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Sample records for relevant clinical studies

  1. Clinical relevance of studies on the accuracy of visual inspection for detecting caries lesions

    DEFF Research Database (Denmark)

    Gimenez, Thais; Piovesan, Chaiana; Braga, Mariana M

    2015-01-01

    Although visual inspection is the most commonly used method for caries detection, and consequently the most investigated, studies have not been concerned about the clinical relevance of this procedure. Therefore, we conducted a systematic review in order to perform a critical evaluation considering...... the clinical relevance and methodological quality of studies on the accuracy of visual inspection for assessing caries lesions. Two independent reviewers searched several databases through July 2013 to identify papers/articles published in English. Other sources were checked to identify unpublished literature...... to clinical relevance and the methodological quality of the studies were evaluated. 96 of the 5,578 articles initially identified met the inclusion criteria. In general, most studies failed in considering some clinically relevant aspects: only 1 included study validated activity status of lesions, no study...

  2. Clinical Relevance of Adipokines

    Directory of Open Access Journals (Sweden)

    Matthias Blüher

    2012-10-01

    Full Text Available The incidence of obesity has increased dramatically during recent decades. Obesity increases the risk for metabolic and cardiovascular diseases and may therefore contribute to premature death. With increasing fat mass, secretion of adipose tissue derived bioactive molecules (adipokines changes towards a pro-inflammatory, diabetogenic and atherogenic pattern. Adipokines are involved in the regulation of appetite and satiety, energy expenditure, activity, endothelial function, hemostasis, blood pressure, insulin sensitivity, energy metabolism in insulin sensitive tissues, adipogenesis, fat distribution and insulin secretion in pancreatic β-cells. Therefore, adipokines are clinically relevant as biomarkers for fat distribution, adipose tissue function, liver fat content, insulin sensitivity, chronic inflammation and have the potential for future pharmacological treatment strategies for obesity and its related diseases. This review focuses on the clinical relevance of selected adipokines as markers or predictors of obesity related diseases and as potential therapeutic tools or targets in metabolic and cardiovascular diseases.

  3. GA(2)LEN skin test study II: clinical relevance of inhalant allergen sensitizations in Europe

    DEFF Research Database (Denmark)

    Burbach, G J; Heinzerling, L M; Edenharter, G

    2009-01-01

    BACKGROUND: Skin prick testing is the standard for diagnosing IgE-mediated allergies. A positive skin prick reaction, however, does not always correlate with clinical symptoms. A large database from a Global Asthma and Allergy European Network (GA(2)LEN) study with data on clinical relevance was ...... the clinical relevance of positive skin prick tests and calls for further studies, which may, ultimately, help increase the positive predictive value of allergy testing.......BACKGROUND: Skin prick testing is the standard for diagnosing IgE-mediated allergies. A positive skin prick reaction, however, does not always correlate with clinical symptoms. A large database from a Global Asthma and Allergy European Network (GA(2)LEN) study with data on clinical relevance...... was used to determine the clinical relevance of sensitizations against the 18 most frequent inhalant allergens in Europe. The study population consisted of patients referred to one of the 17 allergy centres in 14 European countries (n = 3034, median age = 33 years). The aim of the study was to assess...

  4. The clinical relevance and newsworthiness of NIHR HTA-funded research: a cohort study.

    Science.gov (United States)

    Wright, D; Young, A; Iserman, E; Maeso, R; Turner, S; Haynes, R B; Milne, R

    2014-05-07

    To assess the clinical relevance and newsworthiness of the UK National Institute for Health Research (NIHR) Health Technology Assessment (HTA) Programme funded reports. Retrospective cohort study. The cohort included 311 NIHR HTA Programme funded reports publishing in HTA in the period 1 January 2007-31 December 2012. The McMaster Online Rating of Evidence (MORE) system independently identified the clinical relevance and newsworthiness of NIHR HTA publications and non-NIHR HTA publications. The MORE system involves over 4000 physicians rating publications on a scale of relevance (the extent to which articles are relevant to practice) and a scale of newsworthiness (the extent to which articles contain news or something clinicians are unlikely to know). The proportion of reports published in HTA meeting MORE inclusion criteria and mean average relevance and newsworthiness ratings were calculated and compared with publications from the same studies publishing outside HTA and non-NIHR HTA funded publications. 286/311 (92.0%) of NIHR HTA reports were assessed by MORE, of which 192 (67.1%) passed MORE criteria. The average clinical relevance rating for NIHR HTA reports was 5.48, statistically higher than the 5.32 rating for non-NIHR HTA publications (mean difference=0.16, 95% CI 0.04 to 0.29, p=0.01). Average newsworthiness ratings were similar between NIHR HTA reports and non-NIHR HTA publications (4.75 and 4.70, respectively; mean difference=0.05, 95% CI -0.18 to 0.07, p=0.402). NIHR HTA-funded original research reports were statistically higher for newsworthiness than reviews (5.05 compared with 4.64) (mean difference=0.41, 95% CI 0.18 to 0.64, p=0.001). Funding research of clinical relevance is important in maximising the value of research investment. The NIHR HTA Programme is successful in funding projects that generate outputs of clinical relevance.

  5. Clinically relevant potential drug-drug interactions among outpatients: A nationwide database study.

    Science.gov (United States)

    Jazbar, Janja; Locatelli, Igor; Horvat, Nejc; Kos, Mitja

    2018-06-01

    Adverse drug events due to drug-drug interactions (DDIs) represent a considerable public health burden, also in Slovenia. A better understanding of the most frequently occurring potential DDIs may enable safer pharmacotherapy and minimize drug-related problems. The aim of this study was to evaluate the prevalence and predictors of potential DDIs among outpatients in Slovenia. An analysis of potential DDIs was performed using health claims data on prescription drugs from a nationwide database. The Lexi-Interact Module was used as the reference source of interactions. The influence of patient-specific predictors on the risk of potential clinically relevant DDIs was evaluated using logistic regression model. The study population included 1,179,803 outpatients who received 15,811,979 prescriptions. The total number of potential DDI cases identified was 3,974,994, of which 15.6% were potentially clinically relevant. Altogether, 9.3% (N = 191,213) of the total population in Slovenia is exposed to clinically relevant potential DDIs, and the proportion is higher among women and the elderly. After adjustment for cofactors, higher number of medications and older age are associated with higher odds of clinically relevant potential DDIs. The burden of DDIs is highest with drug combinations that increase risk of bleeding, enhance CNS depression or anticholinergic effects or cause cardiovascular complications. The current study revealed that 1 in 10 individuals in the total Slovenian population is exposed to clinically relevant potential DDIs yearly. Taking into account the literature based conservative estimate that approximately 1% of potential DDIs result in negative health outcomes, roughly 1800 individuals in Slovenia experience an adverse health outcome each year as a result of clinically relevant potential interactions alone. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Cerebral activation studies by PET and fMRT, clinical relevance?

    International Nuclear Information System (INIS)

    Brandt, T.

    1997-01-01

    Cerebral activation studies by PET and fMRT will gain increasing clinical relevance for functional neuroanatomy (reading, speaking), localisation of largely unknown cortical functions (vestibular cortex), imaging of subjective complaints of functional impairments (pain, smell, memory), and documentation of neurological rehabilitation at neuronal level (regeneration, compensation, substitution, learning). (orig.) [de

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

    Science.gov (United States)

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

    2011-08-01

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

  8. Is statistical significance clinically important?--A guide to judge the clinical relevance of study findings

    NARCIS (Netherlands)

    Sierevelt, Inger N.; van Oldenrijk, Jakob; Poolman, Rudolf W.

    2007-01-01

    In this paper we describe several issues that influence the reporting of statistical significance in relation to clinical importance, since misinterpretation of p values is a common issue in orthopaedic literature. Orthopaedic research is tormented by the risks of false-positive (type I error) and

  9. Clinical relevance of comorbidity in anxiety disorders : A report from the Netherlands Study of Depression and Anxiety (NESDA)

    NARCIS (Netherlands)

    Hofmeijer-Sevink, Mieke Klein; Batelaan, Neeltje M.; van Megen, Harold J. G. M.; Penninx, Brenda W.; Cath, Danielle C.; van den Hout, Marcel A.; van Balkom, Anton J. L. M.

    Background: To study the clinical relevance of type of comorbidity and number of comorbid disorders in anxiety disorders. Four groups were compared according to sociodemographic-, vulnerability- and clinical factors: single anxiety disorder, anxiety-anxiety comorbidity, anxiety-depressive

  10. Clinical relevance of comorbidity in anxiety disorders: A report from the Netherlands Study of Depression and Anxiety (NESDA)

    NARCIS (Netherlands)

    Klein Hofmeijer-Sevink, M.; Batelaan, N.M.; van Megen, H.J.G.M.; Penninx, B.W.J.H.; Cath, D.C.; van Hout, M.A.; van Balkom, A.J.L.M.

    2012-01-01

    Background: To study the clinical relevance of type of comorbidity and number of comorbid disorders in anxiety disorders. Four groups were compared according to sociodemographic-, vulnerability- and clinical factors: single anxiety disorder, anxiety-anxiety comorbidity, anxiety-depressive

  11. The Netherlands XTC Toxicity (NeXT) study: objectives and methods of a study investigating causality, course, and clinical relevance

    NARCIS (Netherlands)

    de Win, Maartje M. L.; Jager, Gerry; Vervaeke, Hylke K. E.; Schilt, Thelma; Reneman, Liesbeth; Booij, Jan; Verhulst, Frank C.; den Heeten, Gerard J.; Ramsey, Nick F.; Korf, Dirk J.; van den Brink, Wim

    2005-01-01

    This paper describes the objectives and methods of The Netherlands XTC Toxicity (NeXT) study focussing on the causality, course, and clinical relevance of ecstasy neurotoxicity. Previous studies suggest that ecstasy (3,4 methylene-dioxymethamphetamine, MDMA, XTC) is toxic toward brain serotonin

  12. Clinical relevance in anesthesia journals

    DEFF Research Database (Denmark)

    Lauritsen, Jakob; Møller, Ann M

    2006-01-01

    The purpose of this review is to present the latest knowledge and research on the definition and distribution of clinically relevant articles in anesthesia journals. It will also discuss the importance of the chosen methodology and outcome of articles.......The purpose of this review is to present the latest knowledge and research on the definition and distribution of clinically relevant articles in anesthesia journals. It will also discuss the importance of the chosen methodology and outcome of articles....

  13. Clinical Relevance of Nontuberculous Mycobacteria Isolated from Sputum in a Gold Mining Workforce in South Africa: An Observational, Clinical Study

    Directory of Open Access Journals (Sweden)

    Clare L. van Halsema

    2015-01-01

    Full Text Available Background. The clinical relevance of nontuberculous mycobacteria (NTM, detected by liquid more than solid culture in sputum specimens from a South African mining workforce, is uncertain. We aimed to describe the current spectrum and relevance of NTM in this population. Methods. An observational study including individuals with sputum NTM isolates, recruited at workforce tuberculosis screening and routine clinics. Symptom questionnaires were administered at the time of sputum collection and clinical records and chest radiographs reviewed retrospectively. Results. Of 232 individuals included (228 (98% male, median age 44 years, M. gordonae (60 individuals, M. kansasii (50, and M. avium complex (MAC: 38 were the commonest species. Of 38 MAC isolates, only 2 (5.3% were from smear-positive sputum specimens and 30/38 grew in liquid but not solid culture. MAC was especially prevalent among symptomatic, HIV-positive individuals. HIV prevalence was high: 57/74 (77% among those tested. No differences were found in probability of death or medical separation by NTM species. Conclusions. M. gordonae, M. kansasii, and MAC were the commonest NTM among miners with suspected tuberculosis, with most MAC from smear-negative specimens in liquid culture only. HIV testing and identification of key pathogenic NTM in this setting are essential to ensure optimal treatment.

  14. The Power of Phase I Studies to Detect Clinical Relevant QTc Prolongation: A Resampling Simulation Study

    Directory of Open Access Journals (Sweden)

    Georg Ferber

    2015-01-01

    Full Text Available Concentration-effect (CE models applied to early clinical QT data from healthy subjects are described in the latest E14 Q&A document as promising analysis to characterise QTc prolongation. The challenges faced if one attempts to replace a TQT study by thorough ECG assessments in Phase I based on CE models are the assurance to obtain sufficient power and the establishment of a substitute for the positive control to show assay sensitivity providing protection against false negatives. To demonstrate that CE models in small studies can reliably predict the absence of an effect on QTc, we investigated the role of some key design features in the power of the analysis. Specifically, the form of the CE model, inclusion of subjects on placebo, and sparse sampling on the performance and power of this analysis were investigated. In this study, the simulations conducted by subsampling subjects from 3 different TQT studies showed that CE model with a treatment effect can be used to exclude small QTc effects. The number of placebo subjects was also shown to increase the power to detect an inactive drug preventing false positives while an effect can be underestimated if time points around tmax are missed.

  15. Polypharmacy as a Risk Factor for Clinically Relevant Sarcopenia: Results From the Berlin Aging Study II.

    Science.gov (United States)

    König, Maximilian; Spira, Dominik; Demuth, Ilja; Steinhagen-Thiessen, Elisabeth; Norman, Kristina

    2017-12-12

    Sarcopenia affects more than 10% of older adults. Next to age-associated physiologic changes, diseases like diabetes or inflammatory, neurological, malignant and endocrine disorders may contribute to the development of sarcopenia. Likewise, polypharmacy, i.e., multiple drug use, is common among older adults. Although the two conditions frequently co-occur, the association of polypharmacy with sarcopenia has not yet been examined. We investigated the association of polypharmacy and sarcopenia in a large cohort of community-dwelling older adults (60-84 years). Thousand five hundred and two participants from the Berlin Aging Study II were included. Polypharmacy was defined as concurrent use of 5 or more drugs (prescription and nonprescription). Body composition was assessed with dual-energy X-ray absorptiometry, and appendicular lean mass (ALM) was calculated as sum of the four limbs' lean mass. Sarcopenia was defined as low ALM-to-body mass index (BMI)-ratio using validated sex-specific cutoffs. Mean age was 68.7 ± 3.7 years, 50.7% were female. The median (interquartile range) number of drugs was 2 (1-4); 21.1% of subjects reported regular use of ≥5 drugs. Subjects with polypharmacy were more often sarcopenic according to the applied ALM/BMI-cutoffs (16.3% vs 6.9%, p sarcopenia (odds ratio = 2.24, 95% confidence interval [CI] = 1.33-3.75). Polypharmacy is associated with clinically relevant sarcopenia, as assessed by a low ALM/BMI. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  16. Statistical significance versus clinical relevance.

    Science.gov (United States)

    van Rijn, Marieke H C; Bech, Anneke; Bouyer, Jean; van den Brand, Jan A J G

    2017-04-01

    In March this year, the American Statistical Association (ASA) posted a statement on the correct use of P-values, in response to a growing concern that the P-value is commonly misused and misinterpreted. We aim to translate these warnings given by the ASA into a language more easily understood by clinicians and researchers without a deep background in statistics. Moreover, we intend to illustrate the limitations of P-values, even when used and interpreted correctly, and bring more attention to the clinical relevance of study findings using two recently reported studies as examples. We argue that P-values are often misinterpreted. A common mistake is saying that P < 0.05 means that the null hypothesis is false, and P ≥0.05 means that the null hypothesis is true. The correct interpretation of a P-value of 0.05 is that if the null hypothesis were indeed true, a similar or more extreme result would occur 5% of the times upon repeating the study in a similar sample. In other words, the P-value informs about the likelihood of the data given the null hypothesis and not the other way around. A possible alternative related to the P-value is the confidence interval (CI). It provides more information on the magnitude of an effect and the imprecision with which that effect was estimated. However, there is no magic bullet to replace P-values and stop erroneous interpretation of scientific results. Scientists and readers alike should make themselves familiar with the correct, nuanced interpretation of statistical tests, P-values and CIs. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  17. Stability of the elbow joint: relevant anatomy and clinical implications of in vitro biomechanical studies

    NARCIS (Netherlands)

    de Haan, J.; Schep, N. W. L.; Eygendaal, D.; Kleinrensink, G.-J.; Tuinebreijer, W. E.; den Hartog, D.

    2011-01-01

    The aim of this literature review is to describe the clinical anatomy of the elbow joint based on information from in vitro biomechanical studies. The clinical consequences of this literature review are described and recommendations are given for the treatment of elbow joint dislocation.The PubMed

  18. Stability of the Elbow Joint: Relevant Anatomy and Clinical Implications of In Vitro Biomechanical Studies

    NARCIS (Netherlands)

    J. de Haan (Jeroen); D. Eygendaal (Denise); N.W.L. Schep (Niels); G.J. Kleinrensink (Gert Jan); W.E. Tuinebreijer (Wim); D. den Hartog (Dennis)

    2011-01-01

    textabstractAbstract: The aim of this literature review is to describe the clinical anatomy of the elbow joint based on information from in vitro biomechanical studies. The clinical consequences of this literature review are described and recommendations are given for the treatment of elbow joint

  19. The relevance of clinical and radiographic features of jaw lesions: A prospective study

    Directory of Open Access Journals (Sweden)

    Juliane Piragine ARAUJO

    Full Text Available Abstract The study was carried out in a Brazilian population and the aim was to describe the prevalence and the clinic-radiographical features of jaw lesions. In addition, a comparison between the main diagnosis hypothesis and final diagnosis was accessed. A prospective study which evaluated all patients with jaw lesions diagnosed in an Oral Diagnosis Center, between August 2013 and October 2014. A total of 450 patients were observed for the first time, and 130 had some type of jaw lesion. The mean age of the patients was 35.2 years ± 17.86. Among these, 71 were women (54.62% and 87 were Caucasian (66.92%. The mandible was affected more frequently (71.43% than the maxilla (28.57%. Swelling and pain were the most frequent clinical signs and symptoms and were observed in 60 (42.85% and 38 (27.14% cases, respectively. The panoramic x-ray was the main radiographic exam utilized (88.57%. Radiolucent lesions accounted for 89 cases (63.57% and the unilocular form was present in 114 cases (81.43%. A total of 93 cases had histopathological analyses and the periapical cyst was the most frequent lesion. In the other 47 lesions, the diagnosis was conducted by clinical and radiographic management. Bone lesions were frequent, being noted on first visit in approximately 30% of patients; in 1/3 of the cases, the diagnoses were completed with a combination of clinical and radiographic exams.

  20. The Netherlands XTC Toxicity (NeXT) study: objectives and methods of a study investigating causality, course, and clinical relevance.

    Science.gov (United States)

    De Win, Maartje M L; Jager, Gerry; Vervaeke, Hylke K E; Schilt, Thelma; Reneman, Liesbeth; Booij, Jan; Verhulst, Frank C; Den Heeten, Gerard J; Ramsey, Nick F; Korf, Dirk J; Van den Brink, Wim

    2005-01-01

    This paper describes the objectives and methods of The Netherlands XTC Toxicity (NeXT) study focussing on the causality, course, and clinical relevance of ecstasy neurotoxicity. Previous studies suggest that ecstasy (3,4 methylene-dioxymethamphetamine, MDMA, XTC) is toxic toward brain serotonin axons, but most of these studies have serious methodological limitations. The current study is a combination of different approaches with three substudies: (1) a crosssectional substudy among heavy ecstasy users and controls with variation in drug use, which will provide information about potential neurotoxic consequences of ecstasy in relation to other drugs; (2) a prospective cohort substudy in ecstasy-naive subjects with high risk for future ecstasy use, which will provide information on the causality and short-term course of ecstasy use and potential neurotoxicity, and (3) a retrospective cohort substudy in lifetime ecstasy users and matched controls of an existing epidemiological sample that will provide information on long-term course and outcome of ecstasy use in the general population. Neurotoxicity is studied using (a) different imaging techniques (beta-CIT SPECT, 1H-MR spectroscopy, diffusion tensor imaging, perfusion weighted imaging and functional magnetic resonance imaging), and (b) neuropsychological and psychiatric assessments of memory, depression, and personality. The combined results will lead to conclusions that can be used in prevention messages, clinical decision making, and the development of an (inter)national ecstasy policy.

  1. Maintaining the clinical relevance of animal models in translational studies of post-traumatic stress disorder.

    Science.gov (United States)

    Cohen, Hagit; Matar, Michael A; Zohar, Joseph

    2014-01-01

    The diagnosis of Post-Traumatic Stress Disorder (PTSD) is conditional on directly experiencing or witnessing a significantly threatening event and the presence of a certain minimal number of symptoms from each of four symptom clusters (re-experiencing, avoidance, negative cognition and mood, and hyperarousal) at least one month after the event (DSM 5) (American Psychiatric Association 2013). Only a proportion of the population exposed develops symptoms fulfilling the criteria. The individual heterogeneity in responses of stress-exposed animals suggested that adapting clearly defined and reliably reproducible "diagnostic", i.e. behavioral, criteria for animal responses would augment the clinical validity of the analysis of study data. We designed cut-off (inclusion/exclusion) behavioral criteria (CBC) which classify study subjects as being severely, minimally or partially affected by the stress paradigm, to be applied retrospectively in the analysis of behavioral data. Behavioral response classification enables the researcher to correlate (retrospectively) specific anatomic, bio-molecular and physiological parameters with the degree and pattern of the individual behavioral response, and also introduces "prevalence rates" as a valid study-parameter. The cumulative results of our studies indicate that, by classifying the data from individual subjects according to their response patterns, the animal study can more readily be translated into clinical "follow-up" studies and back again. This article will discuss the concept of the model and its background, and present a selection of studies employing and examining the model, alongside the underlying translational rationale of each. © The Author 2014. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  2. Measuring agreement between rating interpretations and binary clinical interpretations of images: a simulation study of methods for quantifying the clinical relevance of an observer performance paradigm

    International Nuclear Information System (INIS)

    Chakraborty, Dev P

    2012-01-01

    Laboratory receiver operating characteristic (ROC) studies, that are often used to evaluate medical imaging systems, differ from ‘live’ clinical interpretations in several respects which could compromise their clinical relevance. The aim was to develop methodology for quantifying the clinical relevance of a laboratory ROC study. A simulator was developed to generate ROC ratings data and binary clinical interpretations classified as correct or incorrect for a common set of images interpreted under clinical and laboratory conditions. The area under the trapezoidal ROC curve (AUC) was used as the laboratory figure-of-merit and the fraction of correct clinical decisions as the clinical figure-of-merit. Conventional agreement measures (Pearson, Spearman, Kendall and kappa) between the bootstrap-induced fluctuations of the two figures of merit were estimated. A jackknife pseudovalue transformation applied to the figures of merit was also investigated as a way to capture agreement existing at the individual image level that could be lost at the figure-of-merit level. It is shown that the pseudovalues define a relevance-ROC curve. The area under this curve (rAUC) measures the ability of the laboratory figure-of-merit-based pseudovalues to correctly classify incorrect versus correct clinical interpretations. Therefore, rAUC is a measure of the clinical relevance of an ROC study. The conventional measures and rAUC were compared under varying simulator conditions. It was found that design details of the ROC study, namely the number of bins, the difficulty level of the images, the ratio of disease-present to disease-absent images and the unavoidable difference between laboratory and clinical performance levels, can lead to serious underestimation of the agreement as indicated by conventional agreement measures, even for perfectly correlated data, while rAUC showed high agreement and was relatively immune to these details. At the same time rAUC was sensitive to factors such

  3. Effects of clinically relevant doses of methyphenidate on spatial memory, behavioral sensitization and open field habituation: a time related study.

    Science.gov (United States)

    Haleem, Darakhshan Jabeen; Inam, Qurrat-ul-Aen; Haleem, Muhammad Abdul

    2015-03-15

    The psychostimulant methylphenidate (MPD) is a first-line drug for the treatment of attention deficit hyperactivity disorder (ADHD). Despite acceptable therapeutic efficacy, there is limited data regarding the long-term consequences of MPD exposure over extended periods. The present study concerns effects of clinically relevant doses of MPD, administered orally to rats for an extended period, on spatial memory, behavioral sensitization and habituation to an open field. Water maze test was used to monitor memory acquisition (2 h after training), retention (day next to training), extinction (1 week after training) and reconsolidation (weekly for 4 weeks). Administration of MPD at doses of 0.25-1.0 mg/kg improved memory acquisition, retention, reconsolidation and impaired memory extinction. Treatment with 0.25 and 0.5 mg/kg MPD for 6 weeks produced a sustained increase in motor activity but higher dose (1.0 mg/kg) elicited behavioral sensitization. High as well as low doses MPD impaired open field habituation. We conclude that clinically relevant doses of MPD enhance memory even if used for extended period. It is suggested that higher (1.0 mg/kg) clinically relevant doses of MPD, if used for extended period, may exacerbate hyperactivity and impulsivity associated with the disease. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Valerian: No Evidence for Clinically Relevant Interactions

    Directory of Open Access Journals (Sweden)

    Olaf Kelber

    2014-01-01

    Full Text Available In recent popular publications as well as in widely used information websites directed to cancer patients, valerian is claimed to have a potential of adverse interactions with anticancer drugs. This questions its use as a safe replacement for, for example, benzodiazepines. A review on the interaction potential of preparations from valerian root (Valeriana officinalis L. root was therefore conducted. A data base search and search in a clinical drug interaction data base were conducted. Thereafter, a systematic assessment of publications was performed. Seven in vitro studies on six CYP 450 isoenzymes, on p-glycoprotein, and on two UGT isoenzymes were identified. However, the methodological assessment of these studies did not support their suitability for the prediction of clinically relevant interactions. In addition, clinical studies on various valerian preparations did not reveal any relevant interaction potential concerning CYP 1A2, 2D6, 2E1, and 3A4. Available animal and human pharmacodynamic studies did not verify any interaction potential. The interaction potential of valerian preparations therefore seems to be low and thereby without clinical relevance. We conclude that there is no specific evidence questioning their safety, also in cancer patients.

  5. [Basic symptoms in schizophrenia, their clinical study and relevance in research].

    Science.gov (United States)

    Miret, Salvador; Fatjó-Vilas, Mar; Peralta, Víctor; Fañanás, Lourdes

    2016-01-01

    Basic symptoms consist of subtle sub-clinical disturbances subjectively experienced by schizophrenia patients. These are mainly related to drive, affect, thinking and language, perception, memory, motor action, central vegetative functions, control of cognitive processes, and stress tolerance. Initially described by Huber, from a phenomenological approach, basic symptoms are part of the earliest features of schizophrenia, and they can evolve along the course of the disorder. Their assessment during the prodromal phase of the disease (together with ultra-high risk criteria) is one of the 2 main approaches that allow the definition of states of clinical risk for the development of psychosis. The present review provides an updated view of the concept of basic symptoms, highlighting its potential value in establishing neurobiological correlates of interest in aetiopathogenic research. Copyright © 2015 SEP y SEPB. Published by Elsevier España. All rights reserved.

  6. Women's Health Initiative estrogen plus progestin clinical trial: a study that does not allow establishing relevant clinical risks.

    Science.gov (United States)

    Aedo, Sócrates; Cavada, Gabriel; Blümel, Juan E; Chedraui, Peter; Fica, Juan; Barriga, Patricio; Brantes, Sergio; Irribarra, Cristina; Vallejo, María; Campodónico, Ítalo

    2015-12-01

    This study aims to determine time differences (differences in restricted mean survival times [RMSTs]) in the onset of invasive breast cancer, coronary heart disease, stroke, pulmonary embolism, colorectal cancer, and hip fracture between the placebo group and the conjugated equine estrogens 0.625 mg plus medroxyprogesterone acetate 2.5 mg group of the Women's Health Initiative (WHI) trial based on survival curves of the original report and to provide adequate interpretation of the clinical effects of a given intervention. Distribution of survival function was obtained from cumulative hazard plots of the WHI report; Monte Carlo simulation was performed to obtain censored observations for each outcome, in which assumptions of the Cox model were evaluated once corresponding hazard ratios had been estimated. Using estimation methods such as numerical integration, pseudovalues, and flexible parametric modeling, we determined differences in RMSTs for each outcome. Obtained cumulative hazard plots, hazard ratios, and outcome rates from the simulated model did not show differences in relation to the original WHI report. The differences in RMST between placebo and conjugated equine estrogens 0.625 mg plus medroxyprogesterone acetate 2.5 mg (in flexible parametric modeling) were 1.17 days (95% CI, -2.25 to 4.59) for invasive breast cancer, 7.50 days (95% CI, 2.90 to 12.11) for coronary heart disease, 2.75 days (95% CI, -0.84 to 6.34) for stroke, 4.23 days (95% CI, 1.82 to 6.64) for pulmonary embolism, -2.73 days (95% CI, -5.32 to -0.13) for colorectal cancer, and -2.77 days (95% CI, -5.44 to -0.1) for hip fracture. The differences in RMST for the outcomes of the WHI study are too small to establish clinical risks related to hormone therapy use.

  7. Making Basic Science Studies in Glaucoma More Clinically Relevant: The Need for a Consensus.

    Science.gov (United States)

    Toris, Carol B; Gelfman, Claire; Whitlock, Andy; Sponsel, William E; Rowe-Rendleman, Cheryl L

    2017-09-01

    Glaucoma is a chronic, progressive, and debilitating optic neuropathy that causes retinal damage and visual defects. The pathophysiologic mechanisms of glaucoma remain ill-defined, and there is an indisputable need for contributions from basic science researchers in defining pathways for translational research. However, glaucoma researchers today face significant challenges due to the lack of a map of integrated pathways from bench to bedside and the lack of consensus statements to guide in choosing the right research questions, techniques, and model systems. Here, we present the case for the development of such maps and consensus statements, which are critical for faster development of the most efficacious glaucoma therapy. We underscore that interrogating the preclinical path of both successful and unsuccessful clinical programs is essential to defining future research. One aspect of this is evaluation of available preclinical research tools. To begin this process, we highlight the utility of currently available animal models for glaucoma and emphasize that there is a particular need for models of glaucoma with normal intraocular pressure. In addition, we outline a series of discoveries from cell-based, animal, and translational research that begin to reveal a map of glaucoma from cell biology to physiology to disease pathology. Completion of these maps requires input and consensus from the global glaucoma research community. This article sets the stage by outlining various approaches to such a consensus. Together, these efforts will help accelerate basic science research, leading to discoveries with significant clinical impact for people with glaucoma.

  8. A clinical decision support system algorithm for intravenous to oral antibiotic switch therapy: validity, clinical relevance and usefulness in a three-step evaluation study.

    Science.gov (United States)

    Akhloufi, H; Hulscher, M; van der Hoeven, C P; Prins, J M; van der Sijs, H; Melles, D C; Verbon, A

    2018-04-26

    To evaluate a clinical decision support system (CDSS) based on consensus-based intravenous to oral switch criteria, which identifies intravenous to oral switch candidates. A three-step evaluation study of a stand-alone CDSS with electronic health record interoperability was performed at the Erasmus University Medical Centre in the Netherlands. During the first step, we performed a technical validation. During the second step, we determined the sensitivity, specificity, negative predictive value and positive predictive value in a retrospective cohort of all hospitalized adult patients starting at least one therapeutic antibacterial drug between 1 and 16 May 2013. ICU, paediatric and psychiatric wards were excluded. During the last step the clinical relevance and usefulness was prospectively assessed by reports to infectious disease specialists. An alert was considered clinically relevant if antibiotics could be discontinued or switched to oral therapy at the time of the alert. During the first step, one technical error was found. The second step yielded a positive predictive value of 76.6% and a negative predictive value of 99.1%. The third step showed that alerts were clinically relevant in 53.5% of patients. For 43.4% it had already been decided to discontinue or switch the intravenous antibiotics by the treating physician. In 10.1%, the alert resulted in advice to change antibiotic policy and was considered useful. This prospective cohort study shows that the alerts were clinically relevant in >50% (n = 449) and useful in 10% (n = 85). The CDSS needs to be evaluated in hospitals with varying activity of infectious disease consultancy services as this probably influences usefulness.

  9. Circulating and brain BDNF levels in stroke rats. Relevance to clinical studies.

    Directory of Open Access Journals (Sweden)

    Yannick Béjot

    Full Text Available BACKGROUND: Whereas brain-derived neurotrophic factor (BDNF levels are measured in the brain in animal models of stroke, neurotrophin levels in stroke patients are measured in plasma or serum samples. The present study was designed to investigate the meaning of circulating BDNF levels in stroke patients. METHODS AND RESULTS: Unilateral ischemic stroke was induced in rats by the injection of various numbers of microspheres into the carotid circulation in order to mimic the different degrees of stroke severity observed in stroke patients. Blood was serially collected from the jugular vein before and after (4 h, 24 h and 8 d embolization and the whole brains were collected at 4, 24 h and 8 d post-embolization. Rats were then selected from their degree of embolization, so that the distribution of stroke severity in the rats at the different time points was large but similar. Using ELISA tests, BDNF levels were measured in plasma, serum and brain of selected rats. Whereas plasma and serum BDNF levels were not changed by stroke, stroke induced an increase in brain BDNF levels at 4 h and 24 h post-embolization, which was not correlated with stroke severity. Individual plasma BDNF levels did not correlate with brain levels at any time point after stroke but a positive correlation (r = 0.67 was observed between individual plasma BDNF levels and stroke severity at 4 h post-embolization. CONCLUSION: Circulating BDNF levels do not mirror brain BDNF levels after stroke, and severe stroke is associated with high plasma BDNF in the very acute stage.

  10. Bioinformatics tools for the analysis of NMR metabolomics studies focused on the identification of clinically relevant biomarkers.

    Science.gov (United States)

    Puchades-Carrasco, Leonor; Palomino-Schätzlein, Martina; Pérez-Rambla, Clara; Pineda-Lucena, Antonio

    2016-05-01

    Metabolomics, a systems biology approach focused on the global study of the metabolome, offers a tremendous potential in the analysis of clinical samples. Among other applications, metabolomics enables mapping of biochemical alterations involved in the pathogenesis of diseases, and offers the opportunity to noninvasively identify diagnostic, prognostic and predictive biomarkers that could translate into early therapeutic interventions. Particularly, metabolomics by Nuclear Magnetic Resonance (NMR) has the ability to simultaneously detect and structurally characterize an abundance of metabolic components, even when their identities are unknown. Analysis of the data generated using this experimental approach requires the application of statistical and bioinformatics tools for the correct interpretation of the results. This review focuses on the different steps involved in the metabolomics characterization of biofluids for clinical applications, ranging from the design of the study to the biological interpretation of the results. Particular emphasis is devoted to the specific procedures required for the processing and interpretation of NMR data with a focus on the identification of clinically relevant biomarkers. © The Author 2015. Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  11. A pilot study to evaluate the clinical relevance of endometriosis-associated nerve fibers in peritoneal endometriotic lesions.

    Science.gov (United States)

    Mechsner, Sylvia; Kaiser, Andrea; Kopf, Andreas; Gericke, Christine; Ebert, Andreas; Bartley, Julia

    2009-12-01

    To investigate the clinical relevance of endometriosis-associated nerve fibers in the development of endometriosis-associated symptoms. Prospective nonrandomized study. University hospital endometriosis center. Fifty-one premenopausal patients underwent surgical laparoscopy because of chronic pelvic pain, dysmenorrhea, or for ovarian cysts. Endometriosis was diagnosed in 44 patients. The preoperative and postoperative pain scores were determined using a standardized questionnaire with a visual analogue scale from 1-10. Patients with peritoneal endometriosis were divided into two groups depending on their preoperative pain score: group A with a pain score of at least 3 or more and group B with a pain score of 2 or less. Patients without peritoneal endometriosis were classified as group C and patients without endometriosis were classified as group D. Immunohistochemical analysis of neurofilament and protein gene product 9.5 were used for nerve fiber detection. Occurrence of endometriosis-associated nerve fibers was correlated with the severity of pelvic pain and/or dysmenorrhea. Peritoneal endometriosis-associated nerve fibers were found significantly more frequently in group A than in group B (82.6% vs. 33.3%). The present study suggests that the presence of endometriosis-associated nerve fibers in the peritoneum is important for the development of endometriosis-associated pelvic pain and dysmenorrhea.

  12. A qualitative study examining methods of accessing and identifying research relevant to clinical practice among rehabilitation clinicians.

    Science.gov (United States)

    Patel, Drasti; Koehmstedt, Christine; Jones, Rebecca; Coffey, Nathan T; Cai, Xinsheng; Garfinkel, Steven; Shaewitz, Dahlia M; Weinstein, Ali A

    2017-01-01

    Research examining the utilization of evidence-based practice (EBP) specifically among rehabilitation clinicians is limited. The objective of this study was to examine how various rehabilitative clinicians including physical therapists, occupational therapists, rehabilitation counselors, and physiatrists are gaining access to literature and whether they are able to implement the available research into practice. A total of 21 total clinicians were interviewed via telephone. Using NVivo, a qualitative analysis of the responses was performed. There were similarities found with respect to the information-seeking behaviors and translation of research across the different clinician types. Lack of time was reported to be a barrier for both access to literature and implementation of research across all clinician types. The majority of clinicians who reported having difficulty with utilizing the published literature indicated that the literature was not applicable to their practice, the research was not specific enough to be put into practice, or the research found was too outdated to be relevant. In addition, having a supportive work environment aided in the search and utilization of research through providing resources central to assisting clinicians in gaining access to health information. Our study identified several barriers that affect EBP for rehabilitation clinicians. The findings suggest the need for researchers to ensure that their work is applicable and specific to clinical practice for implementation to occur.

  13. Study design and rationale for biomedical shirt-based electrocardiography monitoring in relevant clinical situations: ECG-shirt study.

    Science.gov (United States)

    Balsam, Paweł; Lodziński, Piotr; Tymińska, Agata; Ozierański, Krzysztof; Januszkiewicz, Łukasz; Główczyńska, Renata; Wesołowska, Katarzyna; Peller, Michał; Pietrzak, Radosław; Książczyk, Tomasz; Borodzicz, Sonia; Kołtowski, Łukasz; Borkowski, Mariusz; Werner, Bożena; Opolski, Grzegorz; Grabowski, Marcin

    2018-01-01

    Today, the main challenge for researchers is to develop new technologies which may help to improve the diagnoses of cardiovascular disease (CVD), thereby reducing healthcare costs and improving the quality of life for patients. This study aims to show the utility of biomedical shirt-based electrocardiography (ECG) monitoring of patients with CVD in different clinical situations using the Nuubo® ECG (nECG) system. An investigator-initiated, multicenter, prospective observational study was carried out in a cardiology (adult and pediatric) and cardiac rehabilitation wards. ECG monitoring was used with the biomedical shirt in the following four independent groups of patients: 1) 30 patients after pulmonary vein isolation (PVI), 2) 30 cardiac resynchronization therapy (CRT) recipients, 3) 120 patients during cardiac rehabilitation after myocardial infarction, and 4) 40 pediatric patients with supraventricular tachycardia (SVT) before electrophysiology study. Approval for all study groups was obtained from the institutional review board. The biomedical shirt captures the electrocardiographic signal via textile electrodes integrated into a garment. The software allows the visualization and analysis of data such as ECG, heart rate, arrhythmia detecting algorithm and relative position of the body is captured by an electronic device. The major advantages of the nECG system are continuous ECG monitoring during daily activities, high quality of ECG recordings, as well as assurance of a proper adherence due to adequate comfort while wearing the shirt. There are only a few studies that have examined wearable systems, especially in pediatric populations. This study is registered in ClinicalTrials.gov: Identifier NCT03068169. (Cardiol J 2018; 25, 1: 52-59).

  14. [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.

  15. Clinical relevance and scope of accidental extracoronary findings in coronary computed tomography angiography: A cardiac versus thoracic FOV study

    Energy Technology Data Exchange (ETDEWEB)

    Aglan, Iman; Jodocy, Daniel; Hiehs, Stefan; Soegner, Peter; Frank, Renate; Haberfellner, Berhard; Klauser, Andrea; Jaschke, Werner [Department of Radiology II, Innsbruck Medical University, Innsbruck (Austria); Feuchtner, Gudrun M. [Department of Radiology II, Innsbruck Medical University, Innsbruck (Austria)], E-mail: Gudrun.Feuchtner@i-med.ac.at

    2010-04-15

    Objective: To assess the spectrum and clinical relevance of extracoronary findings in coronary CT angiography (CCTA), and to compare a small (cardiac) field of view (FOV) to a large (thoracic) FOV setting. Material and methods: 1084 consecutive patients (mean 57 years) with low-to-intermediate risk of coronary artery disease were enrolled. 542 CCTA scans were interpreted with small FOV (160-190 mm{sup 2}) encompassing the cardiac region. In another 542 CCTA (patients matched for age and gender), read-out of an additional full FOV (>320 mm{sup 2}) covering the thorax was performed. Clinical relevance of extracoronary findings was considered as either 'significant' or 'non-significant'. 'Significant' findings were subclassified as either score 1: findings necessitating immediate therapeutic actions, or score 2: findings with undoubted clinical or prognostic relevance, requiring clinical awareness, follow-up or further investigations (non-urgent). 'Non-significant' findings were assigned to either score 3: findings not requiring follow-up or further tests, or as score 4: irrelevant incidental findings. Results: Significantly more patients with extracoronary findings were identified by using a full FOV with 43.2% (234/542) compared to a small FOV with 33.6% (182/542) (p = 0.001). Similarly, a higher total number of extracoronary findings (n = 394) was found on full FOV compared to small FOV (n = 250) (p < 0.001). The detection rate of clinically significant findings was higher by using full FOV compared to small FOV (25.6% versus 15.4%) (p < 0.001), out of those 2.2% versus 1.8% of findings required immediate actions (score 1), and 23.4% versus 13.6% (p = 0.0001), respectively were of clinical relevance (non-urgent, score 2). The rate of malign findings was 0.2%, and of acute pulmonary embolism 0.1%. More lung pathologies were observed by using full FOV compared to small FOV (22% versus 7%) (p < 0.0001), and the detection rate of

  16. Clinical relevance and scope of accidental extracoronary findings in coronary computed tomography angiography: A cardiac versus thoracic FOV study

    International Nuclear Information System (INIS)

    Aglan, Iman; Jodocy, Daniel; Hiehs, Stefan; Soegner, Peter; Frank, Renate; Haberfellner, Berhard; Klauser, Andrea; Jaschke, Werner; Feuchtner, Gudrun M.

    2010-01-01

    Objective: To assess the spectrum and clinical relevance of extracoronary findings in coronary CT angiography (CCTA), and to compare a small (cardiac) field of view (FOV) to a large (thoracic) FOV setting. Material and methods: 1084 consecutive patients (mean 57 years) with low-to-intermediate risk of coronary artery disease were enrolled. 542 CCTA scans were interpreted with small FOV (160-190 mm 2 ) encompassing the cardiac region. In another 542 CCTA (patients matched for age and gender), read-out of an additional full FOV (>320 mm 2 ) covering the thorax was performed. Clinical relevance of extracoronary findings was considered as either 'significant' or 'non-significant'. 'Significant' findings were subclassified as either score 1: findings necessitating immediate therapeutic actions, or score 2: findings with undoubted clinical or prognostic relevance, requiring clinical awareness, follow-up or further investigations (non-urgent). 'Non-significant' findings were assigned to either score 3: findings not requiring follow-up or further tests, or as score 4: irrelevant incidental findings. Results: Significantly more patients with extracoronary findings were identified by using a full FOV with 43.2% (234/542) compared to a small FOV with 33.6% (182/542) (p = 0.001). Similarly, a higher total number of extracoronary findings (n = 394) was found on full FOV compared to small FOV (n = 250) (p 2 aortic valve orifice area. Conclusions: The interpretation of extracoronary findings on CCTA scans is mandatory given high prevalence of clinically significant findings by using a full 'thoracic' FOV.

  17. A qualitative study examining methods of accessing and identifying research relevant to clinical practice among rehabilitation clinicians

    Directory of Open Access Journals (Sweden)

    Patel D

    2017-12-01

    Full Text Available Drasti Patel,1 Christine Koehmstedt,1 Rebecca Jones,1 Nathan T Coffey,1 Xinsheng Cai,2 Steven Garfinkel,2 Dahlia M Shaewitz,2 Ali A Weinstein1 1Center for Study of Chronic Illness and Disability, College of Health and Human Services, George Mason University, Fairfax, VA, 2American Institutes for Research, Washington, DC, USA Purpose: Research examining the utilization of evidence-based practice (EBP specifically among rehabilitation clinicians is limited. The objective of this study was to examine how various rehabilitative clinicians including physical therapists, occupational therapists, rehabilitation counselors, and physiatrists are gaining access to literature and whether they are able to implement the available research into practice.Methods: A total of 21 total clinicians were interviewed via telephone. Using NVivo, a qualitative analysis of the responses was performed.Results: There were similarities found with respect to the information-seeking behaviors and translation of research across the different clinician types. Lack of time was reported to be a barrier for both access to literature and implementation of research across all clinician types. The majority of clinicians who reported having difficulty with utilizing the published literature indicated that the literature was not applicable to their practice, the research was not specific enough to be put into practice, or the research found was too outdated to be relevant. In addition, having a supportive work environment aided in the search and utilization of research through providing resources central to assisting clinicians in gaining access to health information.Conclusion: Our study identified several barriers that affect EBP for rehabilitation clinicians. The findings suggest the need for researchers to ensure that their work is applicable and specific to clinical practice for implementation to occur. Keywords: health information, information behavior, knowledge utilization

  18. Extracellular vesicles: fundamentals and clinical relevance

    Directory of Open Access Journals (Sweden)

    Wael Nassar

    2015-01-01

    Full Text Available All types of cells of eukaryotic organisms produce and release small nanovesicles into their extracellular environment. Early studies have described these vesicles as ′garbage bags′ only to remove obsolete cellular molecules. Valadi and colleagues, in 2007, were the first to discover the capability of circulating extracellular vesicles (EVs to horizontally transfer functioning gene information between cells. These extracellular vesicles express components responsible for angiogenesis promotion, stromal remodeling, chemoresistance, genetic exchange, and signaling pathway activation through growth factor/receptor transfer. EVs represent an important mode of intercellular communication by serving as vehicles for transfer between cells of membrane and cytosolic proteins, lipids, signaling proteins, and RNAs. They contribute to physiology and pathology, and they have a myriad of potential clinical applications in health and disease. Moreover, vesicles can pass the blood-brain barrier and may perhaps even be considered as naturally occurring liposomes. These cell-derived EVs not only represent a central mediator of the disease microenvironment, but their presence in the peripheral circulation may serve as a surrogate for disease biopsies, enabling real-time diagnosis and disease monitoring. In this review, we′ll be addressing the characteristics of different types of extracellular EVs, as well as their clinical relevance and potential as diagnostic markers, and also define therapeutic options.

  19. EXTRACELLULAR VESICLES: CLASSIFICATION, FUNCTIONS AND CLINICAL RELEVANCE

    Directory of Open Access Journals (Sweden)

    A. V. Oberemko

    2014-12-01

    Full Text Available This review presents a generalized definition of vesicles as bilayer extracellular organelles of all celular forms of life: not only eu-, but also prokaryotic. The structure and composition of extracellular vesicles, history of research, nomenclature, their impact on life processes in health and disease are discussed. Moreover, vesicles may be useful as clinical instruments for biomarkers, and they are promising as biotechnological drug. However, many questions in this area are still unresolved and need to be addressed in the future. The most interesting from the point of view of practical health care represents a direction to study the effect of exosomes and microvesicles in the development and progression of a particular disease, the possibility of adjusting the pathological process by means of extracellular vesicles of a particular type, acting as an active ingredient. Relevant is the further elucidation of the role and importance of exosomes to the surrounding cells, tissues and organs at the molecular level, the prospects for the use of non-cellular vesicles as biomarkers of disease.

  20. Transient ischemic attacks with and without a relevant infarct on computed tomographic scans cannot be distinguished clinically. Dutch Transient Ischemic Attack Study Group

    NARCIS (Netherlands)

    Koudstaal, P. J.; van Gijn, J.; Lodder, J.; Frenken, W. G.; Vermeulen, M.; Franke, C. L.; Hijdra, A.; Bulens, C.

    1991-01-01

    We prospectively studied clinical and computed tomographic (CT) scan findings in 79 patients with a transient ischemic attack (TIA) and a relevant cerebral infarction on CT, also known as cerebral infarction with transient signs (CITS). We compared the results with those of 527 concurrent patients

  1. Comparative analysis of three drug-drug interaction screening systems against probable clinically relevant drug-drug interactions: a prospective cohort study.

    Science.gov (United States)

    Muhič, Neža; Mrhar, Ales; Brvar, Miran

    2017-07-01

    Drug-drug interaction (DDI) screening systems report potential DDIs. This study aimed to find the prevalence of probable DDI-related adverse drug reactions (ADRs) and compare the clinical usefulness of different DDI screening systems to prevent or warn against these ADRs. A prospective cohort study was conducted in patients urgently admitted to medical departments. Potential DDIs were checked using Complete Drug Interaction®, Lexicomp® Online™, and Drug Interaction Checker®. The study team identified the patients with probable clinically relevant DDI-related ADRs on admission, the causality of which was assessed using the Drug Interaction Probability Scale (DIPS). Sensitivity, specificity, and positive and negative predictive values of screening systems to prevent or warn against probable DDI-related ADRs were evaluated. Overall, 50 probable clinically relevant DDI-related ADRs were found in 37 out of 795 included patients taking at least two drugs, most common of them were bleeding, hyperkalemia, digitalis toxicity, and hypotension. Complete Drug Interaction showed the best sensitivity (0.76) for actual DDI-related ADRs, followed by Lexicomp Online (0.50), and Drug Interaction Checker (0.40). Complete Drug Interaction and Drug Interaction Checker had positive predictive values of 0.07; Lexicomp Online had 0.04. We found no difference in specificity and negative predictive values among these systems. DDI screening systems differ significantly in their ability to detect probable clinically relevant DDI-related ADRs in terms of sensitivity and positive predictive value.

  2. Clinically Relevant Anticancer Polymer Paclitaxel Therapeutics

    Directory of Open Access Journals (Sweden)

    Danbo Yang

    2010-12-01

    Full Text Available The concept of utilizing polymers in drug delivery has been extensively explored for improving the therapeutic index of small molecule drugs. In general, polymers can be used as polymer-drug conjugates or polymeric micelles. Each unique application mandates its own chemistry and controlled release of active drugs. Each polymer exhibits its own intrinsic issues providing the advantage of flexibility. However, none have as yet been approved by the U.S. Food and Drug Administration. General aspects of polymer and nano-particle therapeutics have been reviewed. Here we focus this review on specific clinically relevant anticancer polymer paclitaxel therapeutics. We emphasize their chemistry and formulation, in vitro activity on some human cancer cell lines, plasma pharmacokinetics and tumor accumulation, in vivo efficacy, and clinical outcomes. Furthermore, we include a short review of our recent developments of a novel poly(L-g-glutamylglutamine-paclitaxel nano-conjugate (PGG-PTX. PGG-PTX has its own unique property of forming nano-particles. It has also been shown to possess a favorable profile of pharmacokinetics and to exhibit efficacious potency. This review might shed light on designing new and better polymer paclitaxel therapeutics for potential anticancer applications in the clinic.

