP. These results show that transmission of MRSP between infected or colonized dogs and cats and healthy people does occur but is relatively uncommon, while transmission to contact pets occurs frequently, especially when the index case still has clinical signs of MRSP-infection. Copyright © 2011 Elsevier B.V. All rights reserved.

  8. A simple, rapid and validated high-performance liquid chromatography method suitable for clinical measurements of human mercaptalbumin and non-mercaptalbumin.

    Science.gov (United States)

    Yasukawa, Keiko; Shimosawa, Tatsuo; Okubo, Shigeo; Yatomi, Yutaka

    2018-01-01

    Background Human mercaptalbumin and human non-mercaptalbumin have been reported as markers for various pathological conditions, such as kidney and liver diseases. These markers play important roles in redox regulations throughout the body. Despite the recognition of these markers in various pathophysiologic conditions, the measurements of human mercaptalbumin and non-mercaptalbumin have not been popular because of the technical complexity and long measurement time of conventional methods. Methods Based on previous reports, we explored the optimal analytical conditions for a high-performance liquid chromatography method using an anion-exchange column packed with a hydrophilic polyvinyl alcohol gel. The method was then validated using performance tests as well as measurements of various patients' serum samples. Results We successfully established a reliable high-performance liquid chromatography method with an analytical time of only 12 min per test. The repeatability (within-day variability) and reproducibility (day-to-day variability) were 0.30% and 0.27% (CV), respectively. A very good correlation was obtained with the results of the conventional method. Conclusions A practical method for the clinical measurement of human mercaptalbumin and non-mercaptalbumin was established. This high-performance liquid chromatography method is expected to be a powerful tool enabling the expansion of clinical usefulness and ensuring the elucidation of the roles of albumin in redox reactions throughout the human body.

  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-

    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...

  10. Clinical coherent anti-Stokes Raman scattering and multiphoton tomography of human skin with a femtosecond laser and photonic crystal fiber

    International Nuclear Information System (INIS)

    Breunig, Hans Georg; Weinigel, Martin; Bückle, Rainer; Kellner-Höfer, Marcel; König, Karsten; Lademann, Jürgen; Darvin, Maxim E; Sterry, Wolfram

    2013-01-01

    We report on in vivo coherent anti-Stokes Raman scattering spectroscopy (CARS), two-photon fluorescence and second-harmonic-generation imaging on human skin with a novel multimodal clinical CARS/multiphoton tomograph. CARS imaging is realized by a combination of femtosecond pulses with broadband continuum pulses generated by a photonic crystal fiber. The images reveal the microscopic distribution of (i) non-fluorescent lipids, (ii) endogenous fluorophores and (iii) the collagen network inside the human skin in vivo with subcellular resolution. Examples of healthy as well as cancer-affected skin are presented. (letter)

  11. Clinical coherent anti-Stokes Raman scattering and multiphoton tomography of human skin with a femtosecond laser and photonic crystal fiber

    Science.gov (United States)

    Breunig, Hans Georg; Weinigel, Martin; Bückle, Rainer; Kellner-Höfer, Marcel; Lademann, Jürgen; Darvin, Maxim E.; Sterry, Wolfram; König, Karsten

    2013-02-01

    We report on in vivo coherent anti-Stokes Raman scattering spectroscopy (CARS), two-photon fluorescence and second-harmonic-generation imaging on human skin with a novel multimodal clinical CARS/multiphoton tomograph. CARS imaging is realized by a combination of femtosecond pulses with broadband continuum pulses generated by a photonic crystal fiber. The images reveal the microscopic distribution of (i) non-fluorescent lipids, (ii) endogenous fluorophores and (iii) the collagen network inside the human skin in vivo with subcellular resolution. Examples of healthy as well as cancer-affected skin are presented.

  12. Simultaneous GC-ECNICI-MS measurement of nitrite, nitrate and creatinine in human urine and plasma in clinical settings.

    Science.gov (United States)

    Hanff, Erik; Lützow, Moritz; Kayacelebi, Arslan Arinc; Finkel, Armin; Maassen, Mirja; Yanchev, Georgi Radoslavov; Haghikia, Arash; Bavendiek, Udo; Buck, Anna; Lücke, Thomas; Maassen, Norbert; Tsikas, Dimitrios