  3. Clinically Relevant Anticancer Polymer Paclitaxel Therapeutics

    International Nuclear Information System (INIS)

    Yang, Danbo; Yu, Lei; Van, Sang

    2010-01-01

    The concept of utilizing polymers in drug delivery has been extensively explored for improving the therapeutic index of small molecule drugs. In general, polymers can be used as polymer-drug conjugates or polymeric micelles. Each unique application mandates its own chemistry and controlled release of active drugs. Each polymer exhibits its own intrinsic issues providing the advantage of flexibility. However, none have as yet been approved by the U.S. Food and Drug Administration. General aspects of polymer and nano-particle therapeutics have been reviewed. Here we focus this review on specific clinically relevant anticancer polymer paclitaxel therapeutics. We emphasize their chemistry and formulation, in vitro activity on some human cancer cell lines, plasma pharmacokinetics and tumor accumulation, in vivo efficacy, and clinical outcomes. Furthermore, we include a short review of our recent developments of a novel poly(l-γ-glutamylglutamine)-paclitaxel nano-conjugate (PGG-PTX). PGG-PTX has its own unique property of forming nano-particles. It has also been shown to possess a favorable profile of pharmacokinetics and to exhibit efficacious potency. This review might shed light on designing new and better polymer paclitaxel therapeutics for potential anticancer applications in the clinic

  4. Clinically Relevant Anticancer Polymer Paclitaxel Therapeutics

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Danbo [Biomedical Engineering and Technology Institute, Institutes for Advanced Interdisciplinary Research, East China Normal University, 3663 North Zhongshan Road, Shanghai, 200062 (China); Yu, Lei, E-mail: yu-lei@gg.nitto.co.jp [Biomedical Engineering and Technology Institute, Institutes for Advanced Interdisciplinary Research, East China Normal University, 3663 North Zhongshan Road, Shanghai, 200062 (China); Biomedical Group, Nitto Denko Technical Corporation, 501 Via Del Monte, Oceanside, CA 92058 (United States); Van, Sang [Biomedical Group, Nitto Denko Technical Corporation, 501 Via Del Monte, Oceanside, CA 92058 (United States)

    2010-12-23

    The concept of utilizing polymers in drug delivery has been extensively explored for improving the therapeutic index of small molecule drugs. In general, polymers can be used as polymer-drug conjugates or polymeric micelles. Each unique application mandates its own chemistry and controlled release of active drugs. Each polymer exhibits its own intrinsic issues providing the advantage of flexibility. However, none have as yet been approved by the U.S. Food and Drug Administration. General aspects of polymer and nano-particle therapeutics have been reviewed. Here we focus this review on specific clinically relevant anticancer polymer paclitaxel therapeutics. We emphasize their chemistry and formulation, in vitro activity on some human cancer cell lines, plasma pharmacokinetics and tumor accumulation, in vivo efficacy, and clinical outcomes. Furthermore, we include a short review of our recent developments of a novel poly(l-γ-glutamylglutamine)-paclitaxel nano-conjugate (PGG-PTX). PGG-PTX has its own unique property of forming nano-particles. It has also been shown to possess a favorable profile of pharmacokinetics and to exhibit efficacious potency. This review might shed light on designing new and better polymer paclitaxel therapeutics for potential anticancer applications in the clinic.

  5. Serumferritin - diagnostic relevance and clinical usefulness

    Energy Technology Data Exchange (ETDEWEB)

    Linkesch, W [Vienna Univ. (Austria). 2. Medizinische Klinik

    1984-01-01

    The introduction of a WHO Standard for serumferritin effected a standardisation of different methods, improving quality and security for clinical routine diagnostic purposes. Therefore the clinical evaluation of serumferritin gained even more importance. For evaluation of iron stores of children, pregnant women, population studies, patients on hemodialysis or patients with rheumatoid arthritis low serumferritin values give safe results. In addition serumferritin is of clinical usefulness in monitoring therapy of both iron deficiency and iron overload. Evaluating a single serumferritin value one should consider the total clinical situation of the patient. As some tumors can produce and secrete serumferritin, e.g. acute myeloblastic leukemia, germ cell tumors, malignant melanoma, serumferritin might be helpful in monitoring the malignant disease. The ongoing characterization of tissue isoferritin, especially acidic isoferritin, may eventually lead to a clinically significant diagnostic marker of neoplasia.

  6. Serumferritin - diagnostic relevance and clinical usefulness

    International Nuclear Information System (INIS)

    Linkesch, W.

    1984-01-01

    The introduction of a WHO Standard for serumferritin effected a standardisation of different methods, improving quality and security for clinical routine diagnostic purposes. Therefore the clinical evaluation of serumferritin gained even more importance. For evaluation of iron stores of children, pregnant women, population studies, patients on hemodialysis or patients with rheumatoid arthritis low serumferritin values give safe results. In addition serumferritin is of clinical usefulness in monitoring therapy of both iron deficiency and iron overload. Evaluating a single serumferritin value on should consider the total clinical situation of the patient. As some tumors can produce and secrete serumferritin, e. g. acute myeloblastic leukemia, germ cell tumors, malignant melanoma, serumferritin might be helpful in monitoring the malignant disease. The ongoing characterization of tissue isoferritin, especially acidic isoferritin, may eventually lead to a clinically significant diagnostic marker of neoplasia. (Author)

  7. Mirror neurons and their clinical relevance.

    Science.gov (United States)

    Rizzolatti, Giacomo; Fabbri-Destro, Maddalena; Cattaneo, Luigi

    2009-01-01

    One of the most exciting events in neurosciences over the past few years has been the discovery of a mechanism that unifies action perception and action execution. The essence of this 'mirror' mechanism is as follows: whenever individuals observe an action being done by someone else, a set of neurons that code for that action is activated in the observers' motor system. Since the observers are aware of the outcome of their motor acts, they also understand what the other individual is doing without the need for intermediate cognitive mediation. In this Review, after discussing the most pertinent data concerning the mirror mechanism, we examine the clinical relevance of this mechanism. We first discuss the relationship between mirror mechanism impairment and some core symptoms of autism. We then outline the theoretical principles of neurorehabilitation strategies based on the mirror mechanism. We conclude by examining the relationship between the mirror mechanism and some features of the environmental dependency syndromes.

  8. Assessment of the clinical relevance of quantitative sensory testing with Von Frey monofilaments in patients with allodynia and neuropathic pain. A pilot study

    OpenAIRE

    Keizer, D.; van Wijhe, M.; Post, W.J.; Uges, D.R.A.; Wierda, J.M.K.H.

    2007-01-01

    Background: Allodynia is a common and disabling symptom in many patients with neuropathic pain. Whereas quantification of pain mostly depends on subjective pain reports, allodynia can also be measured objectively with quantitative sensory testing. In this pilot study, we investigated the clinical relevance of quantitative sensory testing with Von Frey monofilaments in patients with allodynia as a consequence of a neuropathic pain syndrome, by means of correlating subjective pain scores with p...

  9. Neurovascular Content of the Mandibular Canal and Its Clinical Relevance: A Literature Review of the Related Anatomical and Radiological Studies

    Directory of Open Access Journals (Sweden)

    Eliades Apostolos N.

    2014-11-01

    Full Text Available In literature, anatomical variations of the inferior alveolar nerve branches (infratemporal, extraosseous and intraosseous are reported and their importance in clinical practice is discussed too. The spatial vessels’ position in relationship with the nerve in the mandibular canal was explored, which is of clinical significance in impacted third molar and implant surgery. It is believed that the neurovascular content of the main mandibular canal follows any variations of the mandibular canal i.e. bifid mandibular, retromolar and accessory mental canals. Retrospective studies and case reports reported the presence of multiple foramina on the medial surface of the ramus, near the main mandibular foramen. In some cases, one supplementary mandibular foramen was found to be connected with the lower third molar, which is called “temporal crest canal”. Others found an accessory mandibular foramen that led into a second mandibular canal which joined the main mandibular canal (double anteriorly. The bony canals contained a terminal branch of the anterior trunk of the mandibular nerve or a branch of inferior alveolar nerve before it entered the mandibular foramen.

  10. Clinical Relevance of Alternative Endpoints in Colorectal Cancer First-Line Therapy With Bevacizumab: A Retrospective Study.

    Science.gov (United States)

    Turpin, Anthony; Paget-Bailly, Sophie; Ploquin, Anne; Hollebecque, Antoine; Peugniez, Charlotte; El-Hajbi, Farid; Bonnetain, Franck; Hebbar, Mohamed

    2018-03-01

    We studied the relationship between intermediate criteria and overall survival (OS) in metastatic colorectal cancer (mCRC) patients who received first-line chemotherapy with bevacizumab. We assessed OS, progression-free survival (PFS), duration of disease control (DDC), the sum of the periods in which the disease did not progress, and the time to failure of strategy (TFS), which was defined as the entire period before the introduction of a second-line treatment. Linear correlation and regression models were used, and Prentice criteria were investigated. With a median follow-up of 57.6 months for 216 patients, the median OS was 24.5 months (95% confidence interval [CI], 21.3-29.7). The median PFS, DDC, and TFS were 8.9 (95% CI, 8.4-9.7), 11.0 (95% CI, 9.8-12.4), and 11.1 (95% CI, 10.0-13.0) months, respectively. The correlations between OS and DDC (Pearson coefficient, 0.79 [95% CI, 0.73-0.83], determination coefficient, 0.62) and OS and TFS (Pearson coefficient, 0.79 [95% CI, 0.73-0.84], determination coefficient, 0.63) were satisfactory. Linear regression analysis showed a significant association between OS and DDC, and between OS and TFS. Prentice criteria were verified for TFS as well as DDC. DDC and TFS correlated with OS and are relevant as intermediate criteria in the setting of patients with mCRC treated with a first-line bevacizumab-based regimen. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Clinical relevance of findings in trials of CBT for depression.

    Science.gov (United States)

    Lepping, P; Whittington, R; Sambhi, R S; Lane, S; Poole, R; Leucht, S; Cuijpers, P; McCabe, R; Waheed, W

    2017-09-01

    Cognitive behavioural therapy (CBT) is beneficial in depression. Symptom scores can be translated into Clinical Global Impression (CGI) scale scores to indicate clinical relevance. We aimed to assess the clinical relevance of findings of randomised controlled trials (RCTs) of CBT in depression. We identified RCTs of CBT that used the Hamilton Rating Scale for Depression (HAMD). HAMD scores were translated into Clinical Global Impression - Change scale (CGI-I) scores to measure clinical relevance. One hundred and seventy datasets from 82 studies were included. The mean percentage HAMD change for treatment arms was 53.66%, and 29.81% for control arms, a statistically significant difference. Combined active therapies showed the biggest improvement on CGI-I score, followed by CBT alone. All active treatments had better than expected HAMD percentage reduction and CGI-I scores. CBT has a clinically relevant effect in depression, with a notional CGI-I score of 2.2, indicating a significant clinical response. The non-specific or placebo effect of being in a psychotherapy trial was a 29% reduction of HAMD. Copyright © 2017. Published by Elsevier Masson SAS.

  12. MRI in the early stage of spinal cord injury: does it have clinical relevance? An experimental study

    International Nuclear Information System (INIS)

    Hannmann, T.T.; Freund, M.

    2007-01-01

    Purpose: An experimental technique for producing a ventral spinal trauma which imitates a slipped intervertebral disc or a fractured vertebra was evaluated using magnetic resonance imaging and histology. The results were evaluated with respect to their clinical importance. Materials and Methods: A total of 69 Wistar rats were used for this study. An inflatable angioplasty balloon device was placed dorsally or ventrally to the spinal cord in order to produce a spinal trauma. 30 rats were used to compare neurological pathologies between ventral and dorsal trauma. 30 animals underwent graded ventral spinal cord compression. Magnetic resonance imaging was performed and the results were compared to histology. Results: Using this technique, the balloon device can be placed ventrally to the spinal cord. The compression time had a direct effect on changes on magnetic resonance images and edema in histology, but a longer compression time did not produce increased bleeding. The T2-weighted MRI scans showed hyperintense changes immediately after spinal compression. Therefore, they are the appropriate way for diagnosing acute spinal injuries. Although the T1-weighted MRI scans did not change after spinal compression, they are important for diagnosing epidural hematomas. (orig.)

  13. Treatment-related changes in serum lipids and inflammation: clinical relevance remains unclear. Analyses from the Women's Interagency HIV Study

    Science.gov (United States)

    Parrinello, Christina M; Landay, Alan L; Hodis, Howard N; Gange, Stephen J; Norris, Philip J; Young, Mary; Anastos, Kathryn; Tien, Phyllis C; Xue, Xiaonan; Lazar, Jason; Benning, Lorie; Tracy, Russell P; Kaplan, Robert C

    2014-01-01

    Summary Among 127 HIV-infected women, the magnitude of HDLc increases after HAART initiation predicted the magnitude of concurrent decreases in inflammation biomarkers. After HAART initiation, changes in LDLc and inflammation were unrelated. In the same population, predicted risk of coronary heart disease based upon levels of standard clinical risk factors was similar before and after HAART treatment. Thus, it remains unknown whether short-term treatment-related changes in standard risk factors may appreciably change risk of CVD. PMID:23435295

  14. Blocking Avoidance and Escape Responses: Relations With Clinically Relevant Behaviors

    Directory of Open Access Journals (Sweden)

    Juliana Maria Bubna Popovitz

    Full Text Available Abstract: The current study aims to evaluate the possible effects of interrupting problematic clinically relevant behaviors on the percentage of these responses and of clinical improvement-related responses. Two clients were treated with Functional Analytic Psychotherapy (FAP, alternating two conditions (ABAB. On condition A, procedures to the therapist consisted of responding to the clinical improvement responses, and to description of outside of therapeutic setting behaviors, but therapists were advised to ignore problem behaviors emitted in session. During condition B, therapists followed the same procedures, but they were oriented to block (interrupt problematic responses emitted in session. Results suggest increase in the percentage of problem behaviors during condition B. Results are discussed, highlighting the viability of planning the contingent response the therapist emits to clinically relevant behaviors.

  15. Cerebral activation studies by PET and fMRT, clinical relevance?; Zerebrale Aktivierungsstudien mit PET und fMRT, klinische Relevanz?

    Energy Technology Data Exchange (ETDEWEB)

    Brandt, T. [Neurologische Klinik und Poliklinik, Klinikum Grosshadern, Muenchen Univ. (Germany)

    1997-03-01

    Cerebral activation studies by PET and fMRT will gain increasing clinical relevance for functional neuroanatomy (reading, speaking), localisation of largely unknown cortical functions (vestibular cortex), imaging of subjective complaints of functional impairments (pain, smell, memory), and documentation of neurological rehabilitation at neuronal level (regeneration, compensation, substitution, learning). (orig.) [Deutsch] Zerebrale Aktivierungsstudien mit PET und fMRT erlangen zunehmend klinische Bedeutung fuer die funktionelle Neuroanatomie einzelner und komplexer Hirnleistungen (Lesen, Sprechen), die Lokalisation bislang unzureichend erforschter Hirnfunktionen (vestibulaerer Kortex), die Objektivierung subjektiver Beschwerden und Funktionsausfaelle (Schmerz, Riechen, Gedaechtnis) und die Dokumentation neurologischer Rehabilitation auf neuronaler Ebene (Regeneration, Kompensation, Substitution, Lernen). (orig.)

  16. Quality of reporting of descriptive studies in implant dentistry. Critical aspects in design, outcome assessment and clinical relevance

    NARCIS (Netherlands)

    Meijer, Henny J. A.; Raghoebar, Gerry M.

    Objectives: The aim of this study was to conduct a review on quality of reporting on descriptive studies in implant dentistry using the STROBE Statement and to analyse possible changes in quality of reporting on descriptive studies in implant dentistry over time. Material and Methods: A hand search

  17. Clinical relevance of cimetidine drug interactions.

    Science.gov (United States)

    Shinn, A F

    1992-01-01

    The excellent efficacy and tolerability profiles of H2-antagonists have established these agents as the leading class of antiulcer drugs. Attention has been focused on drug interactions with H2-antagonists as a means of product differentiation and because many patients are receiving multiple drug therapy. The main mechanism of most drug interactions involving cimetidine appears to be inhibition of the hepatic microsomal enzyme cytochrome P450, an effect which may be related to the different structures of H2-antagonists. Ranitidine appears to have less affinity than cimetidine for this system. There have been many published case reports and studies of drug interactions with cimetidine, but many of these have provided pharmacokinetic data only, with little information concerning the clinical significance of these findings. Nevertheless, the coadministration of cimetidine with drugs that have a narrow therapeutic margin (such as theophylline) may potentially result in clinically significant adverse effects. The monitoring of serum concentrations of drugs coadministered with cimetidine may reduce the risk of adverse events but does not abolish the problem. However, for most patients, concomitant administration of cimetidine with drugs possessing a wide therapeutic margin is unlikely to pose a significant problem.

  18. Efficacy of ethanol-based hand foams using clinically relevant amounts: a cross-over controlled study among healthy volunteers

    Directory of Open Access Journals (Sweden)

    Marschall Sigunde

    2010-03-01

    Full Text Available Abstract Background Foams containing 62% ethanol are used for hand decontamination in many countries. A long drying time may reduce the compliance of healthcare workers in applying the recommended amount of foam. Therefore, we have investigated the correlation between the applied amount and drying time, and the bactericidal efficacy of ethanol foams. Methods In a first part of tests, four foams (Alcare plus, Avagard Foam, Bode test foam, Purell Instant Hand Sanitizer containing 62% ethanol, which is commonly used in U.S. hospitals, were applied to 14 volunteers in a total of seven variations, to measure drying times. In a second part of tests, the efficacy of the established amount of foam for a 30 s application time of two foams (Alcare plus, Purell Instant Hand Sanitizer and water was compared to the EN 1500 standard of 2 × 3 mL applications of 2-propanol 60% (v/v, on hands artificially contaminated with Escherichia coli. Each application used a cross-over design against the reference alcohol with 15 volunteers. Results The mean weight of the applied foam varied between 1.78 and 3.09 g, and the mean duration to dryness was between 37 s and 103 s. The correlation between the amount of foam applied and time until hands felt dry was highly significant (p 10-reduction: 3.05 ± 0.45 and Alcare plus (3.58 ± 0.71 was significantly less effective than the reference disinfection (4.83 ± 0.89 and 4.60 ± 0.59, respectively; p 10-reduction of 2.39 ± 0.57. Conclusions When using 62% ethanol foams, the time required for dryness often exceeds the recommended 30 s. Therefore, only a small volume is likely to be applied in clinical practice. Small amounts, however, failed to meet the efficacy requirements of EN 1500 and were only somewhat more effective than water.

  19. Immunoglobulin E sensitization to cross-reactive carbohydrate determinants: epidemiological study of clinical relevance and role of alcohol consumption

    DEFF Research Database (Denmark)

    Linneberg, Allan; Fenger, Runa Vavia; Husemoen, Lise-Lotte

    2010-01-01

    The determinants and biologic significance of IgE-mediated sensitization to cross-reactive carbohydrate determinants (CCDs) are not entirely known. An association between alcohol consumption and CCD sensitization has been reported in studies from Spain and Portugal.......The determinants and biologic significance of IgE-mediated sensitization to cross-reactive carbohydrate determinants (CCDs) are not entirely known. An association between alcohol consumption and CCD sensitization has been reported in studies from Spain and Portugal....

  20. Sentinel lymph node biopsy: clinical relevance

    International Nuclear Information System (INIS)

    Howman-Giles, R.

    2002-01-01

    accurate determination of sentinel nodes in all areas. There is a significant number of unusual and unexpected drainage patterns found in melanoma many of which would be undetectable if only using a gamma probe alone or delayed imaging with large particles. There is also some controversy in breast cancer on the most accurate sentinel node technique and the relevance of extra axillary drainage sites eg internal mammary chain. The sentinel lymph node mapping with lymphoscintigraphy and blue due in association with applications of the gamma probe at surgery for accurate localisation of sentinel nodes is making a significant impact on patient management. This is in particular by more accurate staging and prognostic information with better stratification of patients requiring further regional node dissection and those suitable for adjuvant therapy and specific clinical trials

  1. Anatomic study of the vascular perfusion of the sternum and its clinical relevance in deep sternal wound infection

    Directory of Open Access Journals (Sweden)

    Spindler, Nick

    2017-06-01

    Full Text Available Introduction: Deep sternal wound infections (DSWI are a rare but devastating complication after median sternotomy. Minor perfusion in bone and soft tissue, especially after recruiting the internal mammary artery for bypass supports the development of wound infection and nonunion of the sternal bone. The aim of the study was the macroscopic and radiological presentation of the vascular system supplying the sternum, in particular the compensating blood supply routes in the event that the internal mammary artery is no longer available after use as a bypass vessel.Method: This anatomic study was carried out on the anterior chest wall of 7 specimens. The thorax plates of 7 specimens were analyzed macroscopically after microsurgical preparation. Different anatomic preparations were produced using different contrast or form-giving substances. Radiological analysis and three-dimensional reconstructions were performed to show alternative, collateral sternal vessel perfusion under estimation of the loss of the internal thoracic artery due to a bypass.Results: The length of the ITA (internal thoracic artery, measured from the beginning of the first rib to the division into the superior epigastric artery and musculophrenic artery, was an average of 16.3 cm. On average, 18.5 branches were delivered from each artery, 10 medially to the sternum supply, and the intercostal muscle. Conclusion: Our analysis gives an overview of the macroanatomic vessel system supplying the sternal bone, describing especially a common trunk deriving from the ITA and supplying multiple branches and playing an important role in building a collateral circulation of the sternum.For better evaluation, in vivo CT analysis with contrast media should be performed in patients prior to the operation and directly after the use of the double ITA to demonstrate the change in perfusion of the sternum.In the future, preconditioning of the sternum by coiling the deriving branches could become an

  2. The Clinical Relevance of Psammoma Body and Hashimoto Thyroiditis in Papillary Thyroid Carcinoma: A Large Case-control Study.

    Science.gov (United States)

    Cai, Ye-Feng; Wang, Qing-Xuan; Ni, Chun-Jue; Guo, Gui-Long; Li, Quan; Wang, Ou-Chen; Wu, Liang; Du, Hai-Yan; You, Jie; Zhang, Xiao-Hua

    2015-11-01

    This study aims to investigate the impact of psammoma body (PB) on papillary thyroid carcinoma (PTC), and evaluate the association among PB, Hashimoto thyroiditis (HT), and other clinicopathologic characteristics in PTC patients.We conducted a retrospective case-control study involving 1052 PTC patients who underwent total thyroidectomy or lobectomy with lymph node dissection.Psammoma body was observed in 324 out of 1052 PTC (30.8%) patients. Ultrasonographic (US) calcification (P < 0.001), multifocality of the tumor (P = 0.047), lymph node metastasis (LNM) (P < 0.001), HT (P < 0.001), and Primary tumor (T), Regional lymph nodes (N), Distant metastasis (M) staging (P = 0.001) were significantly related to the presence of PB. The presence of PB was significantly associated with US microcalcification (P < 0.001). In the subgroup with HT, compared with the patients without PB, the patients with PB exhibited a higher frequency of central LNM (54.7% vs 32.1%; P < 0.001) and US microcalcification (94.7% vs 38.8%; P < 0.001), as well as smaller tumors (0.9 ± 0.6 vs 1.3 ± 0.9 cm; P < 0.001). In the subgroup without HT, the patients with PB displayed a higher incidence of lateral LNM (25.8% vs 14.6%; P < 0.001), US microcalcification (87.3% vs 52.5%; P < 0.001), and extrathyroidal extension (47.2% vs 34.8%; P = 0.001), as well as larger tumors (1.3 ± 0.9 vs 1.0 ± 0.8 cm; P < 0.001) than without PB. Moreover, in the subgroup with PB, the PTC patients with HT showed a higher LNM (77.9% vs 57.2%; P < 0.001) and a lower frequency of extrathyroidal extension (20.0% vs 47.2%; P < 0.001) than without HT.Psammoma body is a useful predictor of aggressive tumor behavior in PTC patients. HT with PB shows more aggressive behaviors than non-HT with PB in PTC patients.

  3. [The relevance of clinical risk management].

    Science.gov (United States)

    Gulino, Matteo; Vergallo, Gianluca Montanari; Frati, Paola

    2011-01-01

    Medical activity includes a risk of possible injury or complications for the patients, that should drive the Health Care Institutions to introduce and/ or improve clinical Risk management instruments. Although Italy is still lacking a National project of Clinical Risk Management, a number of efforts have been made by different Italian Regions to introduce instruments of risk management. In addition, most of National Health Care Institutions include actually a Department specifically in charge to manage the clinical risk. Despite the practical difficulties, the results obtained until now suggest that the risk management may represent a useful instrument to contribute to the reduction of errors in clinical conduct. Indeed, the introduction of adequate instruments of prevention and management of clinical risk may help to ameliorate the quality of health care Institution services.

  4. Anatomic variants of the pancreatic duct and their clinical relevance: an MR-guided study in the general population

    International Nuclear Information System (INIS)

    Buelow, Robin; Thiel, Robert; Thamm, Patrick; Messner, Philip; Hosten, Norbert; Kuehn, Jens-Peter; Simon, Peter; Lerch, Markus M.; Mayerle, Julia; Voelzke, Henry

    2014-01-01

    To investigate the frequency of pancreatic duct (PD) variants and their effect on pancreatic exocrine function in a population-based study using non-invasive secretin-stimulated magnetic resonance cholangiopancreatography (sMRCP). Nine hundred and ninety-five volunteers, 457 women and 538 men, aged 51.9 ± 13.4 years, underwent navigator-triggered, T2-weighted, 3D turbo spin echo MRCP on a 1.5 T system after 1 unit/kg secretin administration. Two readers evaluated images for PD variants. Pancreatic exocrine function and morphological signs of chronic pancreatitis such as abnormalities of the main PD, side branch dilatation, and pancreatic cysts were evaluated and related to PD variants using a Kruskal-Wallis test and post hoc analysis. Of all sMRCP, 93.2 % were of diagnostic quality. Interobserver reliability for detection of PD variants was found to be kappa 0.752 (95 %CI, 0.733 - 0.771). Normal PD variants were observed in 90.4 % (n = 838/927). Variants of pancreas divisum was identified in 9.6 % (n = 89/927). Abnormalities of the main PD, side branch dilatation, and pancreatic cysts were observed in 2.4 %, 16.6 %, and 27.7 %, respectively, and were not significantly different between pancreas divisum and non-divisum group (P = 0.122; P = 0.152; P = 0.741). There was no association between PD variants and pancreatic exocrine function (P = 0.367). PD variants including pancreas divisum are not associated with morphological signs of chronic pancreatitis or restriction of pancreatic exocrine function. (orig.)

  5. Anatomic variants of the pancreatic duct and their clinical relevance: an MR-guided study in the general population

    Energy Technology Data Exchange (ETDEWEB)

    Buelow, Robin; Thiel, Robert; Thamm, Patrick; Messner, Philip; Hosten, Norbert; Kuehn, Jens-Peter [University Medicine, Ernst Moritz Arndt University Greifswald, Department of Radiology and Neuroradiology, Greifswald (Germany); Simon, Peter; Lerch, Markus M.; Mayerle, Julia [University Medicine, Ernst Moritz Arndt University Greifswald, Division of Gastroenterology and Department of Medicine A, Greifswald (Germany); Voelzke, Henry [University Medicine, Ernst Moritz Arndt University Greifswald, Institute for Community Medicine, Greifswald (Germany)

    2014-12-15

    To investigate the frequency of pancreatic duct (PD) variants and their effect on pancreatic exocrine function in a population-based study using non-invasive secretin-stimulated magnetic resonance cholangiopancreatography (sMRCP). Nine hundred and ninety-five volunteers, 457 women and 538 men, aged 51.9 ± 13.4 years, underwent navigator-triggered, T2-weighted, 3D turbo spin echo MRCP on a 1.5 T system after 1 unit/kg secretin administration. Two readers evaluated images for PD variants. Pancreatic exocrine function and morphological signs of chronic pancreatitis such as abnormalities of the main PD, side branch dilatation, and pancreatic cysts were evaluated and related to PD variants using a Kruskal-Wallis test and post hoc analysis. Of all sMRCP, 93.2 % were of diagnostic quality. Interobserver reliability for detection of PD variants was found to be kappa 0.752 (95 %CI, 0.733 - 0.771). Normal PD variants were observed in 90.4 % (n = 838/927). Variants of pancreas divisum was identified in 9.6 % (n = 89/927). Abnormalities of the main PD, side branch dilatation, and pancreatic cysts were observed in 2.4 %, 16.6 %, and 27.7 %, respectively, and were not significantly different between pancreas divisum and non-divisum group (P = 0.122; P = 0.152; P = 0.741). There was no association between PD variants and pancreatic exocrine function (P = 0.367). PD variants including pancreas divisum are not associated with morphological signs of chronic pancreatitis or restriction of pancreatic exocrine function. (orig.)

  6. Clinical relevance of findings in trials of CBT for depression

    NARCIS (Netherlands)

    Lepping, P.; Whittington, R.; Sambhi, R.S.; Lane, S.; Poole, R.; Leucht, S.; Cuijpers, P.; McCabe, R.; Waheed, W.

    2017-01-01

    Cognitive behavioural therapy (CBT) is beneficial in depression. Symptom scores can be translated into Clinical Global Impression (CGI) scale scores to indicate clinical relevance. We aimed to assess the clinical relevance of findings of randomised controlled trials (RCTs) of CBT in depression. We

  7. Pertussis leukocytosis: mechanisms, clinical relevance and treatment

    Science.gov (United States)

    Carbonetti, Nicholas H.

    2016-01-01

    The significant and sometimes dramatic rise in the number of circulating white blood cells (leukocytosis) in infants suffering from pertussis (whooping cough) has been recognized for over a century. Although pertussis is a disease that afflicts people of all ages, it can be particularly severe in young infants, and these are the individuals in whom leukocytosis is most pronounced. Very high levels of leukocytosis are associated with poor outcome in infants hospitalized with pertussis and modern treatments are often aimed at reducing the number of leukocytes. Pertussis leukocytosis is caused by pertussis toxin, a soluble protein toxin released by Bordetella pertussis during infection, but the exact mechanisms by which this occurs are still unclear. In this minireview, I discuss the history of clinical and experimental findings on pertussis leukocytosis, possible contributing mechanisms causing this condition and treatments aimed at reducing leukocytosis in hospitalized infants. Since recent studies have detailed significant associations between specific levels of pertussis leukocytosis and fatal outcome, this is a timely review that may stimulate new thinking on how to understand and combat this problem. PMID:27609461

  8. Clinical relevance of pharmacist intervention in an emergency department.

    Science.gov (United States)

    Pérez-Moreno, Maria Antonia; Rodríguez-Camacho, Juan Manuel; Calderón-Hernanz, Beatriz; Comas-Díaz, Bernardino; Tarradas-Torras, Jordi

    2017-08-01

    To evaluate the clinical relevance of pharmacist intervention on patient care in emergencies, to determine the severity of detected errors. Second, to analyse the most frequent types of interventions and type of drugs involved and to evaluate the clinical pharmacist's activity. A 6-month observational prospective study of pharmacist intervention in the Emergency Department (ED) at a 400-bed hospital in Spain was performed to record interventions carried out by the clinical pharmacists. We determined whether the intervention occurred in the process of medication reconciliation or another activity, and whether the drug involved belonged to the High-Alert Medications Institute for Safe Medication Practices (ISMP) list. To evaluate the severity of the errors detected and clinical relevance of the pharmacist intervention, a modified assessment scale of Overhage and Lukes was used. Relationship between clinical relevance of pharmacist intervention and the severity of medication errors was assessed using ORs and Spearman's correlation coefficient. During the observation period, pharmacists reviewed the pharmacotherapy history and medication orders of 2984 patients. A total of 991 interventions were recorded in 557 patients; 67.2% of the errors were detected during medication reconciliation. Medication errors were considered severe in 57.2% of cases and 64.9% of pharmacist intervention were considered relevant. About 10.9% of the drugs involved are in the High-Alert Medications ISMP list. The severity of the medication error and the clinical significance of the pharmacist intervention were correlated (Spearman's ρ=0.728/pclinical pharmacists identified and intervened on a high number of severe medication errors. This suggests that emergency services will benefit from pharmacist-provided drug therapy services. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  9. Clinically relevant incidental cardiovascular findings in CT examinations

    International Nuclear Information System (INIS)

    Voigt, P.; Fahnert, J.; Kahn, T.; Surov, A.; Schramm, D.; Bach, A.G.

    2017-01-01

    Incidental cardiovascular findings are a frequent phenomenon in computed tomography (CT) examinations. As the result of a dedicated PubMed search this article gives a systemic overview of the current literature on the most important incidental cardiovascular findings, their prevalence and clinical relevance. The majority of incidental cardiovascular findings are of only low clinical relevance; however, highly relevant incidental findings, such as aortic aneurysms, thromboses and thromboembolic events can also occasionally be found, especially in oncology patients. The scans from every CT examination should also be investigated for incidental findings as they can be of decisive importance for the further clinical management of patients, depending on their clinical relevance. (orig.) [de

  10. Classification of perimenstrual headache: clinical relevance.

    Science.gov (United States)

    MacGregor, E Anne

    2012-10-01

    Although more than 50% of women with migraine report an association between migraine and menstruation, menstruation has generally considered to be no more than one of a variety of different migraine triggers. In 2004, the second edition of the International Classification of Headache Disorders introduced specific diagnostic criteria for menstrual migraine. Results from research undertaken subsequently lend support to the clinical impression that menstrual migraine should be seen as a distinct clinical entity. This paper reviews the recent research and provides specific recommendations for consideration in future editions of the classification.

  11. Properties and clinical relevance of osteoinductive biomaterials

    NARCIS (Netherlands)

    Habibovic, Pamela

    2005-01-01

    This thesis had two main goals: (¿) to investigate parameters influencing osteoinductive potential of biomaterials in order to unravel the mechanism underlying osteoinduction and (¿¿) to investigate performance of osteoinductive biomaterials orthotopically in order to get insight into their clinical

  12. A systematic review of methodology applied during preclinical anesthetic neurotoxicity studies: important issues and lessons relevant to the design of future clinical research.

    Science.gov (United States)

    Disma, Nicola; Mondardini, Maria C; Terrando, Niccolò; Absalom, Anthony R; Bilotta, Federico

    2016-01-01

    Preclinical evidence suggests that anesthetic agents harm the developing brain thereby causing long-term neurocognitive impairments. It is not clear if these findings apply to humans, and retrospective epidemiological studies thus far have failed to show definitive evidence that anesthetic agents are harmful to the developing human brain. The aim of this systematic review was to summarize the preclinical studies published over the past decade, with a focus on methodological issues, to facilitate the comparison between different preclinical studies and inform better design of future trials. The literature search identified 941 articles related to the topic of neurotoxicity. As the primary aim of this systematic review was to compare methodologies applied in animal studies to inform future trials, we excluded a priori all articles focused on putative mechanism of neurotoxicity and the neuroprotective agents. Forty-seven preclinical studies were finally included in this review. Methods used in these studies were highly heterogeneous-animals were exposed to anesthetic agents at different developmental stages, in various doses and in various combinations with other drugs, and overall showed diverse toxicity profiles. Physiological monitoring and maintenance of physiological homeostasis was variable and the use of cognitive tests was generally limited to assessment of specific brain areas, with restricted translational relevance to humans. Comparison between studies is thus complicated by this heterogeneous methodology and the relevance of the combined body of literature to humans remains uncertain. Future preclinical studies should use better standardized methodologies to facilitate transferability of findings from preclinical into clinical science. © 2015 John Wiley & Sons Ltd.

  13. Clinical relevance of specific cognitive complaints in determining Mild Cognitive Impairment from Cognitively Normal States in a study of Healthy Elderly Controls

    Directory of Open Access Journals (Sweden)

    Marina Avila Villanueva

    2016-10-01

    Full Text Available Introduction: Subjective memory complaints in the elderly have been suggested as an early sign of dementia. This study aims at investigating whether specific cognitive complaints are more useful than others to discriminate Mild Cognitive Impairment (MCI by examining the dimensional structure of the Everyday Memory Questionnaire (EMQ.Material and Methods: A sample of community-dwelling elderly individuals was recruited (766 controls and 78 MCI. The Everyday Memory Questionnaire (EMQ was administered to measure self-perception of cognitive complaints. All participants also underwent a comprehensive clinical and neuropsychological battery. Combined exploratory factor analysis and item response theory were performed to identify the underlying structure of the EMQ. Furthermore, logistic regression analyses were conducted to study whether single cognitive complaints were able to predict MCI.Results: A suitable five-factor solution was found. Each factor focused on a different cognitive domain. Interestingly, just three of them, namely forgetfulness of immediate information, executive functions and prospective memory proved to be effective in distinguishing between cognitively healthy individuals and MCI. Based on these results we propose a shortened EMQ version comprising 10 items (EMQ-10.Discussion: Not all cognitive complaints have the same clinical relevance. Only subjective complaints on specific cognitive domains are able to discriminate MCI. We encourage clinicians to the EMQ-10 as a useful tool to quantify and monitor the progression of individuals who report cognitive complaints.

  14. Refeeding syndrome: clinical and nutritional relevance.

    Science.gov (United States)

    Viana, Larissa de Andrade; Burgos, Maria Goretti Pessoa de Araújo; Silva, Rafaella de Andrade

    2012-01-01

    Feedback syndrome is characterized clinically by neurological alterations, respiratory symptoms, arrhythmias and heart failure few days after refeeding. It happens due to severe electrolyte changes, such as hypophosphatemia, hypomagnesemia and hypokalemia associated with metabolic abnormalities that may occur as a result of nutritional support (oral, enteral or parenteral) in severely malnourished patients. To evaluate its causes and the preventive dietary measures aiming to reduce the morbimortality. Was conducted literature review in SciELO, LILACS, Medline / PUBMED, Cochrane Library and government websites in Portuguese, English and Spanish. The survey was about the last 15 years, selecting the headings: refeeding syndrome, malnutrition, hypophosphatemia, hypokalemia, hypomagnesemia. The monitoring of metabolic parameters and electrolyte levels before starting nutritional support and periodically during feeding should be based on protocols and the duration of therapy. Patients at high risk and other metabolic complications should be followed closely, and depletion of minerals and electrolytes should be replaced before starting the diet. A multidisciplinary team of nutrition therapy can guide and educate other health professionals in prevention, diagnosis and treatment of the syndrome.

  15. 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.

  16. Peripheral Artery Disease and Its Clinical Relevance in Patients with Chronic Obstructive Pulmonary Disease in the COPD and Systemic Consequences-Comorbidities Network Study.

    Science.gov (United States)

    Houben-Wilke, Sarah; Jörres, Rudolf A; Bals, Robert; Franssen, Frits M E; Gläser, Sven; Holle, Rolf; Karch, Annika; Koch, Armin; Magnussen, Helgo; Obst, Anne; Schulz, Holger; Spruit, Martijn A; Wacker, Margarethe E; Welte, Tobias; Wouters, Emiel F M; Vogelmeier, Claus; Watz, Henrik

    2017-01-15

    Knowledge about the prevalence of objectively assessed peripheral artery disease (PAD) and its clinical relevance in patients with chronic obstructive pulmonary disease (COPD) is scarce. We aimed to: (1) assess the prevalence of PAD in COPD compared with distinct control groups; and (2) study the association between PAD and functional capacity as well as health status. The ankle-brachial index was used to diagnose PAD (ankle-brachial index ≤ 0.9). The 6-minute-walk distance, health status (St. George's Respiratory Questionnaire), COPD Assessment Test, and EuroQol-5-Dimensions were assessed in patients enrolled in the German COPD and Systemic Consequences-Comorbidities Network cohort study. Control groups were derived from the Study of Health in Pomerania. A total of 2,088 patients with COPD (61.1% male; mean [SD] age, 65.3 [8.2] years, GOLD (Global Initiative for Chronic Obstructive Lung Disease) stages I-IV: 9.4, 42.5, 37.5, and 10.5%, respectively) were included, of which 184 patients (8.8%; GOLD stage I-IV: 5.1, 7.4, 11.1, and 9.5%, respectively, vs. 5.9% in patients with GOLD stage 0 in the COPD and Systemic Consequences-Comorbidities Network) had PAD. In the Study of Health in Pomerania, PAD ranged from 1.8 to 4.2%. Patients with COPD with PAD had a significantly shorter 6-minute-walk distance (356 [108] vs. 422 [103] m, P COPD Assessment Test: 19.6 [7.4] vs. 17.9 [7.4] points, P = 0.004; EuroQol-5-Dimensions visual analog scale: 51.2 [19.0] vs. 57.2 [19.6], P COPD, 8.8% were diagnosed with PAD, which is higher than the prevalence in control subjects without COPD. PAD was associated with a clinically relevant reduction in functional capacity and health status.

  17. Laboratory exercises to teach clinically relevant chemistry of antibiotics.

    Science.gov (United States)

    El Sayed, Khalid A; Chelette, Candace T

    2014-03-12

    To design, implement, and evaluate student performance on clinically relevant chemical and spectral laboratory exercises on antibiotics. In the first of 2 exercises, second-year pharmacy students enrolled in an integrated laboratory sequence course studied the aqueous stability of ß-lactam antibiotics using a spectral visual approach. In a second exercise, students studied the tendency of tetracycline, rifamycins, and fluoroquinolones to form insoluble chelate complexes (turbidity) with polyvalent metals. On a survey to assess achievement of class learning objectives, students agreed the laboratory activities helped them better retain important information concerning antibiotic stability and interactions. A significant improvement was observed in performance on examination questions related to the laboratory topics for 2012 and 2013 students compared to 2011 students who did not complete the laboratory. A 1-year follow-up examination question administered in a separate course showed >75% of the students were able to identify rifamycins-food interactions compared with laboratory exercises. The use of spectral visual approaches allowed students to investigate antibiotic stability and interactions, thus reinforcing the clinical relevance of medicinal chemistry. Students' performance on questions at the 1-year follow-up suggested increased retention of the concepts learned as a result of completing the exercises.

  18. Classification of first branchial cleft anomalies: is it clinically relevant ...

    African Journals Online (AJOL)

    Background: There are three classification systems for first branchial cleft anomalies currently in use. The Arnot, Work and Olsen classifications describe these lesions on the basis of morphology, tissue of origin and clinical appearance. However, the clinical relevance of these classifications is debated, as they may not be ...

  19. The Personal Relevance of the Social Studies.

    Science.gov (United States)

    VanSickle, Ronald L.

    1990-01-01

    Conceptualizes a personal-relevance framework derived from Ronald L. VanSickle's five areas of life integrated with four general motivating goals from Abraham Maslow's hierarchy of needs and Richard and Patricia Schmuck's social motivation theory. Illustrates ways to apply the personal relevance framework to make social studies more relevant to…

  20. Development of clinically relevant implantable pressure sensors: perspectives and challenges.

    Science.gov (United States)

    Clausen, Ingelin; Glott, Thomas

    2014-09-22

    This review describes different aspects to consider when developing implantable pressure sensor systems. Measurement of pressure is in general highly important in clinical practice and medical research. Due to the small size, light weight and low energy consumption Micro Electro Mechanical Systems (MEMS) technology represents new possibilities for monitoring of physiological parameters inside the human body. Development of clinical relevant sensors requires close collaboration between technological experts and medical clinicians.  Site of operation, size restrictions, patient safety, and required measurement range and resolution, are only some conditions that must be taken into account. An implantable device has to operate under very hostile conditions. Long-term in vivo pressure measurements are particularly demanding because the pressure sensitive part of the sensor must be in direct or indirect physical contact with the medium for which we want to detect the pressure. New sensor packaging concepts are demanded and must be developed through combined effort between scientists in MEMS technology, material science, and biology. Before launching a new medical device on the market, clinical studies must be performed. Regulatory documents and international standards set the premises for how such studies shall be conducted and reported.

  1. Top studies relevant to primary care practice.

    Science.gov (United States)

    Perry, Danielle; Kolber, Michael R; Korownyk, Christina; Lindblad, Adrienne J; Ramji, Jamil; Ton, Joey; Allan, G Michael

    2018-04-01

    To summarize 10 high-quality studies from 2017 that have strong relevance to primary care practice. Study selection involved routine literature surveillance by a group of primary care health professionals. This included screening abstracts of important journals and Evidence Alerts, as well as searching the American College of Physicians Journal Club. Topics of the 2017 articles include whether treating subclinical hypothyroidism improves outcomes or symptoms; whether evolocumab reduces cardiovascular disease as well as low-density lipoprotein levels; whether lifestyle interventions reduce medication use in patients with diabetes; whether vitamin D prevents cardiovascular disease, cancer, or upper respiratory tract infections; whether canagliflozin reduces clinical events in patients with diabetes; how corticosteroid injections affect knee osteoarthritis; whether drained abscesses benefit from antibiotic treatment; whether patients with diabetes benefit from bariatric surgery; whether exenatide reduces clinical events in patients with diabetes; and whether tympanostomy tubes affect outcomes in recurrent acute otitis media or chronic otitis media. We provide brief summaries, context where needed, and final recommendations for 10 studies with potential effects on primary care. We also briefly review 5 "runner-up" studies. Research from 2017 produced several high-quality studies in diabetes management. These have demonstrated benefit for alternative therapies and offered evidence not previously available. This year's selection of studies also provided information on a variety of conditions and therapies that are, or might become, more common in primary care settings. Copyright© the College of Family Physicians of Canada.

  2. Clinical Studies

    DEFF Research Database (Denmark)

    Pallesen, Ulla

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

  3. Streptococcus pyogenes biofilms – formation, biology,and clinical relevance

    Directory of Open Access Journals (Sweden)

    Tomas eFiedler

    2015-02-01

    Full Text Available Streptococcus pyogenes (group A streptococci, GAS is an exclusive human bacterial pathogen. The virulence potential of this species is tremendous. Interactions with humans range from asymptomatic carriage over mild and superficial infections of skin and mucosal membranes up to systemic purulent toxic-invasive disease manifestations. Particularly the latter are a severe threat for predisposed patients and lead to significant death tolls worldwide. This places GAS among the most important Gram-positive bacterial pathogens. Many recent reviews have highlighted the GAS repertoire of virulence factors, regulators and regulatory circuits/networks that enable GAS to colonize the host and to deal with all levels of the host immune defense. This covers in vitro and in vivo studies, including animal infection studies based on mice and more relevant, macaque monkeys. It is now appreciated that GAS, like many other bacterial species, do not necessarily exclusively live in a planktonic lifestyle. GAS is capable of microcolony and biofilm formation on host cells and tissues. We are now beginning to understand that this feature significantly contributes to GAS pathogenesis. In this review we will discuss the current knowledge on GAS biofilm formation, the biofilm-phenotype associated virulence factors, regulatory aspects of biofilm formation, the clinical relevance, and finally contemporary treatment regimens and future treatment options.

  4. Subclinical Hypothyroidism in Children and Adolescents: Is It Clinically Relevant?

    Directory of Open Access Journals (Sweden)

    Aneta Gawlik

    2015-01-01

    Full Text Available Although subclinical hypothyroidism (SH is a common clinical problem, its diagnosis tends to be incidental. According to the definition, it should be asymptomatic, only detectable by screening. The presence or coincidence of any symptoms leads to L-thyroxine treatment. The clinical presentation, especially in younger patients with subclinical hypothyroidism, is still under dispute. Accordingly, the aim of this paper was to review the literature from the past seven years. The literature search identified 1,594 potentially relevant articles, of which 24 met the inclusion criteria. Few studies focus on the symptomatology of subclinical hypothyroidism, and most of them analyzed a small number of subjects. A significant correlation was found by some authors between subclinical hypothyroidism and a higher risk of hypertension, dyslipidemia, and migraine. No evidence of the impact of subclinical hypothyroidism on weight, growth velocity, and puberty was revealed. As the quality of most studies is poor and no definite conclusions can be drawn, randomized, large-scale studies in children and adolescents are warranted to determine the best care for patients with SH.

  5. Clinical Relevance of Discourse Characteristics after Right Hemisphere Brain Damage

    Science.gov (United States)

    Blake, Margaret Lehman

    2006-01-01

    Purpose: Discourse characteristics of adults with right hemisphere brain damage are similar to those reported for healthy older adults, prompting the question of whether changes are due to neurological lesions or normal aging processes. The clinical relevance of potential differences across groups was examined through ratings by speech-language…

  6. [Relevance of drug use in clinical manifestations of schizophrenia].

    Science.gov (United States)

    Arias Horcajadas, F; Sánchez Romero, S; Padín Calo, J J

    2002-01-01

    To study the association between drugs use with schizophrenia clinical manifestations. The sample consists of 82 out-patients with schizophrenia, between 18 and 45 years old. They were evaluated with Addiction Severity Index (ASI) and with Positive and Negative Syndrome Scale (PANSS). A 6 months follow up was carried out. 37,8% patients had lifetime drug dependence (including alcohol and others drugs except for tobacco). The prevalence of dependence for the different drugs were: opioids 9,8%, cocaine 11%, alcohol 29,3%, cannabis 24,4%, tobacco 68,3%, caffeine 15,9%. Drug dependent had more family and legal problems. At the multiple regression analysis it was observed that cannabis and tobacco dependence was associated with a decrease in the PANSS negative symptoms subscale, and on the contrary, alcohol dependence produces a similar intensity increase at that scoring. We don't detect any clinical relevance effects over positive symptoms. Cannabis and tobacco may improve schizophrenia negative symptoms or neuroleptic secondary effects or patients with few negative symptoms may have more predisposition to the use, on the contrary alcohol use can impairment those symptoms.

  7. Assessment of the clinical relevance of quantitative sensory testing with Von Frey monofilaments in patients with allodynia and neuropathic pain. A pilot study

    NARCIS (Netherlands)

    Keizer, D.; van Wijhe, M.; Post, W.J.; Uges, D.R.A.; Wierda, J.M.K.H.

    Background: Allodynia is a common and disabling symptom in many patients with neuropathic pain. Whereas quantification of pain mostly depends on subjective pain reports, allodynia can also be measured objectively with quantitative sensory testing. In this pilot study, we investigated the clinical

  8. Clinical relevance of narrow-band imaging in flexible cystoscopy

    DEFF Research Database (Denmark)

    Drejer, Ditte; Béji, Sami; Munk Nielsen, Anna

    2017-01-01

    urological departments. Patients had either hematuria (n = 483) or known recurrent non-muscle-invasive bladder cancer (NMIBC) (n = 472). High-definition (HD) cystoscopy was performed in white light (WL) and a preliminary clinical decision was made. Then, a second cystoscopy was performed in NBI...... in NBI compared to WL (NBI: 100.0% vs WL: 83.2%, p decision making as a supplement to WL because it yields a significantly higher...... and a conclusive clinical decision was made. A difference between the two decisions that had a clinical impact on the patient was considered clinically relevant. RESULTS: Pathology was found in 216 WL cystoscopies, and additional pathology in 15 NBI cystoscopies (6.9%). Based on NBI, pathology was suspected in 23...