    2017-03-15

    Creatinine in urine is a useful biochemical parameter to correct the urinary excretion rate of endogenous and exogenous substances. Nitrite (ONO - ) and nitrate (ONO 2 - ) are metabolites of nitric oxide (NO), a signalling molecule with multiple biological functions. Under certain and standardized conditions, the concentration of nitrate in the urine is a suitable measure of whole body NO synthesis. The urinary nitrate-to-nitrite molar ratio (U NOx R) may indicate nitrite-dependent renal carbonic anhydrase (CA) activity. In clinical studies, urine is commonly collected by spontaneous micturition. In those cases the nitrate and nitrite excretion must be corrected for creatinine excretion. Pentafluorobenzyl (PFB) bromide (PFB-Br) is a useful derivatization reagent of numerous inorganic and organic compounds, including urinary nitrite, nitrate and creatinine, for highly sensitive and specific quantitation by GC-MS. Here, we report on the simultaneous PFB-Br derivatization (60min, 50°C) of ONO - , O 15 NO - , ONO 2 - , O 15 NO 2 - , creatinine (d o -Crea) and [methylo- 2 H 3 ]creatinine (d 3 -Crea) in acetonic dilutions of native human urine and plasma samples (4:1, v/v) and their simultaneous quantification by GC-MS as PFBNO 2 , PFB 15 NO 2 , PFBONO 2 , PFBO 15 NO 2 , d o -Crea-PFB and d 3 -Crea-PFB, respectively. Electron capture negative-ion chemical ionization (ECNICI) of these derivatives generates anions due to [M-PFB] - , i.e., the starting analytes. Quantification is performed by selected-ion monitoring (SIM) of m/z 46 (ONO - ), m/z 47 (O 15 NO - ), m/z 62 (ONO 2 - ), m/z 63 (O 15 NO 2 - ), m/z 112 (d o -Crea), and m/z 115 (d 3 -Crea). Retention times were 2.97min for PFB-ONO 2 /PFB-O 15 NO 2 , 3.1min for PFB-NO 2 /PFB- 15 NO 2 , and 6.7min for d o -Crea-PFB/d 3 -Crea-PFB. We used this method to investigate the effects of long-term oral NaNO 3 or NaCl (serving as placebo) supplementation (each 0.1mmol/kg body weight per day for 3 weeks) on creatinine excretion

  13. Clinical Trials

    Medline Plus

    Full Text Available ... and compare new treatments with other available treatments. Steps To Avoid Bias The researchers doing clinical trials take steps to avoid bias. "Bias" means that human choices ...

  14. Clinical Trials

    Medline Plus

    Full Text Available Skip to main content U.S. Department of Health & Human Services Health Topics Health Topics A-Z Clinical Trials Publications and Resources Health Education and Awareness The Science Science Home Blood Disorders and ...

  15. Clinical Trials

    Medline Plus

    Full Text Available Skip to main content U.S. Department of Health & Human Services Health Topics Health Topics A-Z Clinical Trials Publications and Resources Health Education and Awareness The Science Science Home Blood Disorders ...

  16. Clinical Trials

    Medline Plus

    Full Text Available ... work best for certain illnesses or groups of people. Clinical trials produce the best data available for ... or animals doesn't always work well in people. Thus, research in humans is needed. For safety ...

  17. Barriers and facilitators to primary care or human immunodeficiency virus clinics providing methadone or buprenorphine for the management of opioid dependence.

    Science.gov (United States)

    Turner, Barbara J; Laine, Christine; Lin, Yi-Ting; Lynch, Kevin

    Federal initiatives aim to increase office-based treatment of opioid dependence, but, to our knowledge, factors associated with willingness to deliver this care have not been defined. The objective of this study was to describe clinics' willingness to provide methadone hydrochloride or buprenorphine hydrochloride for opioid dependence. The design of the study was a survey conducted in New York State. Two hundred sixty-one directors of primary care and/or human immunodeficiency virus specialty clinics (response rate, 61.1%) that serve Medicaid enrollees were questioned. Outcomes were willingness to provide methadone and buprenorphine. Predictors included clinic characteristics, attitudes about drug users and their treatment, and reported barriers and facilitators to treatment. Clinics were more willing to provide buprenorphine than methadone treatment (59.8% vs 32.6%; P methadone. Willingness was positively associated with continuing medical education credits for training, but negatively associated with greater concern about medication abuse. Immediate telephone access to an addiction expert was associated with willingness to provide buprenorphine (AOR, 2.08; 95% CI, 1.15-3.76). Greater willingness to provide methadone was associated with a belief that methadone-treated patients should be seen along with other patients (AOR, 6.20; 95% CI, 1.78-21.64), methadone program affiliation (AOR, 4.76; 95% CI, 1.64-13.82), and having more patients with chronic pain in the clinic (AOR, 2.80; 95% CI, 1.44-5.44). These clinics serving Medicaid enrollees were more receptive to buprenorphine than methadone treatment. Willingness to provide this care was greater in clinics offering human immunodeficiency virus services, treating more chronic pain, or affiliated with methadone programs. Accessible addiction experts and continuing medical education for training may facilitate adoption of this care.

  18. Pluripotent stem cells reveal the developmental biology of human megakaryocytes and provide a source of platelets for clinical application.

    Science.gov (United States)

    Takayama, Naoya; Eto, Koji

    2012-10-01

    Human pluripotent stem cells [PSCs; including human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs)] can infinitely proliferate in vitro and are easily accessible for gene manipulation. Megakaryocytes (MKs) and platelets can be created from human ESCs and iPSCs in vitro and represent a potential source of blood cells for transfusion and a promising tool for studying the human thrombopoiesis. Moreover, disease-specific iPSCs are a powerful tool for elucidating the pathogenesis of hematological diseases and for drug screening. In that context, we and other groups have developed in vitro MK and platelet differentiation systems from human pluripotent stem cells (PSCs). Combining this co-culture system with a drug-inducible gene expression system enabled us to clarify the novel role played by c-MYC during human thrombopoiesis. In the next decade, technical advances (e.g., high-throughput genomic sequencing) will likely enable the identification of numerous gene mutations associated with abnormal thrombopoiesis. Combined with such technology, an in vitro system for differentiating human PSCs into MKs and platelets could provide a novel platform for studying human gene function associated with thrombopoiesis.