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

    Science.gov (United States)

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

    2013-01-01

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

  10. Clinical relevance of quantified fundus autofluorescence in diabetic macular oedema.

    Science.gov (United States)

    Yoshitake, S; Murakami, T; Uji, A; Unoki, N; Dodo, Y; Horii, T; Yoshimura, N

    2015-05-01

    To quantify the signal intensity of fundus autofluorescence (FAF) and evaluate its association with visual function and optical coherence tomography (OCT) findings in diabetic macular oedema (DMO). We reviewed 103 eyes of 78 patients with DMO and 30 eyes of 22 patients without DMO. FAF images were acquired using Heidelberg Retina Angiograph 2, and the signal levels of FAF in the individual subfields of the Early Treatment Diabetic Retinopathy Study grid were measured. We evaluated the association between quantified FAF and the logMAR VA and OCT findings. One hundred and three eyes with DMO had lower FAF signal intensity levels in the parafoveal subfields compared with 30 eyes without DMO. The autofluorescence intensity in the parafoveal subfields was associated negatively with logMAR VA and the retinal thickness in the corresponding subfields. The autofluorescence levels in the parafoveal subfield, except the nasal subfield, were lower in eyes with autofluorescent cystoid spaces in the corresponding subfield than in those without autofluorescent cystoid spaces. The autofluorescence level in the central subfield was related to foveal cystoid spaces but not logMAR VA or retinal thickness in the corresponding area. Quantified FAF in the parafovea has diagnostic significance and is clinically relevant in DMO.

  11. Clinical Relevance of HLA Gene Variants in HBV Infection

    Directory of Open Access Journals (Sweden)

    Li Wang

    2016-01-01

    Full Text Available Host gene variants may influence the natural history of hepatitis B virus (HBV infection. The human leukocyte antigen (HLA system, the major histocompatibility complex (MHC in humans, is one of the most important host factors that are correlated with the clinical course of HBV infection. Genome-wide association studies (GWASs have shown that single nucleotide polymorphisms (SNPs near certain HLA gene loci are strongly associated with not only persistent HBV infection but also spontaneous HBV clearance and seroconversion, disease progression, and the development of liver cirrhosis and HBV-related hepatocellular carcinoma (HCC in chronic hepatitis B (CHB. These variations also influence the efficacy of interferon (IFN and nucleot(side analogue (NA treatment and response to HBV vaccines. Meanwhile, discrepant conclusions were reached with different patient cohorts. It is therefore essential to identify the associations of specific HLA allele variants with disease progression and viral clearance in chronic HBV infection among different ethnic populations. A better understanding of HLA polymorphism relevance in HBV infection outcome would enable us to elucidate the roles of HLA SNPs in the pathogenesis and clearance of HBV in different areas and ethnic groups, to improve strategies for the prevention and treatment of chronic HBV infection.

  12. Prognostic Factors Toward Clinically Relevant Radiographic Progression in Patients With Rheumatoid Arthritis in Clinical Practice: A Japanese Multicenter, Prospective Longitudinal Cohort Study for Achieving a Treat-to-Target Strategy.

    Science.gov (United States)

    Koga, Tomohiro; Okada, Akitomo; Fukuda, Takaaki; Hidaka, Toshihiko; Ishii, Tomonori; Ueki, Yukitaka; Kodera, Takao; Nakashima, Munetoshi; Takahashi, Yuichi; Honda, Seiyo; Horai, Yoshiro; Watanabe, Ryu; Okuno, Hiroshi; Aramaki, Toshiyuki; Izumiyama, Tomomasa; Takai, Osamu; Miyashita, Taiichiro; Sato, Shuntaro; Kawashiri, Shin-Ya; Iwamoto, Naoki; Ichinose, Kunihiro; Tamai, Mami; Origuchi, Tomoki; Nakamura, Hideki; Aoyagi, Kiyoshi; Eguchi, Katsumi; Kawakami, Atsushi

    2016-04-01

    To determine prognostic factors of clinically relevant radiographic progression (CRRP) in patients with rheumatoid arthritis (RA) in clinical practice.We performed a multicenter prospective study in Japan of biological disease-modifying antirheumatic drug (bDMARD)-naive RA patients with moderate to high disease activity treated with conventional synthetic DMARDs (csDMARDs) at study entry. We longitudinally observed 408 patients for 1 year and assessed disease activity every 3 months. CRRP was defined as yearly progression of modified total Sharp score (mTSS) > 3.0 U. We also divided the cohort into 2 groups based on disease duration (<3 vs ≥3 years) and performed a subgroup analysis.CRRP was found in 10.3% of the patients. A multiple logistic regression analysis revealed that the independent variables to predict the development of CRRP were: CRP at baseline (0.30 mg/dL increase, 95% confidence interval [CI] 1.01-1.11), time-integrated Disease Activity Score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR) during the 1 year postbaseline (12.4-unit increase, 95%CI 1.17-2.59), RA typical erosion at baseline (95%CI 1.56-21.1), and the introduction of bDMARDs (95%CI 0.06-0.38). The subgroup analysis revealed that time-integrated DAS28-ESR is not a predictor whereas the introduction of bDMARDs is a significant protective factor for CRRP in RA patients with disease duration <3 years.We identified factors that could be used to predict the development of CRRP in RA patients treated with DMARDs. These variables appear to be different based on the RA patients' disease durations.

  13. Current socioclinical trend of sexually transmitted diseases and relevance of STD clinic: A comparative study from referral tertiary care center of Gwalior, India

    Directory of Open Access Journals (Sweden)

    Sandeep Singh

    2014-01-01

    Full Text Available Objective: Sexually transmitted infections (STIs are the major public health concern in both developed and developing countries regulated by the cultural pattern of gender expression in their society. Thus, it demanded a necessary action to review the changing pattern in (Gwalior, central India where health condition is not in a good fashion with poor socioeconomic status and awareness. Materials and Methods: This is a hospital based cross sectional questionnaire study with a sample size of 222 respondents attending sexually transmitted disease (STD clinic at JAH Gwalior from December 2011 to March 2012 using a random sampling method. Results: Most of the cases among females were in the age group of 20-40 years (152, 84.44% and males were in 18-40 years age group (35, 83.33%. Out of 180, 22 (12.22% females were having non-regular sexual partners. Out of 22 females frequency of consistent, non-consistent, and no condom use with non-regular sexual partners was three (13.63%, two (9.09%, and 17 (77.27%, respectively. Out of 42 males, 22 (52.38% reported having sex with non-regular sexual partners. None of the 15 (100% male subjects having friends or relatives as non-regular sexual partner were using condoms. Statistically significant differences were found as compared to a previous study from same STD clinic are discharge, lower abdominal pain, painful micturition, nodules in genitals as 106 (58.88%; P = 0.0001, 59 (32.77%; P = 0.0007, 25 (13.88%; P = 0.001, and one (0.5%; P = 0.005, respectively and in males with absence of abdominal pain and nodules in genitals as P = 0.016 and 0.03, respectively. Preferred place of treatment of STIs was government facility in both male and females with statistically significant 15.76% (P = 0.0001 of the population seeking no treatment. Discussions: Study suggests a changing trend of the STDs owing to the difference in the clinical presentation of the disease to a previous study from the same STD clinic few years

  14. Factors associated with risk of depression and relevant predictors of screening for depression in clinical practice: a cross-sectional study among HIV-infected individuals in Denmark

    DEFF Research Database (Denmark)

    Slot, Maria; Sodemann, Morten; Gabel, Charlotte

    2015-01-01

    importance that may be used to identify patients at risk of depression. METHODS: In 2013, 212 HIV-infected patients were included in a questionnaire study. We used the Beck Depression Inventory II (BDI-II) to assess the prevalence and severity of depressive symptoms. Patients with a BDI-II score ≥ 20 were...... offered a clinical evaluation by a consultant psychiatrist. Logistic regression was used to determine predictors associated with risk of depression. RESULTS: Symptoms of depression (BDI-II score ≥ 14) were observed in 75 patients (35%), and symptoms of moderate to major depression (BDI-II score ≥ 20...

  15. Metabolism of psilocybin and psilocin: clinical and forensic toxicological relevance.

    Science.gov (United States)

    Dinis-Oliveira, Ricardo Jorge

    2017-02-01

    Psilocybin and psilocin are controlled substances in many countries. These are the two main hallucinogenic compounds of the "magic mushrooms" and both act as agonists or partial agonists at 5-hydroxytryptamine (5-HT) 2A subtype receptors. During the last few years, psilocybin and psilocin have gained therapeutic relevance but considerable physiological variability between individuals that can influence dose-response and toxicological profile has been reported. This review aims to discuss metabolism of psilocybin and psilocin, by presenting all major and minor psychoactive metabolites. Psilocybin is primarily a pro-drug that is dephosphorylated by alkaline phosphatase to active metabolite psilocin. This last is then further metabolized, psilocin-O-glucuronide being the main urinary metabolite with clinical and forensic relevance in diagnosis.

  16. Factors associated with risk of depression and relevant predictors of screening for depression in clinical practice: a cross-sectional study among HIV-infected individuals in Denmark.

    Science.gov (United States)

    Slot, M; Sodemann, M; Gabel, C; Holmskov, J; Laursen, T; Rodkjaer, L

    2015-08-01

    Depression and psychiatric disorders are frequent among HIV-infected individuals. The aim of this study was to determine the prevalence of depression and describe the psychiatric history of HIV-infected individuals in an out-patient clinic in Denmark and to identify factors of clinical importance that may be used to identify patients at risk of depression. In 2013, 212 HIV-infected patients were included in a questionnaire study. We used the Beck Depression Inventory II (BDI-II) to assess the prevalence and severity of depressive symptoms. Patients with a BDI-II score ≥ 20 were offered a clinical evaluation by a consultant psychiatrist. Logistic regression was used to determine predictors associated with risk of depression. Symptoms of depression (BDI-II score ≥ 14) were observed in 75 patients (35%), and symptoms of moderate to major depression (BDI-II score ≥ 20) in 55 patients (26%). There was also a high prevalence of co-occurring mental illness. In a multivariate model, self-reported stress, self-reported perception that HIV infection affects all aspects of life, self-reported poor health, not being satisfied with one's current life situation, previous alcohol abuse, nonadherence to antiretroviral therapy and previously having sought help because of psychological problems were independently associated with risk of depression. Symptoms of depression and co-occurring mental illness are under-diagnosed and under-treated among HIV-infected individuals. We recommend that screening of depression should be conducted regularly to provide a full psychiatric profile to decrease the risk of depression and improve adherence and quality of life in this population. © 2015 British HIV Association.

  17. Searching for Clinically Relevant Biomarkers in Geriatric Oncology.

    Science.gov (United States)

    Katsila, Theodora; Patrinos, George P; Kardamakis, Dimitrios

    2018-01-01

    Ageing, which is associated with a progressive decline and functional deterioration in multiple organ systems, is highly heterogeneous, both inter- and intraindividually. For this, tailored-made theranostics and optimum patient stratification become fundamental, when decision-making in elderly patients is considered. In particular, when cancer incidence and cancer-related mortality and morbidity are taken into account, elderly patient care is a public health concern. In this review, we focus on oncogeriatrics and highlight current opportunities and challenges with an emphasis on the unmet need of clinically relevant biomarkers in elderly cancer patients. We performed a literature search on PubMed and Scopus databases for articles published in English between 2000 and 2017 coupled to text mining and analysis. Considering the top insights, we derived from our literature analysis that information knowledge needs to turn into knowledge growth in oncogeriatrics towards clinically relevant biomarkers, cost-effective practices, updated educational schemes for health professionals (in particular, geriatricians and oncologists), and awareness of ethical issues. We conclude with an interdisciplinary call to omics, geriatricians, oncologists, informatics, and policy-makers communities that Big Data should be translated into decision-making in the clinic.

  18. Saturated norepinephrine transporter occupancy by atomoxetine relevant to clinical doses: a rhesus monkey study with (S,S)-[{sup 18}F]FMeNER-D{sub 2}

    Energy Technology Data Exchange (ETDEWEB)

    Takano, Akihiro; Gulyas, Balazs; Varrone, Andrea; Halldin, Christer [Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Stockholm (Sweden); Maguire, Ralph Paul [Pfizer Global Research and Development, New London, CT (United States); Novartis Institutes for BioMedical Research, Basel (Switzerland)

    2009-08-15

    In a previous PET study on norepinephrine transporter (NET) occupancy in the nonhuman primate brain, the relationship between NET occupancy and atomoxetine plasma concentration, and occupancies among different brain regions, were not demonstrated adequately. It may therefore be difficult to translate the results to the clinical situations. In the present study, the detailed change of NET occupancy was investigated among a wider range of doses in a more advanced manner. Two rhesus monkeys were examined using a high-resolution PET system with (S,S)-[{sup 18}F]FMeNER-D{sub 2} under baseline conditions and after steady-state infusion of different doses of atomoxetine (0.003 to 0.12 mg/kg per hour). NET occupancy of the thalamus, brainstem and anterior cingulate cortex was calculated using BP{sub ND} obtained with the simplified reference tissue model. NET occupancy increased regionally and uniformly as the plasma concentration of atomoxetine increased. The estimated Kd value (the amount to occupy 50% of NET) in the thalamus was 16 ng/ml. The results indicate that clinical doses of atomoxetine would occupy NET almost completely. (orig.)

  19. Saturated norepinephrine transporter occupancy by atomoxetine relevant to clinical doses: a rhesus monkey study with (S,S)-[18F]FMeNER-D2

    International Nuclear Information System (INIS)

    Takano, Akihiro; Gulyas, Balazs; Varrone, Andrea; Halldin, Christer; Maguire, Ralph Paul

    2009-01-01

    In a previous PET study on norepinephrine transporter (NET) occupancy in the nonhuman primate brain, the relationship between NET occupancy and atomoxetine plasma concentration, and occupancies among different brain regions, were not demonstrated adequately. It may therefore be difficult to translate the results to the clinical situations. In the present study, the detailed change of NET occupancy was investigated among a wider range of doses in a more advanced manner. Two rhesus monkeys were examined using a high-resolution PET system with (S,S)-[ 18 F]FMeNER-D 2 under baseline conditions and after steady-state infusion of different doses of atomoxetine (0.003 to 0.12 mg/kg per hour). NET occupancy of the thalamus, brainstem and anterior cingulate cortex was calculated using BP ND obtained with the simplified reference tissue model. NET occupancy increased regionally and uniformly as the plasma concentration of atomoxetine increased. The estimated Kd value (the amount to occupy 50% of NET) in the thalamus was 16 ng/ml. The results indicate that clinical doses of atomoxetine would occupy NET almost completely. (orig.)

  20. Clinical relevance and biology of circulating tumor cells

    Science.gov (United States)

    2011-01-01

    Most breast cancer patients die due to metastases, and the early onset of this multistep process is usually missed by current tumor staging modalities. Therefore, ultrasensitive techniques have been developed to enable the enrichment, detection, isolation and characterization of disseminated tumor cells in bone marrow and circulating tumor cells in the peripheral blood of cancer patients. There is increasing evidence that the presence of these cells is associated with an unfavorable prognosis related to metastatic progression in the bone and other organs. This review focuses on investigations regarding the biology and clinical relevance of circulating tumor cells in breast cancer. PMID:22114869

  1. Mild obstructive sleep apnoea: clinical relevance and approaches to management.

    Science.gov (United States)

    McNicholas, Walter T; Bonsignore, Maria R; Lévy, Patrick; Ryan, Silke

    2016-10-01

    Obstructive sleep apnoea is highly prevalent in the general population worldwide, especially in its mild form. Clinical manifestations correlate poorly with disease severity measured by the apnoea-hypopnoea index (AHI), which complicates diagnosis. Full polysomnography might be more appropriate to assess suspected mild cases because limited ambulatory diagnostic systems are least accurate in mild disease. Treatment options in mild obstructive sleep apnoea include continuous positive airway pressure (CPAP) and oral appliance therapy, in addition to positional therapy and weight reduction when appropriate. The superior efficacy of CPAP in reducing AHI is offset by greater tolerance of oral appliances, especially in mild disease. Although severe obstructive sleep apnoea is associated with adverse health consequences, including cardiometabolic comorbidities, the association with mild disease is unclear, and reports differ regarding the clinical relevance of mild obstructive sleep apnoea. Improved diagnostic techniques and evidence-based approaches to management in mild obstructive sleep apnoea require further research. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Making the history of psychology clinically and philosophically relevant.

    Science.gov (United States)

    Vande Kemp, Hendrika

    2002-08-01

    The author discusses ways to make the history of psychology course relevant for a clinical psychology doctoral program within a multidenominational Protestant theological seminary. She uses a personalist orientation to emphasize the need to integrate psychology, philosophy, and theology. She differentiates among the intrapersonal, interpersonal, impersonal, and transpersonal dimensions of experience. She illustrates the rich multidisciplinary historical roots of contemporary psychology by tracing the the history of the term psychology and examining its meanings in the existential psychology of Søren Kierkegaard and in the 19th-century novel. She includes brief histories of the "new psychology" and of the unconscious. She describes how she uses the field of psychotheological integration to illustrate principles of historiography and summarizes resources used to supplement traditional textbooks.

  3. Clinical relevance of IDH1/2 mutant allele burden during follow-up in acute myeloid leukemia. A study by the French ALFA group

    Science.gov (United States)

    Ferret, Yann; Boissel, Nicolas; Helevaut, Nathalie; Madic, Jordan; Nibourel, Olivier; Marceau-Renaut, Alice; Bucci, Maxime; Geffroy, Sandrine; Celli-Lebras, Karine; Castaigne, Sylvie; Thomas, Xavier; Terré, Christine; Dombret, Hervé; Preudhomme, Claude; Renneville, Aline

    2018-01-01

    Assessment of minimal residual disease has emerged as a powerful prognostic factor in acute myeloid leukemia. In this study, we investigated the potential of IDH1/2 mutations as targets for minimal residual disease assessment in acute myeloid leukemia, since these mutations collectively occur in 15–20% of cases of acute myeloid leukemia and now represent druggable targets. We employed droplet digital polymerase chain reaction assays to quantify IDH1R132, IDH2R140, and IDH2R172 mutations on genomic DNA in 322 samples from 103 adult patients with primary IDH1/2 mutant acute myeloid leukemia and enrolled on Acute Leukemia French Association (ALFA) - 0701 or -0702 clinical trials. The median IDH1/2 mutant allele fraction in bone marrow samples was 42.3% (range, 8.2 – 49.9%) at diagnosis of acute myeloid leukemia, and below the detection limit of 0.2% (range, <0.2 – 39.3%) in complete remission after induction therapy. In univariate analysis, the presence of a normal karyotype, a NPM1 mutation, and an IDH1/2 mutant allele fraction <0.2% in bone marrow after induction therapy were statistically significant predictors of longer disease-free survival. In multivariate analysis, these three variables remained significantly predictive of disease-free survival. In 7/103 (7%) patients, IDH1/2 mutations persisted at high levels in complete remission, consistent with the presence of an IDH1/2 mutation in pre-leukemic hematopoietic stem cells. Five out of these seven patients subsequently relapsed or progressed toward myelodysplastic syndrome, suggesting that patients carrying the IDH1/2 mutation in a pre-leukemic clone may be at high risk of hematologic evolution. PMID:29472349

  4. Dissociative absorption: An empirically unique, clinically relevant, dissociative factor.

    Science.gov (United States)

    Soffer-Dudek, Nirit; Lassri, Dana; Soffer-Dudek, Nir; Shahar, Golan

    2015-11-01

    Research of dissociative absorption has raised two questions: (a) Is absorption a unique dissociative factor within a three-factor structure, or a part of one general dissociative factor? Even when three factors are found, the specificity of the absorption factor is questionable. (b) Is absorption implicated in psychopathology? Although commonly viewed as "non-clinical" dissociation, absorption was recently hypothesized to be specifically associated with obsessive-compulsive symptoms. To address these questions, we conducted exploratory and confirmatory factor analyses on 679 undergraduates. Analyses supported the three-factor model, and a "purified" absorption scale was extracted from the original inclusive absorption factor. The purified scale predicted several psychopathology scales. As hypothesized, absorption was a stronger predictor of obsessive-compulsive symptoms than of general psychopathology. In addition, absorption was the only dissociative scale that longitudinally predicted obsessive-compulsive symptoms. We conclude that absorption is a unique and clinically relevant dissociative tendency that is particularly meaningful to obsessive-compulsive symptoms. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Resveratrol and Calcium Signaling: Molecular Mechanisms and Clinical Relevance

    Directory of Open Access Journals (Sweden)

    Audrey E. McCalley

    2014-06-01

    Full Text Available Resveratrol is a naturally occurring compound contributing to cellular defense mechanisms in plants. Its use as a nutritional component and/or supplement in a number of diseases, disorders, and syndromes such as chronic diseases of the central nervous system, cancer, inflammatory diseases, diabetes, and cardiovascular diseases has prompted great interest in the underlying molecular mechanisms of action. The present review focuses on resveratrol, specifically its isomer trans-resveratrol, and its effects on intracellular calcium signaling mechanisms. As resveratrol’s mechanisms of action are likely pleiotropic, its effects and interactions with key signaling proteins controlling cellular calcium homeostasis are reviewed and discussed. The clinical relevance of resveratrol’s actions on excitable cells, transformed or cancer cells, immune cells and retinal pigment epithelial cells are contrasted with a review of the molecular mechanisms affecting calcium signaling proteins on the plasma membrane, cytoplasm, endoplasmic reticulum, and mitochondria. The present review emphasizes the correlation between molecular mechanisms of action that have recently been identified for resveratrol and their clinical implications.

  6. Clinical relevance is associated with allergen-specific wheal size in skin prick testing

    DEFF Research Database (Denmark)

    Haahtela, T.; Burbach, G. J.; Bachert, C.

    2014-01-01

    , asthma, atopic dermatitis, food allergy). The effects of age, gender, and geographical area on SPT results were assessed. For each allergen, the wheal size in mm with an 80% positive predictive value (PPV) for being clinically relevant was calculated. ResultsDepending on the allergen, from 40% (blatella...... by providing quantitative decision points. MethodsThe GA(2)LEN SPT study with 3068 valid data sets was used to investigate the relationship between SPT results and patient-reported clinical relevance for each of the 18 inhalant allergens as well as SPT wheal size and physician-diagnosed allergy (rhinitis...... SPT reactions had a smaller risk of sensitizations being clinically relevant compared with adults. The 80% PPV varied from 3 to 10mm depending on the allergen. ConclusionThese reading keys' for 18 inhalant allergens can help interpret SPT results with respect to their clinical significance. A SPT form...

  7. Detecting clinically relevant new information in clinical notes across specialties and settings.

    Science.gov (United States)

    Zhang, Rui; Pakhomov, Serguei V S; Arsoniadis, Elliot G; Lee, Janet T; Wang, Yan; Melton, Genevieve B

    2017-07-05

    Automated methods for identifying clinically relevant new versus redundant information in electronic health record (EHR) clinical notes is useful for clinicians and researchers involved in patient care and clinical research, respectively. We evaluated methods to automatically identify clinically relevant new information in clinical notes, and compared the quantity of redundant information across specialties and clinical settings. Statistical language models augmented with semantic similarity measures were evaluated as a means to detect and quantify clinically relevant new and redundant information over longitudinal clinical notes for a given patient. A corpus of 591 progress notes over 40 inpatient admissions was annotated for new information longitudinally by physicians to generate a reference standard. Note redundancy between various specialties was evaluated on 71,021 outpatient notes and 64,695 inpatient notes from 500 solid organ transplant patients (April 2015 through August 2015). Our best method achieved at best performance of 0.87 recall, 0.62 precision, and 0.72 F-measure. Addition of semantic similarity metrics compared to baseline improved recall but otherwise resulted in similar performance. While outpatient and inpatient notes had relatively similar levels of high redundancy (61% and 68%, respectively), redundancy differed by author specialty with mean redundancy of 75%, 66%, 57%, and 55% observed in pediatric, internal medicine, psychiatry and surgical notes, respectively. Automated techniques with statistical language models for detecting redundant versus clinically relevant new information in clinical notes do not improve with the addition of semantic similarity measures. While levels of redundancy seem relatively similar in the inpatient and ambulatory settings in the Fairview Health Services, clinical note redundancy appears to vary significantly with different medical specialties.

  8. Clinical relevance of and risk factors associated with medication administration time errors

    NARCIS (Netherlands)

    Teunissen, R.; Bos, J.; Pot, H.; Pluim, M.; Kramers, C.

    2013-01-01

    PURPOSE: The clinical relevance of and risk factors associated with errors related to medication administration time were studied. METHODS: In this explorative study, 66 medication administration rounds were studied on two wards (surgery and neurology) of a hospital. Data on medication errors were

  9. Clinically Relevant Subsets Identified by Gene Expression Patterns Support a Revised Ontogenic Model of Wilms Tumor: A Children's Oncology Group Study

    Directory of Open Access Journals (Sweden)

    Samantha Gadd

    2012-08-01

    Full Text Available Wilms tumors (WT have provided broad insights into the interface between development and tumorigenesis. Further understanding is confounded by their genetic, histologic, and clinical heterogeneity, the basis of which remains largely unknown. We evaluated 224 WT for global gene expression patterns; WT1, CTNNB1, and WTX mutation; and 11p15 copy number and methylation patterns. Five subsets were identified showing distinct differences in their pathologic and clinical features: these findings were validated in 100 additional WT. The gene expression pattern of each subset was compared with published gene expression profiles during normal renal development. A novel subset of epithelial WT in infants lacked WT1, CTNNB1, and WTX mutations and nephrogenic rests and displayed a gene expression pattern of the postinduction nephron, and none recurred. Three subsets were characterized by a low expression of WT1 and intralobar nephrogenic rests. These differed in their frequency of WT1 and CTNNB1 mutations, in their age, in their relapse rate, and in their expression similarities with the intermediate mesoderm versus the metanephric mesenchyme. The largest subset was characterized by biallelic methylation of the imprint control region 1, a gene expression profile of the metanephric mesenchyme, and both interlunar and perilobar nephrogenic rests. These data provide a biologic explanation for the clinical and pathologic heterogeneity seen within WT and enable the future development of subset-specific therapeutic strategies. Further, these data support a revision of the current model of WT ontogeny, which allows for an interplay between the type of initiating event and the developmental stage in which it occurs.

  10. Identifying Relevant Studies in Software Engineering

    DEFF Research Database (Denmark)

    Zhang, He; Ali Babar, Muhammad; Tell, Paolo

    2011-01-01

    Context: Systematic literature review (SLR) has become an important research methodology in software engineering since the introduction of evidence-based software engineering (EBSE) in 2004. One critical step in applying this methodology is to design and execute appropriate and effective search....... Objective: The main objective of the research reported in this paper is to improve the search step of undertaking SLRs in software engineering (SE) by devising and evaluating systematic and practical approaches to identifying relevant studies in SE. Method: We have systematically selected and analytically...

  11. Combining radiotherapy and ipilimumab induces clinically relevant radiation-induced abscopal effects in metastatic melanoma patients: A systematic review

    Directory of Open Access Journals (Sweden)

    Rodolfo Chicas-Sett

    2018-02-01

    Conclusion: Early clinical outcomes reports suggest that the combination of ipilimumab and RT may improve survival in metastatic melanoma patients. The abscopal responses become a clinically relevant effect of such combination and should be studied in controlled randomized trials.

  12. Identification of clinically relevant viridans streptococci by an oligonucleotide array.

    Science.gov (United States)

    Chen, Chao Chien; Teng, Lee Jene; Kaiung, Seng; Chang, Tsung Chain

    2005-04-01

    Viridans streptococci (VS) are common etiologic agents of subacute infective endocarditis and are capable of causing a variety of pyogenic infections. Many species of VS are difficult to differentiate by phenotypic traits. An oligonucleotide array based on 16S-23S rRNA gene intergenic spacer (ITS) sequences was developed to identify 11 clinically relevant VS. These 11 species were Streptococcus anginosus, S. constellatus, S. gordonii, S. intermedius, S. mitis, S. mutans, S. oralis, S. parasanguinis, S. salivarius, S. sanguinis, and S. uberis. The method consisted of PCR amplification of the ITS regions by using a pair of universal primers, followed by hybridization of the digoxigenin-labeled PCR products to a panel of species-specific oligonucleotides immobilized on a nylon membrane. After 120 strains of the 11 species of VG and 91 strains of other bacteria were tested, the sensitivity and specificity of the oligonucleotide array were found to be 100% (120 of 120 strains) and 95.6% (87 of 91 strains), respectively. S. pneumoniae cross-hybridized to the probes used for the identification of S. mitis, and simple biochemical tests such as optochin susceptibility or bile solubility should be used to differentiate S. pneumoniae from S. mitis. In conclusion, identification of species of VS by use of the present oligonucleotide array is accurate and could be used as an alternative reliable method for species identification of strains of VS.

  13. Assessment of relevant fungal species in clinical solid wastes.

    Science.gov (United States)

    Noman, Efaq Ali; Al-Gheethi, A A; Rahman, Nik Norulaini Nik Ab; Nagao, H; Ab Kadir, M O

    2016-10-01

    The study aimed to determine the fungal diversity in clinical waste samples from a healthcare facility in Penang Malaysia. Different fungi species were detected in 83.75 % of the 92 clinical waste samples that were screened from different sections of the healthcare facility. One hundred fifty fungal isolates comprising of 8 genera and 36 species were obtained. They were purified by using single spore isolation technique. Subsequently, the isolates were identified by phenotypic method based on morphological and culture characteristics on different culture media. Among all fungal isolates, Aspergillus spp. in section Nigri 10.2 %, Aspergillus niger 9.5 %, Aspergillus fumigatus 8.8 %, Penicillium. simplicissium 8 %, Aspergillus tubingensis 7.3 %, Aspergillus terreus var. terreus 6.6 %, Penicillium waksmanii 5.9 % and Curvularia lunata 6.5 % were the most frequent. Among five sections of the Wellness Centre, the clinical wastes collected from the diagnostic labs of haematology section had the highest numbers of fungal species (29 species). Glove wastes had the highest numbers of fungal species (19 species) among 17 types of clinical wastes screened. Among all fungal species, Aspergillus spp. exhibited higher growth at 37 °C than at 28 °C, indicating the potential of these opportunistic fungi to cause diseases in human. These results indicated the potential of hospital wastes as reservoirs for fungal species.

  14. A systematic review of methodology applied during preclinical anesthetic neurotoxicity studies : important issues and lessons relevant to the design of future clinical research

    NARCIS (Netherlands)

    Disma, Nicola; Mondardini, Maria C.; Terrando, Niccolo; Absalom, Anthony R.; Bilotta, Federico

    Preclinical evidence suggests that anesthetic agents harm the developing brain thereby causing long-term neurocognitive impairments. It is not clear if these findings apply to humans, and retrospective epidemiological studies thus far have failed to show definitive evidence that anesthetic agents

  15. Establishment of clinically relevant radioresistant cell lines and their characteristics

    International Nuclear Information System (INIS)

    Fukumoto, Manabu; Kuwahara, Yoshikazu; Suzuki, Masatoshi

    2014-01-01

    Although radiotherapy is one of the major therapeutic modalities for eradicating malignant tumors, the existence of radioresistant cells remains one of the most critical obstacles. Standard radiotherapy consists of fractionated radiation (FR) of 2-Gy X-rays once a day, 5 days a week, over 60 Gy in total. To understand the characteristics of radioresistant cells and to develop more effective radiotherapy, we have established novel radioresistant cell lines by long-term (> 5 years) exposure to moderate doses of fractionated X-rays. While all the parental human cancer cells ceased, their radioresistant derivatives continue to proliferate with daily exposure to 2-Gy FR for more than 30 days. We have coined those cells as 'clinically relevant radioresistant' (CRR) cells. Transplanted tumors into nude mice were also CRR, indicating that CRR cell lines are powerful tools to improve cancer radiotherapy. We have shown that the suppression of autophagic cell death but not apoptosis was mainly involved in cellular radioresistance. An inhibitor of the mTOR pathway which enhances autophagy was effective to overcome CRR tumors induced in nude mice. But the underlined mechanism was not through the inhibition of autophagy. Guanine nucleotide-binding protein 1 (GBP1) over expression was necessary for maintaining the CRR phenotype, but radioresistant cells were not necessarily cancer stem cells (CSCs). Targeting GBP1 positive cancer cells may be a more efficient method in conquering cancer than targeting CSCs. Slight but significant radioresistance was acquired by 0.5 Gy/12 hrs of long-term FR exposures to parental cells for more than 31 days in accordance with cyclinD1 over expression. This acquired radioresistance (ARR) was stably maintained in the tumor cells even on 31 days after the cessation of 0.5-Gy FR. Present observations give a mechanistic insight for ARR of tumor cells through long-term FR exposure, and provide novel therapeutic targets for radiosensitization

  16. Pancreatic hyperamylasemia during acute gastroenteritis: incidence and clinical relevance

    Directory of Open Access Journals (Sweden)

    Pignattari Elena

    2001-09-01

    Full Text Available Abstract Background Many case reports of acute pancreatitis have been reported but, up to now, pancreatic abnormalities during acute gastroenteritis have not been studied prospectively. Objectives To evaluate the incidence and the clinical significance of hyperamylasemia in 507 consecutive adult patients with acute gastroenteritis. Methods The clinical significance of hyperamylasemia, related predisposing factors and severity of gastroenteritis were assessed. Results Hyperamylasemia was detected in 10.2 % of patients studied. Although amylasemia was found over four times the normal values in three cases, the clinical features of acute pancreatitis were recorded in only one case (0.1%. Hyperamylasemia was more likely (17% where a microorganism could be identified in the stools (p Salmonella spp. and in particular S. enteritidis, was the microorganism most frequently associated with hyperamylasemia [17/84 (20.2 % and 10/45 (22.2%, respectively], followed by Rotavirus, Clostridium difficile and Campylobacter spp. Patients with hyperamylasemia had more severe gastroenteritis with an increased incidence of fever (80 % vs 50.6 %, O.R. 3.0; P Conclusions Hyperamylasemia is relatively frequent, and is associated with severe gastroenteritis. However, acute pancreatitis in the setting of acute gastroenteritis, is a rare event.

  17. Stem cell therapy for joint problems using the horse as a clinically relevant animal model

    DEFF Research Database (Denmark)

    Koch, Thomas Gadegaard; Betts, Dean H.

    2007-01-01

    of experimentally induced lesions. The horse lends itself as a good animal model of spontaneous joint disorders that are clinically relevant to similar human disorders. Equine stem cell and tissue engineering studies may be financially feasible to principal investigators and small biotechnology companies...

  18. A Bridge between Two Cultures: Uncovering the Chemistry Concepts Relevant to the Nursing Clinical Practice

    Science.gov (United States)

    Brown, Corina E.; Henry, Melissa L. M.; Barbera, Jack; Hyslop, Richard M.

    2012-01-01

    This study focused on the undergraduate course that covers basic topics in general, organic, and biological (GOB) chemistry at a mid-sized state university in the western United States. The central objective of the research was to identify the main topics of GOB chemistry relevant to the clinical practice of nursing. The collection of data was…

  19. Study of biological effects of varying mixtures of Cf-252 and gamma radiation on the acute radiation syndromes: Relevance to clinical radiotherapy of radioresistant cancer

    International Nuclear Information System (INIS)

    Maruyama, Y.; Wierzbicki, J.; Feola, J.M.

    1993-01-01

    Data for the 30 day bone marrow syndrome (BM-50) and the 6-10 day gastrointestinal (GI-50) syndrome for a one and two fraction schedule and acute and low dose rate irradiation using pure and mixed Cf-252 and photon radiation are presented. The radiation of Cf-252 is a mixture of neutrons and gamma rays. Balb/c mice of both sexes were total body irradiated with acute Co-60, low dose rate Cs-137 and Cf-252 using a 1 x and 2 x schedule. For low linear energy transfer radiations of Co-60 or Cs-137 there was expected to be an increase in the dose to produce the gastrointestinal and bone marrow syndromes with minimal change for Cf-252 neutrons. The proportion of photons in the Cf-252 radiation field were further altered by mixing Cs-137 with the Cf-252 sources and mice were total body irradiated with different proportions of photons to determine the effect on the radiation syndromes. The effects of mixing Cf-252 neutrons with different proportions of photons on the syndromes was determined. There was increase in BM-50 and GI-50 doses with fractionated or low dose rate photon irradiations and the dose modifying factors were 1.3-1.4 for the GI syndrome and 1.2 for the bone marrow syndrome. For Cf-252 there was minimal fractionation effect for the GI-50 syndrome, which increased by 1.1 for x 1 vs. x 2 fractions; for the BM-50 syndrome it rose by a 1.1 factor. For LDR Cs-137 the dose for the GI-50 syndrome rose 2.2-fold. For mixed neutron-photon radiation of 0%, 15%, 35%, and 65% η/γ mixtures, the dose to produce the BM-50 and GI-50 endpoints dropped sharply from 0 to 35% neutrons and remained flat thereafter. For major tissues such as the bone marrow and GI tract, Cf-252 behaved as high linear energy transfer for mixtures of neutrons and gamma rays when the radiations were delivered simultaneously at the low dose rates studied. 35 refs., 3 figs., 2 tabs

  20. Cardiac Remote Conditioning and Clinical Relevance: All Together Now!

    Directory of Open Access Journals (Sweden)

    Kristin Luther

    2015-12-01

    mechanisms related to cardioprotection, and in the last five to ten years, it has become clear that the mechanisms are similar, whether induced by ischemic or non-ischemic stimuli. Taking together much of the data in the literature, we propose that all of these cardioprotective “conditioning” phenomena represent activation from different entry points of a cardiac conditioning network that converges upon specific mediators and effectors of myocardial cell survival, including NF-кB, Stat3/5, protein kinase C, bradykinin, and the mitoKATP channel. Nervous system pathways may represent a novel mechanism for initiating conditioning of the heart and other organs. IPC and RIPC have proven difficult to translate clinically, as they have associated risks and cannot be used in some patients. Because of this, the use of neural and nociceptive stimuli is emerging as a potential non-ischemic and non-traumatic means to initiate cardiac conditioning. Clinical relevance is underscored by the demonstration of postconditioning with one of these modalities, supporting the conclusion that the development of pharmaceuticals and electroceuticals for this purpose is an area ripe for clinical development.

  1. [Clinical research IV. Relevancy of the statistical test chosen].

    Science.gov (United States)

    Talavera, Juan O; Rivas-Ruiz, Rodolfo

    2011-01-01

    When we look at the difference between two therapies or the association of a risk factor or prognostic indicator with its outcome, we need to evaluate the accuracy of the result. This assessment is based on a judgment that uses information about the study design and statistical management of the information. This paper specifically mentions the relevance of the statistical test selected. Statistical tests are chosen mainly from two characteristics: the objective of the study and type of variables. The objective can be divided into three test groups: a) those in which you want to show differences between groups or inside a group before and after a maneuver, b) those that seek to show the relationship (correlation) between variables, and c) those that aim to predict an outcome. The types of variables are divided in two: quantitative (continuous and discontinuous) and qualitative (ordinal and dichotomous). For example, if we seek to demonstrate differences in age (quantitative variable) among patients with systemic lupus erythematosus (SLE) with and without neurological disease (two groups), the appropriate test is the "Student t test for independent samples." But if the comparison is about the frequency of females (binomial variable), then the appropriate statistical test is the χ(2).

  2. Hyperthermic radiosensitization : mode of action and clinical relevance

    NARCIS (Netherlands)

    Kampinga, HH; Dikomey, E

    Purpose: To provide an update on the recent knowledge about the molecular mechanisms of thermal radiosensitization and its possible relevance to thermoradiotherapy. Summary: Hyperthermia is probably the most potent cellular radiosensitizer known to date. Heat interacts with radiation and potentiates

  3. Fibromyalgia and its clinical relevance in renal transplant recipients.

    Science.gov (United States)

    Erkmen Uyar, M; Sezer, S; Bal, Z; Guliyev, O; Tutal, E; Genctoy, G; Kulah, E; Ozdemir Acar, N; Haberal, M

    2015-05-01

    Recent evidence suggests that fibromyalgia syndrome (FS) is associated with inflammation and endothelial dysfunction. Our aim was to determine the prevalence of FS in renal transplant recipients and to identify possible links between FS and clinical and laboratory parameters. Ninety-nine kidney transplant recipients with normal graft functions (37.15 ± 10.83 years old, 67 male) were enrolled in the study. All subjects completed the Fibromyalgia Impact Questionnaire (FIQ). The biochemical and clinical parameters in the 1st post-transplantation year were retrospectively recorded. Cardiovascular parameters, including body composition analyses (Tanita), ambulatory blood pressure monitoring data, and pulse-wave velocity, were cross-sectionally analyzed. Mean FIQ score for the whole group was 21.4 ± 14.7. Eight patients had FIQ score >50, and these patients had significantly higher left ventricular mass index than patients with lower FIQ score (P = .048). Patients were divided according to their physical impairment score (PIS): PIS ≥5 (n = 50) and PIS FIQ (7.6% vs 9.4%; P = .0001) than in other patients. FS in renal transplant recipients was strongly associated with hypertension, arterial stiffness, obesity, and renal allograft dysfunction. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. There’s an App for That? Highlighting the Difficulty in Finding Clinically Relevant Smartphone Applications

    Directory of Open Access Journals (Sweden)

    Warren Wiechmann, MD, MBA

    2016-03-01

    Full Text Available Introduction: The use of personal mobile devices in the medical field has grown quickly, and a large proportion of physicians use their mobile devices as an immediate resource for clinical decisionmaking, prescription information and other medical information. The iTunes App Store (Apple, Inc. contains approximately 20,000 apps in its “Medical” category, providing a robust repository of resources for clinicians; however, this represents only 2% of the entire App Store. The App Store does not have strict criteria for identifying content specific to practicing physicians, making the identification of clinically relevant content difficult. The objective of this study is to quantify the characteristics of existing medical applications in the iTunes App Store that could be used by emergency physicians, residents, or medical students. Methods: We found applications related to emergency medicine (EM by searching the iTunes App Store for 21 terms representing core content areas of EM, such as “emergency medicine,” “critical care,” “orthopedics,” and “procedures.” Two physicians independently reviewed descriptions of these applications in the App Store and categorized each as the following: Clinically Relevant, Book/ Published Source, Non-English, Study Tools, or Not Relevant. A third physician reviewer resolved disagreements about categorization. Descriptive statistics were calculated. Results: We found a total of 7,699 apps from the 21 search terms, of which 17.8% were clinical, 9.6% were based on a book or published source, 1.6% were non-English, 0.7% were clinically relevant patient education resources, and 4.8% were study tools. Most significantly, 64.9% were considered not relevant to medical professionals. Clinically relevant apps make up approximately 6.9% of the App Store’s “Medical” Category and 0.1% of the overall App Store. Conclusion: Clinically relevant apps represent only a small percentage (6.9% of the total App

  5. [Nitrofurantoin--clinical relevance in uncomplicated urinary tract infections].

    Science.gov (United States)

    Stock, Ingo

    2014-07-01

    The nitrofuran derivative nitrofurantoin has been used for more than 60 years for the antibacterial therapy of uncomplicated urinary tract infections (UTI). Despite its long application, this antibiotic retained good activity against Escherichia coli and some other pathogens of uncomplicated urinary tract infections such as Staphylococcus saprophyticus and Enterococcus species. Nitrofurantoin therapy has been shown to be accompanied by numerous adverse drug effects. Among these, there are also serious side effects such as pulmonary reactions and polyneuropathy, which mainly occur in long-term use. Recent studies, however, have shown a good efficacy and tolerability of short-term nitrofurantoin therapy comparable to previous established standard therapeutic regimens applying cotrimoxazole or quinolones. Because of these data and the alarming resistance rates of uropathogenic Escherichia coli to cotrimoxazole and quinolones that have been increased markedly in several countries, the clinical significance ofnitrofurantoin has been raised again. In many current treatment guidelines, e. g., the international clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women published by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases, nitrofurantoin has been recommended as one first-line antibiotic of empiric antibacterial treatment of uncomplicated cystitis in otherwise healthy women. In Germany, however, nitrofurantoin should only be applied if more effective and less risky antibiotics cannot be used. Nitrofurantoin is contraindicated in the last three months of pregnancy and in patients suffering from renal impairment of each degree. Despite compatibility concerns, nitrofurantoin has also been recommended for the re-infection prophylaxis of recurrent uncomplicated urinary tract infections in Germany and several other countries.

  6. Clinical relevance of sarcopenia in chronic kidney disease

    Science.gov (United States)

    Moorthi, Ranjani N.; Avin, Keith G.

    2018-01-01

    Purpose of review In this article, we review sarcopenia in chronic kidney disease (CKD). We aim to present how definitions of sarcopenia from the general population may pertain to those with CKD, its assessment by clinicians and emerging therapies for sarcopenia in CKD. For this review, we limit our description and recommendations to patients with CKD who are not on dialysis. Recent findings Poorer parameters of lean mass, strength and physical function are associated with worsening patient-centered outcomes such as limiting mobility, falls and mortality in CKD; however, the magnitude of these associations are different in those with and without CKD. Sarcopenia in CKD is a balance between skeletal muscle regeneration and catabolism, which are both altered in the uremic environment. Multiple pathways are involved in these derangements, which are briefly reviewed. Differences between commonly used terms cachexia, frailty, protein-energy wasting, dynapenia and sarcopenia are described. Therapeutic options in predialysis CKD are not well studied; therefore, we review exercise options and emerging pharmacological therapies. Summary Sarcopenia, now with its own International Classification of Diseases, 10th Revision (ICD-10) code, is of importance clinically and should be accounted for in research studies in patients with CKD. Multiple therapies for sarcopenia are in development and will hopefully be available for our patients in the future. PMID:28198733

  7. Human tibial torsion - Morphometric assessment and clinical relevance

    Directory of Open Access Journals (Sweden)

    Swati Gandhi

    2014-02-01

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

  8. A comparison of the clinical relevance of thallium- 201 and ...

    African Journals Online (AJOL)

    1990-09-01

    Sep 1, 1990 ... Thallium-201 is at present the radiotracer of choice for the clinical evaluation of myocardial blood flow. Although different technetium-99m-isonitrile agents have been synthesised recently, only 99mTc-melhoxyisobutyl-isonitrile (99mTc_MIBI) has proved to hold promise for clinical implementation. The myo-.

  9. A comparison of the clinical relevance of thallium201 and ...

    African Journals Online (AJOL)

    Thallium-201 is at present the radiotracer of choice for the clinical evaluation of myocardial blood flow. Although different technetium-99m-isonitrile agents have been synthesised recently, only 99mTc-melhoxyisobutyl-isonitrile (99mTc_MIBI) has proved to hold promise for clinical implementation. The myocardial distribution ...

  10. Effect, Feasibility, and Clinical Relevance of Cell Enrichment in Large Volume Fat Grafting: A Systematic Review.

    Science.gov (United States)

    Rasmussen, Bo Sonnich; Lykke Sørensen, Celine; Vester-Glowinski, Peter Viktor; Herly, Mikkel; Trojahn Kølle, Stig-Frederik; Fischer-Nielsen, Anne; Drzewiecki, Krzysztof Tadeusz

    2017-07-01

    Large volume fat grafting is limited by unpredictable volume loss; therefore, methods of improving graft retention have been developed. Fat graft enrichment with either stromal vascular fraction (SVF) cells or adipose tissue-derived stem/stromal cells (ASCs) has been investigated in several animal and human studies, and significantly improved graft retention has been reported. Improvement of graft retention and the feasibility of these techniques are equally important in evaluating the clinical relevance of cell enrichment. We conducted a systematic search of PubMed to identify studies on fat graft enrichment that used either SVF cells or ASCs, and only studies reporting volume assessment were included. A total of 38 articles (15 human and 23 animal) were included to investigate the effects of cell enrichment on graft retention as well as the feasibility and clinical relevance of cell-enriched fat grafting. Improvements in graft retention, the SVF to fat (SVF:fat) ratio, and the ASC concentration used for enrichment were emphasized. We proposed an increased retention rate greater than 1.5-fold relative to nonenriched grafts and a maximum SVF:fat ratio of 1:1 as the thresholds for clinical relevance and feasibility, respectively. Nine studies fulfilled these criteria, whereof 6 used ASCs for enrichment. We found no convincing evidence of a clinically relevant effect of SVF enrichment in humans. ASC enrichment has shown promising results in enhancing graft retention, but additional clinical trials are needed to substantiate this claim and also determine the optimal concentration of SVF cells/ASCs for enrichment. 4. © 2017 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.

  11. Transformational leadership: is this still relevant to clinical leaders?

    Science.gov (United States)

    Lo, David; McKimm, Judy; Till, Alex

    2018-06-02

    Transformational leadership theory has been at the centre of health-care leadership research for the past three decades, has had a tangible influence on the evolution of NHS leadership development strategies, and is still evident in current frameworks. This article provides an overview of the key concepts and weaknesses of transformational leadership theory and discusses its relevance within the context of the NHS working environment.

  12. Decaying relevance of clinical data towards future decisions in data-driven inpatient clinical order sets.

    Science.gov (United States)

    Chen, Jonathan H; Alagappan, Muthuraman; Goldstein, Mary K; Asch, Steven M; Altman, Russ B

    2017-06-01

    Determine how varying longitudinal historical training data can impact prediction of future clinical decisions. Estimate the "decay rate" of clinical data source relevance. We trained a clinical order recommender system, analogous to Netflix or Amazon's "Customers who bought A also bought B..." product recommenders, based on a tertiary academic hospital's structured electronic health record data. We used this system to predict future (2013) admission orders based on different subsets of historical training data (2009 through 2012), relative to existing human-authored order sets. Predicting future (2013) inpatient orders is more accurate with models trained on just one month of recent (2012) data than with 12 months of older (2009) data (ROC AUC 0.91 vs. 0.88, precision 27% vs. 22%, recall 52% vs. 43%, all P<10 -10 ). Algorithmically learned models from even the older (2009) data was still more effective than existing human-authored order sets (ROC AUC 0.81, precision 16% recall 35%). Training with more longitudinal data (2009-2012) was no better than using only the most recent (2012) data, unless applying a decaying weighting scheme with a "half-life" of data relevance about 4 months. Clinical practice patterns (automatically) learned from electronic health record data can vary substantially across years. Gold standards for clinical decision support are elusive moving targets, reinforcing the need for automated methods that can adapt to evolving information. Prioritizing small amounts of recent data is more effective than using larger amounts of older data towards future clinical predictions. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  13. Clinical relevance of radioimmunologic gastrin determination for peptic ulcer

    International Nuclear Information System (INIS)

    Boesl, F.

    1980-01-01

    The clinical validity of the specific and sensitive radioimmunoassay was proved by the verification of the gastrin concentrations (given in the special literature) in the fasting serum of healthy control persons and of defined patient groups: duodenal ulcer, gastric ulcer, peptico-jejunal ulcer, chronically atrophic gastritis with and without pernicious anaemia, pyloric stenosis, gastric carcinoma and renal insufficiency. The result of the examinations carried out with a standardised beverage test was that the serum gastric release, which was basally and postprandially increased with respect to healthy control persons, is significantly increased by selective and proximal vagotomy in patients with chronically recurrent duodenal ulcer. Pyloroplasty has no significant influence on the serum gastrin reaction after selective proximal vagotomy. Contrary to that the reduced basal serum gastrin values of patients with Billroth II gastrectomy could not be stimulated by the beverage test. The basal and postprandial hypergastrinaemia existing after selective proximal vagotomy does not change significantly during the first postoperative year. In order to statistically compare such studies the authos suggests the 'integrated overall gastrin release'. Synchronous measurements of insulin and blood-sugar reactions do not give any indication that hypergastrinaemia, induced by selective proximal vagotomy, causes any change of the endocrine pancreatic function. Several own examples illustrate the higher diagnostic value of the secretin provocative and calcium infusion test in cases of the Zollinger-Ellison syndrome and that of the standardised beverage test in antral G-cell hyperplasia. In most cases the glucagon test is not required. (orig./MG) [de

  14. Effect, Feasibility, and Clinical Relevance of Cell Enrichment in Large Volume Fat Grafting

    DEFF Research Database (Denmark)

    Rasmussen, Bo Sonnich; Lykke Sørensen, Celine; Vester-Glowinski, Peter Viktor

    2017-01-01

    Large volume fat grafting is limited by unpredictable volume loss; therefore, methods of improving graft retention have been developed. Fat graft enrichment with either stromal vascular fraction (SVF) cells or adipose tissue-derived stem/stromal cells (ASCs) has been investigated in several animal...... and human studies, and significantly improved graft retention has been reported. Improvement of graft retention and the feasibility of these techniques are equally important in evaluating the clinical relevance of cell enrichment. We conducted a systematic search of PubMed to identify studies on fat graft...... enrichment that used either SVF cells or ASCs, and only studies reporting volume assessment were included. A total of 38 articles (15 human and 23 animal) were included to investigate the effects of cell enrichment on graft retention as well as the feasibility and clinical relevance of cell-enriched fat...

  15. Clinical Relevance of Brain Volume Measures in Multiple Sclerosis

    DEFF Research Database (Denmark)

    De Stefano, Nicola; Airas, Laura; Grigoriadis, Nikolaos

    2014-01-01

    Multiple sclerosis (MS) is a chronic disease with an inflammatory and neurodegenerative pathology. Axonal loss and neurodegeneration occurs early in the disease course and may lead to irreversible neurological impairment. Changes in brain volume, observed from the earliest stage of MS...... therefore have important clinical implications affecting treatment decisions, with several clinical trials now demonstrating an effect of disease-modifying treatments (DMTs) on reducing brain volume loss. In clinical practice, it may therefore be important to consider the potential impact of a therapy...

  16. Classification of Clinically Relevant Microorganisms in Non-Medical Environments

    National Research Council Canada - National Science Library

    Bowers, Daniel

    2004-01-01

    .... He named them Staphylococcus aureus because of their golden color. S. aureus remains one of the most important pathogens in clinical settings largely due to the rapidity of its evolutionary response to treatment...

  17. What is the clinically relevant change on the ADAS-Cog?

    Science.gov (United States)

    Schrag, Anette; Schott, Jonathan M

    2012-02-01

    To establish the minimal clinically relevant change (MCRC) on the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) for patients with mild Alzheimer's disease (AD). Cohort study. 59 recruiting sites for the Alzheimer's Disease Neuroimaging Initiative. Outpatients with AD in the Alzheimer's Disease Neuroimaging Initiative. The authors applied anchor-based MCRC methodology comparing ADAS-Cog change against clinicians' judgement of clinically relevant worsening between baseline and 6 months in four domains: memory and non-memory cognitive performance; Clinical Dementia Rating Scale; and Functional Assessment Questionnaire. The analysis was repeated for the 6-12-month interval. To support these findings, the authors calculated distribution-based measures including half-baseline SD (1/2 SD) and SEM. 181 patients (baseline ADAS-Cog score 18.5±6.4) had ADAS-Cog data at 0 and 6 months. Those undergoing clinically significant worsening on any of the four anchor questions (n=41-47) had an average ADAS-Cog change of 3.1-3.8 points. Similar results were found for the 177 patients with 6-12-month data. The average 1/2 SD for the baseline ADAS-Cog score was 3.2, and the SEM was 3.7. 3 points decline on the ADAS-Cog may be an appropriate MCRC for clinical trials of patients with early AD. However, further studies assessing the MCRC for improvement on the ADAS-Cog, using patient-based judgement as an anchor, and determining the minimal clinically relevant difference between change on two treatments are required. http://clinicalTrials.gov Identifier: NCT00106899.

  18. Using mixed methods to identify and answer clinically relevant research questions.

    Science.gov (United States)

    Shneerson, Catherine L; Gale, Nicola K

    2015-06-01

    The need for mixed methods research in answering health care questions is becoming increasingly recognized because of the complexity of factors that affect health outcomes. In this article, we argue for the value of using a qualitatively driven mixed method approach for identifying and answering clinically relevant research questions. This argument is illustrated by findings from a study on the self-management practices of cancer survivors and the exploration of one particular clinically relevant finding about higher uptake of self-management in cancer survivors who had received chemotherapy treatment compared with those who have not. A cross-sectional study generated findings that formed the basis for the qualitative study, by informing the purposive sampling strategy and generating new qualitative research questions. Using a quantitative research component to supplement a qualitative study can enhance the generalizability and clinical relevance of the findings and produce detailed, contextualized, and rich answers to research questions that would be unachievable through quantitative or qualitative methods alone. © The Author(s) 2015.

  19. Overview on Clinical Relevance of Intra-Tumor Heterogeneity.

    Science.gov (United States)

    Stanta, Giorgio; Bonin, Serena

    2018-01-01

    Today, clinical evaluation of tumor heterogeneity is an emergent issue to improve clinical oncology. In particular, intra-tumor heterogeneity (ITH) is closely related to cancer progression, resistance to therapy, and recurrences. It is interconnected with complex molecular mechanisms including spatial and temporal phenomena, which are often peculiar for every single patient. This review tries to describe all the types of ITH including morphohistological ITH, and at the molecular level clonal ITH derived from genomic instability and nonclonal ITH derived from microenvironment interaction. It is important to consider the different types of ITH as a whole for any patient to investigate on cancer progression, prognosis, and treatment opportunities. From a practical point of view, analytical methods that are widely accessible today, or will be in the near future, are evaluated to investigate the complex pattern of ITH in a reproducible way for a clinical application.

  20. Overview on Clinical Relevance of Intra-Tumor Heterogeneity

    Directory of Open Access Journals (Sweden)

    Giorgio Stanta

    2018-04-01

    Full Text Available Today, clinical evaluation of tumor heterogeneity is an emergent issue to improve clinical oncology. In particular, intra-tumor heterogeneity (ITH is closely related to cancer progression, resistance to therapy, and recurrences. It is interconnected with complex molecular mechanisms including spatial and temporal phenomena, which are often peculiar for every single patient. This review tries to describe all the types of ITH including morphohistological ITH, and at the molecular level clonal ITH derived from genomic instability and nonclonal ITH derived from microenvironment interaction. It is important to consider the different types of ITH as a whole for any patient to investigate on cancer progression, prognosis, and treatment opportunities. From a practical point of view, analytical methods that are widely accessible today, or will be in the near future, are evaluated to investigate the complex pattern of ITH in a reproducible way for a clinical application.

  1. Clinical Relevance of Steroid Use in Neuro-Oncology.

    Science.gov (United States)

    Ly, K Ina; Wen, Patrick Y

    2017-01-01

    Corticosteroids are commonly used in the management of primary central nervous system (CNS) tumors and CNS metastases to treat cancer- and treatment-related cerebral edema and improve neurologic function. However, they are also associated with significant morbidity and mortality, given their wide range of adverse effects. To review the mechanism of action, pharmacology, and toxicity profile of corticosteroids and to critically appraise the evidence that supports their use in neuro-oncologic practice based on the latest scientific and clinical data. Recent data suggest that corticosteroids may negatively impact survival in glioma patients. In addition, corticosteroids should be incorporated as a standard criterion to assess a patient's clinical and radiographic response to treatment. Corticosteroids should be used judiciously in neuro-oncologic patients, given the potential deleterious effects on clinical outcome and patient survival. Anti-angiogenic agents, which lack these adverse effects, may be a reasonable alternative to corticosteroids.

  2. Taijin Kyofusho and Social Anxiety and their clinical relevance in Indonesia and Switzerland

    OpenAIRE

    Vriends, Noortje; Pfaltz, Monique C.; Novianti, Peppy; Hadiyono, Johana

    2013-01-01

    Background: Taijin Kyofusho (TKS) is an interpersonal fear to offend others and is defined by DSM-IV as a culturally bound syndrome that occurs in Japan and Korea. Recently, cases with TKS have also been recognized in other cultures. The present questionnaire study investigated self-report TKS symptoms and social anxiety symptoms, and their clinical relevance in an Indonesian and Swiss sample. It also investigated if self-construal is associated with TKS and social anxiety, and if self-constr...

  3. Taijin Kyofusho and Social Anxiety and Their Clinical Relevance in Indonesia and Switzerland

    OpenAIRE

    Vriends, N.; Pfaltz, M. C.; Novianti, P.; Hadiyono, J.

    2013-01-01

    Background: Taijin Kyofusho Scale (TKS) is an interpersonal fear to offend others and is defined by Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) as a culturally bound syndrome that occurs in Japan and Korea. Recently, cases with TKS have also been recognized in other cultures. The present questionnaire study investigated self-report TKS symptoms and social anxiety symptoms, and their clinical relevance in an Indonesian and Swiss sample. It also investigated whether self-cons...

  4. Taijin Kyofusho and Social Anxiety and their clinical relevance in Indonesia and Switzerland

    OpenAIRE

    Noortje eVriends; Noortje eVriends; Monique C Pfaltz; Peppy eNovianti; Johana eHadiyono

    2013-01-01

    Background: Taijin Kyofusho (TKS) is an interpersonal fear to offend others and is defined by DSM-IV as a culturally bound syndrome that occurs in Japan and Korea. Recently, cases with TKS have also been recognized in other cultures. The present questionnaire study investigated self-report TKS symptoms and social anxiety symptoms, and their clinical relevance in an Indonesian and Swiss sample. It also investigated if self-construal is associated with TKS and social anxiety, and if self-const...

  5. A Laboratory Course in Clinical Biochemistry Emphasizing Interest and Relevance

    Science.gov (United States)

    Schwartz, Peter L.

    1975-01-01

    Ten laboratory experiments are described which are used in a successful clinical biochemistry laboratory course (e.g. blood alcohol, glucose tolerance, plasma triglycerides, coronary risk index, gastric analysis, vitamin C and E). Most of the experiments are performed on the students themselves using simple equipment with emphasis on useful…

  6. Developing independent investigators for clinical research relevant for Africa

    LENUS (Irish Health Repository)

    Manabe, Yukari C

    2011-12-29

    Abstract Sustainable research capacity building requires training individuals at multiple levels within a supportive institutional infrastructure to develop a critical mass of independent researchers. At many African medical institutions, a PhD is important for academic promotion and is, therefore, an important focal area for capacity building programs. We examine the training at the Infectious Diseases Institute (IDI) as a model for in-country training based on systems capacity building and attention to the academic environment. PhD training in Africa should provide a strong research foundation for individuals to perform independent, original research and to mentor others. Training the next generation of researchers within excellent indigenous academic centers of excellence with strong institutional infrastructure will empower trainees to ask regionally relevant research questions that will benefit Africans.

  7. Corona mortis: an anatomical variation with clinical relevance. Case report.

    Directory of Open Access Journals (Sweden)

    Guillermo Adrián Rivera-Cardona

    2010-12-01

    Full Text Available The obturator artery is one of the parietal branches arising from the internal iliac artery, the anatomical variation from which this artery originates is called “The corona mortis”, generally from the external iliac artery or the inferior epigastric artery. This finding was observed bilaterally in a male cadaver during a pelvis dissection. Clinical consideration of the anatomical variation in the obturator artery, during surgical procedures, is of great importance due to the risk of pelvic hemorrhage.

  8. Prevalence of Potential and Clinically Relevant Statin-Drug Interactions in Frail and Robust Older Inpatients.

    Science.gov (United States)

    Thai, Michele; Hilmer, Sarah; Pearson, Sallie-Anne; Reeve, Emily; Gnjidic, Danijela

    2015-10-01

    A significant proportion of older people are prescribed statins and are also exposed to polypharmacy, placing them at increased risk of statin-drug interactions. To describe the prevalence rates of potential and clinically relevant statin-drug interactions in older inpatients according to frailty status. A cross-sectional study of patients aged ≥65 years who were prescribed a statin and were admitted to a teaching hospital between 30 July and 10 October 2014 in Sydney, Australia, was conducted. Data on socio-demographics, comorbidities and medications were collected using a standardized questionnaire. Potential statin-drug interactions were defined if listed in the Australian Medicines Handbook and three international drug information sources: the British National Formulary, Drug Interaction Facts and Drug-Reax(®). Clinically relevant statin-drug interactions were defined as interactions with the highest severity rating in at least two of the three international drug information sources. Frailty was assessed using the Reported Edmonton Frail Scale. A total of 180 participants were recruited (median age 78 years, interquartile range 14), 35.0% frail and 65.0% robust. Potential statin-drug interactions were identified in 10% of participants, 12.7% of frail participants and 8.5% of robust participants. Clinically relevant statin-drug interactions were identified in 7.8% of participants, 9.5% of frail participants and 6.8% of robust participants. Depending on the drug information source used, the prevalence rates of potential and clinically relevant statin-drug interactions ranged between 14.4 and 35.6% and between 14.4 and 20.6%, respectively. In our study of frail and robust older inpatients taking statins, the overall prevalence of potential statin-drug interactions was low and varied significantly according to the drug information source used.

  9. Vitamin E-drug interactions: molecular basis and clinical relevance.

    Science.gov (United States)

    Podszun, Maren; Frank, Jan

    2014-12-01

    Vitamin E (α-, β-, γ- and δ-tocopherol and -tocotrienol) is an essential factor in the human diet and regularly taken as a dietary supplement by many people, who act under the assumption that it may be good for their health and can do no harm. With the publication of meta-analyses reporting increased mortality in persons taking vitamin E supplements, the safety of the micronutrient was questioned and interactions with prescription drugs were suggested as one potentially underlying mechanism. Here, we review the evidence in the scientific literature for adverse vitamin E-drug interactions and discuss the potential of each of the eight vitamin E congeners to alter the activity of drugs. In summary, there is no evidence from animal models or randomised controlled human trials to suggest that the intake of tocopherols and tocotrienols at nutritionally relevant doses may cause adverse nutrient-drug interactions. Consumption of high-dose vitamin E supplements ( ≥  300 mg/d), however, may lead to interactions with the drugs aspirin, warfarin, tamoxifen and cyclosporine A that may alter their activities. For the majority of drugs, however, interactions with vitamin E, even at high doses, have not been observed and are thus unlikely.

  10. Increased gut permeability in cancer cachexia: mechanisms and clinical relevance.

    Science.gov (United States)

    Bindels, Laure B; Neyrinck, Audrey M; Loumaye, Audrey; Catry, Emilie; Walgrave, Hannah; Cherbuy, Claire; Leclercq, Sophie; Van Hul, Matthias; Plovier, Hubert; Pachikian, Barbara; Bermúdez-Humarán, Luis G; Langella, Philippe; Cani, Patrice D; Thissen, Jean-Paul; Delzenne, Nathalie M

    2018-04-06

    Intestinal disorders often occur in cancer patients, in association with body weight loss, and this alteration is commonly attributed to the chemotherapy. Here, using a mouse model of cancer cachexia induced by ectopic transplantation of C26 cancer cells, we discovered a profound alteration in the gut functions (gut permeability, epithelial turnover, gut immunity, microbial dysbiosis) independently of any chemotherapy. These alterations occurred independently of anorexia and were driven by interleukin 6. Gut dysfunction was found to be resistant to treatments with an anti-inflammatory bacterium ( Faecalibacterium prausnitzii ) or with gut peptides involved in intestinal cell renewal (teduglutide, a glucagon-like peptide 2 analogue). The translational value of our findings was evaluated in 152 colorectal and lung cancer patients with or without cachexia. The serum level of the lipopolysaccharide-binding protein, often presented as a reflection of the bacterial antigen load, was not only increased in cachectic mice and cancer patients, but also strongly correlated with the serum IL-6 level and predictive of death and cachexia occurrence in these patients. Altogether, our data highlight profound alterations of the intestinal homeostasis in cancer cachexia occurring independently of any chemotherapy and food intake reduction, with potential relevance in humans. In addition, we point out the lipopolysaccharide-binding protein as a new biomarker of cancer cachexia related to gut dysbiosis.

  11. Increasing clinical relevance in oral radiology: Benefits and challenges when implementing digital assessment.

    Science.gov (United States)

    de Lange, T; Møystad, A; Torgersen, G R

    2018-02-13

    The aims of the study were to investigate benefits and challenges in implementing a digital examination and study the clinical relevance of the digital examination in relation to clinical training and practice. The study was based on semi-structured focus-group interviews from two distinct student populations (2016 and 2017) in a bachelor programme in dental hygiene. In addition, conversational data from a plenary discussion from the whole second student population (2017) were collected and analysed. The data were approached on basis of content analysis. A benefit experienced in the digital examination was the ease in typing and editing answers on the computer. This suggests an increased effectiveness in computer-based compared to analogue examinations. An additional advantage was the experienced relevance of the examination related to the clinic. This finding refers not only to the digital presentations of images, but also to the entire setting in the clinic and dental practice. The limitations reported by the students were non-optimal viewing conditions for presenting radiographic images and difficulties in obtaining an overview of the assignments compared to paper-based examinations due to the linear digital examination format. The last finding on lacking overview revealed an influence on student performances which should be taken seriously in designing digital examinations. In conclusion, the digital layout increases efficiency and clinical relevance of examinations to a certain extent. Obstacles were found in limitations related to image presentation and lack of overview of the examination. The latter challenge raises questions related to developing suitable assessment software. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Clinical Relevance of Prognostic and Predictive Molecular Markers in Gliomas.

    Science.gov (United States)

    Siegal, Tali

    2016-01-01

    Sorting and grading of glial tumors by the WHO classification provide clinicians with guidance as to the predicted course of the disease and choice of treatment. Nonetheless, histologically identical tumors may have very different outcome and response to treatment. Molecular markers that carry both diagnostic and prognostic information add useful tools to traditional classification by redefining tumor subtypes within each WHO category. Therefore, molecular markers have become an integral part of tumor assessment in modern neuro-oncology and biomarker status now guides clinical decisions in some subtypes of gliomas. The routine assessment of IDH status improves histological diagnostic accuracy by differentiating diffuse glioma from reactive gliosis. It carries a favorable prognostic implication for all glial tumors and it is predictive for chemotherapeutic response in anaplastic oligodendrogliomas with codeletion of 1p/19q chromosomes. Glial tumors that contain chromosomal codeletion of 1p/19q are defined as tumors of oligodendroglial lineage and have favorable prognosis. MGMT promoter methylation is a favorable prognostic marker in astrocytic high-grade gliomas and it is predictive for chemotherapeutic response in anaplastic gliomas with wild-type IDH1/2 and in glioblastoma of the elderly. The clinical implication of other molecular markers of gliomas like mutations of EGFR and ATRX genes and BRAF fusion or point mutation is highlighted. The potential of molecular biomarker-based classification to guide future therapeutic approach is discussed and accentuated.

  13. Taijin kyofusho and social anxiety and their clinical relevance in indonesia and Switzerland.

    Science.gov (United States)

    Vriends, N; Pfaltz, M C; Novianti, P; Hadiyono, J

    2013-01-01

    Taijin Kyofusho Scale (TKS) is an interpersonal fear to offend others and is defined by Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) as a culturally bound syndrome that occurs in Japan and Korea. Recently, cases with TKS have also been recognized in other cultures. The present questionnaire study investigated self-report TKS symptoms and social anxiety symptoms, and their clinical relevance in an Indonesian and Swiss sample. It also investigated whether self-construal is associated with TKS and social anxiety, and if self-construal is a mediator of the expected association between cultural background and social anxiety and TKS symptoms. 311 Indonesian and 349 Swiss university students filled out the Liebowitz Social Anxiety Scale, the Taijin Kyofusho Scale, the Self-Construal Scale, self-report social phobia DSM-IV criteria, and rated their wish for professional help to deal with social fears. TKS and social anxiety symptoms were higher in the Indonesian than the Swiss sample. TKS symptoms were associated with clinical relevance in Indonesia, whereas in Switzerland only social anxiety symptoms were associated with clinical relevance. Independent self-construal was negatively associated and interdependent self-construal was positively associated with TKS and social anxiety symptoms. Interdependent self-construal mediated the association between cultural background and these symptoms. TKS might be a clinically relevant syndrome in all individuals or cultures with an interdependent self-construal or less independent self-construal. The proposal to include the fear of offending others in the DSM-V criteria of social phobia is supported by the present findings.

  14. Taijin Kyofusho and Social Anxiety and their clinical relevance in Indonesia and Switzerland

    Directory of Open Access Journals (Sweden)

    Noortje eVriends

    2013-02-01

    Full Text Available Background: Taijin Kyofusho (TKS is an interpersonal fear to offend others and is defined by DSM-IV as a culturally bound syndrome that occurs in Japan and Korea. Recently, cases with TKS have also been recognized in other cultures. The present questionnaire study investigated self-report TKS symptoms and social anxiety symptoms, and their clinical relevance in an Indonesian and Swiss sample. It also investigated if self-construal is associated with TKS and social anxiety, and if self-construal is a mediator of the expected association between cultural background and social anxiety and TKS symptoms. Method: 311 Indonesian and 349 Swiss university students filled out the Liebowitz Social Anxiety Scale, the Taijin Kyofusho Scale, the Self-Construal Scale, self-report social phobia DSM-IV criteria, and rated their wish for professional help to deal with social fears.Results: TKS and social anxiety symptoms were higher in the Indonesian than the Swiss sample. TKS symptoms were associated with clinical relevance in Indonesia, whereas in Switzerland only social anxiety symptoms were associated with clinical relevance. Independent self-construal was negatively associated and interdependent self-construal was positively associated with TKS and social anxiety symptoms. Interdependent self-construal mediated the association between cultural background and these symptoms.Discussion: TKS might be a clinically relevant syndrome in all individuals or cultures with an interdependent self-construal or less independent self-construal. The proposal to include the fear of offending others in the DSM-V criteria of social phobia is supported by the present findings.

  15. Hepatitis E Virus Mutations: Functional and Clinical Relevance

    Directory of Open Access Journals (Sweden)

    Hoang van Tong

    2016-09-01

    Full Text Available Hepatitis E virus (HEV infection is a major cause of acute hepatitis and affects more than 20 million individuals, with three million symptomatic cases and 56,000 recognized HEV-related deaths worldwide. HEV is endemic in developing countries and is gaining importance in developed countries, due to increased number of autochthone cases. Although HEV replication is controlled by the host immune system, viral factors (especially specific viral genotypes and mutants can modulate HEV replication, infection and pathogenesis. Limited knowledge exists on the contribution of HEV genome variants towards pathogenesis, susceptibility and to therapeutic response. Nonsynonymous substitutions can modulate viral proteins structurally and thus dysregulate virus-host interactions. This review aims to compile knowledge and discuss recent advances on the casual role of HEV heterogeneity and its variants on viral morphogenesis, pathogenesis, clinical outcome and antiviral resistance.

  16. Nocebo phenomena in medicine: their relevance in everyday clinical practice.

    Science.gov (United States)

    Häuser, Winfried; Hansen, Ernil; Enck, Paul

    2012-06-01

    Nocebo phenomena are common in clinical practice and have recently become a popular topic of research and discussion among basic scientists, clinicians, and ethicists. We selectively searched the PubMed database for articles published up to December 2011 that contained the key words "nocebo" or "nocebo effect." By definition, a nocebo effect is the induction of a symptom perceived as negative by sham treatment and/or by the suggestion of negative expectations. A nocebo response is a negative symptom induced by the patient's own negative expectations and/or by negative suggestions from clinical staff in the absence of any treatment. The underlying mechanisms include learning by Pavlovian conditioning and reaction to expectations induced by verbal information or suggestion. Nocebo responses may come about through unintentional negative suggestion on the part of physicians and nurses. Information about possible complications and negative expectations on the patient's part increases the likelihood of adverse effects. Adverse events under treatment with medications sometimes come about by a nocebo effect. Physicians face an ethical dilemma, as they are required not just to inform patients of the potential complications of treatment, but also to minimize the likelihood of these complications, i.e., to avoid inducing them through the potential nocebo effect of thorough patient information. Possible ways out of the dilemma include emphasizing the fact that the proposed treatment is usually well tolerated, or else getting the patient's permission to inform less than fully about its possible side effects. Communication training in medical school, residency training, and continuing medical education would be desirable so that physicians can better exploit the power of words to patients' benefit, rather than their detriment.

  17. Epigenetics in prostate cancer: biologic and clinical relevance.

    Science.gov (United States)

    Jerónimo, Carmen; Bastian, Patrick J; Bjartell, Anders; Carbone, Giuseppina M; Catto, James W F; Clark, Susan J; Henrique, Rui; Nelson, William G; Shariat, Shahrokh F

    2011-10-01

    Prostate cancer (PCa) is one of the most common human malignancies and arises through genetic and epigenetic alterations. Epigenetic modifications include DNA methylation, histone modifications, and microRNAs (miRNA) and produce heritable changes in gene expression without altering the DNA coding sequence. To review progress in the understanding of PCa epigenetics and to focus upon translational applications of this knowledge. PubMed was searched for publications regarding PCa and DNA methylation, histone modifications, and miRNAs. Reports were selected based on the detail of analysis, mechanistic support of data, novelty, and potential clinical applications. Aberrant DNA methylation (hypo- and hypermethylation) is the best-characterized alteration in PCa and leads to genomic instability and inappropriate gene expression. Global and locus-specific changes in chromatin remodeling are implicated in PCa, with evidence suggesting a causative dysfunction of histone-modifying enzymes. MicroRNA deregulation also contributes to prostate carcinogenesis, including interference with androgen receptor signaling and apoptosis. There are important connections between common genetic alterations (eg, E twenty-six fusion genes) and the altered epigenetic landscape. Owing to the ubiquitous nature of epigenetic alterations, they provide potential biomarkers for PCa detection, diagnosis, assessment of prognosis, and post-treatment surveillance. Altered epigenetic gene regulation is involved in the genesis and progression of PCa. Epigenetic alterations may provide valuable tools for the management of PCa patients and be targeted by pharmacologic compounds that reverse their nature. The potential for epigenetic changes in PCa requires further exploration and validation to enable translation to the clinic. Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  18. Clinical relevancy of a sensitive TSH-RIA

    International Nuclear Information System (INIS)

    Seidel, C.; Ziegelitz, D.; Weber, A.; Dittmer, T.; Gerl, H.; Knappe, G.; Correns, H.J.

    1982-01-01

    Based on a sensitive TSH-RIA (measuring range 0.2-25 mU/l, 50%-intercept 2 mU/l, coefficients of between-assay-variation 5-10%) and on nearly 1200 cases, it is demonstrated that clinical results can be received by determination of basal serum TSH alone. Values above 0.5 mU TSH/l indicate positive TRH tests in a good correlation between increasing basal concentrations and pituitary TSH reserve. TSH levels below 0.3 mU/l proceed with negative TRH tests. In selected healthy subjects, we found all TSH values between 0.7 and nearly 5 mU/l (x-bar = 1.99). In euthyroid goiters TSH levels are normally in the same range, but in nodular goiters, subnormal values were found accumulated. TSH levels below 0.3 mU/l are helpful to discover non-suppressibility. Hormone treatment of goiters is successful above all in case of high-normal pretherapeutic TSH values. 'Fine-tuning' of hormone dosage (goiter treatment, postoperative prophylaxis, suppression therapy in thyroid carcinoma) as well as monitoring of thyrotoxicosis treatment is recommended to be performed by means of basal TSH determination. In pituitary disorders, thyroid hormone treatment seems to be necessary only at TSH levels below 0.5 mU/l. Combination of basal TSH and total T 3 is economical and describes nearly all functional situations in diagnosis and treatment of thyroid diseases. (author)

  19. Pulmonary embolism. Clinical relevance, requirements for diagnostic and therapeutic strategies

    International Nuclear Information System (INIS)

    Nowak, F.G.; Halbfass, P.; Hoffmann, E.

    2007-01-01

    In the population the annual incidence of pulmonary embolism amounts to 1.3-2.8 per 1000 at the age of 65-89 years. Mortality reaches about 17% within the first 3 months. Acute pulmonary embolism is characterized by an increase in pulmonary arterial pressure and an impairment of the pulmonary gas exchange. Elevation of the right cardiac pressure up to right heart decompensation may follow. In addition, hypoxemia, hyperventilation, dead space ventilation, right to left shunting, bronchoconstriction, and vasoconstriction may occur. Clinical examination, ECG, laboratory findings such as elevated D-dimer, blood gas analysis, ultrasound examination of the veins of the lower extremities, and transthoracic echocardiography are acutely available diagnostic methods of an emergency department. In addition, extensive diagnostic procedures like pulmonary scintigraphy and pulmonary angiography may be required. The aim is to get a definite diagnosis as quickly as possible to direct therapy. In acute pulmonary embolism with cardiac shock, monitoring and stabilization of the circulatory function as well as an appropriate anticoagulant therapy are essential. In some cases surgery or a local fibrinolytic intervention is indicated. (orig.) [de

  20. Thyroid-Stimulating Hormone Receptor Antibodies in Pregnancy: Clinical Relevance

    Science.gov (United States)

    Bucci, Ines; Giuliani, Cesidio; Napolitano, Giorgio

    2017-01-01

    Graves’ disease is the most common cause of thyrotoxicosis in women of childbearing age. Approximately 1% of pregnant women been treated before, or are being treated during pregnancy for Graves’ hyperthyroidism. In pregnancy, as in not pregnant state, thyroid-stimulating hormone (TSH) receptor (TSHR) antibodies (TRAbs) are the pathogenetic hallmark of Graves’ disease. TRAbs are heterogeneous for molecular and functional properties and are subdivided into activating (TSAbs), blocking (TBAbs), or neutral (N-TRAbs) depending on their effect on TSHR. The typical clinical features of Graves’ disease (goiter, hyperthyroidism, ophthalmopathy, dermopathy) occur when TSAbs predominate. Graves’ disease shows some peculiarities in pregnancy. The TRAbs disturb the maternal as well as the fetal thyroid function given their ability to cross the placental barrier. The pregnancy-related immunosuppression reduces the levels of TRAbs in most cases although they persist in women with active disease as well as in women who received definitive therapy (radioiodine or surgery) before pregnancy. Changes of functional properties from stimulating to blocking the TSHR could occur during gestation. Drug therapy is the treatment of choice for hyperthyroidism during gestation. Antithyroid drugs also cross the placenta and therefore decrease both the maternal and the fetal thyroid hormone production. The management of Graves’ disease in pregnancy should be aimed at maintaining euthyroidism in the mother as well as in the fetus. Maternal and fetal thyroid dysfunction (hyperthyroidism as well as hypothyroidism) are in fact associated with several morbidities. Monitoring of the maternal thyroid function, TRAbs measurement, and fetal surveillance are the mainstay for the management of Graves’ disease in pregnancy. This review summarizes the biochemical, immunological, and therapeutic aspects of Graves’ disease in pregnancy focusing on the role of the TRAbs in maternal and fetal

  1. Thyroid-Stimulating Hormone Receptor Antibodies in Pregnancy: Clinical Relevance

    Directory of Open Access Journals (Sweden)

    Ines Bucci

    2017-06-01

    Full Text Available Graves’ disease is the most common cause of thyrotoxicosis in women of childbearing age. Approximately 1% of pregnant women been treated before, or are being treated during pregnancy for Graves’ hyperthyroidism. In pregnancy, as in not pregnant state, thyroid-stimulating hormone (TSH receptor (TSHR antibodies (TRAbs are the pathogenetic hallmark of Graves’ disease. TRAbs are heterogeneous for molecular and functional properties and are subdivided into activating (TSAbs, blocking (TBAbs, or neutral (N-TRAbs depending on their effect on TSHR. The typical clinical features of Graves’ disease (goiter, hyperthyroidism, ophthalmopathy, dermopathy occur when TSAbs predominate. Graves’ disease shows some peculiarities in pregnancy. The TRAbs disturb the maternal as well as the fetal thyroid function given their ability to cross the placental barrier. The pregnancy-related immunosuppression reduces the levels of TRAbs in most cases although they persist in women with active disease as well as in women who received definitive therapy (radioiodine or surgery before pregnancy. Changes of functional properties from stimulating to blocking the TSHR could occur during gestation. Drug therapy is the treatment of choice for hyperthyroidism during gestation. Antithyroid drugs also cross the placenta and therefore decrease both the maternal and the fetal thyroid hormone production. The management of Graves’ disease in pregnancy should be aimed at maintaining euthyroidism in the mother as well as in the fetus. Maternal and fetal thyroid dysfunction (hyperthyroidism as well as hypothyroidism are in fact associated with several morbidities. Monitoring of the maternal thyroid function, TRAbs measurement, and fetal surveillance are the mainstay for the management of Graves’ disease in pregnancy. This review summarizes the biochemical, immunological, and therapeutic aspects of Graves’ disease in pregnancy focusing on the role of the TRAbs in maternal and

  2. Approaches for Establishing Clinically Relevant Dissolution Specifications for Immediate Release Solid Oral Dosage Forms.

    Science.gov (United States)

    Hermans, Andre; Abend, Andreas M; Kesisoglou, Filippos; Flanagan, Talia; Cohen, Michael J; Diaz, Dorys A; Mao, Y; Zhang, Limin; Webster, Gregory K; Lin, Yiqing; Hahn, David A; Coutant, Carrie A; Grady, Haiyan

    2017-11-01

    This manuscript represents the perspective of the Dissolution Analytical Working Group of the IQ Consortium. The intent of this manuscript is to highlight the challenges of, and to provide a recommendation on, the development of clinically relevant dissolution specifications (CRS) for immediate release (IR) solid oral dosage forms. A roadmap toward the development of CRS for IR products containing active ingredients with a non-narrow therapeutic window is discussed, within the context of mechanistic dissolution understanding, supported by in-human pharmacokinetic (PK) data. Two case studies present potential outcomes of following the CRS roadmap and setting dissolution specifications. These cases reveal some benefits and challenges of pursuing CRS with additional PK data, in light of current regulatory positions, including that of the US Food and Drug Administration (FDA), who generally favor this approach, but with the understanding that both industry and regulatory agency perspectives are still evolving in this relatively new field. The CRS roadmap discussed in this manuscript also describes a way to develop clinically relevant dissolution specifications based primarily on dissolution data for batches used in pivotal clinical studies, acknowledging that not all IR product development efforts need to be supported by additional PK studies, albeit with the associated risk of potentially unnecessarily tight manufacturing controls. Recommendations are provided on what stages during the life cycle investment into in vivo studies may be valuable. Finally, the opportunities for CRS within the context of post-approval changes, Modeling and Simulation (M&S), and the application of biowaivers, are briefly discussed.

  3. Sensitization to lupine flour: is it clinically relevant?

    NARCIS (Netherlands)

    de Jong, N. W.; van Maaren, M. S.; Vlieg-Boersta, B. J.; Dubois, A. E. J.; de Groot, H.; Gerth van Wijk, R.

    2010-01-01

    Lupinus angustifolius (blue lupine) is used for human and animal consumption. Currently, the lupine content in bread varies from 0% to 10% and from 0.5% to 3% in pastry. Although lupine flour is present in many products, anaphylaxis on lupine flour is rarely seen. The aim of our study was to

  4. Whole-Exome Sequencing Reveals Clinically Relevant Variants in Family Affected with Autism Spectrum Disorder

    Directory of Open Access Journals (Sweden)

    Jiaxiu Zhou

    2016-10-01

    Full Text Available Chromosomal microarray (CMA has been suggested as a first tier clinical diagnostic test for ASD. High-throughput sequencing (HTS has associated hundreds of genes associated with ASD. Whole Exome Sequencing (WES was used in combination with CMA to identify clinically-relevant ASD variants. In prior work, a trio-based (father, mother, and proband WGS (Whole Genome Sequencing was used to reveal clinically-relevant de novo, or inherited, rare variants in half (16 / 32 of the ASD families in which all probands had normal, or VOUS (Variant of Uncertain Clinical Significance, CMA results. In this study, after CMA screening chromosome structural abnormalities of a proband affected with ASD, a WES was performed on the patient and parents. Some rare de novo, and inherited, variants were detected using trio-based bioinformatics analysis. ASD variants were ranked by SFARI Gene score, HPO (human phenotype ontology, protein function damage, and manual searching PubMed. Sanger sequencing was used to validated some candidate variants in family members. A de novo homozygous mutation in SPG11 (p.C209F, two inherited, compound-heterozygote mutations in SCN9A (p.Q10R and p.R1893H and BEST1 (p.A135V and p.A297V were confirmed. Heterozygous mutations in TSC1 (p.S487C and SHANK2 (p.Arg569His inherited from mother were also confirmed.

  5. Retrieving clinically relevant diabetic retinopathy images using a multi-class multiple-instance framework

    Science.gov (United States)

    Chandakkar, Parag S.; Venkatesan, Ragav; Li, Baoxin

    2013-02-01

    Diabetic retinopathy (DR) is a vision-threatening complication from diabetes mellitus, a medical condition that is rising globally. Unfortunately, many patients are unaware of this complication because of absence of symptoms. Regular screening of DR is necessary to detect the condition for timely treatment. Content-based image retrieval, using archived and diagnosed fundus (retinal) camera DR images can improve screening efficiency of DR. This content-based image retrieval study focuses on two DR clinical findings, microaneurysm and neovascularization, which are clinical signs of non-proliferative and proliferative diabetic retinopathy. The authors propose a multi-class multiple-instance image retrieval framework which deploys a modified color correlogram and statistics of steerable Gaussian Filter responses, for retrieving clinically relevant images from a database of DR fundus image database.

  6. Perfect 24-h management of hypertension: clinical relevance and perspectives.

    Science.gov (United States)

    Kario, K

    2017-04-01

    Out-of-office blood pressure (BP) measured by home BP monitoring, or ambulatory BP monitoring, was demonstrated to be superior to office BP for the prediction of cardiovascular events. The J-HOP study of a nationwide Japanese cohort demonstrated that morning home BP is the best stroke predictor. In the prospective HONEST study of >21 000 hypertensives, on-treatment morning home BP was shown to be a strong predictor both of future coronary artery disease and stroke events. In subjects whose office BP was maintained at ⩾150 mm Hg, there was no increase in cardiovascular events when their morning systolic BP was well-controlled at artificial intelligence technology with the innovation of wearable continuous surge BP monitoring will contribute to 'anticipation medicine' with the goal of zero cardiovascular events.

  7. Review of relevant studies of isolated systems

    DEFF Research Database (Denmark)

    Hansen, L.H.; Lundsager, P.

    2001-01-01

    The report presents the results of a review of studies relating to integration of wind energy in isolated power supply systems, based on a systematic literature survey. The purpose of the study is to develop a methodology consisting of a set of guidelinesfor wind energy projects in isolated energy...... systems and a set of tools and models that are operational on an engineering level. The review is based on a literature search in the ETDE Energy Database with a main search covering the period 7/88 to 6/97 andsupplemented by partial update periods. A few newer references have been included in the review...... have been organised according to the following keywords: methods & guides, economics, concept ofapplication, system solutions, case studies, financial programmes, dedicated software tools. None of the found references presents methods or tools that contradict the philosophy of Risø's methodology...

  8. MDMA, methamphetamine, and CYP2D6 pharmacogenetics: what is clinically relevant?

    Directory of Open Access Journals (Sweden)

    Rafael eDe La Torre

    2012-11-01

    Full Text Available In vitro human studies show that the metabolism of most amphetamine-like psychostimulants is regulated by the polymorphic cytochrome P450 isozyme CYP2D6. Two compounds, methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA, were selected as archetypes to discuss the translation and clinical significance of in vitro to in vivo findings. Both compounds were chosen based on their differential interaction with CYP2D6 and their high abuse prevalence in society. Methamphetamine behaves as both a weak substrate and competitive inhibitor of CYP2D6, while MDMA acts as a high affinity substrate and potent mechanism-based inhibitor (MBI of the enzyme. The MBI behavior of MDMA on CYP2D6 implies that subjects, irrespective of their genotype/phenotype, are phenocopied to the poor metabolizer phenotype. The fraction of metabolic clearance regulated by CYP2D6 for both drugs is substantially lower than expected from in vitro studies. Other isoenzymes of cytochrome P450 and a relevant contribution of renal excretion play a part in their clearance. These facts tune down the potential contribution of CYP2D6 polymorphism in the clinical outcomes of both substances. Globally, the clinical relevance of CYP2D6 polymorphism is lower than that predicted by in vitro studies.

  9. Bone markers during acute burn care: Relevance to clinical practice?

    Science.gov (United States)

    Rousseau, Anne-Françoise; Damas, Pierre; Delanaye, Pierre; Cavalier, Etienne

    2017-02-01

    Bone changes are increasingly described after burn. How bone markers could help to detect early bone changes or to screen burn patients at higher risk of demineralization is still not made clear. We performed an observational study assessing the changes in serum bone markers after moderate burn. Adults admitted in the first 24h following burn extended on >10% body surface area were included. Serum levels of collagen type 1 cross-linked C-telopeptide (CTX), tartrate-resistant acid phosphatase 5b (TRAP), type 1 procollagen N-terminal (P1NP) and bone alkaline phosphatase (b-ALP) were measured at admission and every week during the first month. Data are expressed as median [min-max]. Bone markers were measured in 20 patients: 18 men, 2 women (including one post-menopausal). Age was 46 [19-86] years old, burn surface area reached 15 [7-85] %. Twelve patients completed the study. All biomarkers mainly remained into normal ranges during evolution. A huge variability was observed regarding biomarkers evolution. Patient's evolution was not linear and could fluctuate from a decrease to an increase of blood concentrations. There was not necessarily a consistency between the two formation or the two resorption markers. Variations observed between two consecutive measurements were lesser than the accepted critical difference in almost one third of the cases. Considering available data, role and interest of bone markers in management of burn related bone disease remain unclear. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

  10. Clinical and immunological relevance of antibodies in solid organ transplantation.

    Science.gov (United States)

    Mehra, N K; Baranwal, A K

    2016-12-01

    The two important issues affecting recipients of solid organ transplants and of importance to immunologists are (i) sensitization of the recipient to HLA antigens and the resultant humoral immune response leading to the development of anti-HLA antibodies; and ii) development of robust assays for early detection of humoral rejection post-transplant. Evidence from several studies clearly indicates that presence of circulating anti-HLA antibodies especially donor specific leads to early graft loss and high titres of DSA may even lead to hyperacute or accelerated acute rejection. Long-term graft survival too is adversely affected by the presence of either pre- or post-transplant DSA. HLA matching status of the recipient - donor pair - is an important factor in the modulation of humoral response following transplantation and in a way affects de novo development of DSA. Data collected over the past decade clearly indicate significantly lower level of DSAs in optimally matched donor-recipient pairs. HLA mismatches especially those on HLA-DR and HLA-C loci have wider implications on post-transplant graft survival. The presence of circulating anti-HLA antibodies leads to endothelial damage in the newly grafted organ through complement dependent or independent pathways. Although detection of C4d deposition in renal biopsies serves as an important indicator of humoral rejection, its absence does not preclude the presence of DSAs and humoral rejection, and hence, it cannot be relied upon in every case. The emergence of epitope-based screening for anti-HLA antibodies on Luminex platform with high degree of sensitivity has revolutionized the screening for anti-HLA antibodies and DSAs. Studies indicate that humoral response to non-HLA antigens might also have a detrimental effect on allograft survival. High titres of such circulating antibodies may even lead to hyperacute rejection. Pre-emptive testing of solid organ recipients, especially kidney transplant recipients for anti

  11. Systematic reviews: guidance relevant for studies of older people.

    Science.gov (United States)

    Shenkin, Susan D; Harrison, Jennifer K; Wilkinson, Tim; Dodds, Richard M; Ioannidis, John P A

    2017-09-01

    Systematic reviews and meta-analyses are increasingly common. This article aims to provide guidance for people conducting systematic reviews relevant to the healthcare of older people. An awareness of these issues will also help people reading systematic reviews to determine whether the results will influence their clinical practice. It is essential that systematic reviews are performed by a team which includes the required technical and clinical expertise. Those performing reviews for the first time should ensure they have appropriate training and support. They must be planned and performed in a transparent and methodologically robust way: guidelines are available. The protocol should be written-and if possible published-before starting the review. Geriatricians will be interested in a table of baseline characteristics, which will help to determine if the studied samples or populations are similar to their patients. Reviews of studies of older people should consider how they will manage issues such as different age cut-offs; non-specific presentations; multiple predictors and outcomes; potential biases and confounders. Systematic reviews and meta-analyses may provide evidence to improve older people's care, or determine where new evidence is required. Newer methodologies, such as meta-analyses of individual level data, network meta-analyses and umbrella reviews, and realist synthesis, may improve the reliability and clinical utility of systematic reviews. © The Author 2017. Published by Oxford University Press on behalf of the British Geriatrics Society.

  12. Hydroxyurea could be a good clinically relevant iron chelator.

    Science.gov (United States)

    Italia, Khushnooma; Colah, Roshan; Ghosh, Kanjaksha

    2013-01-01

    Our previous study showed a reduction in serum ferritin of β-thalassemia patients on hydroxyurea therapy. Here we aimed to evaluate the efficacy of hydroxyurea alone and in combination with most widely used iron chelators like deferiprone and deferasirox for reducing iron from experimentally iron overloaded mice. 70 BALB/c mice received intraperitonial injections of iron-sucrose. The mice were then divided into 8 groups and were orally given hydroxyurea, deferiprone or deferasirox alone and their combinations for 4 months. CBC, serum-ferritin, TBARS, sTfr and hepcidin were evaluated before and after iron overload and subsequently after 4 months of drug therapy. All animals were then killed. Iron staining of the heart and liver tissue was done using Perl's Prussian Blue stain. Dry weight of iron in the heart and liver was determined by atomic absorption spectrometry. Increased serum-ferritin, TBARS, hepcidin and dry weight of iron in the liver and heart showed a significant reduction in groups treated with iron chelators with maximum reduction in the group treated with a combination of deferiprone, deferasirox and hydroxyurea. Thus hydroxyurea proves its role in reducing iron from iron overloaded mice. The iron chelating effect of these drugs can also be increased if given in combination.

  13. Hydroxyurea could be a good clinically relevant iron chelator.

    Directory of Open Access Journals (Sweden)

    Khushnooma Italia

    Full Text Available Our previous study showed a reduction in serum ferritin of β-thalassemia patients on hydroxyurea therapy. Here we aimed to evaluate the efficacy of hydroxyurea alone and in combination with most widely used iron chelators like deferiprone and deferasirox for reducing iron from experimentally iron overloaded mice. 70 BALB/c mice received intraperitonial injections of iron-sucrose. The mice were then divided into 8 groups and were orally given hydroxyurea, deferiprone or deferasirox alone and their combinations for 4 months. CBC, serum-ferritin, TBARS, sTfr and hepcidin were evaluated before and after iron overload and subsequently after 4 months of drug therapy. All animals were then killed. Iron staining of the heart and liver tissue was done using Perl's Prussian Blue stain. Dry weight of iron in the heart and liver was determined by atomic absorption spectrometry. Increased serum-ferritin, TBARS, hepcidin and dry weight of iron in the liver and heart showed a significant reduction in groups treated with iron chelators with maximum reduction in the group treated with a combination of deferiprone, deferasirox and hydroxyurea. Thus hydroxyurea proves its role in reducing iron from iron overloaded mice. The iron chelating effect of these drugs can also be increased if given in combination.

  14. Long Pentraxin 3: Experimental and Clinical Relevance in Cardiovascular Diseases

    Directory of Open Access Journals (Sweden)

    Fabrizia Bonacina

    2013-01-01

    Full Text Available Pentraxin 3 (PTX3 is an essential component of the humoral arm of innate immunity and belongs, together with the C-reactive protein (CRP and other acute phase proteins, to the pentraxins' superfamily: soluble, multifunctional, pattern recognition proteins. Pentraxins share a common C-terminal pentraxin domain, which in the case of PTX3 is coupled to an unrelated long N-terminal domain. PTX3 in humans, like CRP, correlates with surrogate markers of atherosclerosis and is independently associated with the risk of developing vascular events. Studies addressing the potential physiopathological role of CRP in the cardiovascular system were so far inconclusive and have been limited by the fact that the sequence and regulation have not been conserved during evolution between mouse and man. On the contrary, the conservation of sequence, gene organization, and regulation of PTX3 supports the translation of animal model findings in humans. While PTX3 deficiency is associated with increased inflammation, cardiac damage, and atherosclerosis, the overexpression limits carotid restenosis after angioplasty. These observations point to a cardiovascular protective effect of PTX3 potentially associated with the ability of tuning inflammation and favor the hypothesis that the increased levels of PTX3 in subjects with cardiovascular diseases may reflect a protective physiological mechanism, which correlates with the immunoinflammatory response observed in several cardiovascular disorders.

  15. Clinical relevance of syncope and presyncope induced by tilt testing.

    Science.gov (United States)

    Zyśko, Dorota; Gajek, Jacek; Koźluk, Edward; Agrawal, Anil Kumar; Smereka, Jacek; Checiński, Igor

    2009-08-01

    The authors investigated the relation between presyncope and syncope induced by tilt testing (HUTT) and demographics, medical history and HUTT data.The demographics, syncopal burden, data regarding the spontaneous syncope and reproduction of symptoms during HUTT were compared among patients with induced syncope and presyncope. The study group consisted of 574 patients (371 women, 203 men), aged 43.7 +/- 18.5 years. Patients with syncope induced by HUTT (418 patients, 63.9% women) had a higher number of syncopal episodes in their medical history. Stepwise logistic regression revealed that syncope provocation was independently related to the cardiodepressive type of neurocardiogenic reaction (OR 7.8, CI 4.2-14.4, P < 0.001), NTG use (OR 1.7, CI: 1.0-2.7, P < 0.05), the reproduction of the symptoms during HUTT (OR 2.0, CI: 1.3-3.1, P < 0.01) and the higher number of syncopal episodes (OR 2.0, CI: 1.3-3.0, P < 0.01). In patients with positive HUTT during a passive phase it was related to the cardiodepressive type of reaction (OR 26.5, CI: 5.9-118.5, P < 0.001). In the group with positive HUTT after NTG syncope was related to the cardiodepressive type (OR 5.7, CI: 2.9-11.2, P < 0.001), vasovagal history (OR 2.0, CI: 1.2-3.3, P < 0.01), reproduction of the spontaneous symptoms (OR 1.9, CI: 1.1-3.1, P < 0.05) and higher number of syncopal episodes (OR 2.1, CI: 1.3-3.3, P < 0.01). Syncope is more frequently a HUTT outcome than presyncope. The provocation of syncope in the passive phase of HUTT depends only on the cardiodepressive type of neurocardiogenic reaction. The induction of presyncope after nitroglycerin provocation is related to the possibility of a false positive reaction.