  19. Genotyping of human parvovirus B19 in clinical samples from Brazil and Paraguay using heteroduplex mobility assay, single-stranded conformation polymorphism and nucleotide sequencing

    Directory of Open Access Journals (Sweden)

    Marcos César Lima de Mendonça

    2011-06-01

    Full Text Available Heteroduplex mobility assay, single-stranded conformation polymorphism and nucleotide sequencing were utilised to genotype human parvovirus B19 samples from Brazil and Paraguay. Ninety-seven serum samples were collected from individuals presenting with abortion or erythema infectiosum, arthropathies, severe anaemia and transient aplastic crisis; two additional skin samples were collected by biopsy. After the procedure, all clinical samples were classified as genotype 1.

  20. Genetic variation in the Cytb gene of human cerebral Taenia solium cysticerci recovered from clinically and radiologically heterogeneous patients with neurocysticercosis

    Directory of Open Access Journals (Sweden)

    Hector Palafox-Fonseca

    2013-11-01

    Full Text Available Neurocysticercosis (NC is a clinically and radiologically heterogeneous parasitic disease caused by the establishment of larval Taenia solium in the human central nervous system. Host and/or parasite variations may be related to this observed heterogeneity. Genetic differences between pig and human-derived T. solium cysticerci have been reported previously. In this study, 28 cysticerci were surgically removed from 12 human NC patients, the mitochondrial gene that encodes cytochrome b was amplified from the cysticerci and genetic variations that may be related to NC heterogeneity were characterised. Nine different haplotypes (Ht, which were clustered in four haplogroups (Hg, were identified. Hg 3 and 4 exhibited a tendency to associate with age and gender, respectively. However, no significant associations were found between NC heterogeneity and the different T. solium cysticerci Ht or Hg. Parasite variants obtained from patients with similar NC clinical or radiological features were genetically closer than those found in groups of patients with a different NC profile when using the Mantel test. Overall, this study establishes the presence of genetic differences in the Cytb gene of T. solium isolated from human cysticerci and suggests that parasite variation could contribute to NC heterogeneity.

  1. A literature review on cardiovascular risk in human immunodeficiency virus-infected patients: implications for clinical management

    Directory of Open Access Journals (Sweden)

    Mansueto Gomes Neto

    Full Text Available INTRODUCTION: In recent years, there has been growing concern about an increasing rate of cardiovascular diseases in human immunodeficiency virus-infected patients, which could be associated with side effects of highly active antiretroviral therapy. It is likely that the metabolic disorders related to anti-human immunodeficiency virus treatment will eventually translate into a increased cardiovascular risk in patients submitted to such regimens. OBJECTIVE: To evaluate if human immunodeficiency virus-infected patients receiving highly active antiretroviral therapy are at higher risk of cardiovascular diseases than human immunodeficiency virus infected patients not receiving highly active antiretroviral therapy, or the general population. RESEARCH DESIGN AND METHODS: We conducted a computer-based search in representative databases, and also performed manual tracking of citations in selected articles. RESULT: The available evidence suggests an excess risk of cardiovascular events in human immunodeficiency virus-infected persons compared to non-human immunodeficiency virus infected individuals. The use of highly active antiretroviral therapy is associated with increased levels of total cholesterol, triglycerides, low-density lipoprotein and morphological signs of cardiovascular diseases. Some evidence suggested that human immunodeficiency virus-infected individuals on highly active antiretroviral therapy regimens are at increased risk of dyslipidemia, ischemic heart disease, and myocardial infarction, particularly if the highly active antiretroviral therapy regimen contains a protease inhibitor. CONCLUSION: Physicians must weigh the cardiovascular risk against potential benefits when prescribing highly active antiretroviral therapy. Careful cardiac screening is warranted for patients who are being evaluated for, or who are receiving highly active antiretroviral therapy regimens, particularly for those with known underlying cardiovascular risk

  2. Rabies Virus Exposure of Brazilian Free-ranging Wildlife from Municipalities without Clinical Cases in Humans or in Terrestrial Wildlife.

    Science.gov (United States)

    Marcelo Azevedo de Paula Antunes, João; de Castro Demoner, Larissa; Morosini de Andrade Cruvinel, Tatiana; Paula Kataoka, Ana; Fátima Alves Martorelli, Luzia; Puglia Machado, Gustavo; Megid, Jane

    2017-07-01

    Rabies is a zoonosis that causes thousands of animal and human deaths worldwide. Serological studies provide information concerning rabies virus circulation among animals and humans. We evaluated the circulation of the rabies virus in wildlife in nine municipalities of São Paulo State, Brazil. We took blood samples from 27 terrestrial animals of nine different mammalian species in locations without cases of rabies in human and wild terrestrial mammals. Sera were tested with the use of the rapid fluorescent focus inhibition test (RFFIT) for the detection of rabies virus-neutralizing antibodies (RVNA). The RFFIT was positive in 100% of the samples, with many (81.48%) showing protective titer levels (>0.5 IU/mL) with other samples (18.52%) showing titers representing exposure (rabies virus in municipalities without a history of human rabies cases, which demonstrated a need for research to understand the role of these animals in the circulation and transmission of the disease.

  3. Anti-VEGF strategies - from antibodies to tyrosine kinase inhibitors: background and clinical development in human cancer.