  16. Clinical relevance of metronidazole and peripheral neuropathy: a systematic review of the literature.

    Science.gov (United States)

    Goolsby, Tiffany A; Jakeman, Bernadette; Gaynes, Robert P

    2018-03-01

    The objective of this paper was to review and evaluate the literature on metronidazole-associated peripheral neuropathy and determine the relevance in clinical practice. MEDLINE/PubMed, EBSCO, and Google Scholar were searched through February 2017 using the search terms metronidazole and peripheral neuropathy, or polyneuropathy, or paresthesia, or neurotoxicity. Relevant case reports, retrospective studies, surveys, and review articles were included. Bibliographies of all relevant articles were reviewed for additional sources. Overall, metronidazole is generally well tolerated, but serious neurotoxicity, including peripheral neuropathy, has been reported. The overall incidence of peripheral neuropathy associated with metronidazole is unknown. Our review found 36 case reports (40 unique patients) of metronidazole-associated peripheral neuropathy, with most cases (31/40) receiving a >42 g total (>4 weeks) of therapy. In addition, we reviewed 13 clinical studies and found varying rates of peripheral neuropathy from 0 to 50%. Within these clinical studies, we found a higher incidence of peripheral neuropathy in patients receiving >42 g total (>4 weeks) of metronidazole compared with those patients receiving ≤42 g total (17.9% vs. 1.7%). Nearly all patients had complete resolution of symptoms. In conclusion, peripheral neuropathy is rare in patients who receive ≤42 g total of metronidazole. Patients who receive higher total doses may be at higher risk of peripheral neuropathy, but symptoms resolve after discontinuation of therapy in most patients. Antimicrobial stewardship programs may consider use of antibiotic combinations that include metronidazole over broad-spectrum alternatives when treating with ≤42 g total of the drug (≤4 weeks). Published by Elsevier B.V.

  17. Two clinically relevant pressures of carbon dioxide pneumoperitoneum cause hepatic injury in a rabbit model

    OpenAIRE

    Li, Jun; Liu, Ying-Hai; Ye, Zhan-Yong; Liu, He-Nian; Ou, Shan; Tian, Fu-Zhou

    2011-01-01

    AIM: To observe the hepatic injury induced by carbon dioxide pneumoperitoneum (CDP) in rabbits, compare the effects of low- and high-pressure pneumoperitoneum, and to determine the degree of hepatic injury induced by these two clinically relevant CDP pressures.

  18. 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

  19. Enrichment methods to detect bone marrow micrometastases in breast carcinoma patients: clinical relevance

    International Nuclear Information System (INIS)

    Choesmel, Valérie; Pierga, Jean-Yves; Nos, Claude; Vincent-Salomon, Anne; Sigal-Zafrani, Brigitte; Thiery, Jean-Paul; Blin, Nathalie

    2004-01-01

    Improving technologies for the detection and purification of bone marrow (BM) micrometastatic cells in breast cancer patients should lead to earlier prognosis of the risk of relapse and should make it possible to design more appropriate therapies. The technique used has to overcome the challenges resulting from the small number of target cells (one per million hematopoietic cells) and the heterogeneous expression of micrometastatic cell markers. In the present study, we have assessed the clinical relevance of current methods aimed at detecting rare disseminated carcinoma cells. BM aspirates from 32 carcinoma patients were screened for the presence of micrometastatic cells positive for epithelial cell adhesion molecule and positive for cytokeratins, using optimized immunodetection methods. A comparison with data obtained for 46 control BM aspirates and a correlation with the clinical status of patients were performed. We developed a sensitive and efficient immunomagnetic protocol for the enrichment of BM micrometastases. This method was used to divide 32 breast carcinoma patients into three categories according to their epithelial cell adhesion molecule status. These categories were highly correlated with the recently revised American Joint Committee on Cancer staging system for breast cancer, demonstrating the clinical relevance of this simple and reliable immunomagnetic technique. We also evaluated immunocytochemical detection of cytokeratin-positive cells and cytomorphological parameters. Immunocytochemistry-based methods for the detection of BM micrometastases did not provide any information about the clinical status of patients, but helped to refine the immunomagnetic data by confirming the presence of micrometastases in some cases. We also tested a new density gradient centrifugation system, able to enrich the tumor fraction of BM specimens by twofold to threefold as compared with standard Ficoll methods. These improved methods for the detection of

  20. Clinical Empathy and Narrative Competence: The Relevance of Reading Talmudic Legends as Literary Fiction

    Directory of Open Access Journals (Sweden)

    John H. Davidson

    2015-04-01

    Full Text Available The “curative potential” in almost any clinical setting depends on a caregiver establishing and maintaining an empathic connection with patients so as to achieve “narrative competence” in discerning and acting in accord with their preferences and best interests. The “narrative medicine” model of shared “close reading of literature and reflective writing” among clinicians as a means of fostering a capacity for clinical empathy has gained validation with recent empirical studies demonstrating the enhancement of theory of mind (ToM, broadly conceived as empathy, in readers of literary fiction. Talmudic legends, like that of Rabbi Judah’s death, are under-appreciated, relevant sources of literary fiction for these efforts. The limitations of narrative medicine are readily counterbalanced by simultaneously practiced attention to traditional bioethical principles, including—especially—beneficence, non-maleficence, and autonomy.

  1. Clinical empathy and narrative competence: the relevance of reading talmudic legends as literary fiction.

    Science.gov (United States)

    Davidson, John H

    2015-04-01

    The "curative potential" in almost any clinical setting depends on a caregiver establishing and maintaining an empathic connection with patients so as to achieve "narrative competence" in discerning and acting in accord with their preferences and best interests. The "narrative medicine" model of shared "close reading of literature and reflective writing" among clinicians as a means of fostering a capacity for clinical empathy has gained validation with recent empirical studies demonstrating the enhancement of theory of mind (ToM), broadly conceived as empathy, in readers of literary fiction. Talmudic legends, like that of Rabbi Judah's death, are under-appreciated, relevant sources of literary fiction for these efforts. The limitations of narrative medicine are readily counterbalanced by simultaneously practiced attention to traditional bioethical principles, including-especially-beneficence, non-maleficence, and autonomy.

  2. Psychometric properties and clinical relevance of the adolescent sleep hygiene scale in Dutch adolescents.

    Science.gov (United States)

    de Bruin, Eduard J; van Kampen, Ris K A; van Kooten, Tamar; Meijer, Anne Marie

    2014-07-01

    This study investigated reliability, validity, and clinical relevance of the Adolescent Sleep Hygiene Scale (ASHS) in Dutch adolescents. The Dutch translation of the ASHS was administered to 186 normal-sleeping adolescents and 112 adolescents with insomnia. Their sleep variables were measured using sleep logs and questionnaires. From the insomnia group, scores were also obtained after six weeks of cognitive behavioral therapy for insomnia (n=58) or waiting list (n=22). The full scale of the ASHS had acceptable internal consistency. The results showed moderate to strong correlations of the ASHS (domains) with sleep quality, sleep duration and chronic sleep reduction. Furthermore, the Dutch ASHS was able to discriminate between normal sleepers and adolescents with insomnia, and scores of adolescents with insomnia improved after treatment. These findings confirm the importance of sleep hygiene in adolescent sleep, and contribute to the validity of the ASHS and its applicability in research and clinical practice. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Free software to analyse the clinical relevance of drug interactions with antiretroviral agents (SIMARV®) in patients with HIV/AIDS.

    Science.gov (United States)

    Giraldo, N A; Amariles, P; Monsalve, M; Faus, M J

    Highly active antiretroviral therapy has extended the expected lifespan of patients with HIV/AIDS. However, the therapeutic benefits of some drugs used simultaneously with highly active antiretroviral therapy may be adversely affected by drug interactions. The goal was to design and develop a free software to facilitate analysis, assessment, and clinical decision making according to the clinical relevance of drug interactions in patients with HIV/AIDS. A comprehensive Medline/PubMed database search of drug interactions was performed. Articles that recognized any drug interactions in HIV disease were selected. The publications accessed were limited to human studies in English or Spanish, with full texts retrieved. Drug interactions were analyzed, assessed, and grouped into four levels of clinical relevance according to gravity and probability. Software to systematize the information regarding drug interactions and their clinical relevance was designed and developed. Overall, 952 different references were retrieved and 446 selected; in addition, 67 articles were selected from the citation lists of identified articles. A total of 2119 pairs of drug interactions were identified; of this group, 2006 (94.7%) were drug-drug interactions, 1982 (93.5%) had an identified pharmacokinetic mechanism, and 1409 (66.5%) were mediated by enzyme inhibition. In terms of clinical relevance, 1285 (60.6%) drug interactions were clinically significant in patients with HIV (levels 1 and 2). With this information, a software program that facilitates identification and assessment of the clinical relevance of antiretroviral drug interactions (SIMARV ® ) was developed. A free software package with information on 2119 pairs of antiretroviral drug interactions was designed and developed that could facilitate analysis, assessment, and clinical decision making according to the clinical relevance of drug interactions in patients with HIV/AIDS. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Yeast identification in routine clinical microbiology laboratory and its clinical relevance

    Directory of Open Access Journals (Sweden)

    S Agarwal

    2011-01-01

    Full Text Available Rapid identification of yeast infections is helpful in prompt appropriate antifungal therapy. In the present study, the usefulness of chromogenic medium, slide culture technique and Vitek2 Compact (V2C has been analysed. A total of 173 clinical isolates of yeast species were included in the study. An algorithm to identify such isolates in routine clinical microbiology laboratory was prepared and followed. Chromogenic medium was able to identify Candida albicans, C. tropicalis, C. krusei, C. parapsilosis and Trichosporon asahii. Chromogenic medium was also helpful in identifying "multi-species" yeast infections. The medium was unable to provide presumptive identification of C. pelliculosa, C. utilis, C. rugosa, C. glabrata and C. hemulonii. Vitek 2 compact (V2C differentiated all pseudohypae non-producing yeast species. The algorithm followed was helpful in timely presumptive identification and final diagnosis of yeast infections, including multi-species yeast infections.

  5. An ERP Study on Self-Relevant Object Recognition

    Science.gov (United States)

    Miyakoshi, Makoto; Nomura, Michio; Ohira, Hideki

    2007-01-01

    We performed an event-related potential study to investigate the self-relevance effect in object recognition. Three stimulus categories were prepared: SELF (participant's own objects), FAMILIAR (disposable and public objects, defined as objects with less-self-relevant familiarity), and UNFAMILIAR (others' objects). The participants' task was to…

  6. Clinical relevance of retrieval cues for attenuating context renewal of fear.

    Science.gov (United States)

    Culver, Najwa C; Stoyanova, Milena; Craske, Michelle G

    2011-03-01

    The present studies investigated if retrieval cues (reminder objects) can attenuate context renewal of fear. In Study 1, 32 participants completed exposure in one of two contexts; 1-week follow-up testing occurred in a novel or the same context. Results indicated significant renewal of fear for those tested in a novel context. In Study 2, 40 participants completed exposure in one of these contexts; half were presented with cues. One week later, all were tested in a novel context with or without cues. Results indicated weak attenuation of context renewal for participants re-presented with cues. In Study 3, 18 participants completed exposure in one of two maximally distinct contexts; all with cues. One week later, participants were tested in a novel context with or without cues. Results indicated no group differences. These findings suggest that clinical relevance of this set of cues for attenuating context renewal may be limited. Copyright © 2010 Elsevier Ltd. All rights reserved.

  7. Paediatric case mix in a rural clinical school is relevant to future practice.

    Science.gov (United States)

    Wright, Helen M; Maley, Moira A L; Playford, Denese E; Nicol, Pam; Evans, Sharon F

    2017-11-29

    Exposure to a representative case mix is essential for clinical learning, with logbooks established as a way of demonstrating patient contacts. Few studies have reported the paediatric case mix available to geographically distributed students within the same medical school. Given international interest in expanding medical teaching locations to rural contexts, equitable case exposure in rural relative to urban settings is topical. The Rural Clinical School of Western Australia locates students up to 3500 km from the urban university for an academic year. There is particular need to examine paediatric case mix as a study reported Australian graduates felt unprepared for paediatric rotations. We asked: Does a rural clinical school provide a paediatric case mix relevant to future practice? How does the paediatric case mix as logged by rural students compare with that by urban students? The 3745 logs of 76 urban and 76 rural consenting medical students were categorised by presenting symptoms and compared to the Australian Institute of Health and Welfare (AIHW) database Major Diagnostic Categories (MDCs). Rural and urban students logged core paediatric cases, in similar order, despite the striking difference in geographic locations. The pattern of overall presenting problems closely corresponded to Australian paediatric hospital admissions. Rural students logged 91% of cases in secondary healthcare settings; urban students logged 90% of cases in tertiary settings. The top four presenting problems were ENT/respiratory, gastrointestinal/urogenital, neurodevelopmental and musculoskeletal; these made up 60% of all cases. Rural and urban students logged similar proportions of infants, children and adolescents, with a variety of case morbidity. Rural clinical school students logged a mix of core paediatric cases relevant to illnesses of Australian children admitted to public hospitals, with similar order and pattern by age group to urban students, despite major differences

  8. [Relevance of Vascular Trauma in Trauma Care - Impact on Clinical Course and Mortality].

    Science.gov (United States)

    Lech, L; Jerkku, T; Kanz, K-G; Wierer, M; Mutschler, W; Koeppel, T A; Lefering, R; Banafsche, R

    2016-10-01

    There is a lack of evidence as to the relevance of vascular trauma (VT) in patients with severe injuries. Therefore, we reviewed registry data in the present study in order to systematically objectify the effect of VT in these patients. This study aimed to provide an adequate picture of the relevance of vascular trauma and to identify adverse prognostic factors. In a retrospective analysis of records from the TraumaRegister DGU® (TR-DGU) in two subgroups with moderate and severe VT, we examined the records for differences in terms of morbidity, mortality, follow-up and prognostic parameters compared to patients without VT with the same ISS. From a total of 42,326 patients, 2,961 (7 %) had a VT, and in 2,437 cases a severe VT (AIS ≥ 3) was diagnosed (5.8 %). In addition to a higher incidence of shock and a 2 to 3-fold increase in fluid replacement and erythrocyte transfusion, patients with severe VT had a 60 % higher rate of multiple organ failure, and in-hospital mortality was twice as high (33.8 %). The massively increased early mortality (8.0 vs. 25.2 %) clearly illustrates how severely injured patients are placed at risk by the presence of a relevant VT with a comparable ISS. In our opinion, due to an unexpected poor prognosis in the TR-DGU data for vascular injuries, increased attention is required in the care of severely injured patients. Based on our comprehensive analysis of negative prognostic factors, a further adjustment to the standards of vascular medicine could be advisable. The influence of the level of care provided by the admitting hospital and the relevance of a further hospital transfer to prognosis and clinical outcome is currently being analysed. Georg Thieme Verlag KG Stuttgart · New York.

  9. A clinically relevant major cross-reactive allergen from mesquite tree pollen.

    Science.gov (United States)

    Dhyani, A; Singh, B P; Arora, N; Jain, V K; Sridhara, S

    2008-10-01

    Prosopis juliflora (mesquite) is one of the major sources of pollinosis in tropical and semi-arid countries of the world. The present study was undertaken to purify and characterize a major cross-reactive allergen from this tree species. Mesquite pollen extract was purified using reverse-phase chromatography. Allergen characterization was done by electrophoresis, enzyme-linked immunosorbent assay (ELISA) and Western blotting. Clinical relevance of the purified protein was analyzed by in vivo (skin tests) and in vitro experiments such as ELISA, histamine release, peripheral blood mononuclear cells (PBMC) proliferation and cytokine assays. Cross-reactivity of purified protein with allergenic tree species and lima bean (food) was assessed by inhibition assays. A 66-kDa protein was purified from mesquite pollen extract using octadecyl silica resin. Purified protein recognized 90% of mesquite-sensitized patients in skin test and ELISA. It induced significant histamine release in allergic patients' blood and interleukin-4 secretion in the PBMC culture supernatants. Inhibition assays suggested close allergenic relationship of this protein with Ailanthus excelsa, Cassia siamea, Salvadora persica pollen and Phaseolus lunatus (lima bean - an edible legume). A 66-kDa major cross-reactive allergen was isolated from mesquite pollen using single-step purification procedure. The protein seems relevant for clinical applications in allergic disorders.

  10. Abundances of Clinically Relevant Antibiotic Resistance Genes and Bacterial Community Diversity in the Weihe River, China

    Directory of Open Access Journals (Sweden)

    Xiaojuan Wang

    2018-04-01

    Full Text Available The spread of antibiotic resistance genes in river systems is an emerging environmental issue due to their potential threat to aquatic ecosystems and public health. In this study, we used droplet digital polymerase chain reaction (ddPCR to evaluate pollution with clinically relevant antibiotic resistance genes (ARGs at 13 monitoring sites along the main stream of the Weihe River in China. Six clinically relevant ARGs and a class I integron-integrase (intI1 gene were analyzed using ddPCR, and the bacterial community was evaluated based on the bacterial 16S rRNA V3–V4 regions using MiSeq sequencing. The results indicated Proteobacteria, Actinobacteria, Cyanobacteria, and Bacteroidetes as the dominant phyla in the water samples from the Weihe River. Higher abundances of blaTEM, strB, aadA, and intI1 genes (103 to 105 copies/mL were detected in the surface water samples compared with the relatively low abundances of strA, mecA, and vanA genes (0–1.94 copies/mL. Eight bacterial genera were identified as possible hosts of the intI1 gene and three ARGs (strA, strB, and aadA based on network analysis. The results suggested that the bacterial community structure and horizontal gene transfer were associated with the variations in ARGs.

  11. Motivation factors for suicidal behavior and their clinical relevance in admitted psychiatric patients.

    Directory of Open Access Journals (Sweden)

    Naoki Hayashi

    Full Text Available Suicidal behavior (SB is a major, worldwide health concern. To date there is limited understanding of the associated motivational aspects which accompany this self-initiated conduct.To develop a method for identifying motivational features associated with SB by studying admitted psychiatric patients, and to examine their clinical relevance.By performing a factor analytic study using data obtained from a patient sample exhibiting high suicidality and a variety of SB methods, Motivations for SB Scale (MSBS was constructed to measure the features. Data included assessments of DSM-IV psychiatric and personality disorders, suicide intent, depressive symptomatology, overt aggression, recent life events (RLEs and methods of SB, collated from structured interviews. Association of identified features with clinical variables was examined by correlation analyses and MANCOVA.Factor analyses elicited a 4-factor solution composed of Interpersonal-testing (IT, Interpersonal-change (IC, Self-renunciation (SR and Self-sustenance (SS. These factors were classified according to two distinctions, namely interpersonal vs. intra-personal directedness, and the level of assumed influence by SB or the relationship to prevailing emotions. Analyses revealed meaningful links between patient features and clinical variables. Interpersonal-motivations (IT and IC were associated with overt aggression, low suicidality and RLE discord or conflict, while SR was associated with depression, high suicidality and RLE separation or death. Borderline personality disorder showed association with IC and SS. When self-strangulation was set as a reference SB method, self-cutting and overdose-taking were linked to IT and SS, respectively.The factors extracted in this study largely corresponded to factors from previous studies, implying that they may be useful in a wider clinical context. The association of these features with SB-related factors suggests that they constitute an integral part

  12. Assessing the relevance of ecotoxicological studies for regulatory decision making.

    Science.gov (United States)

    Rudén, Christina; Adams, Julie; Ågerstrand, Marlene; Brock, Theo Cm; Poulsen, Veronique; Schlekat, Christian E; Wheeler, James R; Henry, Tala R

    2017-07-01

    Regulatory policies in many parts of the world recognize either the utility of or the mandate that all available studies be considered in environmental or ecological hazard and risk assessment (ERA) of chemicals, including studies from the peer-reviewed literature. Consequently, a vast array of different studies and data types need to be considered. The first steps in the evaluation process involve determining whether the study is relevant to the ERA and sufficiently reliable. Relevance evaluation is typically performed using existing guidance but involves application of "expert judgment" by risk assessors. In the present paper, we review published guidance for relevance evaluation and, on the basis of the practical experience within the group of authors, we identify additional aspects and further develop already proposed aspects that should be considered when conducting a relevance assessment for ecotoxicological studies. From a regulatory point of view, the overarching key aspect of relevance concerns the ability to directly or indirectly use the study in ERA with the purpose of addressing specific protection goals and ultimately regulatory decision making. Because ERA schemes are based on the appropriate linking of exposure and effect estimates, important features of ecotoxicological studies relate to exposure relevance and biological relevance. Exposure relevance addresses the representativeness of the test substance, environmental exposure media, and exposure regime. Biological relevance deals with the environmental significance of the test organism and the endpoints selected, the ecological realism of the test conditions simulated in the study, as well as a mechanistic link of treatment-related effects for endpoints to the protection goal identified in the ERA. In addition, uncertainties associated with relevance should be considered in the assessment. A systematic and transparent assessment of relevance is needed for regulatory decision making. The relevance

  13. Isolation, speciation, and antibiogram of clinically relevant non-diphtherial Corynebacteria (Diphtheroids

    Directory of Open Access Journals (Sweden)

    B S Reddy

    2012-01-01

    Full Text Available Purpose: Coryneform or the non-diphtherial Corynebacterium species largely remains a neglected group with the traditional consideration of these organisms as contaminants. This concept, however, is slowly changing in the light of recent observations. This study has been done to find out the species distribution and antibiogram of various members of the clinically relevant Coryneform group, isolated from various clinical materials. Materials and Methods: One hundred and fourteen non-duplicate isolates of diphtheroids from various clinical isolates were selected for the study. The isolates were identified to the species level by using a battery of tests; and antimicrobial susceptibility was tested by using a combination of Clinical and Laboratory Standards Institute (CLSI and the British Society for Antimicrobial Chemotherapy (BSAC guidelines, in the absence of definitive CLSI guidelines. Results: Corynebacterium amycolatum was the predominant species (35.9% in our series followed by the CDC Group G organisms (15.7%. Each of the remaining 19 species comprised of less than 10% of the isolates. More than half the total isolates were resistant to the penicillins, erythromycin, and clindamycin; while excellent activity (all the strains being susceptible was shown by vancomycin, linezolid, and tigecycline. Chloramphenicol and tetracycline also had good activity in inhibiting more than 80% of the isolates. Multiply drug resistance was exhibited by all the species. Conclusion: This study was an attempt to establish the clinical significance of coryneform organisms. The high level of resistance shown by this group to some of the common antibacterial agents highlights the importance of processing these isolates in select conditions to guide the clinicians towards an appropriate therapy.

  14. Relevance of MICA and other non-HLA antibodies in clinical transplantation.

    Science.gov (United States)

    Sumitran-Holgersson, Suchitra

    2008-10-01

    The clinical importance of HLA-specific antibodies for organ allograft outcome is well established. In the past few years, there has been an increasing interest in non-HLA antigens as targets of injury in organ transplant recipients. This increased interest has been spurred by the fact that HLA-identical kidney transplants also undergo immunological rejections. Polymorphisms within non-HLA genes associated with evoking an immune response to alloantigens are currently being studied for their association with transplant outcome. Non-HLA antigens, such as the polymorphic MHC class I-related chain A (MICA), expressed on endothelial cells have been implicated in the pathogenesis of hyperacute, acute and chronic organ allograft rejections. Use of endothelial cells as targets may clarify the specificities of other clinically relevant non-HLA antibodies in graft rejections. This review summarizes past and current knowledge of the clinical importance and specificities of non-HLA antibodies, and mechanisms by which these antibodies may contribute to graft destruction in clinical transplantation. The aims of current research into the role of non-HLA antigens and their genetics in predicting outcome are to develop an improved insight into the basic science of transplantation and to develop a risk or prognostic index for use in the clinical setting. Non-HLA antibody responses are receiving increasing interest in acute and chronic rejection and specificity, affinity, and pathogenicity need to be investigated to estimate their contribution. Undoubtedly, this will continue to be an area of interest in terms of fully understanding the role of non-HLA antigens as targets of immune-mediated injury and the potential for clinical intervention.

  15. Fungal-bacterial interactions and their relevance to oral health: linking the clinic and the bench.

    Science.gov (United States)

    Diaz, Patricia I; Strausbaugh, Linda D; Dongari-Bagtzoglou, Anna

    2014-01-01

    High throughput sequencing has accelerated knowledge on the oral microbiome. While the bacterial component of oral communities has been extensively characterized, the role of the fungal microbiota in the oral cavity is largely unknown. Interactions among fungi and bacteria are likely to influence oral health as exemplified by the synergistic relationship between Candida albicans and oral streptococci. In this perspective, we discuss the current state of the field of fungal-bacterial interactions in the context of the oral cavity. We highlight the need to conduct longitudinal clinical studies to simultaneously characterize the bacterial and fungal components of the human oral microbiome in health and during disease progression. Such studies need to be coupled with investigations using disease-relevant models to mechanistically test the associations observed in humans and eventually identify fungal-bacterial interactions that could serve as preventive or therapeutic targets for oral diseases.

  16. In Vivo Photoacoustic and Fluorescence Cystography Using Clinically Relevant Dual Modal Indocyanine Green

    Directory of Open Access Journals (Sweden)

    Sungjo Park

    2014-10-01

    Full Text Available Conventional X-ray-based cystography uses radio-opaque materials, but this method uses harmful ionizing radiation and is not sensitive. In this study, we demonstrate nonionizing and noninvasive photoacoustic (PA and fluorescence (FL cystography using clinically relevant indocyanine green (ICG in vivo. After transurethral injection of ICG into rats through a catheter, their bladders were photoacoustically and fluorescently visualized. A deeply positioned bladder below the skin surface (i.e., ~1.5–5 mm was clearly visible in the PA and FL image using a laser pulse energy of less than 2 mJ/cm2 (1/15 of the safety limit. Then, the in vivo imaging results were validated through in situ studies. Our results suggest that dual modal cystography can provide a nonionizing and noninvasive imaging tool for bladder mapping.

  17. Fungal-bacterial interactions and their relevance to oral health: linking the clinic and the bench

    Directory of Open Access Journals (Sweden)

    Patricia I Diaz

    2014-07-01

    Full Text Available High throughput sequencing has accelerated knowledge on the oral microbiome. While the bacterial component of oral communities has been extensively characterized, the role of the fungal microbiota in the oral cavity is largely unknown. Interactions among fungi and bacteria are likely to influence oral health as exemplified by the synergistic relationship between Candida albicans and oral streptococci. In this perspective, we discuss the current state of the field of fungal-bacterial interactions in the context of the oral cavity. We highlight the need to conduct longitudinal clinical studies to simultaneously characterize the bacterial and fungal components of the human oral microbiome in health and during disease progression. Such studies need to be coupled with investigations using disease-relevant models to mechanistically test the associations observed in humans and eventually identify fungal-bacterial interactions that could serve as preventive or therapeutic targets for oral diseases.

  18. Assessing Hospital Physicians' Acceptance of Clinical Information Systems: A Review of the Relevant Literature

    Directory of Open Access Journals (Sweden)

    Bram Pynoo

    2013-06-01

    Full Text Available In view of the tremendous potential benefits of clinical information systems (CIS for the quality of patient care; it is hard to understand why not every CIS is embraced by its targeted users, the physicians. The aim of this study is to propose a framework for assessing hospital physicians' CIS-acceptance that can serve as a guidance for future research into this area. Hereto, a review of the relevant literature was performed in the ISI Web-of-Science database. Eleven studies were withheld from an initial dataset of 797 articles. Results show that just as in business settings, there are four core groups of variables that influence physicians' acceptance of a CIS: its usefulness and ease of use, social norms, and factors in the working environment that facilitate use of the CIS (such as providing computers/workstations, compatibility between the new and existing system.... We also identified some additional variables as predictors of CIS-acceptance.

  19. Biomarkers for AAA: Encouraging steps but clinical relevance still to be delivered.

    Science.gov (United States)

    Htun, Nay Min; Peter, Karlheinz

    2014-10-01

    Potential biomarkers have been investigated using proteomic studies in a variety of diseases. Some biomarkers have central roles in both diagnosis and monitoring of various disorders in clinical medicine, such as troponins, brain natriuretic peptide, and C-reactive protein. Although several biomarkers have been suggested in human abdominal aortic aneurysm (AAA), reliable markers have been lacking. In this issue, Moxon et al. [Proteomics Clin Appl. 2014, 8, 762-772] undertook a broad and systematic proteomic approach toward identification of biomarkers in a commonly used AAA mouse model (AAA created by angiotensin-II infusion). In this mouse model, apolipoprotein C1 and matrix metalloproteinase-9 were identified as novel biomarkers of stable AAA. This finding represents an important step forward, toward a clinically relevant role of biomarkers in AAA. This also encourages for further studies toward the identification of biomarkers (or their combinations) that can predict AAA progression and rupture, which would represent a major progress in AAA management and would establish an AAA biomarker as a much anticipated clinical tool. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Technological Advances in Cardiovascular Safety Assessment Decrease Preclinical Animal Use and Improve Clinical Relevance.

    Science.gov (United States)

    Berridge, Brian R; Schultze, A Eric; Heyen, Jon R; Searfoss, George H; Sarazan, R Dustan

    2016-12-01

    Cardiovascular (CV) safety liabilities are significant concerns for drug developers and preclinical animal studies are predominately where those liabilities are characterized before patient exposures. Steady progress in technology and laboratory capabilities is enabling a more refined and informative use of animals in those studies. The application of surgically implantable and telemetered instrumentation in the acute assessment of drug effects on CV function has significantly improved historical approaches that involved anesthetized or restrained animals. More chronically instrumented animals and application of common clinical imaging assessments like echocardiography and MRI extend functional and in-life structural assessments into the repeat-dose setting. A growing portfolio of circulating CV biomarkers is allowing longitudinal and repeated measures of cardiac and vascular injury and dysfunction better informing an understanding of temporal pathogenesis and allowing earlier detection of undesirable effects. In vitro modeling systems of the past were limited by their lack of biological relevance to the in vivo human condition. Advances in stem cell technology and more complex in vitro modeling platforms are quickly creating more opportunity to supplant animals in our earliest assessments for liabilities. Continuing improvement in our capabilities in both animal and nonanimal modeling should support a steady decrease in animal use for primary liability identification and optimize the translational relevance of the animal studies we continue to do. © The Author 2016. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  1. A rule-based electronic phenotyping algorithm for detecting clinically relevant cardiovascular disease cases.

    Science.gov (United States)

    Esteban, Santiago; Rodríguez Tablado, Manuel; Ricci, Ricardo Ignacio; Terrasa, Sergio; Kopitowski, Karin

    2017-07-14

    The implementation of electronic medical records (EMR) is becoming increasingly common. Error and data loss reduction, patient-care efficiency increase, decision-making assistance and facilitation of event surveillance, are some of the many processes that EMRs help improve. In addition, they show a lot of promise in terms of data collection to facilitate observational epidemiological studies and their use for this purpose has increased significantly over the recent years. Even though the quantity and availability of the data are clearly improved thanks to EMRs, still, the problem of the quality of the data remains. This is especially important when attempting to determine if an event has actually occurred or not. We sought to assess the sensitivity, specificity, and agreement level of a codes-based algorithm for the detection of clinically relevant cardiovascular (CaVD) and cerebrovascular (CeVD) disease cases, using data from EMRs. Three family physicians from the research group selected clinically relevant CaVD and CeVD terms from the international classification of primary care, Second Edition (ICPC-2), the ICD 10 version 2015 and SNOMED-CT 2015 Edition. These terms included both signs, symptoms, diagnoses and procedures associated with CaVD and CeVD. Terms not related to symptoms, signs, diagnoses or procedures of CaVD or CeVD and also those describing incidental findings without clinical relevance were excluded. The algorithm yielded a positive result if the patient had at least one of the selected terms in their medical records, as long as it was not recorded as an error. Else, if no terms were found, the patient was classified as negative. This algorithm was applied to a randomly selected sample of the active patients within the hospital's HMO by 1/1/2005 that were 40-79 years old, had at least one year of seniority in the HMO and at least one clinical encounter. Thus, patients were classified into four groups: (1) Negative patients (2) Patients with Ca

  2. First branchial cleft anomaly: clinical insight into its relevance in otolaryngology with pediatric considerations.

    Science.gov (United States)

    Maithani, Tripti; Pandey, Apporva; Dey, Debraj; Bhardwaj, Aparna; Singh, V P

    2014-01-01

    First branchial cleft anomalies (FBCA) represent a small subset of congenital malformations in neck. Prime objective of this study is to share our experience with FBCA, emphasize its relevance in otolaryngology and deal with its pediatric perspective. Embryology, pathologic anatomy and varied spectra of clinical presentations of FBCA are discussed. Along with this we have illustrated three different cases; all of them were of pediatric age group and were misdiagnosed by their treating specialists elsewhere. In this article we have also laid special emphasis on its pediatric considerations. FBCA are mostly misdiagnosed due to their unfamiliar clinical signs and symptoms. Swellings may masquerade as other neck masses. Majority of patients give a history of previous incision and drainage. While dealing with pediatric patients the important factors to be kept in mind are the age of child, superficial course of facial nerve, any associated agenesis of parotid gland. Alteration in surgical technique may be required in children. A thorough medical examination with high index of clinical suspicion should be kept in mind while dealing with such anomalies. Owing to their complex presentation and close relation with facial nerve they are challenging lesions for surgeons.

  3. Polanyi's tacit knowing and the relevance of epistemology to clinical medicine.

    Science.gov (United States)

    Henry, Stephen G

    2010-04-01

    Most clinicians take for granted a simple, reductionist understanding of medical knowledge that is at odds with how they actually practice medicine; routine medical decisions incorporate more complicated kinds of information than most standard accounts of medical reasoning suggest. A better understanding of the structure and function of knowledge in medicine can lead to practical improvements in clinical medicine. This understanding requires some familiarity with epistemology, the study of knowledge and its structure, in medicine. Michael Polanyi's theory of tacit knowing is advanced as the basis for developing a more accurate understanding of medical knowledge. Tacit knowing, which explores the taken-for-granted background knowledge that underlies all human knowing, is explained in detail with a focus on its relevance for clinical medicine. The implications of recognizing tacit knowing in medicine and medical decisions are discussed. These include the ability to explain the importance of the clinical encounter in medical practice, mechanisms for analysing patient and doctor as persons, and the need for humility given the uncertainty that the tacit dimension injects into all medical decisions. This more robust medical epistemology allows clinicians to better articulate the nature and importance of patient-centred care, to avoid pitfalls inherent in reductionist approaches to medical knowledge, and to think more clearly about the relationships between medicine and health care at the individual and population levels.

  4. Clinically relevant pain relief with an ibuprofen-releasing foam dressing

    DEFF Research Database (Denmark)

    Fogh, Karsten; Andersen, Maibritt B; Bischoff-Mikkelsen, Morten

    2012-01-01

    The objective of this 6-week, 120-patient, double-blind, randomized, controlled trial was to investigate if a foam dressing with ibuprofen provided clinically relevant pain relief (PAR) for exuding, painful venous leg ulcers in comparison with a similar foam dressing without ibuprofen. Primary......) and the corresponding number needed to treat (NNT). Wound-related parameters such as ulcer healing, ulcer area reduction, and peri-ulcer skin condition as well as adverse events were recorded during all 6 weeks of the investigation. PAR was significantly greater in the ibuprofen foam group than the comparator group (p...... = 0.0438). There were 34% responders in the ibuprofen foam group vs. 19% in the comparator group (NNT = 6.8). When evening data were analyzed separately to evaluate PAR over daytime, NNT was 5.3. Wound healing parameters and adverse events were comparable. In conclusion, in this study, the ibuprofen...

  5. Selecting relevant and feasible measurement instruments for the revised Dutch clinical practice guideline for physical therapy in patients after stroke

    NARCIS (Netherlands)

    Otterman, Nicoline; Veerbeek, Janne; Schiemanck, Sven; van der Wees, Philip; Nollet, Frans; Kwakkel, Gert

    2017-01-01

    Purpose: To select relevant and feasible instruments for the revision of the Dutch clinical practice guideline for physical therapy in patients with stroke. Methods: In this implementation study a comprehensive proposal for ICF categories and matching instruments was developed, based on reliability

  6. Selecting relevant and feasible measurement instruments for the revised Dutch clinical practice guideline for physical therapy in patients after stroke

    NARCIS (Netherlands)

    Otterman, N.; Veerbeek, J.; Schiemanck, S.; Wees, P.J. van der; Nollet, F.; Kwakkel, G.

    2017-01-01

    PURPOSE: To select relevant and feasible instruments for the revision of the Dutch clinical practice guideline for physical therapy in patients with stroke. METHODS: In this implementation study a comprehensive proposal for ICF categories and matching instruments was developed, based on reliability

  7. Time-driven activity-based costing in an outpatient clinic environment: development, relevance and managerial impact.

    Science.gov (United States)

    Demeere, Nathalie; Stouthuysen, Kristof; Roodhooft, Filip

    2009-10-01

    Healthcare managers are continuously urged to provide better patient services at a lower cost. To cope with these cost pressures, healthcare management needs to improve its understanding of the relevant cost drivers. Through a case study, we show how to perform a time-driven activity-based costing of five outpatient clinic's departments and provide evidence of the benefits of such an analysis.

  8. Clinical relevance of the gap between pre-marketing trials and medical practice : the case of the cardiovascular drugs

    NARCIS (Netherlands)

    Wieringa, N F; Denig, P; de Graeff, P A; Vos, R

    OBJECTIVES/BACKGROUND: The external validity of trial results of new cardiovascular drugs is limited, because the short-term studies are performed with relatively small, highly selected populations. Using qualitative methods, we examined the clinical relevance of under-representation of subgroups of

  9. Effect of specific or random c-DNA priming on sensitivity of tyrosinase nested RT-PCR : Potential clinical relevance

    NARCIS (Netherlands)

    Calogero, A; Hospers, GAP; Timmer-Bosscha, H; Mulder, NH; Schraffordt Koops, H.

    2000-01-01

    The reverse transcriptase polymerase chain reaction (RT-PCR) can be of clinical relevance in identifying malignant melanoma cells in blood or tissues of patients at risk for disseminated melanoma. The diagnostic value of this marker however, is still controversial. The objective of this study was to

  10. Clinical relevance of the ROC and free-response paradigms for comparing imaging system efficacies

    International Nuclear Information System (INIS)

    Chakraborty, D. P.

    2010-01-01

    Observer performance studies are widely used to assess medical imaging systems. Unlike technical/engineering measurements observer performance include the entire imaging chain and the radiologist. However, the widely used receiver operating characteristic (ROC) method ignores lesion localisation information. The free-response ROC (FROC) method uses the location information to appropriately reward or penalise correct or incorrect localizations, respectively. This paper describes a method for improving the clinical relevance of FROC studies. The method consists of assigning appropriate risk values to the different lesions that may be present on a single image. A high-risk lesion is one that is critical to detect and act upon, and is assigned a higher risk value than a low-risk lesion, one that is relatively innocuous. Instead of simply counting the number of lesions that are detected, as is done in conventional FROC analysis, a risk-weighted count is used. This has the advantage of rewarding detections of high-risk lesions commensurately more than detections of lower risk lesions. Simulations were used to demonstrate that the new method, termed case-based analysis, results in a higher figure of merit for an expert who detects more high-risk lesions than a naive observer who detects more low-risk lesions, even though both detect the same total number of lesions. Conventional free-response analysis is unable to distinguish between the two types of observers. This paper also comments on the issue of clinical relevance of ROC analysis vs. FROC for tasks that involve lesion localisation. (authors)

  11. MR assessment of the repaired rotator cuff: prevalence, size, location, and clinical relevance of tendon rerupture

    International Nuclear Information System (INIS)

    Mellado, J.M.; Calmet, J.; Ballabriga, J.; Gine, J.; Olona, M.; Camins, A.; Perez del Palomar, L.

    2006-01-01

    The objectives of this study were to use magnetic resonance (MR) imaging to evaluate the prevalence, size, location, and clinical relevance of tendon rerupture following complete repair of full-thickness rotator cuff tear (RCT). A total of 78 surgically proven full-thickness rotator cuff tears in 74 patients were retrospectively included in the study. Clinical assessment was performed using the University of California at Los Angeles score. Postoperative MR imaging was evaluated to determine prevalence, size, and location of tendon rerupture. At a mean 48.4 months' follow-up, 62 shoulders (79.5%) had favorable outcomes and 45 shoulders (57.6%) showed rerupture on MR imaging studies. Reruptures were significantly more prevalent among patients with intermediate-to-bad outcomes (81.3%), with surgically demonstrated two-tendon tears (78.9%) or three-tendon tears (100%), and with preoperative fatty degeneration of the supraspinatus muscle greater than 1 (91.6%). Reruptures were also significantly larger in those subgroups. Complete repair of RCT of all sizes may have favorable outcomes in a significant proportion of patients in spite of a high prevalence of reruptures. Preoperative tear size and degree of muscle fatty degeneration influence the prevalence and rerupture size. After repair of supraspinatus tears, reruptures tend to invade the posterior aspect of the tendon. (orig.)

  12. Rotational patient setup errors in IGRT with XVI system in Elekta Synergy and their clinical relevance

    International Nuclear Information System (INIS)

    Madhusudhana Sresty, N.V.N.; Muralidhar, K.R.; Raju, A.K.; Sha, R.L.; Ramanjappa

    2008-01-01

    The goal of Image Guided Radiotherapy (IGRT) is to improve the accuracy of treatment delivery. In this technique, it is possible to get volumetric images of patient anatomy before delivery of treatment.XVI( release 3.5) system in Elekta Synergy linear accelerator (Elekta,Crawley,UK) has the potential to ensure that, the relative positions of the target volume is same as in the treatment plan. It involves acquiring planar images produced by a kilo Voltage cone beam rotating about the patient in the treatment position. After 3 dimensional match between reference and localization images, the system gives rotational errors also along with translational shifts. One can easily perform translational shifts with treatment couch. But rotational shifts cannot be performed. Most of the studies dealt with translational shifts only. Few studies reported regarding rotational errors. It is found that in the treatment of elongated targets, even small rotational errors can show difference in results. The main objectives of this study is 1) To verify the magnitude of rotational errors in different clinical sites observed and to compare with the other reports. 2) To find its clinical relevance 3) To find difference in rotational shift results with improper selection of kV collimator

  13. MR assessment of the repaired rotator cuff: prevalence, size, location, and clinical relevance of tendon rerupture

    Energy Technology Data Exchange (ETDEWEB)

    Mellado, J.M. [Hospital Reina Sofia de Tudela, Servicio de Radiodiagnostico, Tudela, Navarra (Spain); Calmet, J.; Ballabriga, J.; Gine, J. [Hospital Universitari de Tarragona Joan XXIII, Servei de Cirurgia Ortopedica i Traumatologia, Tarragona (Spain); Olona, M. [Hospital Universitari de Tarragona Joan XXIII, Servei de Medicina Preventiva i Epidemiologia, Tarragona (Spain); Camins, A. [Hospital Universitari de Tarragona Joan XXIII, Institut de Diagnostic per la Imatge, Tarragona (Spain); Perez del Palomar, L. [Hospital Ernest Lluch, Servicio de Radiologia, Calatayud, Zaragoza (Spain)

    2006-10-15

    The objectives of this study were to use magnetic resonance (MR) imaging to evaluate the prevalence, size, location, and clinical relevance of tendon rerupture following complete repair of full-thickness rotator cuff tear (RCT). A total of 78 surgically proven full-thickness rotator cuff tears in 74 patients were retrospectively included in the study. Clinical assessment was performed using the University of California at Los Angeles score. Postoperative MR imaging was evaluated to determine prevalence, size, and location of tendon rerupture. At a mean 48.4 months' follow-up, 62 shoulders (79.5%) had favorable outcomes and 45 shoulders (57.6%) showed rerupture on MR imaging studies. Reruptures were significantly more prevalent among patients with intermediate-to-bad outcomes (81.3%), with surgically demonstrated two-tendon tears (78.9%) or three-tendon tears (100%), and with preoperative fatty degeneration of the supraspinatus muscle greater than 1 (91.6%). Reruptures were also significantly larger in those subgroups. Complete repair of RCT of all sizes may have favorable outcomes in a significant proportion of patients in spite of a high prevalence of reruptures. Preoperative tear size and degree of muscle fatty degeneration influence the prevalence and rerupture size. After repair of supraspinatus tears, reruptures tend to invade the posterior aspect of the tendon. (orig.)

  14. Understanding Magnetic Resonance Imaging of Knee Cartilage Repair: A Focus on Clinical Relevance.

    Science.gov (United States)

    Hayashi, Daichi; Li, Xinning; Murakami, Akira M; Roemer, Frank W; Trattnig, Siegfried; Guermazi, Ali

    2017-06-01

    The aims of this review article are (a) to describe the principles of morphologic and compositional magnetic resonance imaging (MRI) techniques relevant for the imaging of knee cartilage repair surgery and their application to longitudinal studies and (b) to illustrate the clinical relevance of pre- and postsurgical MRI with correlation to intraoperative images. First, MRI sequences that can be applied for imaging of cartilage repair tissue in the knee are described, focusing on comparison of 2D and 3D fast spin echo and gradient recalled echo sequences. Imaging features of cartilage repair tissue are then discussed, including conventional (morphologic) MRI and compositional MRI techniques. More specifically, imaging techniques for specific cartilage repair surgery techniques as described above, as well as MRI-based semiquantitative scoring systems for the knee cartilage repair tissue-MR Observation of Cartilage Repair Tissue and Cartilage Repair OA Knee Score-are explained. Then, currently available surgical techniques are reviewed, including marrow stimulation, osteochondral autograft, osteochondral allograft, particulate cartilage allograft, autologous chondrocyte implantation, and others. Finally, ongoing research efforts and future direction of cartilage repair tissue imaging are discussed.

  15. Reporting the results of meta-analyses: a plea for incorporating clinical relevance referring to an example.

    Science.gov (United States)

    Bartels, Ronald H M A; Donk, Roland D; Verhagen, Wim I M; Hosman, Allard J F; Verbeek, André L M

    2017-11-01

    The results of meta-analyses are frequently reported, but understanding and interpreting them is difficult for both clinicians and patients. Statistical significances are presented without referring to values that imply clinical relevance. This study aimed to use the minimal clinically important difference (MCID) to rate the clinical relevance of a meta-analysis. This study is a review of the literature. This study is a review of meta-analyses relating to a specific topic, clinical results of cervical arthroplasty. The outcome measure used in the study was the MCID. We performed an extensive literature search of a series of meta-analyses evaluating a similar subject as an example. We searched in Pubmed and Embase through August 9, 2016, and found articles concerning meta-analyses of the clinical outcome of cervical arthroplasty compared with that of anterior cervical discectomy with fusion in cases of cervical degenerative disease. We evaluated the analyses for statistical significance and their relation to MCID. MCID was defined based on results in similar patient groups and a similar disease entity reported in the literature. We identified 21 meta-analyses, only one of which referred to MCID. However, the researchers used an inappropriate measurement scale and, therefore, an incorrect MCID. The majority of the conclusions were based on statistical results without mentioning clinical relevance. The majority of the articles we reviewed drew conclusions based on statistical differences instead of clinical relevance. We recommend introducing the concept of MCID while reporting the results of a meta-analysis, as well as mentioning the explicit scale of the analyzed measurement. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Development of a clinically relevant impingement test method for a mobile bearing lumbar total disc replacement.

    Science.gov (United States)

    Siskey, Ryan; Peck, Jonathan; Mehta, Hitesh; Kosydar, Allison; Kurtz, Steven; Hill, Genevieve

    2016-09-01

    Total disc arthroplasty is an alternative therapy to spinal fusion for the treatment of neck or low back pain and is hypothesized to reduce the risk of disease progression to the adjacent spinal levels. Radiographic and retrieval analyses of various total disc replacements (TDRs) have shown evidence of impingement damage. Impingement of TDRs can occur when the device reaches the limits of its functional range of motion, causing contact between peripheral regions of the device. Impingement can be associated with increased wear and mechanical damage; however, impingement conditions are not simulated in current standardized mechanical bench test methods. This study explored the test conditions necessary to apply clinically relevant impingement loading to a lumbar TDR in vitro. An experimental protocol was developed and evaluated using in vivo retrievals for qualitative and quantitative validation. Retrieval analysis was conducted on a set of 11 size 3 retrieved Charité devices using American Society for Testing and Materials F561 as a guide. The impingement range of motion was determined using a combination of modeling and experiments, and was used as an input in vitro testing. A 1-million cycle in vitro test was then conducted, and the in vitro samples were characterized using methods similar to the retreived devices. All in vitro tested samples exhibited impingement regions and damage patterns consistent with retrieved devices. Consistent with the retrievals, the impingement damage on the rim was a combination of abrasive wear and plastic deformation. Micro computed tomography (microCT) was used to quantitatively assess rim damage due to impingement. Rim penetration was statistically lower in the retrievals when compared with both in vitro groups. Rim elongation was comparable among all groups. The simulated-facet group had statistically greater angular rim deformations than the retrieval group and the no-facet group. Results demonstrate that clinically relevant

  17. The efficacy of chiropractic manipulation for back pain : Blinded review of relevant randomized clinical trials

    NARCIS (Netherlands)

    Assendelft, W. J J; Koes, B. W.; Van der Heijden, G. J M G; Bouter, L. M.

    1992-01-01

    Objective: To assess the efficacy of chiropractic for patients with back pain. Data Sources: Randomized clinical trials (RCTs) on spinal manipulation were identified with a Medline search (1966-1990), by citation tracking, and by manual examination of the relevant chiropractic reference systems

  18. Clinically relevant incidental cardiovascular findings in CT examinations; Klinisch relevante kardiovaskulaere Zufallsbefunde bei CT-Untersuchungen

    Energy Technology Data Exchange (ETDEWEB)

    Voigt, P.; Fahnert, J.; Kahn, T.; Surov, A. [Universitaetsklinikum Leipzig, Klinik fuer Diagnostische und Interventionelle Radiologie, Leipzig (Germany); Schramm, D.; Bach, A.G. [Universitaetsklinikum Halle (Saale), Klinik fuer Radiologie, Halle (Germany)

    2017-04-15

    Incidental cardiovascular findings are a frequent phenomenon in computed tomography (CT) examinations. As the result of a dedicated PubMed search this article gives a systemic overview of the current literature on the most important incidental cardiovascular findings, their prevalence and clinical relevance. The majority of incidental cardiovascular findings are of only low clinical relevance; however, highly relevant incidental findings, such as aortic aneurysms, thromboses and thromboembolic events can also occasionally be found, especially in oncology patients. The scans from every CT examination should also be investigated for incidental findings as they can be of decisive importance for the further clinical management of patients, depending on their clinical relevance. (orig.) [German] Inzidentelle kardiovaskulaere Befunde sind ein haeufiges Phaenomen bei CT-Untersuchungen. Mit dieser Arbeit soll nach gezielter PubMed-Recherche ein systematischer Literaturueberblick ueber die wichtigsten kardiovaskulaeren Zufallsbefunde sowie deren Haeufigkeit und klinische Relevanz gegeben werden. Die Mehrzahl der inzidentellen kardiovaskulaeren Befunde sind klinisch nur von untergeordneter Bedeutung, allerdings werden immer wieder auch hochgradig relevante Zufallsbefunde wie beispielsweise Aortenaneurysmata oder - gerade bei onkologischen Patienten - Thrombosen und thrombembolische Ereignisse detektiert. Jede CT-Untersuchung sollte gezielt nach inzidentellen Befunden durchsucht werden, da diese je nach klinischer Relevanz von entscheidender Bedeutung fuer das weitere klinische Management des Patienten sein koennen. (orig.)

  19. Clinical relevance of routinely measured vital signs in hospitalized patients: a systematic review

    NARCIS (Netherlands)

    Storm-Versloot, Marja N.; Verweij, Lotte; Lucas, Cees; Ludikhuize, Jeroen; Goslings, J. Carel; Legemate, Dink A.; Vermeulen, Hester

    2014-01-01

    Conflicting evidence exists on the effectiveness of routinely measured vital signs on the early detection of increased probability of adverse events. To assess the clinical relevance of routinely measured vital signs in medically and surgically hospitalized patients through a systematic review.

  20. Macrotrabecular-massive hepatocellular carcinoma: A distinctive histological subtype with clinical relevance.

    Science.gov (United States)

    Ziol, Marianne; Poté, Nicolas; Amaddeo, Giuliana; Laurent, Alexis; Nault, Jean-Charles; Oberti, Frédéric; Costentin, Charlotte; Michalak, Sophie; Bouattour, Mohamed; Francoz, Claire; Pageaux, Georges Philippe; Ramos, Jeanne; Decaens, Thomas; Luciani, Alain; Guiu, Boris; Vilgrain, Valérie; Aubé, Christophe; Derman, Jonathan; Charpy, Cécile; Zucman-Rossi, Jessica; Barget, Nathalie; Seror, Olivier; Ganne-Carrié, Nathalie; Paradis, Valérie; Calderaro, Julien

    2017-12-27

    We recently identified a novel histological subtype of hepatocellular carcinoma, designated as "macrotrabecular-massive" (MTM-HCC) and associated with specific molecular features. In order to assess the clinical relevance of this novel variant, we aimed to investigate its prognostic value in two large series of patients with HCC treated either by surgical resection or radiofrequency ablation (RFA). We retrospectively included 237 HCC surgical samples and 284 HCC liver biopsies from patients treated by surgical resection and RFA, respectively. Histological slides were reviewed by pathologists specialized in liver disease, and the MTM-HCC subtype was defined by the presence of a predominant (>50%) macrotrabecular architecture (more than 6 cells thick). The main clinical and biological features were recorded at baseline. Clinical endpoints were early and overall recurrence. The MTM-HCC subtype was identified in 12% of the whole cohort (16% of surgically resected samples, 8.5% of liver biopsy samples). It was associated at baseline with known poor prognostic factors (tumor size, AFP level, satellite nodules and vascular invasion). Multivariate analysis showed that MTM-HCC subtype was an independent predictor of early and overall recurrence (surgical series: OR 3.03 (1.38-6.65), p=0.006 and 2.76 (1.63-4.67), pvalue was retained even after patients stratification according to common clinical, biological and pathological features of aggressiveness. No other baseline parameter was independently associated to recurrence in the RFA series. The MTM-HCC subtype, reliably observed in 12% of patients eligible for a curative treatment, represents an aggressive form of HCC that may require more specific therapeutic strategies. This article is protected by copyright. All rights reserved. © 2017 by the American Association for the Study of Liver Diseases.

  1. A conscious mouse model of gastric ileus using clinically relevant endpoints

    Directory of Open Access Journals (Sweden)

    Shao Yuanlin

    2005-06-01

    Full Text Available Abstract Background Gastric ileus is an unsolved clinical problem and current treatment is limited to supportive measures. Models of ileus using anesthetized animals, muscle strips or isolated smooth muscle cells do not adequately reproduce the clinical situation. Thus, previous studies using these techniques have not led to a clear understanding of the pathophysiology of ileus. The feasibility of using food intake and fecal output as simple, clinically relevant endpoints for monitoring ileus in a conscious mouse model was evaluated by assessing the severity and time course of various insults known to cause ileus. Methods Delayed food intake and fecal output associated with ileus was monitored after intraperitoneal injection of endotoxin, laparotomy with bowel manipulation, thermal injury or cerulein induced acute pancreatitis. The correlation of decreased food intake after endotoxin injection with gastric ileus was validated by measuring gastric emptying. The effect of endotoxin on general activity level and feeding behavior was also determined. Small bowel transit was measured using a phenol red marker. Results Each insult resulted in a transient and comparable decrease in food intake and fecal output consistent with the clinical picture of ileus. The endpoints were highly sensitive to small changes in low doses of endotoxin, the extent of bowel manipulation, and cerulein dose. The delay in food intake directly correlated with delayed gastric emptying. Changes in general activity and feeding behavior were insufficient to explain decreased food intake. Intestinal transit remained unchanged at the times measured. Conclusion Food intake and fecal output are sensitive markers of gastric dysfunction in four experimental models of ileus. In the mouse, delayed gastric emptying appears to be the major cause of the anorexic effect associated with ileus. Gastric dysfunction is more important than small bowel dysfunction in this model. Recovery of

  2. The clinical relevance of sensitization to pollen-related fruits and vegetables in unselected pollen-sensitized adults

    DEFF Research Database (Denmark)

    Osterballe, M.; Hansen, T.K.; Mørtz, Charlotte G

    2005-01-01

    BACKGROUND: Previous studies have described cross-reactivity between fresh fruits, vegetables and pollen. However, no data demonstrates the clinical relevance of sensitization to pollen-related fruits and vegetables in unselected pollen-sensitized adults with and without symptoms in the pollen...... season. OBJECTIVE: The aim of this study was to estimate the clinical relevance of sensitization to pollen-related fruits and vegetables in unselected pollen-sensitized adults and to examine the diagnostic value of skin-prick test (SPT), histamine release and specific IgE compared with the outcome...... of oral challenge. METHODS: In total, 936 unselected adults (female : male 479 : 457, median age 33.7 years) were examined for pollen sensitization and clinical cross-reactivity with pollen-related fruits and vegetables by questionnaire, SPT, histamine release, specific IgE and oral challenge. RESULTS...

  3. Clinically relevant risk factors for suicide: Comparison between clinical group with passive suicidal ideation, active suicidal ideation and without suicidal ideation

    OpenAIRE

    Miloseva, Lence; Cuijpers, Pim; Stojcev, Saso; Niklewski, Gunter; Richter, Kneginja; Jovevska, Svetlana; Arsova, Roza; Serafimov, Aleksandar

    2015-01-01

    Introduction: In recent years, researchers and clinicians do not treat passive suicidal ideation as a clinically relevant risk factor for suicide, while underestimating the strength of this desire to die, compared with making a plan for suicide in individuals having active suicidal ideation. This research study is clinically prospective, cross-sequential, but also partly retrospective because it involves also variables from the past, such as patients’ history data (number of suicidal attempts...

  4. Using language models to identify relevant new information in inpatient clinical notes.

    Science.gov (United States)

    Zhang, Rui; Pakhomov, Serguei V; Lee, Janet T; Melton, Genevieve B

    2014-01-01

    Redundant information in clinical notes within electronic health record (EHR) systems is ubiquitous and may negatively impact the use of these notes by clinicians, and, potentially, the efficiency of patient care delivery. Automated methods to identify redundant versus relevant new information may provide a valuable tool for clinicians to better synthesize patient information and navigate to clinically important details. In this study, we investigated the use of language models for identification of new information in inpatient notes, and evaluated our methods using expert-derived reference standards. The best method achieved precision of 0.743, recall of 0.832 and F1-measure of 0.784. The average proportion of redundant information was similar between inpatient and outpatient progress notes (76.6% (SD=17.3%) and 76.7% (SD=14.0%), respectively). Advanced practice providers tended to have higher rates of redundancy in their notes compared to physicians. Future investigation includes the addition of semantic components and visualization of new information.

  5. Pharmacology of dextromethorphan: Relevance to dextromethorphan/quinidine (Nuedexta®) clinical use.

    Science.gov (United States)

    Taylor, Charles P; Traynelis, Stephen F; Siffert, Joao; Pope, Laura E; Matsumoto, Rae R

    2016-08-01

    Dextromethorphan (DM) has been used for more than 50years as an over-the-counter antitussive. Studies have revealed a complex pharmacology of DM with mechanisms beyond blockade of N-methyl-d-aspartate (NMDA) receptors and inhibition of glutamate excitotoxicity, likely contributing to its pharmacological activity and clinical potential. DM is rapidly metabolized to dextrorphan, which has hampered the exploration of DM therapy separate from its metabolites. Coadministration of DM with a low dose of quinidine inhibits DM metabolism, yields greater bioavailability and enables more specific testing of the therapeutic properties of DM apart from its metabolites. The development of the drug combination DM hydrobromide and quinidine sulfate (DM/Q), with subsequent approval by the US Food and Drug Administration for pseudobulbar affect, led to renewed interest in understanding DM pharmacology. This review summarizes the interactions of DM with brain receptors and transporters and also considers its metabolic and pharmacokinetic properties. To assess the potential clinical relevance of these interactions, we provide an analysis comparing DM activity from in vitro functional assays with the estimated free drug DM concentrations in the brain following oral DM/Q administration. The findings suggest that DM/Q likely inhibits serotonin and norepinephrine reuptake and also blocks NMDA receptors with rapid kinetics. Use of DM/Q may also antagonize nicotinic acetylcholine receptors, particularly those composed of α3β4 subunits, and cause agonist activity at sigma-1 receptors. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  6. A Vietnamese man with selective mutism: the relevance of multiple interacting 'cultures' in clinical psychiatry.

    Science.gov (United States)

    Hollifield, Michael; Geppert, Cynthia; Johnson, Yuam; Fryer, Carol

    2003-09-01

    Multiple cultural variables have effects on the psychobiology and behavioral manifestations of illness, as do patient and physician perceptions of illness. The interaction among these variables is at the heart of clinical psychiatry. This case of a Vietnamese man with selective mutism underscores the relevance of the 'cultures' of medicine, psychiatry, and war and trauma on the manifestations of illness and illness perceptions by patient and physician. The discussion focuses on how these cultures interact and play a crucial role in formulating diagnosis and treatment planning. Suggestions are given for shifts in medical education that will encourage relevant cultural paradigms to make their way into educational and clinical systems, which in turn should improve cultural competence in clinical psychiatry.

  7. Strategic characterization of anti-drug antibody responses for the assessment of clinical relevance and impact.

    Science.gov (United States)

    Tatarewicz, Suzanna M; Mytych, Daniel T; Manning, Marta Starcevic; Swanson, Steven J; Moxness, Michael S; Chirmule, Narendra

    2014-06-01

    All therapeutic proteins have the potential to induce anti-drug antibodies (ADA). Clinically relevant ADA can impact efficacy and/or safety of a biological therapeutic. Immunogenicity assessment strategy evaluates binding and neutralizing ADA, and the need for additional characterization (e.g., epitope, titer and so on) is determined using a risk-based approach. The choice of characterization assays depends on the type, application and immunogenicity of the therapeutic. ADA characterization can impact the interpretation of the risk profile of a given therapeutic, and offers insight into opportunities for risk mitigation and management. This article describes common ADA characterization methods. Strategic assessment and characterization of clinically relevant ADA are discussed, in order to support clinical options for safe and effective patient care and disease management.

  8. Role of tissue engineered collagen based tridimensional implant on the healing response of the experimentally induced large Achilles tendon defect model in rabbits: a long term study with high clinical relevance.

    Science.gov (United States)

    Meimandi-Parizi, Abdolhamid; Oryan, Ahmad; Moshiri, Ali

    2013-05-14

    Tendon injury is one of the orthopedic conditions poses with a significant clinical challenge to both the surgeons and patients. The major limitations to manage these injuries are poor healing response and development of peritendinous adhesions in the injured area. This study investigated the effectiveness of a novel collagen implant on tendon healing in rabbits. Seventy five mature White New-Zealand rabbits were divided into treated (n = 55) and control (n = 20) groups. The left Achilles tendon was completely transected and 2 cm excised. The defects of the treated animals were filled with collagen implants and repaired with sutures, but in control rabbits the defects were sutured similarly but the gap was left untreated. Changes in the injured and normal contralateral tendons were assessed weekly by measuring the diameter, temperature and bioelectrical characteristics of the injured area. Clinical examination was done and scored. Among the treated animals, small pilot groups were euthanized at 5, 10, 15, 20, 30, 40 and 60 (n = 5 at each time interval) and the remainder (n = 20) and the control animals at 120 days post injury (DPI). The lesions of all animals were examined at macroscopic and microscopic levels and the dry matter content, water delivery and water uptake characteristics of the lesions and normal contralateral tendons of both groups were analyzed at 120 DPI. This novel collagen implant was biodegradable, biocompatible and possibly could be considered as a substitute for auto and allografts in clinical practice in near future.

  9. A retrospective study of relevant diagnostic procedures in vulvodynia

    DEFF Research Database (Denmark)

    Petersen, Christina Damsted; Kristensen, Ellids; Lundvall, Lene

    2009-01-01

    OBJECTIVE: To identify objective clinical signs of vulvodynia and determine specific diagnostic tests for vulvodynia in women referred to a vulvar outpatient clinic for vulval complaints. STUDY DESIGN: A retrospective study was performed of the medical records of 201 consecutive Danish patients s...

  10. Music's relevance for children with cancer: music therapists' qualitative clinical data-mining research.

    Science.gov (United States)

    O'Callaghan, Clare; Dun, Beth; Baron, Annette; Barry, Philippa

    2013-01-01

    Music is central in most children's lives. Understanding its relevance will advance efficacious pediatric supportive cancer care. Qualitative clinical data-mining uncovered four music therapists' perspectives about music and music therapy's relevance for pediatric oncology patients up to 14 years old. Inductive and comparative thematic analysis was performed on focus group transcripts and qualitative interrater reliability integrated. Music can offer children a safe haven for internalizing a healthy self-image alongside patient identity. Music therapy can calm, relieve distress, promote supportive relationships, enable self-care, and inspire playful creativity, associated with "normalcy" and hope. Preferred music and music therapy should be available in pediatric oncology.

  11. Radiation transformation studies: are they relevant to radiation protection problems?

    International Nuclear Information System (INIS)

    Seymour, C.B.; Mothersill, C.

    1988-01-01

    Because of the difficulties of studying radio-carcinogenesis in humans, several in vitro systems are utilised. These cell transformation systems are reviewed, with particular emphasis on their relevance to human radiological protection problems. Most available systems use rodent fibroblasts. These are discussed in detail. Attention is drawn to certain artefacts which can cause problems with interpretation of such data. The relevance of these systems is questionable because of species differences, particularly concerning life span and because most human tumours are derived from epithelial cells. New epithelial culture systems and three-dimensional tissue culture methods becoming available are discussed in the light of their potential for addressing radiation protection problems. (author)

  12. Clinical subtypes of delirium and their relevance for daily clinical practice: a systematic review

    NARCIS (Netherlands)

    de Rooij, S. E.; Schuurmans, M. J.; van der Mast, R. C.; Levi, M. [=Marcel M.

    2005-01-01

    Background Delirium is a disorder that besides four essential features consists of different combinations of symptoms. We reviewed the clinical classification of clusters of symptoms in two or three delirium subtypes. The possible implications of this subtype classification may be several. The

  13. Hypersensitivities for acetaldehyde and other agents among cancer cells null for clinically relevant Fanconi anemia genes.

    Science.gov (United States)

    Ghosh, Soma; Sur, Surojit; Yerram, Sashidhar R; Rago, Carlo; Bhunia, Anil K; Hossain, M Zulfiquer; Paun, Bogdan C; Ren, Yunzhao R; Iacobuzio-Donahue, Christine A; Azad, Nilofer A; Kern, Scott E

    2014-01-01

    Large-magnitude numerical distinctions (>10-fold) among drug responses of genetically contrasting cancers were crucial for guiding the development of some targeted therapies. Similar strategies brought epidemiological clues and prevention goals for genetic diseases. Such numerical guides, however, were incomplete or low magnitude for Fanconi anemia pathway (FANC) gene mutations relevant to cancer in FANC-mutation carriers (heterozygotes). We generated a four-gene FANC-null cancer panel, including the engineering of new PALB2/FANCN-null cancer cells by homologous recombination. A characteristic matching of FANCC-null, FANCG-null, BRCA2/FANCD1-null, and PALB2/FANCN-null phenotypes was confirmed by uniform tumor regression on single-dose cross-linker therapy in mice and by shared chemical hypersensitivities to various inter-strand cross-linking agents and γ-radiation in vitro. Some compounds, however, had contrasting magnitudes of sensitivity; a strikingly high (19- to 22-fold) hypersensitivity was seen among PALB2-null and BRCA2-null cells for the ethanol metabolite, acetaldehyde, associated with widespread chromosomal breakage at a concentration not producing breaks in parental cells. Because FANC-defective cancer cells can share or differ in their chemical sensitivities, patterns of selective hypersensitivity hold implications for the evolutionary understanding of this pathway. Clinical decisions for cancer-relevant prevention and management of FANC-mutation carriers could be modified by expanded studies of high-magnitude sensitivities. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  14. Study of the reactor relevance of the NET design concept

    International Nuclear Information System (INIS)

    Reynolds, P.; Worraker, W.J.

    1987-08-01

    The objective of the study was to explore the reactor relevance of NET, i.e. whether the technologies and design principles proposed for NET can be directly extrapolated to a demonstration power reactor (DEMO). The main areas of study were those near to the plasma, namely the divertor, first wall and tritium breeding blanket. Other aspects which were investigated were tritium permeation and recovery, reactor maintenance, afterheat and effects of disruptions. The principal results of the study are briefly presented; the details of the work are given in fourteen appendices. These appendices were selected for INIS and indexed separately. The overall conclusion of the study is that the NET design is only partly relevant to the design requirements of a DEMO reactor. (U.K.)

  15. Online drug databases: a new method to assess and compare inclusion of clinically relevant information.

    Science.gov (United States)

    Silva, Cristina; Fresco, Paula; Monteiro, Joaquim; Rama, Ana Cristina Ribeiro

    2013-08-01

    Evidence-Based Practice requires health care decisions to be based on the best available evidence. The model "Information Mastery" proposes that clinicians should use sources of information that have previously evaluated relevance and validity, provided at the point of care. Drug databases (DB) allow easy and fast access to information and have the benefit of more frequent content updates. Relevant information, in the context of drug therapy, is that which supports safe and effective use of medicines. Accordingly, the European Guideline on the Summary of Product Characteristics (EG-SmPC) was used as a standard to evaluate the inclusion of relevant information contents in DB. To develop and test a method to evaluate relevancy of DB contents, by assessing the inclusion of information items deemed relevant for effective and safe drug use. Hierarchical organisation and selection of the principles defined in the EGSmPC; definition of criteria to assess inclusion of selected information items; creation of a categorisation and quantification system that allows score calculation; calculation of relative differences (RD) of scores for comparison with an "ideal" database, defined as the one that achieves the best quantification possible for each of the information items; pilot test on a sample of 9 drug databases, using 10 drugs frequently associated in literature with morbidity-mortality and also being widely consumed in Portugal. Main outcome measure Calculate individual and global scores for clinically relevant information items of drug monographs in databases, using the categorisation and quantification system created. A--Method development: selection of sections, subsections, relevant information items and corresponding requisites; system to categorise and quantify their inclusion; score and RD calculation procedure. B--Pilot test: calculated scores for the 9 databases; globally, all databases evaluated significantly differed from the "ideal" database; some DB performed

  16. Intraductal papillary mucinous neoplasms of the pancreas: reporting clinically relevant features.

    Science.gov (United States)

    Del Chiaro, Marco; Verbeke, Caroline

    2017-05-01

    Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas can exhibit a wide spectrum of macroscopic and microscopic appearances. This not only causes occasional difficulties for the reporting pathologist in distinguishing these tumours from other lesions, but is also relevant clinically. As evidence accumulates, it becomes clear that multiple macroscopic and histological features of these neoplasms are relevant to the risk for malignant transformation and, consequently, of prime importance for clinical patient management. The need for detailed reporting is therefore increasing. This review discusses the panoply of gross and microscopic features of IPMN as well as the recommendations from recent consensus meetings regarding the pathology reporting on this tumour entity. © 2016 John Wiley & Sons Ltd.

  17. Risk-adjusted Outcomes of Clinically Relevant Pancreatic Fistula Following Pancreatoduodenectomy: A Model for Performance Evaluation.

    Science.gov (United States)

    McMillan, Matthew T; Soi, Sameer; Asbun, Horacio J; Ball, Chad G; Bassi, Claudio; Beane, Joal D; Behrman, Stephen W; Berger, Adam C; Bloomston, Mark; Callery, Mark P; Christein, John D; Dixon, Elijah; Drebin, Jeffrey A; Castillo, Carlos Fernandez-Del; Fisher, William E; Fong, Zhi Ven; House, Michael G; Hughes, Steven J; Kent, Tara S; Kunstman, John W; Malleo, Giuseppe; Miller, Benjamin C; Salem, Ronald R; Soares, Kevin; Valero, Vicente; Wolfgang, Christopher L; Vollmer, Charles M

    2016-08-01

    To evaluate surgical performance in pancreatoduodenectomy using clinically relevant postoperative pancreatic fistula (CR-POPF) occurrence as a quality indicator. Accurate assessment of surgeon and institutional performance requires (1) standardized definitions for the outcome of interest and (2) a comprehensive risk-adjustment process to control for differences in patient risk. This multinational, retrospective study of 4301 pancreatoduodenectomies involved 55 surgeons at 15 institutions. Risk for CR-POPF was assessed using the previously validated Fistula Risk Score, and pancreatic fistulas were stratified by International Study Group criteria. CR-POPF variability was evaluated and hierarchical regression analysis assessed individual surgeon and institutional performance. There was considerable variability in both CR-POPF risk and occurrence. Factors increasing the risk for CR-POPF development included increasing Fistula Risk Score (odds ratio 1.49 per point, P ratio 3.30, P performance outliers were identified at the surgeon and institutional levels. Of the top 10 surgeons (≥15 cases) for nonrisk-adjusted performance, only 6 remained in this high-performing category following risk adjustment. This analysis of pancreatic fistulas following pancreatoduodenectomy demonstrates considerable variability in both the risk and occurrence of CR-POPF among surgeons and institutions. Disparities in patient risk between providers reinforce the need for comprehensive, risk-adjusted modeling when assessing performance based on procedure-specific complications. Furthermore, beyond inherent patient risk factors, surgical decision-making influences fistula outcomes.

  18. Clinical relevance of surgical site infection as defined by the criteria of the Centers for Disease Control and Prevention

    DEFF Research Database (Denmark)

    Henriksen, N A; Meyhoff, C S; Wetterslev, J

    2010-01-01

    Surgical site infection (SSI) is a common complication after abdominal surgery and the Centers for Disease Control and Prevention (CDC) criteria are commonly used for diagnosis and surveillance. The aim of this study was to evaluate whether SSI diagnosed according to CDC is clinically relevant (C...... a suitable standard definition for monitoring and identifying SSI, even if some cases of less clinically significant superficial SSI are included.......Surgical site infection (SSI) is a common complication after abdominal surgery and the Centers for Disease Control and Prevention (CDC) criteria are commonly used for diagnosis and surveillance. The aim of this study was to evaluate whether SSI diagnosed according to CDC is clinically relevant...... hospital stay or referral to an intensive care unit for SSI. The rate of CRSSI was 38 of 54 (70%) in patients with CDC-diagnosed SSI and none in patients without a CDC-diagnosed SSI. Sixty-one percent of the CDC-diagnosed SSIs were superficial, of which 48% were considered clinically relevant...

  19. [Enduring relevance. An introduction to the clinical contributions of K. R. Eissler].

    Science.gov (United States)

    Garcia, Emanuel E

    2007-01-01

    The author offers a personal selection and discussion of papers that epitomize the enduring relevance of Eissler's contributions to psychoanalytic therapy. The innovations of technique embodied by these works (on parameters, schizophrenia, adolescence, cure, fees, and the treatment of the dying patient) reveal a therapeutic approach that is a natural extension of psychoanalytic science: patient-centered, maximally comprehensive and appropriately flexible. Firsthand observations of Eissler's clinical manner and a selected bibliography are also presented.

  20. Biomarkers for Early Detection of Clinically Relevant Prostate Cancer. A Multi-Institutional Validation Trial

    Science.gov (United States)

    2016-10-01

    aim 2: Evaluate a panel of four-kallikrein plasma-based markers to determine the presence of or progression to clinically relevant prostate cancer...and sent to Genomic Health, Inc. for processing. Task 3: Analysis of scientific Aim 2: Evaluate a panel of four-kallikrein plasma-based markers to...site: FHCRC) PCA3 and the TMPRSS2:ERG fusion are prostate cancer-specific biomarkers that hold promise for stratifying risk in the setting of AS

  1. Opportunities for Cancer-relevant Innovative Technologies with Transformative Potential | Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    The National Cancer Institute (NCI) is seeking input from the community on identifying priorities with regards to supporting innovative technology development for cancer-relevant research. While the NCI provides support for technology development through a variety of mechanisms, it is important to understand whether or not these are sufficient for catalyzing and supporting the development of tools with significant potential for advancing important fields of cancer research or clinical care.

  2. The Role and Clinical Relevance of Disseminated Tumor Cells in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Malgorzata Banys

    2014-01-01

    Full Text Available Tumor cell dissemination is a common phenomenon observed in most cancers of epithelial origin. One-third of breast cancer patients present with disseminated tumor cells (DTCs in bone marrow at time of diagnosis; these patients, as well as patients with persistent DTCs, have significantly worse clinical outcome than DTC-negative patients. Since DTC phenotype may differ from the primary tumor with regard to ER and HER2 status, reevaluation of predictive markers on DTCs may optimize treatment choices. In the present review, we report on the clinical relevance of DTC detection in breast cancer.

  3. Clinically Relevant Physical Benefits of Exercise Interventions in Breast Cancer Survivors.

    Science.gov (United States)

    Kirkham, Amy A; Bland, Kelcey A; Sayyari, Sarah; Campbell, Kristin L; Davis, Margot K

    2016-02-01

    Evidence is currently limited for the effect of exercise on breast cancer clinical outcomes. However, several of the reported physical benefits of exercise, including peak oxygen consumption, functional capacity, muscle strength and lean mass, cardiovascular risk factors, and bone health, have established associations with disability, cardiovascular disease risk, morbidity, and mortality. This review will summarize the clinically relevant physical benefits of exercise interventions in breast cancer survivors and discuss recommendations for achieving these benefits. It will also describe potential differences in intervention delivery that may impact outcomes and, lastly, describe current physical activity guidelines for cancer survivors.

  4. Prolactinomas : clinical studies

    NARCIS (Netherlands)

    Kars, Marleen

    2008-01-01

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

  5. [EDNOS is an eating disorder of clinical relevance, on a par with anorexia and bulimia nervosa].

    Science.gov (United States)

    Dingemans, A E; van Furth, E F

    2015-01-01

    The category 'eating disorder 'not otherwise specified'' (EDNOS) in DSM-IV is restricted to eating disorders of clinical severity that do not completely fulfil the criteria for anorexia and bulimia nervosa. The EDNOS category is, by definition, often regarded as a a residual category and in principle designed to incorporate a small group of patients with atypical characteristics. Health insurance companies argue that the treatment of patients diagnosed with EDNOS should not be treated in mental health institutions and therefore should not get their treatment costs reimbursed by the insurance companies. The most important argument of the insurance companies is that patients in the EDNOS category do not display serious psychiatric symptoms. The aim of this paper is to show that EDNOS is an eating disorder category of clinical relevance. The article provides a critical overview of literature on EDNOS which studies the prevalence, severity and course of the disorder. We also discuss to what extent the fifth version of dsm solves the problems relating to this residual category. We reviewed the literature. The classification given in DSM-IV is not an accurate reflection of clinical reality. Half of the patients presenting with an eating disorder and seeking treatment do meet the criteria for EDNOS. The duration and the severity of eating disorder psychopathology, the presence of comorbidity, the mortality, and the use of the mental health care services by individuals with an eating disorder appear to be very similar in EDNOS patients and in patients with anorexia and bulimia nervosa. Eating disorder classifications can be regarded as snapshots taken throughout the course of an illness. Over of the years patients can be afflicted with various subtypes of an eating disorder. DSM-5 places fewer patients in the EDNOS category that did DSM-IV. In the latest version of dsm, namely DSM-5, the number of patients with an eating disorder classified as EDNOS has declined. There

  6. Clinical relevance and prognostic value of radiographic findings in Zenker's diverticulum.

    Science.gov (United States)

    Mantsopoulos, Konstantinos; Psychogios, Georgios; Karatzanis, Alexander; Künzel, Julian; Lell, Michael; Zenk, Johannes; Koch, Michael

    2014-03-01

    The aim of this study was to evaluate the clinical relevance and prognostic value of preoperative and postoperative oesophagography in patients with Zenker's diverticulum. The medical records of 155 patients who underwent surgical treatment (with an endoscopic or transcervical approach) for Zenker's diverticulum between 1992 and 2010 in a tertiary referral centre were retrospectively evaluated. The size of the diverticula on oesophagography, recognizable muscular septum, and protection of the diverticulum were assessed relative to the surgical procedures performed. The incidence of diverticular remnants on postoperative oesophagography was also assessed relative to the surgical procedure. It was investigated whether the detection of a residual pharyngeal pouch and filling of it with contrast medium were related to the patients' immediate postoperative symptoms and the development of symptomatic recurrence. Larger diverticula (Brombart III-IV) were manageable significantly more often with endoscopic procedures (P = 0.007). Residual diverticulum and filling with contrast medium were strongly associated with prolonged dysphagia immediately postoperatively (P = 0.005 and P = 0.009, respectively). However, these parameters failed to correlate significantly with a symptomatic recurrence. Preoperative oesophagography proved to be extremely important for surgical planning, with the surgeon's personal preference seeming to be the driving indicator in many cases. Postoperative oesophagography is only useful for excluding postoperative complications in the immediate postoperative phase and did not have a prognostic value as to a recurrence of the disease.

  7. Dose-dependent cytotoxicity of clinically relevant cobalt nanoparticles and ions on macrophages in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Young-Min; Xia Zhidao; Glyn-Jones, Sion; Beard, David; Gill, Harinderjit S; Murray, David W, E-mail: young-min.kwon@ndos.ox.ac.u [Nuffield Department of Orthopaedic Surgery, University of Oxford, Oxford OX3 7LD (United Kingdom)

    2009-04-15

    Despite the satisfactory short-term implant survivorship of metal-on-metal hip resurfacing arthroplasty, periprosthetic soft-tissue masses such as pseudotumours are being increasingly reported. Cytotoxic effects of cobalt or chromium have been suggested to play a role in its aetiology. The aim of this study was to investigate the effects of clinically relevant metal nanoparticles and ions on the viability of macrophages in vitro. A RAW 264.7 murine macrophage cell line was cultured in the presence of either: (1) cobalt, chromium and titanium nanoparticles sized 30-35 nm; or (2) cobalt sulphate and chromium chloride. Two methods were used to quantify cell viability: Alamar Blue assay and Live/Dead assay. The cytotoxicity was observed only with cobalt. Cobalt nanoparticles and ions demonstrated dose-dependent cytotoxic effects on macrophages in vitro: the cytotoxic concentrations of nanoparticles and ions were 1 x 10{sup 12} particles ml{sup -1} and 1000 {mu}M, respectively. The high concentration of cobalt nanoparticles required for cytotoxicity of macrophages in vitro suggests that increased production of cobalt nanoparticles in vivo, due to excessive MoM implant wear, may lead to local adverse biological effects. Therefore, cytotoxicity of high concentrations of metal nanoparticles phagocytosed by macrophages located in the periprosthetic tissues may be an important factor in pathogenesis of pseudotumours.

  8. Polymorphisms in drug-metabolizing enzymes: What is their clinical relevance and why do they exist?

    Energy Technology Data Exchange (ETDEWEB)

    Nebert, D.W. [Univ. of Cincinnati Medical Center, OH (United States)

    1997-02-01

    The beautiful report by Sachse in this issue of the journal represents the culmination of 2 decades of increasingly exciting work on the {open_quotes}debrisoquine oxidation polymorphism,{close_quotes} one of dozens of pharmacogenetic or ecogenetic polymorphisms that have been shown to have an important impact on innumerable clinical diseases. Pharmacogenetics is the study of the hereditary basis of the differences in responses to drugs. Ecogenetics is the broader field of interindividual differences in response to all environmental chemical and physical agents (e.g., heavy metals, insecticides, compounds formed during combustion, and UV radiation). It is now clear that each of us has his or her own {open_quotes}individual fingerprint{close_quotes} of unique alleles encoding the so-called drug-metabolizing enzymes (DMEs) and the receptors that regulate these enzymes. In this invited editorial, I first introduce the current thinking in the field of DME (and DME-receptor) research and how DMEs have evolved from animal-plant interactions. I then describe the debrisoquine oxidation polymorphism, as well as two other relevant DME polymorphisms; show the relationship between these polymorphisms and human disease; provide examples of synergistic effects caused by the combination of two DME polymorphisms; and discuss the ethical considerations of such research. Last, I speculate on why these allelic frequencies of the DME genes might exist in human populations in the first place. 35 refs.

  9. Identifying clinically relevant drug resistance genes in drug-induced resistant cancer cell lines and post-chemotherapy tissues.

    Science.gov (United States)

    Tong, Mengsha; Zheng, Weicheng; Lu, Xingrong; Ao, Lu; Li, Xiangyu; Guan, Qingzhou; Cai, Hao; Li, Mengyao; Yan, Haidan; Guo, You; Chi, Pan; Guo, Zheng

    2015-12-01

    Until recently, few molecular signatures of drug resistance identified in drug-induced resistant cancer cell models can be translated into clinical practice. Here, we defined differentially expressed genes (DEGs) between pre-chemotherapy colorectal cancer (CRC) tissue samples of non-responders and responders for 5-fluorouracil and oxaliplatin-based therapy as clinically relevant drug resistance genes (CRG5-FU/L-OHP). Taking CRG5-FU/L-OHP as reference, we evaluated the clinical relevance of several types of genes derived from HCT116 CRC cells with resistance to 5-fluorouracil and oxaliplatin, respectively. The results revealed that DEGs between parental and resistant cells, when both were treated with the corresponding drug for a certain time, were significantly consistent with the CRG5-FU/L-OHP as well as the DEGs between the post-chemotherapy CRC specimens of responders and non-responders. This study suggests a novel strategy to extract clinically relevant drug resistance genes from both drug-induced resistant cell models and post-chemotherapy cancer tissue specimens.

  10. Impairment of cocaine-mediated behaviours in mice by clinically relevant Ras-ERK inhibitors

    Science.gov (United States)

    Papale, Alessandro; Morella, Ilaria Maria; Indrigo, Marzia Tina; Bernardi, Rick Eugene; Marrone, Livia; Marchisella, Francesca; Brancale, Andrea; Spanagel, Rainer; Brambilla, Riccardo; Fasano, Stefania

    2016-01-01

    Ras-ERK signalling in the brain plays a central role in drug addiction. However, to date, no clinically relevant inhibitor of this cascade has been tested in experimental models of addiction, a necessary step toward clinical trials. We designed two new cell-penetrating peptides - RB1 and RB3 - that penetrate the brain and, in the micromolar range, inhibit phosphorylation of ERK, histone H3 and S6 ribosomal protein in striatal slices. Furthermore, a screening of small therapeutics currently in clinical trials for cancer therapy revealed PD325901 as a brain-penetrating drug that blocks ERK signalling in the nanomolar range. All three compounds have an inhibitory effect on cocaine-induced ERK activation and reward in mice. In particular, PD325901 persistently blocks cocaine-induced place preference and accelerates extinction following cocaine self-administration. Thus, clinically relevant, systemically administered drugs that attenuate Ras-ERK signalling in the brain may be valuable tools for the treatment of cocaine addiction. DOI: http://dx.doi.org/10.7554/eLife.17111.001 PMID:27557444

  11. Identification and content validation of wound therapy clinical endpoints relevant to clinical practice and patient values for FDA approval. Part 1. Survey of the wound care community.

    Science.gov (United States)

    Driver, Vickie R; Gould, Lisa J; Dotson, Peggy; Gibbons, Gary W; Li, William W; Ennis, William J; Kirsner, Robert S; Eaglstein, William H; Bolton, Laura L; Carter, Marissa J

    2017-05-01

    Wounds that exhibit delayed healing add extraordinary clinical, economic, and personal burdens to patients, as well as to increasing financial costs to health systems. New interventions designed to ease such burdens for patients with cancer, renal, or ophthalmologic conditions are often cleared for approval by the U.S. Food and Drug Administration (FDA) using multiple endpoints but the requirement of complete healing as a primary endpoint for wound products impedes FDA clearance of interventions that can provide other clinical or patient-centered benefits for persons with wounds. A multidisciplinary group of wound experts undertook an initiative, in collaboration with the FDA, to identify and content validate supporting FDA criteria for qualifying wound endpoints relevant to clinical practice (CP) and patient-centered outcomes (PCO) as primary outcomes in clinical trials. As part of the initiative, a research study was conducted involving 628 multidisciplinary expert wound clinicians and researchers from 4 different groups: the interdisciplinary core advisory team; attendees of the Spring 2015 Symposium on Advanced Wound Care (SAWC); clinicians employed by a national network of specialty clinics focused on comprehensive wound care; and Association for the Advancement of Wound Care (AAWC) and Wound Healing Society (WHS) members who had not previously completed the survey. The online survey assessed 28 literature-based wound care endpoints for their relevance and importance to clinical practice and clinical research. Fifteen of the endpoints were evaluated for their relevance to improving quality of life. Twenty-two endpoints had content validity indexes (CVI) ≥ 0.75, and 15 were selected as meriting potential inclusion as additional endpoints for FDA approval of future wound care interventions. This study represents an important first step in identifying and validating new measurable wound care endpoints for clinical research and practice and for regulatory

  12. Clinical relevance of surgical site infection as defined by the criteria of the Centers for Disease Control and Prevention

    DEFF Research Database (Denmark)

    Henriksen, N A; Meyhoff, C S; Wetterslev, J

    2010-01-01

    Surgical site infection (SSI) is a common complication after abdominal surgery and the Centers for Disease Control and Prevention (CDC) criteria are commonly used for diagnosis and surveillance. The aim of this study was to evaluate whether SSI diagnosed according to CDC is clinically relevant...... diagnosed with SSI and a matched control group (N=46) without SSI according to the CDC criteria after laparotomy. Two blinded experienced surgeons evaluated the hospital records and determined whether patients had CRSSI, based on the following criteria: antibiotic treatment, surgical intervention, prolonged...... hospital stay or referral to an intensive care unit for SSI. The rate of CRSSI was 38 of 54 (70%) in patients with CDC-diagnosed SSI and none in patients without a CDC-diagnosed SSI. Sixty-one percent of the CDC-diagnosed SSIs were superficial, of which 48% were considered clinically relevant...

  13. Palbociclib has no clinically relevant effect on the QTc interval in patients with advanced breast cancer.

    Science.gov (United States)

    Durairaj, Chandrasekar; Ruiz-Garcia, Ana; Gauthier, Eric R; Huang, Xin; Lu, Dongrui R; Hoffman, Justin T; Finn, Richard S; Joy, Anil A; Ettl, Johannes; Rugo, Hope S; Zheng, Jenny; Wilner, Keith D; Wang, Diane D

    2018-03-01

    The aim of this study was to assess the potential effects of palbociclib in combination with letrozole on QTc. PALOMA-2, a phase 3, randomized, double-blind, placebo-controlled trial, compared palbociclib plus letrozole with placebo plus letrozole in postmenopausal women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer. The study included a QTc evaluation substudy carried out as a definitive QT interval prolongation assessment for palbociclib. Time-matched triplicate ECGs were performed at 0, 2, 4, 6, and 8 h at baseline (Day 0) and on Cycle 1 Day 14. Additional ECGs were collected from all patients for safety monitoring. The QT interval was corrected for heart rate using Fridericia's correction (QTcF), Bazett's correction (QTcB), and a study-specific correction factor (QTcS). In total, 666 patients were randomized 2 : 1 to palbociclib plus letrozole or placebo plus letrozole. Of these, 125 patients were enrolled in the QTc evaluation substudy. No patients in the palbociclib plus letrozole arm of the substudy (N=77) had a maximum postbaseline QTcS or QTcF value of ≥ 480 ms, or a maximum increase from clock time-matched baseline for QTcS or QTcF values of ≥ 60 ms. The upper bounds of the one-sided 95% confidence interval for the mean change from time-matched baseline for QTcS, QTcF, and QTcB at all time points and at steady-state Cmax following repeated administration of 125 mg palbociclib were less than 10 ms. Palbociclib, when administered with letrozole at the recommended therapeutic dosing regimen, did not prolong the QT interval to a clinically relevant extent.

  14. 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

  15. Efficacy of long-term milnacipran treatment in patients meeting different thresholds of clinically relevant pain relief: subgroup analysis of a randomized, double-blind, placebo-controlled withdrawal study

    Directory of Open Access Journals (Sweden)

    Mease PJ

    2014-11-01

    Full Text Available Philip J Mease,1 Daniel J Clauw,2 Joel M Trugman,3 Robert H Palmer,3 Yong Wang3 1Swedish Medical Center and University of Washington, Seattle, WA, USA; 2Chronic Pain and Fatigue Research Center, University of Michigan Health System, Ann Arbor, MI, USA; 3Forest Research Institute, Jersey City, NJ, USA Background: Fibromyalgia patients from a long-term, open-label study of milnacipran (50–200 mg/day were eligible to participate in a 12-week, randomized, placebo-controlled withdrawal study. The withdrawal study evaluated loss of therapeutic response in patients who achieved ≥50% pain improvements after receiving up to 3.25 years of milnacipran. This post-hoc analysis investigated whether patients who met lower thresholds of pain improvement also experienced worsening of fibromyalgia symptoms upon treatment withdrawal. Method: Among patients who received milnacipran ≥100 mg/day during the long-term study, three subgroups were identified based on percentage of pain reduction at randomization: ≥50% (protocol-defined "responders"; n=150; ≥30% to <50% (patients with clinically meaningful pain improvement; n=61; and <30% (n=110. Efficacy assessments included the visual analog scale (VAS for pain, Fibromyalgia Impact Questionnaire-Revised (FIQR, 36-Item Short-Form Health Survey Physical Component Summary (SF-36 PCS, and Beck Depression Inventory (BDI. Results: In the ≥30 to <50% subgroup, significant worsening in pain was detected after treatment withdrawal. The difference between placebo and milnacipran in mean VAS score changes for this subgroup (+9.0, P<0.05 was similar to the difference in protocol-defined responders (+9.4, P<0.05. In the <30% subgroup, no worsening in pain was observed in either treatment arm. However, patients in this subgroup experienced significant worsening in FIQR scores after treatment withdrawal (placebo, +6.9; milnacipran, -2.8; P<0.001, as well as worsening in SF-36 PCS and BDI scores. Conclusion: Patients who

  16. Precision Oncology Medicine: The Clinical Relevance of Patient-Specific Biomarkers Used to Optimize Cancer Treatment.

    Science.gov (United States)

    Schmidt, Keith T; Chau, Cindy H; Price, Douglas K; Figg, William D

    2016-12-01

    Precision medicine in oncology is the result of an increasing awareness of patient-specific clinical features coupled with the development of genomic-based diagnostics and targeted therapeutics. Companion diagnostics designed for specific drug-target pairs were the first to widely utilize clinically applicable tumor biomarkers (eg, HER2, EGFR), directing treatment for patients whose tumors exhibit a mutation susceptible to an FDA-approved targeted therapy (eg, trastuzumab, erlotinib). Clinically relevant germline mutations in drug-metabolizing enzymes and transporters (eg, TPMT, DPYD) have been shown to impact drug response, providing a rationale for individualized dosing to optimize treatment. The use of multigene expression-based assays to analyze an array of prognostic biomarkers has been shown to help direct treatment decisions, especially in breast cancer (eg, Oncotype DX). More recently, the use of next-generation sequencing to detect many potential "actionable" cancer molecular alterations is further shifting the 1 gene-1 drug paradigm toward a more comprehensive, multigene approach. Currently, many clinical trials (eg, NCI-MATCH, NCI-MPACT) are assessing novel diagnostic tools with a combination of different targeted therapeutics while also examining tumor biomarkers that were previously unexplored in a variety of cancer histologies. Results from ongoing trials such as the NCI-MATCH will help determine the clinical utility and future development of the precision-medicine approach. © 2016, The American College of Clinical Pharmacology.

  17. Clinical relevance of ErbB-2/HER2 nuclear expression in breast cancer

    International Nuclear Information System (INIS)

    Schillaci, Roxana; Charreau, Eduardo H; Maronna, Esteban; Roa, Juan C; Elizalde, Patricia V; Guzmán, Pablo; Cayrol, Florencia; Beguelin, Wendy; Díaz Flaqué, María C; Proietti, Cecilia J; Pineda, Viviana; Palazzi, Jorge; Frahm, Isabel

    2012-01-01

    The biological relevance of nuclear ErbB-2/HER2 (NuclErbB-2) presence in breast tumors remains unexplored. In this study we assessed the clinical significance of ErbB-2 nuclear localization in primary invasive breast cancer. The reporting recommendations for tumor marker prognostic studies (REMARK) guidelines were used as reference. Tissue microarrays from a cohort of 273 primary invasive breast carcinomas from women living in Chile, a Latin American country, were examined for membrane (MembErbB-2) and NuclErbB-2 expression by an immunofluorescence (IF) protocol we developed. ErbB-2 expression was also evaluated by immunohistochemistry (IHC) with a series of antibodies. Correlation between NuclErbB-2 and MembErbB-2, and between NuclErbB-2 and clinicopathological characteristics of tumors was studied. The prognostic value of NuclErbB-2 in overall survival (OS) was evaluated using Kaplan-Meier method, and Cox model was used to explore NuclErbB-2 as independent prognostic factor for OS. The IF protocol we developed showed significantly higher sensitivity for detection of NuclErbB-2 than IHC procedures, while its specificity and sensitivity to detect MembErbB-2 were comparable to those of IHC procedures. We found 33.6% NuclErbB-2 positivity, 14.2% MembErbB-2 overexpression by IF, and 13.0% MembErbB-2 prevalence by IHC in our cohort. We identified NuclErbB-2 positivity as a significant independent predictor of worse OS in patients with MembErbB-2 overexpression. NuclErbB-2 was also a biomarker of lower OS in tumors that overexpress MembErbB-2 and lack steroid hormone receptors. We revealed a novel role for NuclErbB-2 as an independent prognostic factor of poor clinical outcome in MembErbB-2-positive breast tumors. Our work indicates that patients presenting NuclErbB-2 may need new therapeutic strategies involving specific blockage of ErbB-2 nuclear migration

  18. Clinical relevance of ErbB-2/HER2 nuclear expression in breast cancer

    Directory of Open Access Journals (Sweden)

    Schillaci Roxana

    2012-02-01

    Full Text Available Abstract Background The biological relevance of nuclear ErbB-2/HER2 (NuclErbB-2 presence in breast tumors remains unexplored. In this study we assessed the clinical significance of ErbB-2 nuclear localization in primary invasive breast cancer. The reporting recommendations for tumor marker prognostic studies (REMARK guidelines were used as reference. Methods Tissue microarrays from a cohort of 273 primary invasive breast carcinomas from women living in Chile, a Latin American country, were examined for membrane (MembErbB-2 and NuclErbB-2 expression by an immunofluorescence (IF protocol we developed. ErbB-2 expression was also evaluated by immunohistochemistry (IHC with a series of antibodies. Correlation between NuclErbB-2 and MembErbB-2, and between NuclErbB-2 and clinicopathological characteristics of tumors was studied. The prognostic value of NuclErbB-2 in overall survival (OS was evaluated using Kaplan-Meier method, and Cox model was used to explore NuclErbB-2 as independent prognostic factor for OS. Results The IF protocol we developed showed significantly higher sensitivity for detection of NuclErbB-2 than IHC procedures, while its specificity and sensitivity to detect MembErbB-2 were comparable to those of IHC procedures. We found 33.6% NuclErbB-2 positivity, 14.2% MembErbB-2 overexpression by IF, and 13.0% MembErbB-2 prevalence by IHC in our cohort. We identified NuclErbB-2 positivity as a significant independent predictor of worse OS in patients with MembErbB-2 overexpression. NuclErbB-2 was also a biomarker of lower OS in tumors that overexpress MembErbB-2 and lack steroid hormone receptors. Conclusions We revealed a novel role for NuclErbB-2 as an independent prognostic factor of poor clinical outcome in MembErbB-2-positive breast tumors. Our work indicates that patients presenting NuclErbB-2 may need new therapeutic strategies involving specific blockage of ErbB-2 nuclear migration.

  19. Identification and Validation of Clinically Relevant Clusters of Severe Fatigue in Rheumatoid Arthritis.

    Science.gov (United States)

    Basu, Neil; Jones, Gareth T; Macfarlane, Gary J; Druce, Katie L

    The considerable heterogeneity of rheumatoid arthritis (RA)-related fatigue is the greatest challenge to determining pathogenesis. The identification of homogenous subtypes of severe fatigue would inform the design and analysis of experiments seeking to characterize the likely numerous causal pathways that underpin the symptom. This study aimed to identify and validate such fatigue subtypes in patients with RA. Data were obtained from patients recruited to the British Society for Rheumatology Biologics register for RA, as either receiving traditional disease-modifying antirheumatic drugs (DMARD cohort, n = 522) or commencing anti-tumor necrosis factor therapy (anti-TNF cohort, n = 3909). In those reporting severe fatigue (Short-Form 36 vitality ≤ 12.5), this cross-sectional analysis applied hierarchical clustering with weighted-average linkage identified clusters of pain, fatigue, mental health (all Short-Form 36), disability (Health Assessment Questionnaire), and inflammation (erythrocyte sedimentation rate) in the DMARD cohort. K-means clustering sought to validate the solution in the anti-TNF cohort. Clusters were characterized using a priori generated symptom definitions and between-cluster comparisons. Four severe fatigue clusters, labeled as basic (46%), affective (40%), inflammatory (4.5%), and global (8.9%) were identified in the DMARD cohort. All clusters had severe levels of pain and disability and were distinguished by the presence/absence of poor mental health and high inflammation. The same symptom clusters were present in the anti-TNF cohort, although the proportion of participants in each cluster differed (basic = 28.7%; affective = 30.2%; global = 24.1%; inflammatory = 16.9%). Among RA patients with severe fatigue, recruited to two diverse RA cohorts, clinically relevant clusters were identified and validated. These may provide the basis for future mechanistic studies and ultimately support a stratified approach to fatigue management.