    LENUS (Irish Health Repository)

    Korpanty, Grzegorz

    2012-01-01

    Tumour angiogenesis (formation of new blood vessels supporting tumour growth and metastasis) is a result of complex interactions between the tumour and the surrounding microenvironment. Targeting tumours with anti-angiogenic therapy remains an exciting area of preclinical and clinical studies. Although many significant advances have been achieved and the clinical use of anti-angiogenic drugs is now well recognized in many solid malignancies, these therapies fall short of their anticipated clinical benefits and leave many unanswered questions like exact mechanism of action, patients\\' selection and monitoring response to anti-angiogenic drugs. Tumour angiogenesis is controlled by complex signaling cascades and ongoing research into molecular mechanisms of tumour angiogenesis not only helps to understand its basic mechanisms but hopefully will identify new therapeutic targets. In 2012, both monoclonal antibodies and small molecule tyrosine kinase inhibitors remain the two major clinically useful therapeutic options that interfere with tumour angiogenesis in many solid malignancies.

  4. Novel Polymerase Gene Mutations for Human Adaptation in Clinical Isolates of Avian H5N1 Influenza Viruses.

    Directory of Open Access Journals (Sweden)

    Yasuha Arai

    2016-04-01

    Full Text Available A major determinant in the change of the avian influenza virus host range to humans is the E627K substitution in the PB2 polymerase protein. However, the polymerase activity of avian influenza viruses with a single PB2-E627K mutation is still lower than that of seasonal human influenza viruses, implying that avian viruses require polymerase mutations in addition to PB2-627K for human adaptation. Here, we used a database search of H5N1 clade 2.2.1 virus sequences with the PB2-627K mutation to identify other polymerase adaptation mutations that have been selected in infected patients. Several of the mutations identified acted cooperatively with PB2-627K to increase viral growth in human airway epithelial cells and mouse lungs. These mutations were in multiple domains of the polymerase complex other than the PB2-627 domain, highlighting a complicated avian-to-human adaptation pathway of avian influenza viruses. Thus, H5N1 viruses could rapidly acquire multiple polymerase mutations that function cooperatively with PB2-627K in infected patients for optimal human adaptation.

  5. 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.

  6. Naturally Occurring Canine Invasive Urinary Bladder Cancer: A Complementary Animal Model to Improve the Success Rate in Human Clinical Trials of New Cancer Drugs

    Directory of Open Access Journals (Sweden)

    Christopher M. Fulkerson

    2017-01-01

    Full Text Available Genomic analyses are defining numerous new targets for cancer therapy. Therapies aimed at specific genetic and epigenetic targets in cancer cells as well as expanded development of immunotherapies are placing increased demands on animal models. Traditional experimental models do not possess the collective features (cancer heterogeneity, molecular complexity, invasion, metastasis, and immune cell response critical to predict success or failure of emerging therapies in humans. There is growing evidence, however, that dogs with specific forms of naturally occurring cancer can serve as highly relevant animal models to complement traditional models. Invasive urinary bladder cancer (invasive urothelial carcinoma (InvUC in dogs, for example, closely mimics the cancer in humans in pathology, molecular features, biological behavior including sites and frequency of distant metastasis, and response to chemotherapy. Genomic analyses are defining further intriguing similarities between InvUC in dogs and that in humans. Multiple canine clinical trials have been completed, and others are in progress with the aim of translating important findings into humans to increase the success rate of human trials, as well as helping pet dogs. Examples of successful targeted therapy studies and the challenges to be met to fully utilize naturally occurring dog models of cancer will be reviewed.

  7. Naturally Occurring Canine Invasive Urinary Bladder Cancer: A Complementary Animal Model to Improve the Success Rate in Human Clinical Trials of New Cancer Drugs.

    Science.gov (United States)

    Fulkerson, Christopher M; Dhawan, Deepika; Ratliff, Timothy L; Hahn, Noah M; Knapp, Deborah W

    2017-01-01

    Genomic analyses are defining numerous new targets for cancer therapy. Therapies aimed at specific genetic and epigenetic targets in cancer cells as well as expanded development of immunotherapies are placing increased demands on animal models. Traditional experimental models do not possess the collective features (cancer heterogeneity, molecular complexity, invasion, metastasis, and immune cell response) critical to predict success or failure of emerging therapies in humans. There is growing evidence, however, that dogs with specific forms of naturally occurring cancer can serve as highly relevant animal models to complement traditional models. Invasive urinary bladder cancer (invasive urothelial carcinoma (InvUC)) in dogs, for example, closely mimics the cancer in humans in pathology, molecular features, biological behavior including sites and frequency of distant metastasis, and response to chemotherapy. Genomic analyses are defining further intriguing similarities between InvUC in dogs and that in humans. Multiple canine clinical trials have been completed, and others are in progress with the aim of translating important findings into humans to increase the success rate of human trials, as well as helping pet dogs. Examples of successful targeted therapy studies and the challenges to be met to fully utilize naturally occurring dog models of cancer will be reviewed.