  20. Pharmacokinetics of (synthetic) cannabinoids in pigs and their relevance for clinical and forensic toxicology.

    Science.gov (United States)

    Schaefer, Nadine; Wojtyniak, Jan-Georg; Kettner, Mattias; Schlote, Julia; Laschke, Matthias W; Ewald, Andreas H; Lehr, Thorsten; Menger, Michael D; Maurer, Hans H; Schmidt, Peter H

    2016-06-24

    Synthetic cannabinoids (SCs) are gaining increasing importance in clinical and forensic toxicology. They are consumed without any preclinical safety studies. Thus, controlled human pharmacokinetic (PK) studies are not allowed, although being relevant for interpretation of analytical results in cases of misuse or poisoning. As alternative, in a controlled animal experiment, six pigs per drug received a single intravenous dose of 200μg/kg BW each of Δ(9)-tetrahydrocannabinol (THC), 4-ethylnaphthalen-1-yl-(1-pentylindol-3-yl)methanone (JWH-210), or 2-(4-methoxyphenyl)-1-(1-pentyl-indol-3-yl)methanone (RCS-4). In addition, six pigs received a combination of the three drugs with the identical dose each. The drugs were determined in serum using LC-MS/MS. A population (pop) PK analysis revealed that a three-compartment model described best the PK data of all three cannabinoids. Central volumes of distribution were estimated at 0.29L/kg, 0.20L/kg, and 0.67L/kg for THC, JWH-210, and RCS-4, respectively. Clearances were 0.042L/min/kg, 0.048L/min/kg, and 0.093L/min/kg for THC, JWH-210, and RCS-4, respectively. The popPK THC pig model was upscaled to humans using allometric techniques. Comparison with published human data revealed that the concentration-time profiles could successfully be predicted. These findings indicate that pigs in conjunction with PK modeling technique may serve as a tool for prediction of human PK of SCs. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. Clinical Relevance of Gene Copy Number Variation in Metastatic Clear Cell Renal Cell Carcinoma.

    Science.gov (United States)

    Nouhaud, François-Xavier; Blanchard, France; Sesboue, Richard; Flaman, Jean-Michel; Sabourin, Jean-Christophe; Pfister, Christian; Di Fiore, Frédéric

    2018-02-23

    Gene copy number variations (CNVs) have been reported to be frequent in renal cell carcinoma (RCC), with potential prognostic value for some. However, their clinical utility, especially to guide treatment of metastatic disease remains to be established. Our objectives were to assess CNVs on a panel of selected genes and determine their clinical relevance in patients who underwent treatment of metastatic RCC. The genetic assessment was performed on frozen tissue samples of clear cell metastatic RCC using quantitative multiplex polymerase chain reaction of short fluorescent fragment method to detect CNVs on a panel of 14 genes of interest. The comparison of the electropherogram obtained from both tumor and normal renal adjacent tissue allowed for CNV identification. The clinical, biologic, and survival characteristics were assessed for their associations with the most frequent CNVs. Fifty patients with clear cell metastatic RCC were included. The CNV rate was 21.4%. The loss of CDKN2A and PLG was associated with a higher tumor stage (P relevance, especially those located on CDKN2A, PLG, and ALDOB, in a homogeneous cohort of patients with clear cell metastatic RCC. Copyright © 2018 Elsevier Inc. All rights reserved.

  2. Relevance of positive cardiovascular outcome trial results in clinical practice: perspectives from the Academy for Cardiovascular Risk, Outcomes and Safety Studies in Type 2 Diabetes (ACROSS T2D

    Directory of Open Access Journals (Sweden)

    Schernthaner G

    2017-12-01

    Full Text Available Guntram Schernthaner,1 Kamlesh Khunti,2 Chaim Lotan,3 Michel Burnier,4 Heinz Drexel,5 Martin Prázný61Department of Medicine I, Rudolfstiftung Hospital, Vienna, Austria; 2Diabetes Research Centre, Leicester General Hospital, Leicester, UK; 3Cardiovascular Division, Hadassah Medical Centre, Jerusalem, Israel; 4Division of Nephrology and Hypertension Consultation, University Hospital of Lausanne, Lausanne, Switzerland; 5Vorarlberg Institute for Vascular Investigation and Treatment, Feldkirch, Austria; 6Charles University, Prague, Czech RepublicAbstract: Type 2 diabetes (T2D imposes a substantial disease burden, predominantly from cardiovascular disease (CVD, which accounts for >50% of deaths in this population and leads to a 12-year reduction in the life expectancy of a 60-year-old male patient with T2D and CVD compared with the general population. The results from mandatory cardiovascular outcome trials (CVOTs are therefore of great interest in the field. The Academy for Cardiovascular Risk, Outcomes and Safety Studies in Type 2 Diabetes meeting program aims to bring together experts from several associated disciplines to provide fair and balanced resources for those involved in the management of patients with T2D. This publication represents the opinions of the faculty on the key learnings from the meeting held in Vienna in the spring of 2017. In particular, we detail how data from the EMPA-REG OUTCOME® [cardiovascular outcomes trial of empagliflozin] and Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER® (liraglutide CVOTs can be practically interpreted across clinical specialities. It is hoped that this translation of CVOT data will achieve a dual treatment paradigm for the management of both raised glucose levels and CV risk in patients with T2D. Keywords: type 2 diabetes, cardiovascular disease, CVOT, SGLT2 inhibitors, GLP-1 agonists, DPP-4 inhibitors

  3. Towards a clinically relevant lentiviral transduction protocol for primary human CD34 hematopoietic stem/progenitor cells.

    Directory of Open Access Journals (Sweden)

    Michelle Millington

    2009-07-01

    Full Text Available Hematopoietic stem cells (HSC, in particular mobilized peripheral blood stem cells, represent an attractive target for cell and gene therapy. Efficient gene delivery into these target cells without compromising self-renewal and multi-potency is crucial for the success of gene therapy. We investigated factors involved in the ex vivo transduction of CD34(+ HSCs in order to develop a clinically relevant transduction protocol for gene delivery. Specifically sought was a protocol that allows for efficient transduction with minimal ex vivo manipulation without serum or other reagents of animal origin.Using commercially available G-CSF mobilized peripheral blood (PB CD34(+ cells as the most clinically relevant target, we systematically examined factors including the use of serum, cytokine combinations, pre-stimulation time, multiplicity of infection (MOI, transduction duration and the use of spinoculation and/or retronectin. A self-inactivating lentiviral vector (SIN-LV carrying enhanced green fluorescent protein (GFP was used as the gene delivery vehicle. HSCs were monitored for transduction efficiency, surface marker expression and cellular function. We were able to demonstrate that efficient gene transduction can be achieved with minimal ex vivo manipulation while maintaining the cellular function of transduced HSCs without serum or other reagents of animal origin.This study helps to better define factors relevant towards developing a standard clinical protocol for the delivery of SIN-LV into CD34(+ cells.

  4. 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

  5. Automatic classification and detection of clinically relevant images for diabetic retinopathy

    Science.gov (United States)

    Xu, Xinyu; Li, Baoxin

    2008-03-01

    We proposed a novel approach to automatic classification of Diabetic Retinopathy (DR) images and retrieval of clinically-relevant DR images from a database. Given a query image, our approach first classifies the image into one of the three categories: microaneurysm (MA), neovascularization (NV) and normal, and then it retrieves DR images that are clinically-relevant to the query image from an archival image database. In the classification stage, the query DR images are classified by the Multi-class Multiple-Instance Learning (McMIL) approach, where images are viewed as bags, each of which contains a number of instances corresponding to non-overlapping blocks, and each block is characterized by low-level features including color, texture, histogram of edge directions, and shape. McMIL first learns a collection of instance prototypes for each class that maximizes the Diverse Density function using Expectation- Maximization algorithm. A nonlinear mapping is then defined using the instance prototypes and maps every bag to a point in a new multi-class bag feature space. Finally a multi-class Support Vector Machine is trained in the multi-class bag feature space. In the retrieval stage, we retrieve images from the archival database who bear the same label with the query image, and who are the top K nearest neighbors of the query image in terms of similarity in the multi-class bag feature space. The classification approach achieves high classification accuracy, and the retrieval of clinically-relevant images not only facilitates utilization of the vast amount of hidden diagnostic knowledge in the database, but also improves the efficiency and accuracy of DR lesion diagnosis and assessment.

  6. Clinically applied medical ethnography: relevance to cultural competence in patient care.

    Science.gov (United States)

    Engebretson, Joan

    2011-06-01

    Medical anthropology provides an excellent resource for nursing research that is relevant to clinical nursing. By expanding the understanding of ethnographic research beyond ethnicity, nurses can conduct research that explores patient's constructions and explanatory models of health and healing and how they make meaning out of chronic conditions and negotiate daily life. These findings can have applicability to culturally competent care at both the organizational or systems level, as well as in the patient/provider encounter. Individual patient care can be improved by applying ethnographic research findings to build provider expertise and then using a cultural negotiation process for individualized patient care. Copyright © 2011. Published by Elsevier Inc.

  7. The clinical relevance of assessing advanced glycation endproducts accumulation in diabetes

    Directory of Open Access Journals (Sweden)

    Hillebrands Jan-Luuk

    2008-10-01

    Full Text Available Abstract Cardiovascular disease is the major cause of morbidity and mortality associated with diabetes. There is increasing evidence that advanced glycation endproducts (AGEs play a pivotal role in atherosclerosis, in particular in diabetes. AGE accumulation is a measure of cumulative metabolic and oxidative stress, and may so represent the "metabolic memory". Furthermore, increased AGE accumulation is closely related to the development of cardiovascular complications in diabetes. This review article will focus on the clinical relevance of measuring AGE accumulation in diabetic patients by focusing on AGE formation, AGEs as predictors of long-term complications, and interventions against AGEs.

  8. Promoting culturally competent chronic pain management using the clinically relevant continuum model.

    Science.gov (United States)

    Monsivais, Diane B

    2011-06-01

    This article reviews the culture of biomedicine and current practices in pain management education, which often merge to create a hostile environment for effective chronic pain care. Areas of cultural tensions in chronic pain frequently involve the struggle to achieve credibility regarding one's complaints of pain (or being believed that the pain is real) and complying with pain medication protocols. The clinically relevant continuum model is presented as a framework allowing providers to approach care from an evidence-based, culturally appropriate (patient centered) perspective that takes into account the highest level of evidence available, provider expertise, and patient preferences and values. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. Clinically relevant magnetic resonance imaging (MRI findings in elite swimmers’ shoulders

    Directory of Open Access Journals (Sweden)

    Arno Celliers

    2017-01-01

    Objective: To assess clinically relevant MRI findings in the shoulders of symptomatic and asymptomatic elite swimmers. Method: Twenty (aged 16–23 years elite swimmers completed questionnaires on their swimming training, pain and shoulder function. MRI of both shoulders (n = 40 were performed and all swimmers were given a standardised clinical shoulder examination. Results: Both shoulders of 11 male and 9 female elite swimmers (n = 40 were examined. Eleven of the 40 shoulders were clinically symptomatic and 29 were asymptomatic. The most common clinical finding in both the symptomatic and asymptomatic shoulders was impingement during internal rotation, with impingement in 54.5% of the symptomatic shoulders and in 31.0% of the asymptomatic shoulders. The most common MRI findings in the symptomatic and asymptomatic shoulders were supraspinatus tendinosis (45.5% vs. 20.7%, subacromial subdeltoid fluid (45.5% vs. 34.5%, increased signal in the AC Joint (45.5% vs. 37.9% and AC joint arthrosis (36.4% vs. 34.5%. Thirty-nine (97.5% of the shoulders showed abnormal MRI features. Conclusion: MRI findings in the symptomatic and asymptomatic shoulders of young elite swimmers are similar and care should be taken when reporting shoulder MRIs in these athletes. Asymptomatic shoulders demonstrate manifold MRI abnormalities that may be radiologically significant but appear not to be clinically significant.

  10. The clinical relevance of plasma CD147/basigin in biopsy-proven kidney diseases.

    Science.gov (United States)

    Mori, Yoshiko; Masuda, Tomohiro; Kosugi, Tomoki; Yoshioka, Tomoki; Hori, Mayuko; Nagaya, Hiroshi; Maeda, Kayaho; Sato, Yuka; Kojima, Hiroshi; Kato, Noritoshi; Ishimoto, Takuji; Katsuno, Takayuki; Yuzawa, Yukio; Kadomatsu, Kenji; Maruyama, Shoichi

    2017-12-12

    Precise understanding of kidney disease activity is needed to design therapeutic strategies. CD147/basigin is involved in the pathogenesis of acute kidney injury and renal fibrosis through inflammatory cell infiltration. The present study examined the clinical relevance of CD147 in biopsy-proven kidney diseases that lead to the progression of chronic kidney disease. Kidney biopsy specimens and plasma and urine samples were obtained from patients with kidney diseases, including IgA nephropathy (IgAN), Henoch-Schönlein purpura nephritis (HSPN), diabetic kidney disease (DKD), focal segmental glomerulosclerosis (FSGS), and membranous nephropathy (MN), who underwent renal biopsy between 2011 and 2014. Plasma and urinary CD147 levels were measured and evaluated for their ability to reflect histological features. Disease activity of IgAN tissues was evaluated according to the Oxford classification and the Japanese histological grading system. In biopsy tissues, CD147 induction was detected in injured lesions representing renal inflammation. Plasma CD147 values correlated with eGFR in patients with inflammation-related kidney diseases such as IgAN, HSPN, and DKD. Particularly in IgAN patients, plasma CD147 levels were correlated with injured regions comprising more than 50% of glomeruli or with tubular atrophy/interstitial injury in biopsy tissues. Proteinuria showed a closer correlation with urinary values of CD147 and L-FABP. Of note, plasma and urinary CD147 levels showed a strong correlation with eGFR or proteinuria, respectively, only in DKD patients. Evaluation of plasma and urinary CD147 levels might provide key insights for the understanding of the activity of various kidney diseases.

  11. Anatomical masking of pressure footprints based on the Oxford Foot Model: validation and clinical relevance.

    Science.gov (United States)

    Giacomozzi, Claudia; Stebbins, Julie A

    2017-03-01

    Plantar pressure analysis is widely used in the assessment of foot function. In order to assess regional loading, a mask is applied to the footprint to sub-divide it into regions of interest (ROIs). The most common masking method is based on geometric features of the footprint (GM). Footprint masking based on anatomical landmarks of the foot has been implemented more recently, and involves the integration of a 3D motion capture system, plantar pressure measurement device, and a multi-segment foot model. However, thorough validation of anatomical masking (AM) using pathological footprints has not yet been presented. In the present study, an AM method based on the Oxford Foot Model (OFM) was compared to an equivalent GM. Pressure footprints from 20 young healthy subjects (HG) and 20 patients with clubfoot (CF) were anatomically divided into 5 ROIs using a subset of the OFM markers. The same foot regions were also identified by using a standard GM method. Comparisons of intra-subject coefficient of variation (CV) showed that the OFM-based AM was at least as reliable as the GM for all investigated pressure parameters in all foot regions. Clinical relevance of AM was investigated by comparing footprints from HG and CF groups. Contact time, maximum force, force-time integral and contact area proved to be sensitive parameters that were able to distinguish HG and CF groups, using both AM and GM methods However, the AM method revealed statistically significant differences between groups in 75% of measured variables, compared to 62% using a standard GM method, indicating that the AM method is more sensitive for revealing differences between groups. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Clinically Relevant Cut-off Points for the Diagnosis of Sarcopenia in Older Korean People.

    Science.gov (United States)

    Choe, Yu-Ri; Joh, Ju-Youn; Kim, Yeon-Pyo

    2017-11-09

    The optimal criteria applied to older Korean people have not been defined. We aimed to define clinically relevant cut-off points for older Korean people and to compare the predictive validity with other definitions of sarcopenia. Nine hundred and sixteen older Koreans (≥65 years) were included in this cross-sectional observational study. We used conditional inference tree analysis to determine cut-off points for height-adjusted grip strength (GS) and appendicular skeletal muscle mass (ASM), for use in the diagnosis of sarcopenia. We then compared the Korean sarcopenia criteria with the Foundation for the National Institutes of Health and Asian Working Group for Sarcopenia criteria, using frailty, assessed with the Korean Frailty Index, as an outcome variable. For men, a residual GS (GSre) of ≤ 0.25 was defined as weak, and a residual ASM (ASMre) of ≤ 1.29 was defined as low. Corresponding cut-off points for women were a GSre of ≤ 0.17 and an ASMre of ≤ 0.69. GSre and ASMre values were adjusted for height. In logistic regression analysis with new cut-off points, the adjusted odds ratios for pre-frail or frail status in the sarcopenia group were 3.23 (95% confidence interval [CI] 1.33-7.83) for the men and 1.74 (95% CI 0.91-3.35) for the women. In receiver operating characteristic curve analysis, the unadjusted area under the curve for Korean sarcopenia criteria in men and women were 0.653 and 0.608, respectively (p sarcopenia in older Korean people. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  13. Automated detection of retinal landmarks for the identification of clinically relevant regions in fundus photography

    Science.gov (United States)

    Ometto, Giovanni; Calivá, Francesco; Al-Diri, Bashir; Bek, Toke; Hunter, Andrew

    2016-03-01

    Automatic, quick and reliable identification of retinal landmarks from fundus photography is key for measurements used in research, diagnosis, screening and treating of common diseases affecting the eyes. This study presents a fast method for the detection of the centre of mass of the vascular arcades, optic nerve head (ONH) and fovea, used in the definition of five clinically relevant areas in use for screening programmes for diabetic retinopathy (DR). Thirty-eight fundus photographs showing 7203 DR lesions were analysed to find the landmarks manually by two retina-experts and automatically by the proposed method. The automatic identification of the ONH and fovea were performed using template matching based on normalised cross correlation. The centre of mass of the arcades was obtained by fitting an ellipse on sample coordinates of the main vessels. The coordinates were obtained by processing the image with hessian filtering followed by shape analyses and finally sampling the results. The regions obtained manually and automatically were used to count the retinal lesions falling within, and to evaluate the method. 92.7% of the lesions were falling within the same regions based on the landmarks selected by the two experts. 91.7% and 89.0% were counted in the same areas identified by the method and the first and second expert respectively. The inter-repeatability of the proposed method and the experts is comparable, while the 100% intra-repeatability makes the algorithm a valuable tool in tasks like analyses in real-time, of large datasets and of intra-patient variability.

  14. Clinical relevance and discriminatory value of elevated liver aminotransferase levels for dengue severity.

    Science.gov (United States)

    Lee, Linda K; Gan, Victor C; Lee, Vernon J; Tan, Adriana S; Leo, Yee Sin; Lye, David C

    2012-01-01

    Elevation of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) is prominent in acute dengue illness. The World Health Organization (WHO) 2009 dengue guidelines defined AST or ALT ≥ 1000 units/liter (U/L) as a criterion for severe dengue. We aimed to assess the clinical relevance and discriminatory value of AST or ALT for dengue hemorrhagic fever (DHF) and severe dengue. We retrospectively studied and classified polymerase chain reaction positive dengue patients from 2006 to 2008 treated at Tan Tock Seng Hospital, Singapore according to WHO 1997 and 2009 criteria for dengue severity. Of 690 dengue patients, 31% had DHF and 24% severe dengue. Elevated AST and ALT occurred in 86% and 46%, respectively. Seven had AST or ALT ≥ 1000 U/L. None had acute liver failure but one patient died. Median AST and ALT values were significantly higher with increasing dengue severity by both WHO 1997 and 2009 criteria. However, they were poorly discriminatory between non-severe and severe dengue (e.g., AST area under the receiver operating characteristic [ROC] curve=0.62; 95% confidence interval [CI]: 0.57-0.67) and between dengue fever (DF) and DHF (AST area under the ROC curve=0.56; 95% CI: 0.52-0.61). There was significant overlap in AST and ALT values among patients with dengue with or without warning signs and severe dengue, and between those with DF and DHF. Although aminotransferase levels increased in conjunction with dengue severity, AST or ALT values did not discriminate between DF and DHF or non-severe and severe dengue.

  15. Development and application of two independent real-time PCR assays to detect clinically relevant Mucorales species.

    Science.gov (United States)

    Springer, Jan; Goldenberger, Daniel; Schmidt, Friderike; Weisser, Maja; Wehrle-Wieland, Elisabeth; Einsele, Hermann; Frei, Reno; Löffler, Jürgen

    2016-03-01

    PCR-based detection of Mucorales species could improve diagnosis of suspected invasive fungal infection, leading to a better patient outcome. This study describes two independent probe-based real-time PCR tests for detection of clinically relevant Mucorales, targeting specific fragments of the 18S and the 28S rRNA genes. Both assays have a short turnaround time, allow fast, specific and very sensitive detection of clinically relevant Mucorales and have the potential to be used as quantitative tests. They were validated on various clinical samples (fresh and formalin-fixed paraffin-embedded specimens, mainly biopsies, n = 17). The assays should be used as add-on tools to complement standard techniques; a combined approach of both real-time PCR assays has 100 % sensitivity. Genus identification by subsequent sequencing is possible for amplicons of the 18S PCR assay. In conclusion, combination of the two independent Mucorales assays described in this study, 18S and 28S, detected all clinical samples associated with proven Mucorales infection (n = 10). Reliable and specific identification of Mucorales is a prerequisite for successful antifungal therapy as these fungi show intrinsic resistance to voriconazole and caspofungin.

  16. Assessment and clinical relevance of non-fasting and postprandial triglycerides

    DEFF Research Database (Denmark)

    Kolovou, Genovefa D; Mikhailidis, Dimitri P; Kovar, Jan

    2011-01-01

    An Expert Panel group of scientists and clinicians met to consider several aspects related to non-fasting and postprandial triglycerides (TGs) and their role as risk factors for cardiovascular disease (CVD). In this context, we review recent epidemiological studies relevant to elevated non...

  17. Evaluation of exome filtering techniques for the analysis of clinically relevant genes.

    Science.gov (United States)

    Kernohan, Kristin D; Hartley, Taila; Alirezaie, Najmeh; Robinson, Peter N; Dyment, David A; Boycott, Kym M

    2018-02-01

    A significant challenge facing clinical translation of exome sequencing is meaningful and efficient variant interpretation. Each exome contains ∼500 rare coding variants; laboratories must systematically and efficiently identify which variant(s) contribute to the patient's phenotype. In silico filtering is an approach that reduces analysis time while decreasing the chances of incidental findings. We retrospectively assessed 55 solved exomes using available datasets as in silico filters: Online Mendelian Inheritance in Man (OMIM), Orphanet, Human Phenotype Ontology (HPO), and Radboudumc University Medical Center curated panels. We found that personalized panels produced using HPO terms for each patient had the highest success rate (100%), while producing considerably less variants to assess. HPO panels also captured multiple diagnoses in the same individual. We conclude that custom HPO-derived panels are an efficient and effective way to identify clinically relevant exome variants. © 2017 Wiley Periodicals, Inc.

  18. 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

  19. Echography of clinically relevant disorders in the genital tract of female dromedary camels.

    Science.gov (United States)

    Ali, Ahmed; Derar, Derar; Alsamri, Ali; Al Sobayil, Fahd

    2017-07-01

    The aim of this study was to characterize the clinically relevant genital tract disorders of dromedary camels. Reproductive tract examinations were performed via transrectal palpation, ultrasonography and vaginal exploration. The ultrasonic appearance of the reproductive pathology was described and compared with its morphology at laparotomy, after surgical removal, during postmortem examination or upon slaughter. Diagnosis was also confirmed by histopathology. The most frequently encountered follicular structures were larger than typical follicles (56/338, 16.6%) having three echo textures: 1) thin walls and clear hyperechogenic content (11.6%); 2) thick walls and few fibrous trabeculae (33.7%); and 3) thick walls and many echogenic transecting fibrinous strands (54.7%). Corpora lutea with non-echoic central cavity (5/31, 16.1%) were greater in diameter than those with no cavity (26/31, 83.9%) (P=0.03). A granulosa cell tumor (1/338, 0.3%) was multilocular and honeycombed in shape. Presence of a large, well-demarcated, hypoechogenic sac lateral to or beneath the uterine horn encasing the ovary was diagnostic for ovarian hydrobursitis (102/338, 30.2%). Hydrosalpinx and pyosalpinx (6/338, 1.8%) were beaded in appearance, with the ovary located outside these structures. Clinical endometritis/cervicitis (122, 36.1%) was characterized by changes in the homogeneity in about half of the cases. A greatly dilated uterus with clear, hypoechogenic or echogenic contents with signs of hydrometra and pyometra, respectively, was another categorization of a reproductive pathology (24/338, 7.1%). Highly reflective, linear structures were observed in cases with intrauterine fetal bone retention (1/338, 0.3%). In conclusion, reproductive pathologies in dromedary camels can be efficiently imaged by use of ultrasonic technologies, thus familiarizing the practitioner with these disorders and facilitating application of these technologies so that suitable treatment can occur is important

  20. BALANOPOSTHITIS: A CLINICAL STUDY

    Directory of Open Access Journals (Sweden)

    Raju

    2015-01-01

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

  1. Lack of Clinical Relevance of ANA and ASMA Positivity in Patients with Liver Transplantation without a History of Autoimmune Diseases.

    Science.gov (United States)

    Pellegrini, Lucienne; Parrilli, Gianpaolo; Santonicola, Antonella; Cinquanta, Luigi; Caputo, Cesare; Ciacci, Carolina; Zingone, Fabiana

    2017-01-01

    The relevance of isolated autoimmunity elevation in orthotopic liver transplantation (OLT) patients is unknown. Our aim was to analyse how serum autoantibodies change in time and to evaluate their clinical relevance in OLT patients. Patients were invited to provide samples to evaluate ANA, AMA, ASMA, and LKM at the time of enrolment ( T 0), after 6 months ( T 6), and after 12 months ( T 12). We included 114 patients in the study (76% males, median age 62.5 years), finding isolated elevation of at least one serum antibody in up to 80% of them. We described fluctuating positive autoantibodies in the one year of observation, with only 45.6% of patients positive for ANA and less than 2% positive for ASMA, at all three times. Isolated elevation of tissue antibodies was not related to gender, age, HCC at transplant, early rejection, cause of transplantation, immunotherapy taken, and age at the time of the study. We did not detect a higher prevalence of positive autoimmunity in patients with signs of liver injury. ANA and ASMA evaluation in patients with liver transplantation and no history of autoimmune disease has no clinical relevance, since it varies in time and is not related to any risk factors or liver injury. Routine autoimmunity evaluation should be avoided.

  2. Existing reporting guidelines for clinical trials are not completely relevant for implantable medical devices: a systematic review.

    Science.gov (United States)

    Motte, Anne-France; Diallo, Stéphanie; van den Brink, Hélène; Châteauvieux, Constance; Serrano, Carole; Naud, Carole; Steelandt, Julie; Alsac, Jean-Marc; Aubry, Pierre; Cour, Florence; Pellerin, Olivier; Pineau, Judith; Prognon, Patrice; Borget, Isabelle; Bonan, Brigitte; Martelli, Nicolas

    2017-11-01

    The aim of this study was to determine relevant items for reporting clinical trials on implantable medical devices (IMDs) and to identify reporting guidelines which include these items. A panel of experts identified the most relevant items for evaluating IMDs from an initial list based on reference papers. We then conducted a systematic review of articles indexed in MEDLINE. We retrieved reporting guidelines from the EQUATOR network's library for health research reporting. Finally, we screened these reporting guidelines to find those using our set of reporting items. Seven relevant reporting items were selected that related to four topics: randomization, learning curve, surgical setting, and device information. A total of 348 reporting guidelines were identified, among which 26 met our inclusion criteria. However, none of the 26 reporting guidelines presented all seven items together. The most frequently reported item was timing of randomization (65%). On the contrary, device information and learning curve effects were poorly specified. To our knowledge, this study is the first to identify specific items related to IMDs in reporting guidelines for clinical trials. We have shown that no existing reporting guideline is totally suitable for these devices. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Nicotine at clinically relevant concentrations affects atrial inward rectifier potassium current sensitive to acetylcholine.

    Science.gov (United States)

    Bébarová, Markéta; Matejovič, Peter; Švecová, Olga; Kula, Roman; Šimurdová, Milena; Šimurda, Jiří

    2017-05-01

    Nicotine abuse is associated with variety of diseases including arrhythmias, most often atrial fibrillation (AF). Altered inward rectifier potassium currents including acetylcholine-sensitive current I K(Ach) are known to be related to AF pathogenesis. Since relevant data are missing, we aimed to investigate I K(Ach) changes at clinically relevant concentrations of nicotine. Experiments were performed by the whole cell patch clamp technique at 23 ± 1 °C on isolated rat atrial myocytes. Nicotine was applied at following concentrations: 4, 40 and 400 nM; ethanol at 20 mM (∼0.09%). Nicotine at 40 and 400 nM significantly activated constitutively active component of I K(Ach) with the maximum effect at 40 nM (an increase by ∼100%); similar effect was observed at -110 and -50 mV. Changes at 4 nM nicotine were negligible on average. Coapplication of 40 nM nicotine and 20 mM ethanol (which is also known to activate this current) did not show cumulative effect. In the case of acetylcholine-induced component of I K(Ach) , a dual effect of nicotine and its correlation with the current magnitude in control were apparent: the current was increased by nicotine in the cells showing small current in control and vice versa. The effect of 40 and 400 nM nicotine on acetylcholine-induced component of I K(Ach) was significantly different at -110 and -50 mV. We conclude that nicotine at clinically relevant concentrations significantly increased constitutively active component of I K(Ach) and showed a dual effect on its acetylcholine-induced component, similarly as ethanol. Synchronous application of nicotine and ethanol did not cause additive effect.

  4. Colonization, Pathogenicity, Host Susceptibility and Therapeutics for Staphylococcus aureus: What is the Clinical Relevance?1

    Science.gov (United States)

    Tong, Steven Y.C.; Chen, Luke F.; Fowler, Vance G.

    2011-01-01

    Staphylococcus aureus is a human commensal that can also cause a broad spectrum of clinical disease. Factors associated with clinical disease are myriad and dynamic and include pathogen virulence, antimicrobial resistance and host susceptibility. Additionally, infection control measures aimed at the environmental niches of S. aureus and therapeutic advances continue to impact upon the incidence and outcomes of staphylococcal infections. This review article focuses on the clinical relevance of advances in our understanding of staphylococcal colonization, virulence, host susceptibility and therapeutics. Over the past decade key developments have arisen. First, rates of nosocomial methicillin-resistant S. aureus (MRSA) infections have significantly declined in many countries. Second, we have made great strides in our understanding of the molecular pathogenesis of S. aureus in general and community-associated MRSA in particular. Third, host risk factors for invasive staphylococcal infections, such as advancing age, increasing numbers of invasive medical interventions, and a growing proportion of patients with healthcare contact, remain dynamic. Finally, several new antimicrobial agents active against MRSA have become available for clinical use. Humans and S. aureus co-exist and the dynamic interface between host, pathogen and our attempts to influence these interactions will continue to rapidly change. Although progress has been made in the past decade, we are likely to face further surprises such as the recent waves of community-associated MRSA. PMID:22160374

  5. Altered DNA Methylation Patterns Associated With Clinically Relevant Increases in PTSD Symptoms and PTSD Symptom Profiles in Military Personnel.

    Science.gov (United States)

    Martin, Christiana; Cho, Young-Eun; Kim, Hyungsuk; Yun, Sijung; Kanefsky, Rebekah; Lee, Hyunhwa; Mysliwiec, Vincent; Cashion, Ann; Gill, Jessica

    2018-05-01

    Military personnel experience posttraumatic stress disorder (PTSD), which is associated with differential DNA methylation across the whole genome. However, the relationship between these DNA methylation patterns and clinically relevant increases in PTSD severity is not yet clearly understood. The purpose of this study was to identify differences in DNA methylation associated with PTSD symptoms and investigate DNA methylation changes related to increases in the severity of PTSD in military personnel. In this pilot study, a cross-sectional comparison was made between military personnel with PTSD (n = 8) and combat-matched controls without PTSD (n = 6). Symptom measures were obtained, and genome-wide DNA methylation was measured using methylated DNA immunoprecipitation (MeDIP-seq) from whole blood samples at baseline and 3 months later. A longitudinal comparison measured DNA methylation changes in military personnel with clinically relevant increases in PTSD symptoms between time points (PTSD onset) and compared methylation patterns to controls with no clinical changes in PTSD. In military personnel with elevated PTSD symptoms 3 months following baseline, 119 genes exhibited reduced methylation and 8 genes exhibited increased methylation. Genes with reduced methylation in the PTSD-onset group relate to the canonical pathways of netrin signaling, Wnt/Ca + pathway, and axonal guidance signaling. These gene pathways relate to neurological disorders, and the current findings suggest that these epigenetic changes potentially relate to PTSD symptomology. This study provides some novel insights into the role of epigenetic changes in PTSD symptoms and the progression of PTSD symptoms in military personnel.

  6. Relevance of Retinal Thickness Changes in the OCT Inner and Outer Rings to Predict Progression to Clinical Macular Edema

    DEFF Research Database (Denmark)

    Vujosevic, Stela; Varano, Monica; Egan, Catherine

    2015-01-01

    PURPOSE: To characterize the relevance of macular thickness changes in the inner and outer rings in the progression of macular edema in eyes/patients with diabetes type 2. METHODS: A total of 374 type 2 diabetic patients with mild nonproliferative diabetic retinopathy (ETDRS levels 20-35) were...... included in a 12-month prospective observational study to identify retinopathy progression. Retinal thickness analyses were performed in 194 eyes/patients using Cirrus SD- OCT and 166 eyes/patients using Spectralis SD-OCT. The DRCR.net classification of subclinical and clinical macular edema was used....... A composite grading of macular edema is proposed in this study. RESULTS: A total of 317 eyes/patients completed the study. SD-OCT identified clinical macular edema in 24 eyes/patients (6.7%) and subclinical macular edema in 104 eyes/patients (28.9%) at baseline. Increased thickness of the central subfield...

  7. Prevention of ventilator-associated pneumonia in the intensive care unit: A review of the clinically relevant recent advancements

    Directory of Open Access Journals (Sweden)

    Holly Keyt

    2014-01-01

    Full Text Available Ventilator-associated pneumonia (VAP is one of the most commonly encountered hospital-acquired infections in intensive care units and is associated with significant morbidity and high costs of care. The pathophysiology, epidemiology, treatment and prevention of VAP have been extensively studied for decades, but a clear prevention strategy has not yet emerged. In this article we will review recent literature pertaining to evidence-based VAP-prevention strategies that have resulted in clinically relevant outcomes. A multidisciplinary strategy for prevention of VAP is recommended. Those interventions that have been shown to have a clinical impact include the following: (i Non-invasive positive pressure ventilation for able patients, especially in immunocompromised patients, with acute exacerbation of chronic obstructive pulmonary disease or pulmonary oedema, (ii Sedation and weaning protocols for those patients who do require mechanical ventilation, (iii Mechanical ventilation protocols including head of bed elevation above 30 degrees and oral care, and (iv Removal of subglottic secretions. Other interventions, such as selective digestive tract decontamination, selective oropharyngeal decontamination and antimicrobial-coated endotracheal tubes, have been tested in different studies. However, the evidence for the efficacy of these measures to reduce VAP rates is not strong enough to recommend their use in clinical practice. In numerous studies, the implementation of VAP prevention bundles to clinical practice was associated with a significant reduction in VAP rates. Future research that considers clinical outcomes as primary endpoints will hopefully result in more detailed prevention strategies.

  8. THE RELEVANCE OF SOCIO-LEGAL STUDIES IN LEGAL SCIENCE

    Directory of Open Access Journals (Sweden)

    Victor Imanuel W. Nalle

    2015-02-01

    Full Text Available Some law schools in Indonesia reject socio-legal studies with epistemological arguments that puts jurisprudence as sui generis. Rejection is based argument that jurisprudence is a normative science. In fact socio-legal studies in the development of jurisprudence outside Indonesia has long existed and contributed to the legal reform. Socio-legal studies also significant for legal reform. It is caused by the existence of non doctrinal aspect in law making and implementation of the law. Therefore the position and relevance of socio-legal research is not related to the benefits that provided for the development of national law or jurisprudence. Beberapa fakultas hukum di Indonesia menolak penelitian sosio-legal dengan argumentasi epistemologis yang menempatkan ilmu hukum sebagai sui generis. Penolakan tersebut didasarkan argumentasi bahwa ilmu hukum adalah ilmu yang bersifat normatif. Kenyataannya studi sosio-legal dalam perkembangan ilmu hukum di luar Indonesia telah lama eksis dan berperan dalam pembaharuan hukum. Selain itu, studi sosiolegal juga berperan dalam pembaharuan hukum. Hal ini disebabkan adanya aspek-aspek nondoktrinal yang berperan dalam pembentukan hukum dan implementasi hukum di masyarakat. Oleh karena itu kedudukan dan relevansi penelitian sosio-legal pada ada tidaknya manfaat yang diberikan bagi perkembangan hukum nasional ataupun ilmu hukum.

  9. THE RELEVANCE OF SOCIO-LEGAL STUDIES IN LEGAL SCIENCE

    Directory of Open Access Journals (Sweden)

    Victor Imanuel W. Nalle

    2015-02-01

    Full Text Available Some law schools in Indonesia reject socio-legal studies with epistemological arguments that puts jurisprudence as sui generis. Rejection is based argument that jurisprudence is a normative science. In fact socio-legal studies in the development of jurisprudence outside Indonesia has long existed and contributed to the legal reform. Socio-legal studies also significant for legal reform. It is caused by the existence of non doctrinal aspect in law making and implementation of the law. Therefore the position and relevance of socio-legal research is not related to the benefits that provided for the development of national law or jurisprudence.   Beberapa fakultas hukum di Indonesia menolak penelitian sosio-legal dengan argumentasi epistemologis yang menempatkan ilmu hukum sebagai sui generis. Penolakan tersebut didasarkan argumentasi bahwa ilmu hukum adalah ilmu yang bersifat normatif. Kenyataannya studi sosio-legal dalam perkembangan ilmu hukum di luar Indonesia telah lama eksis dan berperan dalam pembaharuan hukum. Selain itu, studi sosiolegal juga berperan dalam pembaharuan hukum. Hal ini disebabkan adanya aspek-aspek nondoktrinal yang berperan dalam pembentukan hukum dan implementasi hukum di masyarakat. Oleh karena itu kedudukan dan relevansi penelitian sosio-legal pada ada tidaknya manfaat yang diberikan bagi perkembangan hukum nasional ataupun ilmu hukum.

  10. A systematic review on the effect of sweeteners on glycemic response and clinically relevant outcomes

    Directory of Open Access Journals (Sweden)

    Wiebe Natasha

    2011-11-01

    Full Text Available Abstract Background The major metabolic complications of obesity and type 2 diabetes may be prevented and managed with dietary modification. The use of sweeteners that provide little or no calories may help to achieve this objective. Methods We did a systematic review and network meta-analysis of the comparative effectiveness of sweetener additives using Bayesian techniques. MEDLINE, EMBASE, CENTRAL and CAB Global were searched to January 2011. Randomized trials comparing sweeteners in obese, diabetic, and healthy populations were selected. Outcomes of interest included weight change, energy intake, lipids, glycated hemoglobin, markers of insulin resistance and glycemic response. Evidence-based items potentially indicating risk of bias were assessed. Results Of 3,666 citations, we identified 53 eligible randomized controlled trials with 1,126 participants. In diabetic participants, fructose reduced 2-hour blood glucose concentrations by 4.81 mmol/L (95% CI 3.29, 6.34 compared to glucose. Two-hour blood glucose concentration data comparing hypocaloric sweeteners to sucrose or high fructose corn syrup were inconclusive. Based on two ≤10-week trials, we found that non-caloric sweeteners reduced energy intake compared to the sucrose groups by approximately 250-500 kcal/day (95% CI 153, 806. One trial found that participants in the non-caloric sweetener group had a decrease in body mass index compared to an increase in body mass index in the sucrose group (-0.40 vs 0.50 kg/m2, and -1.00 vs 1.60 kg/m2, respectively. No randomized controlled trials showed that high fructose corn syrup or fructose increased levels of cholesterol relative to other sweeteners. Conclusions Considering the public health importance of obesity and its consequences; the clearly relevant role of diet in the pathogenesis and maintenance of obesity; and the billions of dollars spent on non-caloric sweeteners, little high-quality clinical research has been done. Studies are

  11. Expanding the scope and relevance of health interventions: Moving beyond clinical trials and behavior change models

    Directory of Open Access Journals (Sweden)

    Khary K. Rigg

    2014-07-01

    Full Text Available An overemphasis on clinical trials and behavior change models has narrowed the knowledge base that can be used to design interventions. The overarching point is that the process of overanalyzing variables is impeding the process of gaining insight into the everyday experiences that shape how people define health and seek treatment. This claim is especially important to health decision-making and behavior change because subtle interpretations often influence the decisions that people make. This manuscript provides a critique of traditional approaches to developing health interventions, and theoretically justifies what and why changes are warranted. The limited scope of these models is also discussed, and an argument is made to adopt a strategy that includes the perceptions of people as necessary for understanding health and health-related decision-making. Three practical strategies are suggested to be used with the more standard approaches to assessing the effectiveness and relevance of health interventions.

  12. New Insights into the Surgical Management of Tetralogy of Fallot: Physiological Fundamentals and Clinical Relevance.

    Science.gov (United States)

    Bove, Thierry; François, Katrien; De Wolf, Daniel

    2015-01-01

    The surgical treatment of tetralogy of Fallot can be considered as a success story in the history of congenital heart diseases. Since the early outcome is no longer the main issue, the focus moved to the late sequelae of TOF repair, i.e. the pulmonary insufficiency and the secondary adaptation of the right ventricle. This review provides recent insights into the pathophysiological alterations of the right ventricle in relation to the reconstruction of the right ventricular outflow tract after repair of tetralogy of Fallot. Its clinical relevance is documented by addressing the policy changes regarding the optimal management at the time of surgical repair as well as properly defining criteria and timing for late pulmonary valve implantation.

  13. Advances on the molecular characterization, clinical relevance, and detection methods of Gadiform parvalbumin allergens.

    Science.gov (United States)

    Fernandes, Telmo J R; Costa, Joana; Carrapatoso, Isabel; Oliveira, Maria Beatriz P P; Mafra, Isabel

    2017-10-13

    Gadiform order includes several fish families, from which Gadidae and Merlucciidae are part of, comprising the most commercially important and highly appreciated fish species, such as cod, pollock, haddock, and hake. Parvalbumins, classified as calcium-binding proteins, are considered the main components involved in the majority of fish allergies. Nine and thirteen parvalbumins were identified in different fish species from Gadidae and Merlucciidae families, respectively. This review intends to describe their molecular characterization and the clinical relevance, as well as the prevalence of fish allergy. In addition, the main protein- and DNA-based methods to detect fish allergens are fully reviewed owing to their importance in the safeguard of sensitized/allergic individuals.

  14. Disposable inkjet-printed electrochemical platform for detection of clinically relevant HER-2 breast cancer biomarker.

    Science.gov (United States)

    Carvajal, Susanita; Fera, Samantha N; Jones, Abby L; Baldo, Thaisa A; Mosa, Islam M; Rusling, James F; Krause, Colleen E

    2018-05-01

    Rapidly fabricated, disposable sensor platforms hold tremendous promise for point-of-care detection. Here, we present an inexpensive (Receptor 2 (HER-2). Capture antibodies were bound to a chemically modified surface on the WEA and placed into a microfluidic device. A full sandwich immunoassay was constructed following a simultaneous injection of target protein, biotinylated antibody, and polymerized horseradish peroxide labels into the microfluidic device housing the WEA. With an ultra fast assay time, of only 15mins a clinically relevant limit of detection of 12pgmL -1 was achieved. Excellent reproducibility and sensitivity were observed through recovery assays preformed in human serum with recoveries ranging from 76% to 103%. These easily fabricated and scalable electrochemical sensor platforms can be readily adapted for multiplex detection following this rapid assay protocol for cancer diagnostics. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. Clinically relevant radioresistant cells efficiently repair DNA double-strand breaks induced by X-rays

    International Nuclear Information System (INIS)

    Kuwahara, Yoshikazu; Baba, Taisuke; Nakagawa, Hironobu; Shimura, Tsutomu; Yamamoto, Yoichiro; Fukumoto, Manabu; Li Li; Ohkubo, Yasuhito

    2009-01-01

    Radiotherapy is one of the major therapeutic modalities for eradicating malignant tumors. However, the existence of radioresistant cells remains one of the most critical obstacles in radiotherapy and radiochemotherapy. Standard radiotherapy for tumor treatment consists of approximately 2 Gy once a day, 5 days a week, over a period of 5-8 weeks. To understand the characteristics of radioresistant cells and to develop more effective radiotherapy, we established a novel radioresistant cell line, HepG2-8960-R with clinical relevance from parental HepG2 cells by long-term fractionated exposure to 2 Gy of X-rays. HepG2-8960-R cells continued to proliferate with daily exposure to 2 Gy X-rays for more than 30 days, while all parental HepG2 cells ceased. After exposure to fractionated 2 Gy X-rays, induction frequencies of micronuclei and remaining foci of γ-H2AX in HepG2-8960-R were less than those in HepG2. Flow cytometric analysis revealed that the proportion of cells in S- and G2/M-phase of the cell cycle was higher in HepG2-8960-R than in HepG2. These suggest that the response of clinically relevant radioresistant (CRR) cells to fractionated radiation is not merely an accumulated response to each fractionated radiation. This is the first report on the establishment of a CRR cell line from an isogenic parental cell line. (author)

  16. Direct toxic effects of aqueous extract of cigarette smoke on cardiac myocytes at clinically relevant concentrations

    International Nuclear Information System (INIS)

    Yamada, Shigeyuki; Zhang Xiuquan; Kadono, Toshie; Matsuoka, Nobuhiro; Rollins, Douglas; Badger, Troy; Rodesch, Christopher K.; Barry, William H.

    2009-01-01

    Aims: Our goal was to determine if clinically relevant concentrations of aqueous extract of cigarette smoke (CSE) have direct deleterious effects on ventricular myocytes during simulated ischemia, and to investigate the mechanisms involved. Methods: CSE was prepared with a smoking chamber. Ischemia was simulated by metabolic inhibition (MI) with cyanide (CN) and 0 glucose. Adult rabbit and mouse ventricular myocyte [Ca 2+ ] i was measured by flow cytometry using fluo-3. Mitochondrial [Ca 2+ ] was measured with confocal microscopy, and Rhod-2 fluorescence. The mitochondrial permeability transition (MPT) was detected by TMRM fluorescence and myocyte contracture. Myocyte oxidative stress was quantified by dichlorofluorescein (DCF) fluorescence with confocal microscopy. Results: CSE 0.1% increased myocyte contracture caused by MI. The nicotine concentration (HPLC) in 0.1% CSE was 15 ng/ml, similar to that in humans after smoking cigarettes. CSE 0.1% increased mitochondrial Ca 2+ uptake, and increased the susceptibility of mitochondria to the MPT. CSE 0.1% increased DCF fluorescence in isolated myocytes, and increased [Ca 2+ ] i in paced myocytes exposed to 2.0 mM CN, 0 glucose (P-MI). These effects were inhibited by the superoxide scavenger Tiron. The effect of CSE on [Ca 2+ ] i during P-MI was also prevented by ranolazine. Conclusions: CSE in clinically relevant concentrations increases myocyte [Ca 2+ ] i during simulated ischemia, and increases myocyte susceptibility to the MPT. These effects appear to be mediated at least in part by oxidative radicals in CSE, and likely contribute to the effects of cigarette smoke to increase myocardial infarct size, and to decrease angina threshold

  17. Trapping of Syntaxin1a in Presynaptic Nanoclusters by a Clinically Relevant General Anesthetic

    Directory of Open Access Journals (Sweden)

    Adekunle T. Bademosi

    2018-01-01

    Full Text Available Summary: Propofol is the most commonly used general anesthetic in humans. Our understanding of its mechanism of action has focused on its capacity to potentiate inhibitory systems in the brain. However, it is unknown whether other neural mechanisms are involved in general anesthesia. Here, we demonstrate that the synaptic release machinery is also a target. Using single-particle tracking photoactivation localization microscopy, we show that clinically relevant concentrations of propofol and etomidate restrict syntaxin1A mobility on the plasma membrane, whereas non-anesthetic analogs produce the opposite effect and increase syntaxin1A mobility. Removing the interaction with the t-SNARE partner SNAP-25 abolishes propofol-induced syntaxin1A confinement, indicating that syntaxin1A and SNAP-25 together form an emergent drug target. Impaired syntaxin1A mobility and exocytosis under propofol are both rescued by co-expressing a truncated syntaxin1A construct that interacts with SNAP-25. Our results suggest that propofol interferes with a step in SNARE complex formation, resulting in non-functional syntaxin1A nanoclusters. : Bademosi et al. use single-molecule imaging microscopy to understand how general anesthetics might affect presynaptic release mechanisms. They find that a clinically relevant concentration of propofol targets the presynaptic release machinery by specifically restricting syntaxin1A mobility on the plasma membrane. This suggests an alternate target process for these drugs. Keywords: super-resolution microscopy, sptPALM, propofol, etomidate, SNARE, Drosophila melanogaster, PC12, syntaxin1A, SNAP-25, neurotransmission

  18. Per-beam, planar IMRT QA passing rates do not predict clinically relevant patient dose errors

    Energy Technology Data Exchange (ETDEWEB)

    Nelms, Benjamin E.; Zhen Heming; Tome, Wolfgang A. [Canis Lupus LLC and Department of Human Oncology, University of Wisconsin, Merrimac, Wisconsin 53561 (United States); Department of Medical Physics, University of Wisconsin, Madison, Wisconsin 53705 (United States); Departments of Human Oncology, Medical Physics, and Biomedical Engineering, University of Wisconsin, Madison, Wisconsin 53792 (United States)

    2011-02-15

    Purpose: The purpose of this work is to determine the statistical correlation between per-beam, planar IMRT QA passing rates and several clinically relevant, anatomy-based dose errors for per-patient IMRT QA. The intent is to assess the predictive power of a common conventional IMRT QA performance metric, the Gamma passing rate per beam. Methods: Ninety-six unique data sets were created by inducing four types of dose errors in 24 clinical head and neck IMRT plans, each planned with 6 MV Varian 120-leaf MLC linear accelerators using a commercial treatment planning system and step-and-shoot delivery. The error-free beams/plans were used as ''simulated measurements'' (for generating the IMRT QA dose planes and the anatomy dose metrics) to compare to the corresponding data calculated by the error-induced plans. The degree of the induced errors was tuned to mimic IMRT QA passing rates that are commonly achieved using conventional methods. Results: Analysis of clinical metrics (parotid mean doses, spinal cord max and D1cc, CTV D95, and larynx mean) vs IMRT QA Gamma analysis (3%/3 mm, 2/2, 1/1) showed that in all cases, there were only weak to moderate correlations (range of Pearson's r-values: -0.295 to 0.653). Moreover, the moderate correlations actually had positive Pearson's r-values (i.e., clinically relevant metric differences increased with increasing IMRT QA passing rate), indicating that some of the largest anatomy-based dose differences occurred in the cases of high IMRT QA passing rates, which may be called ''false negatives.'' The results also show numerous instances of false positives or cases where low IMRT QA passing rates do not imply large errors in anatomy dose metrics. In none of the cases was there correlation consistent with high predictive power of planar IMRT passing rates, i.e., in none of the cases did high IMRT QA Gamma passing rates predict low errors in anatomy dose metrics or vice versa

  19. Per-beam, planar IMRT QA passing rates do not predict clinically relevant patient dose errors

    International Nuclear Information System (INIS)

    Nelms, Benjamin E.; Zhen Heming; Tome, Wolfgang A.