  8. Population Genomics and the Statistical Values of Race:An Interdisciplinary Perspective on the Biological Classification of Human Populations and Implications for Clinical Genetic Epidemiological Research

    Directory of Open Access Journals (Sweden)

    Koffi N. Maglo

    2016-02-01

    Full Text Available The biological status and biomedical significance of the concept of race as applied to humans continue to be contentious issues despite the use of advanced statistical and clustering methods to determine continental ancestry. It is thus imperative for researchers to understand the limitations as well as potential uses of the concept of race in biology and biomedicine. This paper deals with the theoretical assumptions behind cluster analysis in human population genomics. Adopting an interdisciplinary approach, it demonstrates that the hypothesis that attributes the clustering of human populations to frictional effects of landform barriers at continental boundaries is empirically incoherent. It then contrasts the scientific status of the cluster and cline constructs in human population genomics, and shows how cluster may be instrumentally produced. It also shows how statistical values of race vindicate Darwin’s argument that race is evolutionarily meaningless. Finally, the paper explains why, due to spatiotemporal parameters, evolutionary forces and socio-cultural factors influencing population structure, continental ancestry may be pragmatically relevant to global and public health genomics. Overall, this work demonstrates that, from a biological systematic and evolutionary taxonomical perspective, human races/continental groups or clusters have no natural meaning or objective biological reality. In fact, the utility of racial categorizations in research and in clinics can be explained by spatiotemporal parameters, socio-cultural factors and evolutionary forces affecting disease causation and treatment response.

  9. Applying clinically proven human techniques for contraception and fertility to endangered species and zoo animals: a review.

    Science.gov (United States)

    Silber, Sherman J; Barbey, Natalie; Lenahan, Kathy; Silber, David Z

    2013-12-01

    Reversible contraception that does not alter natural behavior is a critical need for managing zoo populations. In addition to reversible contraception, other fertility techniques perfected in humans may be useful, such as in vitro fertilization (IVF) or oocyte and embryo banking for endangered species like amphibians and Mexican wolves (Canis lupus baileyi). Furthermore, the genetics of human fertility can give a better understanding of fertility in more exotic species. Collaborations were established to apply human fertility techniques to the captive population. Reversible vasectomy might be one solution for reversible contraception that does not alter behavior. Reversible approaches to vasectomy, avoiding secondary epididymal disruption, were attempted in South American bush dogs (Speothos venaticus), chimpanzees (Pan troglodytes), gorillas (Gorilla gorilla), Przewalski's horse (Equus przewalski poliakov), and Sika deer (Cervus nippon) in a variety of zoos around the world. These techniques were first perfected in > 4,000 humans before attempting them in zoo animals. In vitro fertilization with gestational surrogacy was used to attempt to break the vicious cycle of hand rearing of purebred orangutans, and egg and ovary vitrification in humans have led to successful gamete banking for Mexican wolves and disappearing amphibians. The study of the human Y chromosome has even explained a mechanism of extinction related to global climate change. The best results with vasectomy reversal (normal sperm counts, pregnancy, and live offspring) were obtained when the original vasectomy was performed "open-ended," so as to avoid pressure-induced epididymal disruption. The attempt at gestational surrogacy for orangutans failed because of severe male infertility and the lack of success with human ovarian hyperstimulation protocols. Vitrification of oocytes is already being employed for the Amphibian Ark Project and for Mexican wolves. Vasectomy can be a reversible contraception

  10. [Comparison of human papilloma virus infection status between men who have sex with men recruited from gay bathhouses and HIV voluntary counseling and testing clinics respectively in Urumqi].

    Science.gov (United States)

    Tian, T; Cai, A J; Huang, B X; Abidan, Ainiwaer; Wang, H; Dai, J H

    2017-01-10

    Objective: To understand the human papilloma virus (HPV) infection status in men who have sex with men (MSM) recruited from gay bathhouses and HIV voluntary counseling and testing (VCT) clinics in Urumqi, Xinjiang Uygur autonomous region, and identify the associated risk factors. Methods: A total of 200 MSM aged ≥18 years were recruited by using the " snowballing" sampling method from gay bathhouses and VCT clinics in Urumqi during March-May, 2016. The MSM recruited completed questionnaires after filling in the informed consent form. The information about their demographic characteristics and sexual behaviors were collected, and anal swabs were collected from them for HPV genotyping. Results: The overall HPV infection rate was 54.0 % . The HPV infection rate was 66.7 % (74/111) in MSM from gay bathhouses and 38.2 % (34/89) in MSM from VCT clinics and the high risk type HPV infection rate was 39.6 % (44/111) in MSM from gay bathhouses and 14.6 % (13/89) in MSM from VCT clinics, the differences were significant ( χ (2)=16.112, P prevalence of HPV in MSM from gay bathhouses was higher than that in MSM from VCT clinics, indicating that close attention should be paid to the behavior intervention in MSM.

  11. Measurement of caffeine and its three primary metabolites in human plasma by HPLC-ESI-MS/MS and clinical application.

    Science.gov (United States)

    Chen, Feng; Hu, Zhe-Yi; Parker, Robert B; Laizure, S Casey

    2017-06-01

    Caffeine is a mild stimulant with significant potential for abuse, being consumed in larger doses with the widespread availability of energy drinks and by novel routes of administration such as inspired powder, oral sprays and electronic cigarettes. How these recent changes in caffeine consumption affecting caffeine disposition and abuse potential is of growing concern. In the study of caffeine disposition in humans, it is common to only measure the caffeine concentration; however, caffeine's three major metabolites (paraxanthine, theobromine and theophylline) retain central nervous system stimulant activity that may contribute to the overall pharmacological activity and toxicity. Therefore, it would be scientifically more rigorous to measure caffeine and its major metabolites in the evaluation of caffeine disposition in human subjects. Herein, we report a method for the simultaneous quantification of caffeine and its three major metabolites in human plasma by high-performance liquid chromatography coupled to electrospray tandem mass spectrometry (HPLC-ESI-MS/MS). Human plasma samples were treated by simple protein precipitation and the analytes were separated using a 6 min gradient program. Precision and accuracy were well within in the 15% acceptance range. The simple sample preparation, short runtime, sensitivity and the inclusion of caffeine's major metabolites make this assay methodology optimal for the study of caffeine's pharmacokinetics and pharmacodynamics in human subjects. Copyright © 2016 John Wiley & Sons, Ltd.

  12. Regulatory approval and a first-in-human phase I clinical trial of a monoclonal antibody produced in transgenic tobacco plants.

    Science.gov (United States)

    Ma, Julian K-C; Drossard, Jürgen; Lewis, David; Altmann, Friedrich; Boyle, Julia; Christou, Paul; Cole, Tom; Dale, Philip; van Dolleweerd, Craig J; Isitt, Valerie; Katinger, Dietmar; Lobedan, Martin; Mertens, Hubert; Paul, Mathew J; Rademacher, Thomas; Sack, Markus; Hundleby, Penelope A C; Stiegler, Gabriela; Stoger, Eva; Twyman, Richard M; Vcelar, Brigitta; Fischer, Rainer

    2015-10-01

    Although plant biotechnology has been widely investigated for the production of clinical-grade monoclonal antibodies, no antibody products derived from transgenic plants have yet been approved by pharmaceutical regulators for clinical testing. In the Pharma-Planta project, the HIV-neutralizing human monoclonal antibody 2G12 was expressed in transgenic tobacco (Nicotiana tabacum). The scientific, technical and regulatory demands of good manufacturing practice (GMP) were addressed by comprehensive molecular characterization of the transgene locus, confirmation of genetic and phenotypic stability over several generations of transgenic plants, and by establishing standard operating procedures for the creation of a master seed bank, plant cultivation, harvest, initial processing, downstream processing and purification. The project developed specifications for the plant-derived antibody (P2G12) as an active pharmaceutical ingredient (API) based on (i) the guidelines for the manufacture of monoclonal antibodies in cell culture systems; (ii) the draft European Medicines Agency Points to Consider document on quality requirements for APIs produced in transgenic plants; and (iii) de novo guidelines developed with European national regulators. From the resulting process, a GMP manufacturing authorization was issued by the competent authority in Germany for transgenic plant-derived monoclonal antibodies for use in a phase I clinical evaluation. Following preclinical evaluation and ethical approval, a clinical trial application was accepted by the UK national pharmaceutical regulator. A first-in-human, double-blind, placebo-controlled, randomized, dose-escalation phase I safety study of a single vaginal administration of P2G12 was carried out in healthy female subjects. The successful completion of the clinical trial marks a significant milestone in the commercial development of plant-derived pharmaceutical proteins. © 2015 Society for Experimental Biology, Association of

  13. From the ideal market to the ideal clinic: constructing a normative standard of fairness for human subjects research.

    Science.gov (United States)

    Phillips, Trisha

    2011-02-01

    Preventing exploitation in human subjects research requires a benchmark of fairness against which to judge the distribution of the benefits and burdens of a trial. This paper proposes the ideal market and its fair market price as a criterion of fairness. The ideal market approach is not new to discussions about exploitation, so this paper reviews Wertheimer's inchoate presentation of the ideal market as a principle of fairness, attempt of Emanuel and colleagues to apply the ideal market to human subjects research, and Ballantyne's criticisms of both the ideal market and the resulting benchmark of fairness. It argues that the criticism of this particular benchmark is on point, but the rejection of the ideal market is mistaken. After presenting a complete account of the ideal market, this paper proposes a new method for applying the ideal market to human subjects research and illustrates the proposal by considering a sample case.

  14. Functionalized Magnetic Resonance Contrast Agent Selectively Binds to Glycoprotein IIb/IIIa on Activated Human Platelets under Flow Conditions and Is Detectable at Clinically Relevant Field Strengths

    Directory of Open Access Journals (Sweden)

    Constantin von zur Mühlen

    2008-03-01

    Full Text Available Recent progress in molecular magnetic resonance imaging (MRI provides the opportunity to image cells and cellular receptors using microparticles of iron oxide (MPIOs. However, imaging targets on vessel walls remains challenging owing to the quantity of contrast agents delivered to areas of interest under shear stress conditions. We evaluated ex vivo binding characteristics of a functional MRI contrast agent to ligand-induced binding sites (LIBSs on activated glycoprotein IIb/IIIa receptors of human platelets, which were lining rupture-prone atherosclerotic plaques and could therefore facilitate detection of platelet-mediated pathology in atherothrombotic disease. MPIOs were conjugated to anti-LIBS single-chain antibodies (LIBS-MPIO or control antibodies (control MPIO. Ex vivo binding to human platelet-rich clots in a dose-dependent manner was confirmed on a 3 T clinical MRI scanner and by histology (p < .05 for LIBS-MPIO vs control MPIO. By using a flow chamber setup, significant binding of LIBS-MPIO to a platelet matrix was observed under venous and arterial flow conditions, but not for control MPIO (p < .001. A newly generated MRI contrast agent detects activated human platelets at clinically relevant magnetic field strengths and binds to platelets under venous and arterial flow conditions, conveying high payloads of contrast to specific molecular targets. This may provide the opportunity to identify vulnerable, rupture-prone atherosclerotic plaques via noninvasive MRI.

  15. Movement in the body and clinical estimation of technetium-labeled macroagglutinated human serum albumin injection (sup(99m)Tc-MAA)

    International Nuclear Information System (INIS)

    Suzuki, Masaaki; Nomura, Shigeo; Ueda, Nobuo; Matsushima, Hiroaki; Hazue, Masaaki.

    1978-01-01

    As a basic study, sup(99m)Tc-MMA was given intravenously to rats and 11 human cases which were going to have lung scintigram, and its movements in the body were observed with the progress of time. As clinical studies, sup(99m)Tc-MMA was given intravenously to 219 cases in which lung scintigraphy was performed. Observation was made by gamma camera, and utility of gamma camera was estimated. Radioactivity accumulated in the lung reached the maximum value 5 minutes after the intravenous injection, and thereafter, it decreased with the progress of time. Its biological half-life was 10 hours, and effective half-life was 315 hours. In human, it reached the maximum value just after the intravenous injection, and the biological half-life was 16.1 hours, and the effective half-life was 4.4 hours. Main excretion route in rat and human was urinary tract. The analysis of excreta in urine by chromatography demonstrated that 60% of this drug was metabolized. Clinically, clear lung scintigrams of all 219 cases were obtained. Side effects of sup(99m)Tc-MMA were not recognized, and its utility was recognized. The biological calculative base was set up from the basic data, and estimation was made concerning exposure dose by MIRD method. (J.P.N.)

  16. 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...

  17. Simultaneous determination of glucose, triglycerides, urea, cholesterol, albumin and total protein in human plasma by Fourier transform infrared spectroscopy: direct clinical biochemistry without reagents.

    Science.gov (United States)

    Jessen, Torben E; Höskuldsson, Agnar T; Bjerrum, Poul J; Verder, Henrik; Sørensen, Lars; Bratholm, Palle S; Christensen, Bo; Jensen, Lene S; Jensen, Maria A B

    2014-09-01

    Direct measurement of chemical constituents in complex biologic matrices without the use of analyte specific reagents could be a step forward toward the simplification of clinical biochemistry. Problems related to reagents such as production errors, improper handling, and lot-to-lot variations would be eliminated as well as errors occurring during assay execution. We describe and validate a reagent free method for direct measurement of six analytes in human plasma based on Fourier-transform infrared spectroscopy (FTIR). Blood plasma is analyzed without any sample preparation. FTIR spectrum of the raw plasma is recorded in a sampling cuvette specially designed for measurement of aqueous solutions. For each analyte, a mathematical calibration process is performed by a stepwise selection of wavelengths giving the optimal least-squares correlation between the measured FTIR signal and the analyte concentration measured by conventional clinical reference methods. The developed calibration algorithms are subsequently evaluated for their capability to predict the concentration of the six analytes in blinded patient samples. The correlation between the six FTIR methods and corresponding reference methods were 0.87albumin and total protein in human plasma. Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  18. The Challenges of First-in-Human Stem Cell Clinical Trials: What Does This Mean for Ethics and Institutional Review Boards?

    Directory of Open Access Journals (Sweden)

    Roger A. Barker

    2018-05-01

    Full Text Available Stem cell-based clinical interventions are increasingly advancing through preclinical testing and approaching clinical trials. The complexity and diversity of these approaches, and the confusion created by unproven and untested stem cell-based “therapies,” create a growing need for a more comprehensive review of these early-stage human trials to ensure they place the patients at minimal risk of adverse events but are also based on solid evidence of preclinical efficacy with a clear scientific rationale for that effect. To address this issue and supplement the independent review process, especially that of the ethics and institutional review boards who may not be experts in stem cell biology, the International Society for Stem Cell Research (ISSCR has developed a set of practical questions to cover the major issues for which clear evidence-based answers need to be obtained before approving a stem cell-based trial. Keywords: human stem cell-derived interventions, early phase clinical trials, institutional review and ethics boards, review process, guidelines

  19. 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

  20. High Prevalence of Escherichia coli-Producing CTX-M-15 Extended-Spectrum Beta-Lactamases in Poultry and Human Clinical Isolates in Romania.

    Science.gov (United States)

    Maciuca, Iuliana E; Williams, Nicola J; Tuchilus, Cristina; Dorneanu, Olivia; Guguianu, Eleonora; Carp-Carare, Catalin; Rimbu, Cristina; Timofte, Dorina

    2015-12-01

    Use of antibiotics in food animals may contribute to development and spread of resistant organisms, particularly so in some countries. The aim of this study was two-fold; first, to establish the prevalence of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli in chicken production in a region within Romania. Second, to study the relatedness of ESBL-producing E. coli isolates recovered from broilers, abattoir workers where the chickens were slaughtered and from the human clinical specimens from two regional hospitals. The results indicated a very high (69%) rate of carriage of ESBL and AmpC-producing E. coli in chickens with 36% CTX-M producers. Sequencing showed that chickens in Romania have the highest worldwide prevalence (53%) of blaCTX-M-15 reported in poultry E. coli isolates. The majority (53%) of the extended-spectrum cephalosporin-resistant E. coli carried plasmid-mediated blaampC genes, mostly blaCMY-2 type, one of the highest prevalences reported in Europe. The predominant CTX-M type found in the human clinical E. coli isolates was blaCTX-M-15 and most isolates coharbored blaOXA-1, blaTEM, and aac(6')-ib-cr. The majority (60%) of the human clinical isolates belonged to the pandemic virulent clone B2-ST131. The clonal relationship between broiler and the human CTX-M-producing E. coli isolates was assessed by macrorestriction pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST), which indicated strain diversity with no common STs found between human and poultry isolates. Moreover, IncI1 was the most prevalent replicon found in broiler ESBL-producing E. coli isolates and also in transconjugants, indicating that plasmids and not clonal spread may play a role in the transfer of blaCTX-M genes. This study identifies a high prevalence of ESBL-producing E. coli from broiler chickens in Romania with a high occurrence incidence of blaCTX-M-15, which reflects the main ESBL type found in human E. coli infections in this

  1. Clinical trials of boron neutron capture therapy [in humans] [at Beth Israel Deaconess Medical Center][at Brookhaven National Laboratory

    International Nuclear Information System (INIS)

    Wallace, Christine

    2001-01-01

    Assessment of research records of Boron Neutron Capture Therapy was conducted at Brookhaven National Laboratory and Beth Israel Deaconess Medical Center using the Code of Federal Regulations, FDA Regulations and Good Clinical Practice Guidelines. Clinical data were collected FR-om subjects' research charts, and differences in conduct of studies at both centers were examined. Records maintained at Brookhaven National Laboratory were not in compliance with regulatory standards. Beth Israel's records followed federal regulations. Deficiencies discovered at both sites are discussed in the reports

  2. [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.

  3. Gene expression data from acetaminophen-induced toxicity in human hepatic in vitro systems and clinical liver samples

    Directory of Open Access Journals (Sweden)

    Robim M. Rodrigues

    2016-06-01

    Full Text Available This data set is composed of transcriptomics analyses of (i liver samples from patients suffering from acetaminophen-induced acute liver failure (ALF and (ii hepatic cell systems exposed to acetaminophen and their respective controls. The in vitro systems include widely employed cell lines i.e. HepaRG and HepG2 cells as well as a novel stem cell-derived model i.e. human skin-precursors-derived hepatocyte-like cells (hSKP-HPC. Data from primary human hepatocytes was also added to the data set “Open TG-GATEs: a large-scale toxicogenomics database” (Igarashi et al., 2015 [1]. Changes in gene expression due to acetaminophen intoxication as well as comparative information between human in vivo and in vitro samples are provided. The microarray data have been deposited in NCBI׳s Gene Expression Omnibus and are accessible through GEO Series accession number GEO: GSE74000. The provided data is used to evaluate the predictive capacity of each hepatic in vitro system and can be directly compared with large-scale publically available toxicogenomics databases. Further interpretation and discussion of these data feature in the corresponding research article “Toxicogenomics-based prediction of acetaminophen-induced liver injury using human hepatic cell systems” (Rodrigues et al., 2016 [2].

  4. An Interactive Method for Teaching Anatomy of the Human Eye for Medical Students in Ophthalmology Clinical Rotations

    Science.gov (United States)

    Kivell, Tracy L.; Doyle, Sara K.; Madden, Richard H.; Mitchell, Terry L.; Sims, Ershela L.

    2009-01-01

    Much research has shown the benefits of additional anatomical learning and dissection beyond the first year of medical school human gross anatomy, all the way through postgraduate medical training. We have developed an interactive method for teaching eye and orbit anatomy to medical students in their ophthalmology rotation at Duke University…

  5. Clinical responses to adoptive T-cell transfer can be modeled in an autologous immune-humanized mouse model

    DEFF Research Database (Denmark)

    Jespersen, Henrik; Lindberg, Mattias F; Donia, Marco

    2017-01-01

    Immune checkpoint inhibitors and adoptive cell transfer (ACT) of autologous tumor-infiltrating T cells have shown durable responses in patients with melanoma. To study ACT and immunotherapies in a humanized model, we have developed PDXv2.0 - a melanoma PDX model where tumor cells and tumor...

  6. Comparison of human immunodeficiency virus type 1 tropism profiles in clinical samples by the Trofile and MT-2 assays

    NARCIS (Netherlands)

    Coakley, Eoin; Reeves, Jacqueline D.; Huang, Wei; Mangas-Ruiz, Marga; Maurer, Irma; Harskamp, Agnes M.; Gupta, Soumi; Lie, Yolanda; Petropoulos, Christos J.; Schuitemaker, Hanneke; van 't Wout, Angélique B.

    2009-01-01

    The recent availability of CCR5 antagonists as anti-human immunodeficiency virus (anti-HIV) therapeutics has highlighted the need to accurately identify CXCR4-using variants in patient samples when use of this new drug class is considered. The Trofile assay (Monogram Biosciences) has become the

  7. In vivo 1H spectroscopy of the human brain at 1.5 tesla. Preliminary experience at a clinical installation

    DEFF Research Database (Denmark)

    Henriksen, O; Larsson, H; Jensen, K M

    1990-01-01

    In vivo localized water suppressed proton spectroscopy of human brain was carried out on 15 healthy volunteers and 2 patients suffering from a brain tumour and an infarction, respectively. The measureme