    2011-01-01

    Purpose: The purpose of this work is to determine the statistical correlation between per-beam, planar IMRT QA passing rates and several clinically relevant, anatomy-based dose errors for per-patient IMRT QA. The intent is to assess the predictive power of a common conventional IMRT QA performance metric, the Gamma passing rate per beam. Methods: Ninety-six unique data sets were created by inducing four types of dose errors in 24 clinical head and neck IMRT plans, each planned with 6 MV Varian 120-leaf MLC linear accelerators using a commercial treatment planning system and step-and-shoot delivery. The error-free beams/plans were used as ''simulated measurements'' (for generating the IMRT QA dose planes and the anatomy dose metrics) to compare to the corresponding data calculated by the error-induced plans. The degree of the induced errors was tuned to mimic IMRT QA passing rates that are commonly achieved using conventional methods. Results: Analysis of clinical metrics (parotid mean doses, spinal cord max and D1cc, CTV D95, and larynx mean) vs IMRT QA Gamma analysis (3%/3 mm, 2/2, 1/1) showed that in all cases, there were only weak to moderate correlations (range of Pearson's r-values: -0.295 to 0.653). Moreover, the moderate correlations actually had positive Pearson's r-values (i.e., clinically relevant metric differences increased with increasing IMRT QA passing rate), indicating that some of the largest anatomy-based dose differences occurred in the cases of high IMRT QA passing rates, which may be called ''false negatives.'' The results also show numerous instances of false positives or cases where low IMRT QA passing rates do not imply large errors in anatomy dose metrics. In none of the cases was there correlation consistent with high predictive power of planar IMRT passing rates, i.e., in none of the cases did high IMRT QA Gamma passing rates predict low errors in anatomy dose metrics or vice versa. Conclusions: There is a lack of correlation between

  20. Does transcutaneous electrical nerve stimulation (TENS have a clinically relevant analgesic effect on different pain conditions? A literature review

    Directory of Open Access Journals (Sweden)

    Asami Naka

    2013-07-01

    Full Text Available Transcutaneous electric nerve stimulation (TENS is a standard therapy used in different painful conditions such as low back pain, diabetic polyneuropathy or arthrosis. However, literature reviews focusing on the effects and the clinical implication of this method in various painful conditions are yet scarce. The purpose of this literature research was to determine, whether TENS provides an analgesic effect on common painful conditions in clinical practice. Literature research was performed using three data bases (Pubmed, Embase, Cochrane Database, focusing on papers published in the space of time from 2007 to 2012. Papers were evaluated from two reviewers independently concerning the clinical outcome, taking account for the level of external evidence according to the German Cochrane levels of evidence (Ia – IV. 133 papers of varying methodological quality dealing with different painful conditions were selected in total. A clinically relevant analgesic effect was described in 90 painful conditions (67%. In 30 painful states (22%, the outcome was inconclusive due to the study design. No significant analgesic effect of TENS was observed in 15 painful conditions (11%. The vast majority of the papers were classified as Cochrane evidence level Ib (n = 64; 48%, followed by level Ia (n = 23; 17%, level III (n = 18; 14%, level IV (n = 15; 11%, level IIb (n = 10; 8% and level IIa (n = 3; 2%. Most of the studies revealed an analgesic effect in various painful conditions, confirming the usefulness of TENS in clinical practice.

  1. Mechanism of Action of Prostate Stem Cell Antigen Targeted Antibody Therapy and its Relevance to Clinical Application in Prostate Cancer

    National Research Council Canada - National Science Library

    Reiter, Robert; Tran, Chau

    2008-01-01

    .... A better understanding of PSCA function and its antibody activity will enable rational patient selection and trial design all of which are particularly relevant to subsequent clinical trials of PSCA antibody...

  2. Mechanism of Action of Prostate Stem Cell Antigen Targeted Antibody Therapy and Its Relevance to Clinical Application in Prostate Cancer

    National Research Council Canada - National Science Library

    Reiter, Robert; Tran, Chau

    2007-01-01

    .... A better understanding of PSCA function and its antibody activity will enable rational patient selection and trial design, all of which are particularly relevant to subsequent clinical trials of PSCA antibody...

  3. Clinical relevance of "withdrawal therapy" as a form of hormonal manipulation for breast cancer

    Directory of Open Access Journals (Sweden)

    Robertson John FR

    2011-09-01

    Full Text Available Abstract Background It has been shown in in-vitro experiments that "withdrawal" of tamoxifen inhibits growth of tumor cells. However, evidence is scarce when this is extrapolated into clinical context. We report our experience to verify the clinical relevance of "withdrawal therapy". Methods Breast cancer patients since 1998 who fulfilled the following criteria were selected from the departmental database and the case-notes were retrospectively reviewed: (1 estrogen receptor positive, operable primary breast cancer in elderly (age > 70 years, locally advanced or metastatic breast cancer; (2 disease deemed suitable for treatment by hormonal manipulation; (3 disease assessable by UICC criteria; (4 received "withdrawal" from a prior endocrine agent as a form of therapy; (5 on "withdrawal therapy" for ≥ 6 months unless they progressed prior. Results Seventeen patients with median age of 84.3 (53.7-92.5 had "withdrawal therapy" as second to tenth line of treatment following prior endocrine therapy using tamoxifen (n = 10, an aromatase inhibitor (n = 5, megestrol acetate (n = 1 or fulvestrant (n = 1. Ten patients (58.8% had clinical benefit (CB (complete response/partial response/stable disease ≥ 6 months with a median duration of Clinical Benefit (DoCB of 10+ (7-27 months. Two patients remain on "withdrawal therapy" at the time of analysis. Conclusion "Withdrawal therapy" appears to produce sustained CB in a significant proportion of patients. This applies not only to "withdrawal" from tamoxifen, but also from other categories of endocrine agents. "Withdrawal" from endocrine therapy is, therefore, a viable intercalating option between endocrine agents to minimise resistance and provide additional line of therapy. It should be considered as part of the sequencing of endocrine therapy.

  4. Technical Note: Display window setting: An important factor for detecting subtle but clinically relevant artifacts in daily CT quality control.

    Science.gov (United States)

    Long, Zaiyang; Bruesewitz, Michael R; Sheedy, Emily N; Powell, Michele A; Kramer, Jacqualynn C; Supalla, Randall R; Colvin, Chance M; Bechel, Jessica R; Favazza, Christopher P; Kofler, James M; Leng, Shuai; McCollough, Cynthia H; Yu, Lifeng

    2016-12-01

    This study aimed to investigate the influence of display window setting on technologist performance detecting subtle but clinically relevant artifacts in daily computed tomography (CT) quality control (dQC) images. Fifty three sets of dQC images were retrospectively selected, including 30 sets without artifacts, and 23 with subtle but clinically relevant artifacts. They were randomized and shown to six CT technologists (two new and four experienced). Each technologist reviewed all images in each of two sessions, one with a display window width (WW) of 100 HU, which is currently recommended by the American College of Radiology, and the other with a narrow WW of 40 HU, both at a window level of 0 HU. For each case, technologists rated the presence of image artifacts based on a five point scale. The area under the receiver operating characteristic curve (AUC) was used to evaluate the artifact detection performance. At a WW of 100 HU, the AUC (95% confidence interval) was 0.658 (0.576, 0.740), 0.532 (0.429, 0.635), and 0.616 (0.543, 0.619) for the experienced, new, and all technologists, respectively. At a WW of 40 HU, the AUC was 0.768 (0.687, 0.850), 0.546 (0.433, 0.658), and 0.694 (0.619, 0.769), respectively. The performance significantly improved at WW of 40 HU for experienced technologists (p = 0.009) and for all technologists (p = 0.040). Use of a narrow display WW significantly improved technologists' performance in dQC for detecting subtle but clinically relevant artifacts as compared to that using a 100 HU display WW.

  5. Clinical and Neurobiological Relevance of Current Animal Models of Autism Spectrum Disorders

    Science.gov (United States)

    Kim, Ki Chan; Gonzales, Edson Luck; Lázaro, María T.; Choi, Chang Soon; Bahn, Geon Ho; Yoo, Hee Jeong; Shin, Chan Young

    2016-01-01

    Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social and communication impairments, as well as repetitive and restrictive behaviors. The phenotypic heterogeneity of ASD has made it overwhelmingly difficult to determine the exact etiology and pathophysiology underlying the core symptoms, which are often accompanied by comorbidities such as hyperactivity, seizures, and sensorimotor abnormalities. To our benefit, the advent of animal models has allowed us to assess and test diverse risk factors of ASD, both genetic and environmental, and measure their contribution to the manifestation of autistic symptoms. At a broader scale, rodent models have helped consolidate molecular pathways and unify the neurophysiological mechanisms underlying each one of the various etiologies. This approach will potentially enable the stratification of ASD into clinical, molecular, and neurophenotypic subgroups, further proving their translational utility. It is henceforth paramount to establish a common ground of mechanistic theories from complementing results in preclinical research. In this review, we cluster the ASD animal models into lesion and genetic models and further classify them based on the corresponding environmental, epigenetic and genetic factors. Finally, we summarize the symptoms and neuropathological highlights for each model and make critical comparisons that elucidate their clinical and neurobiological relevance. PMID:27133257

  6. Education in the clinical context: establishing a strategic framework to ensure relevance.

    Science.gov (United States)

    Henderson, Amanda; Fox, Robyn; Armit, Lyn

    2008-01-01

    Quality contemporary practice relies on nurses to provide health care within an embedded nexus of clinical, professional and organisational learning that leads them through a career trajectory that encourages lifelong development. Within complex health service environments this is fraught with difficulties. Enhancing practice is multifaceted requiring not just education for the acquisition of skills and abilities but time and space for reflection on experience within the clinical context. This ultimately leads to professional knowledge development. Queensland Health has developed a Nursing and Midwifery Staff Development Framework to assist nurses in structuring their experiences in the practice setting to enable their professional goals. Learning is guided within this framework through its collective modus operandi, that is, the development of teams that overlap to identify and progress the educational agenda; resources to develop consistent relevant learning material that incorporates evidence obtained through practices and the literature; and educator and clinician networks across health services throughout the state, and furthermore, links with the tertiary sector to assist in marketing, applicability and synergy with further education.

  7. Detection of Adriamycin-DNA adducts by accelerator mass spectrometry at clinically relevant Adriamycin concentrations.

    Science.gov (United States)

    Coldwell, Kate E; Cutts, Suzanne M; Ognibene, Ted J; Henderson, Paul T; Phillips, Don R

    2008-09-01

    Limited sensitivity of existing assays has prevented investigation of whether Adriamycin-DNA adducts are involved in the anti-tumour potential of Adriamycin. Previous detection has achieved a sensitivity of a few Adriamycin-DNA adducts/10(4) bp DNA, but has required the use of supra-clinical drug concentrations. This work sought to measure Adriamycin-DNA adducts at sub-micromolar doses using accelerator mass spectrometry (AMS), a technique with origins in geochemistry for radiocarbon dating. We have used conditions previously validated (by less sensitive decay counting) to extract [(14)C]Adriamycin-DNA adducts from cells and adapted the methodology to AMS detection. Here we show the first direct evidence of Adriamycin-DNA adducts at clinically-relevant Adriamycin concentrations. [(14)C]Adriamycin treatment (25 nM) resulted in 4.4 +/- 1.0 adducts/10(7) bp ( approximately 1300 adducts/cell) in MCF-7 breast cancer cells, representing the best sensitivity and precision reported to date for the covalent binding of Adriamycin to DNA. The exceedingly sensitive nature of AMS has enabled over three orders of magnitude increased sensitivity of Adriamycin-DNA adduct detection and revealed adduct formation within an hour of drug treatment. This method has been shown to be highly reproducible for the measurement of Adriamycin-DNA adducts in tumour cells in culture and can now be applied to the detection of these adducts in human tissues.

  8. Clinical Relevance of Androgen Receptor Splice Variants in Castration-Resistant Prostate Cancer.

    Science.gov (United States)

    Maughan, Benjamin L; Antonarakis, Emmanuel S

    2015-12-01

    Metastatic castration-resistant prostate cancer (mCRPC) currently benefits from a wealth of treatment options, yet still remains lethal in the vast majority of patients. It is becoming increasingly understood that this disease entity continues to evolve over time, acquiring additional and diverse resistance mechanisms with each subsequent therapy used. This dynamic relationship between treatment pressure and disease resistance can be challenging for the managing clinician. The recent discovery of alternate splice variants of the androgen receptor (AR) is one potential mechanism of escape in mCRPC, and recognizing this resistance mechanism might be important for optimal treatment selection for our patients. AR-V7 appears to be the most relevant AR splice variant, and early clinical data suggest that it is a negative prognostic marker in mCRPC. Emerging evidence also suggests that detection of AR-V7 may be associated with resistance to novel hormonal therapy (abiraterone and enzalutamide) but may be compatible with sensitivity to taxane chemotherapy (docetaxel and cabazitaxel). Adding to this complexity is the observation that AR-V7 is a dynamic marker whose status may change across time and depending on selective pressures induced by different therapies. Finally, it is possible that AR-V7 may represent a therapeutic target in mCRPC if drugs can be designed that degrade or inhibit AR splice variants or block their transcriptional activity. Several such agents (including galeterone, EPI-506, and bromodomain/BET inhibitors) are now in clinical development.

  9. Sterol Composition of Clinically Relevant Mucorales and Changes Resulting from Posaconazole Treatment.

    Science.gov (United States)

    Müller, Christoph; Neugebauer, Thomas; Zill, Patrizia; Lass-Flörl, Cornelia; Bracher, Franz; Binder, Ulrike

    2018-05-19

    Mucorales are fungi with increasing importance in the clinics. Infections take a rapidly progressive course resulting in high mortality rates. The ergosterol biosynthesis pathway and sterol composition are of interest, since they are targeted by currently applied antifungal drugs. Nevertheless, Mucorales often exhibit resistance to these drugs, resulting in therapeutic failure. Here, sterol patterns of six clinically relevant Mucorales ( Lichtheimia corymbifera , Lichtheimia ramosa , Mucor circinelloides , Rhizomucor pusillus , Rhizopus arrhizus , and Rhizopus microsporus ) were analysed in a targeted metabolomics fashion after derivatization by gas chromatography-mass spectrometry. Additionally, the effect of posaconazole (POS) treatment on the sterol pattern of R. arrhizus was evaluated. Overall, fifteen different sterols were detected with species dependent variations in the total and relative sterol amount. Sterol analysis from R. arrhizus hyphae confronted with sublethal concentrations of posaconazole revealed the accumulation of 14-methylergosta-8,24-diene-3,6-diol, which is a toxic sterol that was previously only detected in yeasts. Sterol content and composition were further compared to the well-characterized pathogenic mold Aspergillus fumigatus . This work contributes to a better understanding of the ergosterol biosynthesis pathway of Mucorales, which is essential to improve antifungal efficacy, the identification of targets for novel drug design, and to investigate the combinatorial effects of drugs targeting this pathway.

  10. The clinical implications and biologic relevance of neurofilament expression in gastroenteropancreatic neuroendocrine neoplasms.

    Science.gov (United States)

    Schimmack, Simon; Lawrence, Ben; Svejda, Bernhard; Alaimo, Daniele; Schmitz-Winnenthal, Hubertus; Fischer, Lars; Büchler, Markus W; Kidd, Mark; Modlin, Irvin

    2012-05-15

    Although gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) exhibit widely divergent behavior, limited biologic information (apart from Ki-67) is available to characterize malignancy. Therefore, the identification of alternative biomarkers is a key unmet need. Given the role of internexin alpha (INA) in neuronal development, the authors assessed its function in neuroendocrine cell systems and the clinical implications of its expression as a GEP-NEN biomarker. Functional assays were undertaken to investigate the mechanistic role of INA in the pancreatic BON cell line. Expression levels of INA were investigated in 50 pancreatic NENs (43 primaries, 7 metastases), 43 small intestinal NENs (25 primaries, 18 metastases), normal pancreas (n = 10), small intestinal mucosa (n = 16), normal enterochromaffin (EC) cells (n = 9), mouse xenografts (n = 4) and NEN cell lines (n = 6) using quantitative polymerase chain reaction, Western blot, and immunostaining analyses. In BON cells, decreased levels of INA messenger RNA and protein were associated with the inhibition of both proliferation and mitogen-activated protein kinase (MAPK) signaling. INA was not expressed in normal neuroendocrine cells but was overexpressed (from 2-fold to 42-fold) in NEN cell lines and murine xenografts. In pancreatic NENs, INA was overexpressed compared with pancreatic adenocarcinomas and normal pancreas (27-fold [P = .0001], and 9-fold [P = .02], respectively). INA transcripts were correlated positively with Ki-67 (correlation coefficient [r] = 0.5; P biologic information relevant to delineation of both pancreatic NEN tumor phenotypes and clinical behavior. Copyright © 2011 American Cancer Society.

  11. ABDOMINAL TRAUMA- CLINICAL STUDY

    Directory of Open Access Journals (Sweden)

    Vanaja Ratnakumari Billa

    2017-08-01

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

  12. Patient-reported symptoms during radiotherapy : Clinically relevant symptom burden in patients treated with palliative and curative intent.

    Science.gov (United States)

    Körner, Philipp; Ehrmann, Katja; Hartmannsgruber, Johann; Metz, Michaela; Steigerwald, Sabrina; Flentje, Michael; van Oorschot, Birgitt

    2017-07-01

    The benefits of patient-reported symptom assessment combined with integrated palliative care are well documented. This study assessed the symptom burden of palliative and curative-intent radiation oncology patients. Prior to first consultation and at the end of RT, all adult cancer patients planned to receive fractionated percutaneous radiotherapy (RT) were asked to answer the Edmonton Symptom Assessment Scale (ESAS; nine symptoms from 0 = no symptoms to 10 = worst possible symptoms). Mean values were used for curative vs. palliative and pre-post comparisons, and the clinical relevance was evaluated (symptom values ≥ 4). Of 163 participating patients, 151 patients (90.9%) completed both surveys (116 curative and 35 palliative patients). Before beginning RT, 88.6% of palliative and 72.3% of curative patients showed at least one clinically relevant symptom. Curative patients most frequently named decreased general wellbeing (38.6%), followed by tiredness (35.0%), anxiety (32.4%), depression (30.0%), pain (26.3%), lack of appetite (23.5%), dyspnea (17.8%), drowsiness (8.0%) and nausea (6.1%). Palliative patients most frequently named decreased general wellbeing (62.8%), followed by pain (62.8%), tiredness (60.0%), lack of appetite (40.0%), anxiety (38.0%), depression (33.3%), dyspnea (28.5%), drowsiness (25.7%) and nausea (14.2%). At the end of RT, the proportion of curative and palliative patients with a clinically relevant symptom had increased significantly to 79.8 and 91.4%, respectively; whereas the proportion of patients reporting clinically relevant pain had decreased significantly (42.8 vs. 62.8%, respectively). Palliative patients had significantly increased tiredness. Curative patients reported significant increases in pain, tiredness, nausea, drowsiness, lack of appetite and restrictions in general wellbeing. Assessment of patient-reported symptoms was successfully realized in radiation oncology routine. Overall, both groups showed a high symptom

  13. Patient-reported symptoms during radiotherapy. Clinically relevant symptom burden in patients treated with palliative and curative intent

    International Nuclear Information System (INIS)

    Koerner, Philipp; Ehrmann, Katja; Hartmannsgruber, Johann; Metz, Michaela; Steigerwald, Sabrina; Flentje, Michael; Oorschot, Birgitt van

    2017-01-01

    The benefits of patient-reported symptom assessment combined with integrated palliative care are well documented. This study assessed the symptom burden of palliative and curative-intent radiation oncology patients. Prior to first consultation and at the end of RT, all adult cancer patients planned to receive fractionated percutaneous radiotherapy (RT) were asked to answer the Edmonton Symptom Assessment Scale (ESAS; nine symptoms from 0 = no symptoms to 10 = worst possible symptoms). Mean values were used for curative vs. palliative and pre-post comparisons, and the clinical relevance was evaluated (symptom values ≥ 4). Of 163 participating patients, 151 patients (90.9%) completed both surveys (116 curative and 35 palliative patients). Before beginning RT, 88.6% of palliative and 72.3% of curative patients showed at least one clinically relevant symptom. Curative patients most frequently named decreased general wellbeing (38.6%), followed by tiredness (35.0%), anxiety (32.4%), depression (30.0%), pain (26.3%), lack of appetite (23.5%), dyspnea (17.8%), drowsiness (8.0%) and nausea (6.1%). Palliative patients most frequently named decreased general wellbeing (62.8%), followed by pain (62.8%), tiredness (60.0%), lack of appetite (40.0%), anxiety (38.0%), depression (33.3%), dyspnea (28.5%), drowsiness (25.7%) and nausea (14.2%). At the end of RT, the proportion of curative and palliative patients with a clinically relevant symptom had increased significantly to 79.8 and 91.4%, respectively; whereas the proportion of patients reporting clinically relevant pain had decreased significantly (42.8 vs. 62.8%, respectively). Palliative patients had significantly increased tiredness. Curative patients reported significant increases in pain, tiredness, nausea, drowsiness, lack of appetite and restrictions in general wellbeing. Assessment of patient-reported symptoms was successfully realized in radiation oncology routine. Overall, both groups showed a high symptom burden

  14. Clinical relevance of β₂-glycoprotein-I plasma levels in antiphospholipid syndrome (APS).

    Science.gov (United States)

    Banzato, Alessandra; Pengo, Vittorio

    2014-06-01

    Antiphospholipid syndrome (APS) is characterized by the presence of antiphospholipid (aPL) antibodies associated with thrombosis or pregnancy morbidity. The antibodies mainly involved in this disorder are directed against β2-glycoprotein I (β2-GPI). β2-GPI plasma level is usually not reported in studies on APS, because it is not regarded as relevant to the diagnosis and prognosis of APS. Nevertheless its measurement may be important for understanding the pathophysiology of the syndrome. This review summarizes available data from the literature on plasma concentrations of β2-GPI in patients with different antibody profiles.

  15. The relevance of cytokines in the radiation-induced lung reaction. Experimental basis and clinical significance

    International Nuclear Information System (INIS)

    Ruebe, C.E.; Ruebe, C.; Rodemann, H.P.

    2004-01-01

    Methods: published data on radiation-induced cytokine expression from experimental and clinical studies are reviewed. Results and conclusion: the major pro-inflammatory cytokines in the radiation response of the lung include tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), and interleukin-6 (IL-6). Transforming growth factor-β (TGF-β) appears to be of particular importance in the development of lung fibrosis. First approaches with radioprotective agents and gene therapy to modify radiation-induced cytokine expression have been investigated for prevention of late effects of irradiation lung damage in animal experiments. Preliminary data of clinical studies suggest that elevated plasma TGF-β-levels during radiotherapy may predict the development of symptomatic radiation pneumonitis. The biological impacts of endogenous radiation-induced cytokine production by tumor cells in respect of tumor behavior, potential damage to normal tissue, and clinical status of the host still need to be determined more precisely. (orig.)

  16. Prediction of Clinically Relevant Safety Signals of Nephrotoxicity through Plasma Metabolite Profiling

    Directory of Open Access Journals (Sweden)

    W. B. Mattes

    2013-01-01

    Full Text Available Addressing safety concerns such as drug-induced kidney injury (DIKI early in the drug pharmaceutical development process ensures both patient safety and efficient clinical development. We describe a unique adjunct to standard safety assessment wherein the metabolite profile of treated animals is compared with the MetaMap Tox metabolomics database in order to predict the potential for a wide variety of adverse events, including DIKI. To examine this approach, a study of five compounds (phenytoin, cyclosporin A, doxorubicin, captopril, and lisinopril was initiated by the Technology Evaluation Consortium under the auspices of the Drug Safety Executive Council (DSEC. The metabolite profiles for rats treated with these compounds matched established reference patterns in the MetaMap Tox metabolomics database indicative of each compound’s well-described clinical toxicities. For example, the DIKI associated with cyclosporine A and doxorubicin was correctly predicted by metabolite profiling, while no evidence for DIKI was found for phenytoin, consistent with its clinical picture. In some cases the clinical toxicity (hepatotoxicity, not generally seen in animal studies, was detected with MetaMap Tox. Thus metabolite profiling coupled with the MetaMap Tox metabolomics database offers a unique and powerful approach for augmenting safety assessment and avoiding clinical adverse events such as DIKI.

  17. FDG PET and CT in locally advanced adenocarcinomas of the distal oesophagus. Clinical relevance of a discordant PET finding

    International Nuclear Information System (INIS)

    Stahl, A.; Wieder, H.; Schwaiger, M.; Weber, W.A.; Stollfuss, J.; Ott, K.; Fink, U.

    2005-01-01

    Aim: the incidence of adenocarcinomas of the distal oesophagus (ADE) has dramatically increased in Western countries. The clinical importance of a FDG PET finding discordant with CT was determined in patients with locally advanced ADE. In addition, tumour standardized uptake values (SUV) were correlated with patient survival. Patients, methods: 40 consecutive patients were analyzed retrospectively. All patients underwent an attenuation corrected FDG PET scan (neck, chest, abdomen) and contrast enhanced helical CT of the chest and abdomen. PET and CT scans were reviewed independently and concomitantly with respect to metastases in predefined lymph node sites and organs. Any discordance between PET and CT was assessed for clinical relevance. Clinical relevance was defined as a change in the overall therapeutic concept (curative vs. palliative). Follow-up imaging and histological evaluation served as the gold standard. Mean tumour SUVs were determined by 1.5 cm regions of interest placed over the tumour's maximum. Results: when read independently from the CT scan FDG PET indicated a clinically relevant change in tumour stage in 9/40 patients (23%) and a non-relevant change in 11/40 patients (28%). PET was correct in 5/9 patients (56%) with clinically relevant discordances. In 4/9 patients PET was incorrect (3 false positive due to suspicion of MI-lymph nodes or lung metastases, 1 false negative in disseminated liver metastases). With concomitant reading, PET indicated a clinically relevant change in tumour stage in 6/40 patients (15%) and a non-relevant change in 5/40 patients (13%). PET was correct in 5/6 patients (83%) with clinically relevant discordances. The patient with disseminated liver disease remained the single false negative. Overall, the benefit from PET was based on its higher diagnostic accuracy at organ sites. Tumour SUV did not correlate with patient survival. Conclusion: about half of discordances between FDG PET and CT are clinically relevant

  18. Matrix metalloproteinases in gastric inflammation and cancer : clinical relevance and prognostic impact

    NARCIS (Netherlands)

    Kubben, Francois Jozef Gerard Marie

    2007-01-01

    The studies in this thesis describe the clinical impact of several matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in H. pylori-induced gastritis and gastric cancer. In patients with H. pylori-induced gastritis, significantly increased mucosal MMP-9 levels were

  19. Depression of home cage wheel running: a reliable and clinically relevant method to assess migraine pain in rats.

    Science.gov (United States)

    Kandasamy, Ram; Lee, Andrea T; Morgan, Michael M

    2017-12-01

    The development of new anti-migraine treatments is limited by the difficulty inassessing migraine pain in laboratory animals. Depression of activity is one of the few diagnostic criteria formigraine that can be mimicked in rats. The goal of the present study was to test the hypothesis thatdepression of home cage wheel running is a reliable and clinically relevant method to assess migraine painin rats. Adult female rats were implanted with a cannula to inject allyl isothiocyanate (AITC) onto the dura to induce migraine pain, as has been shown before. Rats recovered from implantation surgery for 8 days in cages containing a running wheel. Home cage wheel running was recorded 23 h a day. AITC and the migraine medication sumatriptan were administered in the hour prior to onset of the dark phase. Administration of AITC caused a concentration-dependent decrease in wheel running that lasted 3 h. The duration and magnitude of AITC-induced depression of wheel running was consistent following three repeated injections spaced 48 h apart. Administration of sumatriptan attenuated AITC-induced depressionof wheel running when a large dose (1 mg/kg) was administered immediately following AITC administration. Wheel running patterns did not change when sumatriptan was given to naïve rats. These data indicate that home cage wheel running is a sensitive, reliable, and clinically relevant method to assess migraine pain in the rat.

  20. The effects of clinically relevant doses of amphetamine and methylphenidate on signal detection and DRL in rats

    Science.gov (United States)

    Andrzejewski, Matthew E.; Spencer, Robert C.; Harris, Rachel L.; Feit, Elizabeth C.; McKee, Brenda L.; Berridge, Craig W.

    2014-01-01

    Low dose amphetamine (AMPH) and methylphenidate (MPH, Ritalin®) are the most widely prescribed and most effective pharmacotherapy for attention-deficit/hyperactivity disorder (ADHD). Certain low, clinically relevant doses of MPH improve sustained attention and working memory in normal rats, in contrast to higher doses that impair cognitive ability and induce locomotor activity. However, the effects of AMPH of MPH on sustained attention and behavioral inhibition remain poorly characterized. The present experiments examined the actions of AMPH (0.1 and 0.25 mg/kg) and MPH (0.5 and 1.0 mg/kg) in a rat model of 1) sustained attention, where signal and blank trials were interspersed randomly and occurred at unpredictable times, and 2) behavioral inhibition, using a differential reinforcement of low rate (DRL) schedule. In a signal detection paradigm, both 0.5 mg/kg and 1.0 mg/kg MPH and 0.25 mg/kg AMPH improve sustained attention, however neither AMPH nor MPH improve behavioral inhibition on DRL. Taken together with other recent studies, it appears that clinically-relevant doses of AMPH and MPH may preferentially improve attention-related behavior while having little effect on behavioral inhibition. These observations provide additional insight into the basic behavioral actions of low-dose psychostimulants and further suggest that the use of sustained attention tasks may be important in the development of novel pharmacological treatments for ADHD. PMID:24467844

  1. The Facts About Sexual (Dys)function in Schizophrenia: An Overview of Clinically Relevant Findings

    Science.gov (United States)

    de Boer, Marrit K.; Castelein, Stynke; Wiersma, Durk; Schoevers, Robert A.; Knegtering, Henderikus

    2015-01-01

    A limited number of studies have evaluated sexual functioning in patients with schizophrenia. Most patients show an interest in sex that differs little from the general population. By contrast, psychiatric symptoms, institutionalization, and psychotropic medication contribute to frequently occurring impairments in sexual functioning. Women with schizophrenia have a better social outcome, longer lasting (sexual) relationships, and more offspring than men with schizophrenia. Still, in both sexes social and interpersonal impairments limit the development of stable sexual relationships. Although patients consider sexual problems to be highly relevant, patients and clinicians not easily discuss these spontaneously, leading to an underestimation of their prevalence and contributing to decreased adherence to treatment. Studies using structured interviews or questionnaires result in many more patients reporting sexual dysfunctions. Although sexual functioning can be impaired by different factors, the use of antipsychotic medication seems to be an important factor. A comparison of different antipsychotics showed high frequencies of sexual dysfunction for risperidone and classical antipsychotics, and lower frequencies for clozapine, olanzapine, quetiapine, and aripiprazole. Postsynaptic dopamine antagonism, prolactin elevation, and α1-receptor blockade may be the most relevant factors in the pathogenesis of antipsychotic-induced sexual dysfunction. Psychosocial strategies to treat antipsychotic-induced sexual dysfunction include psychoeducation and relationship counseling. Pharmacological strategies include lowering the dose or switching to a prolactin sparing antipsychotic. Also, the addition of a dopamine agonist, aripiprazole, or a phosphodiesterase-5 inhibitor has shown some promising results, but evidence is currently scarce. PMID:25721311

  2. Fungal Contaminants in Drinking Water Regulation? A Tale of Ecology, Exposure, Purification and Clinical Relevance

    Directory of Open Access Journals (Sweden)

    Monika Novak Babič

    2017-06-01

    Full Text Available Microbiological drinking water safety is traditionally monitored mainly by bacterial parameters that indicate faecal contamination. These parameters correlate with gastro-intestinal illness, despite the fact that viral agents, resulting from faecal contamination, are usually the cause. This leaves behind microbes that can cause illness other than gastro-intestinal and several emerging pathogens, disregarding non-endemic microbial contaminants and those with recent pathogenic activity reported. This white paper focuses on one group of contaminants known to cause allergies, opportunistic infections and intoxications: Fungi. It presents a review on their occurrence, ecology and physiology. Additionally, factors contributing to their presence in water distribution systems, as well as their effect on water quality are discussed. Presence of opportunistic and pathogenic fungi in drinking water can pose a health risk to consumers due to daily contact with water, via several exposure points, such as drinking and showering. The clinical relevance and influence on human health of the most common fungal contaminants in drinking water is discussed. Our goal with this paper is to place fungal contaminants on the roadmap of evidence based and emerging threats for drinking water quality safety regulations.

  3. Biofilm Formation and Resistance to Fungicides in Clinically Relevant Members of the Fungal Genus Fusarium

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    Hafize Sav

    2018-01-01

    Full Text Available Clinically relevant members of the fungal genus, Fusarium, exhibit an extraordinary genetic diversity and cause a wide spectrum of infections in both healthy individuals and immunocompromised patients. Generally, Fusarium species are intrinsically resistant to all systemic antifungals. We investigated whether the presence or absence of the ability to produce biofilms across and within Fusarium species complexes is linked to higher resistance against antifungals. A collection of 41 Fusarium strains, obtained from 38 patients with superficial and systemic infections, and three infected crops, were tested, including 25 species within the Fusarium fujikuroi species complex, 14 from the Fusarium solani species complex (FSSC, one Fusarium dimerum species complex, and one Fusarium oxysporum species complex isolate. Of all isolates tested, only seven strains from two species of FSSC, five F. petroliphilum and two F. keratoplasticum strains, recovered from blood, nail scrapings, and nasal biopsy samples, could produce biofilms under the tested conditions. In the liquid culture tested, sessile biofilm-forming Fusarium strains exhibited elevated minimum inhibitory concentrations (MICs for amphotericin B, voriconazole, and posaconazole, compared to their planktonic counterparts, indicating that the ability to form biofilm may significantly increase resistance. Collectively, this suggests that once a surface adherent biofilm has been established, therapies designed to kill planktonic cells of Fusarium are ineffective.

  4. Presence and Persistence of Viable, Clinically Relevant Legionella pneumophila Bacteria in Garden Soil in the Netherlands.

    Science.gov (United States)

    van Heijnsbergen, E; van Deursen, A; Bouwknegt, M; Bruin, J P; de Roda Husman, A M; Schalk, J A C

    2016-09-01

    Garden soils were investigated as reservoirs and potential sources of pathogenic Legionella bacteria. Legionella bacteria were detected in 22 of 177 garden soil samples (12%) by amoebal coculture. Of these 22 Legionella-positive soil samples, seven contained Legionella pneumophila Several other species were found, including the pathogenic Legionella longbeachae (4 gardens) and Legionella sainthelensi (9 gardens). The L. pneumophila isolates comprised 15 different sequence types (STs), and eight of these STs were previously isolated from patients according to the European Working Group for Legionella Infections (EWGLI) database. Six gardens that were found to be positive for L. pneumophila were resampled after several months, and in three gardens, L. pneumophila was again isolated. One of these gardens was resampled four times throughout the year and was found to be positive for L. pneumophila on all occasions. Tracking the source of infection for sporadic cases of Legionnaires' disease (LD) has proven to be hard. L. pneumophila ST47, the sequence type that is most frequently isolated from LD patients in the Netherlands, is rarely found in potential environmental sources. As L. pneumophila ST47 was previously isolated from a garden soil sample during an outbreak investigation, garden soils were investigated as reservoirs and potential sources of pathogenic Legionella bacteria. The detection of viable, clinically relevant Legionella strains indicates that garden soil is a potential source of Legionella bacteria, and future research should assess the public health implication of the presence of L. pneumophila in garden soil. Copyright © 2016 van Heijnsbergen et al.

  5. Extracellular membrane vesicles in blood products-biology and clinical relevance

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    Emilija Krstova Krajnc

    2016-01-01

    Full Text Available Extracellular membrane vesicles are fragments shed from plasma membranes off all cell types that are undergoing apoptosis or are being subjected to various types of stimulation or stress.  Even in the process of programmed cell death (apoptosis, cell fall apart of varying size vesicles. They expose phosphatidylserine (PS on the outer leaflet of their membrane, and bear surface membrane antigens reflecting their cellular origin. Extracellular membrane vesicles have been isolated from many types of biological fluids, including serum, cerebrospinal fluid, urine, saliva, tears and conditioned culture medium. Flow cytometry is one of the many different methodological approaches that have been used to analyze EMVs. The method attempts to characterize the EMVs cellular origin, size, population, number, and structure. EMVs are present and accumulate in blood products (erythrocytes, platelets as well as in fresh frozen plasma during storage. The aim of this review is to highlight the importance of extracellular vesicles as a cell-to-cell communication system and the role in the pathogenesis of different diseases. Special emphasis will be given to the implication of extracellular membrane vesicles in blood products and their clinical relevance. Although our understanding of the role of  EMVs in disease is far from comprehensive, they display promise as biomarkers for different diseases in the future and also as a marker of quality and safety in the quality control of blood products.

  6. Presence and Persistence of Viable, Clinically Relevant Legionella pneumophila Bacteria in Garden Soil in the Netherlands

    Science.gov (United States)

    van Heijnsbergen, E.; van Deursen, A.; Bouwknegt, M.; Bruin, J. P.; Schalk, J. A. C.

    2016-01-01

    ABSTRACT Garden soils were investigated as reservoirs and potential sources of pathogenic Legionella bacteria. Legionella bacteria were detected in 22 of 177 garden soil samples (12%) by amoebal coculture. Of these 22 Legionella-positive soil samples, seven contained Legionella pneumophila. Several other species were found, including the pathogenic Legionella longbeachae (4 gardens) and Legionella sainthelensi (9 gardens). The L. pneumophila isolates comprised 15 different sequence types (STs), and eight of these STs were previously isolated from patients according to the European Working Group for Legionella Infections (EWGLI) database. Six gardens that were found to be positive for L. pneumophila were resampled after several months, and in three gardens, L. pneumophila was again isolated. One of these gardens was resampled four times throughout the year and was found to be positive for L. pneumophila on all occasions. IMPORTANCE Tracking the source of infection for sporadic cases of Legionnaires' disease (LD) has proven to be hard. L. pneumophila ST47, the sequence type that is most frequently isolated from LD patients in the Netherlands, is rarely found in potential environmental sources. As L. pneumophila ST47 was previously isolated from a garden soil sample during an outbreak investigation, garden soils were investigated as reservoirs and potential sources of pathogenic Legionella bacteria. The detection of viable, clinically relevant Legionella strains indicates that garden soil is a potential source of Legionella bacteria, and future research should assess the public health implication of the presence of L. pneumophila in garden soil. PMID:27316958

  7. Development of a new microtiter plate format for clinically relevant assays.

    Science.gov (United States)

    Piletska, Elena V; Piletsky, Stanislav S; Whitcombe, Michael J; Chianella, Iva; Piletsky, Sergey A

    2012-02-21

    A new format for the microtiter plate-based assays was proposed. The novelty involves the use of disk-shaped inserts for immobilization of biological and chemical reagents. The internal opening of the disks allows measurements of the reactions by standard microtiter plate readers without any additional steps involving liquid handling. Ideally the plate end-users just have to add the sample and take the measurement without any need of multiple reagent additions or transfer of the liquid to a different plate. The novel assay format also allows handling of reagents which are not soluble in an aqueous environment. As a proof of concept we describe here several model reactions which are compatible with microtiter plate format, such as monitoring enzymatic reactions catalyzed by glucose oxidase (GOx) and urease, measurements of proteins by BCA assay, analysis of pH, and concentration of antioxidants. The "mix and match" approach in the disk-shape format allows multiplexing and could be particularly useful for high throughput screening. One of the potential application areas for this novel assay format could be in a multianalyte system for measurement of clinically relevant analytes in primary care.

  8. Fungal Contaminants in Drinking Water Regulation? A Tale of Ecology, Exposure, Purification and Clinical Relevance

    Science.gov (United States)

    Novak Babič, Monika; Gunde-Cimerman, Nina; Vargha, Márta; Tischner, Zsófia; Magyar, Donát; Veríssimo, Cristina; Sabino, Raquel; Viegas, Carla; Meyer, Wieland; Brandão, João

    2017-01-01

    Microbiological drinking water safety is traditionally monitored mainly by bacterial parameters that indicate faecal contamination. These parameters correlate with gastro-intestinal illness, despite the fact that viral agents, resulting from faecal contamination, are usually the cause. This leaves behind microbes that can cause illness other than gastro-intestinal and several emerging pathogens, disregarding non-endemic microbial contaminants and those with recent pathogenic activity reported. This white paper focuses on one group of contaminants known to cause allergies, opportunistic infections and intoxications: Fungi. It presents a review on their occurrence, ecology and physiology. Additionally, factors contributing to their presence in water distribution systems, as well as their effect on water quality are discussed. Presence of opportunistic and pathogenic fungi in drinking water can pose a health risk to consumers due to daily contact with water, via several exposure points, such as drinking and showering. The clinical relevance and influence on human health of the most common fungal contaminants in drinking water is discussed. Our goal with this paper is to place fungal contaminants on the roadmap of evidence based and emerging threats for drinking water quality safety regulations.

  9. Routine conventional karyotyping of lymphoma staging bone marrow samples does not contribute clinically relevant information.

    Science.gov (United States)

    Nardi, Valentina; Pulluqi, Olja; Abramson, Jeremy S; Dal Cin, Paola; Hasserjian, Robert P

    2015-06-01

    Bone marrow (BM) evaluation is an important part of lymphoma staging, which guides patient management. Although positive staging marrow is defined as morphologically identifiable disease, such samples often also include flow cytometric analysis and conventional karyotyping. Cytogenetic analysis is a labor-intensive and costly procedure and its utility in this setting is uncertain. We retrospectively reviewed pathological reports of 526 staging marrow specimens in which conventional karyotyping had been performed. All samples originated from a single institution from patients with previously untreated Hodgkin and non-Hodgkin lymphomas presenting in an extramedullary site. Cytogenetic analysis revealed clonal abnormalities in only eight marrow samples (1.5%), all of which were positive for lymphoma by morphologic evaluation. Flow cytometry showed a small clonal lymphoid population in three of the 443 morphologically negative marrow samples (0.7%). Conventional karyotyping is rarely positive in lymphoma staging marrow samples and, in our cohort, the BM karyotype did not contribute clinically relevant information in the vast majority of cases. Our findings suggest that karyotyping should not be performed routinely on BM samples taken to stage previously diagnosed extramedullary lymphomas unless there is pathological evidence of BM involvement by lymphoma. © 2015 Wiley Periodicals, Inc.

  10. Silica desiccant packets for storage and transport of Streptococcus pneumoniae and other clinically relevant species.

    Directory of Open Access Journals (Sweden)

    Casey L Pell

    Full Text Available Bacterial isolates are often transported between laboratories for research and diagnostic purposes. Silica desiccant packets (SDPs, which are inexpensive and do not require freezing, were evaluated for storage and recovery of bacterial isolates. Conditions such as inoculum size, swab type and temperature of storage were investigated using ten Streptococcus pneumoniae isolates. The optimized protocol was then tested using 49 additional S. pneumoniae isolates representing 40 serogroups. Overall, S. pneumoniae growth was considered satisfactory (>100 colony forming units for 98/109 (89.9% and 20/20 (100% swabs after 14 days at room temperature or 28 days at 4° C, respectively. Storage in SDPs did not impact on the ability of S. pneumoniae isolates to be subsequently serotyped. When the survival of nine other clinically relevant bacterial species was tested, seven were viable after 28 days at room temperature, the exceptions being Neisseria gonorrhoeae and Haemophilus influenzae. SDPs are suitable for transport and short-term storage of bacterial species including S. pneumoniae.

  11. Comparative transcriptional analysis of clinically relevant heat stress response in Clostridium difficile strain 630.

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    Nigel G Ternan

    Full Text Available Clostridium difficile is considered to be one of the most important causes of health care-associated infections worldwide. In order to understand more fully the adaptive response of the organism to stressful conditions, we examined transcriptional changes resulting from a clinically relevant heat stress (41 °C versus 37 °C in C. difficile strain 630 and identified 341 differentially expressed genes encompassing multiple cellular functional categories. While the transcriptome was relatively resilient to the applied heat stress, we noted upregulation of classical heat shock genes including the groEL and dnaK operons in addition to other stress-responsive genes. Interestingly, the flagellin gene (fliC was downregulated, yet genes encoding the cell-wall associated flagellar components were upregulated suggesting that while motility may be reduced, adherence--to mucus or epithelial cells--could be enhanced during infection. We also observed that a number of phage associated genes were downregulated, as were genes associated with the conjugative transposon Tn5397 including a group II intron, thus highlighting a potential decrease in retromobility during heat stress. These data suggest that maintenance of lysogeny and genome wide stabilisation of mobile elements could be a global response to heat stress in this pathogen.

  12. Attentional bias modification based on visual probe task: methodological issues, results and clinical relevance

    Directory of Open Access Journals (Sweden)

    Fernanda Machado Lopes

    2015-12-01

    Full Text Available Introduction: Attentional bias, the tendency that a person has to drive or maintain attention to a specific class of stimuli, may play an important role in the etiology and persistence of mental disorders. Attentional bias modification has been studied as a form of additional treatment related to automatic processing. Objectives: This systematic literature review compared and discussed methods, evidence of success and potential clinical applications of studies about attentional bias modification (ABM using a visual probe task. Methods: The Web of Knowledge, PubMed and PsycInfo were searched using the keywords attentional bias modification, attentional bias manipulation and attentional bias training. We selected empirical studies about ABM training using a visual probe task written in English and published between 2002 and 2014. Results: Fifty-seven studies met inclusion criteria. Most (78% succeeded in training attention in the predicted direction, and in 71% results were generalized to other measures correlated with the symptoms. Conclusions: ABM has potential clinical utility, but to standardize methods and maximize applicability, future studies should include clinical samples and be based on findings of studies about its effectiveness.

  13. [18F]FDG in recurrent breast cancer: diagnostic performances, clinical impact and relevance of induced changes in management

    International Nuclear Information System (INIS)

    Grahek, Dany; Montravers, Francoise; Kerrou, Khaldoun; Aide, Nicolas; Talbot, Jean-Noel; Lotz, Jean-Pierre

    2004-01-01

    Prognosis and management of patients with recurrent breast cancer depend on the spread of the disease. The aim of this study was to evaluate the performance of fluorine-18 fluorodeoxyglucose gamma camera positron emission tomography (FDG-GPET) in detecting breast cancer recurrence, its clinical impact and the relevance of induced changes in management. Patients (n=134) with suspicion of recurrence either clinically or on conventional imaging (suspected recurrence: SR) or with an isolated increase in tumour marker levels (occult recurrence: OR) underwent FDG-GPET on a coincidence gamma camera. The reference standard for evaluation of accuracy, either histology (n=26) or follow-up for 1 year (n=49), was available in 75 (56%) patients. A questionnaire was sent to the referring clinician to evaluate the impact of FDG on management. Responses were obtained for 75 patients. Information regarding both approaches was available for 46 patients (46/134=34%). At the patient level, the sensitivity of FDG-GPET was 84%, significantly higher than the 63% sensitivity for conventional modalities, and the specificity was 78% versus 61%. The values for FDG-GPET were 81% and 86% respectively in the SR group and 90% and 73% respectively in the OR group, without any significant difference between these settings. The rate of change in management was 44% overall, 43% in the SR group and 45% in the OR group. Within the two groups, intermodality (major) changes were more frequent than intramodality (minor) changes. In the 46 patients for whom both approaches were available, 93% of management modifications were relevant (validated by biopsy or clinical follow-up). The results of this retrospective study show that FDG-GPET has an important role to play in patient management by confirming and evaluating the extent of recurrence or by localising occult recurrence (orig.)

  14. A new cognitive evaluation battery for Down syndrome and its relevance for clinical trials

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    Susana ede Sola

    2015-06-01

    Full Text Available The recent prospect of pharmaceutical interventions for cognitive impairment of Down syndrome(DS has boosted a number of clinical trials in this population. However, running the trials has raised some methodological challenges and questioned the prevailing methodology used to evaluate cognitive functioning of DS individuals. This is usually achieved by comparing DS individuals to matched healthy controls of the same mental age. We propose a new tool, the TESDAD Battery that uses comparison with age-matched typically developed adults. This is an advantageous method for probing the clinical efficacy of DS therapies, allowing the interpretation and prediction of functional outcomes in clinical trials. In our DS population the TESDAD battery permitted a quantitative assessment of cognitive defects, which indicated language dysfunction and deficits in executive function, as the most important contributors to other cognitive and adaptive behavior outcomes as predictors of functional change in DS. Concretely, auditory comprehension and functional academics showed the highest potential as end-point measures of therapeutic intervention for clinical trials: the former as a cognitive key target for therapeutic intervention, and the latter as a primary functional outcome measure of clinical efficacy. Our results also emphasize the need to explore the modulating effects of IQ, gender and age on cognitive enhancing treatments. Noticeably, women performed significantly better than men of the same age and IQ in most cognitive tests, with the most consistent differences occurring in memory and executive functioning and negative trends rarely emerged on quality of life linked to the effect of age after adjusting for IQ and gender. In sum, the TESDAD battery is a useful neurocognitive tool for probing the clinical efficacy of experimental therapies in interventional studies in the DS population suggesting that age-matched controls are advantageous for determining

  15. Phenotypic and genotypic characterization of clinically relevant bacteria isolated from dental waste and waste workers' hands, mucosas and coats.

    Science.gov (United States)

    Tagliaferri, T L; Vieira, C D; de Carvalho, M A R; Ladeira, L C D; Magalhães, P P; de Macêdo Farias, L; Dos Santos, S G

    2017-10-01

    Infectious wastes are potential sources of pathogenic micro-organisms, which may represent a risk to the professionals who manage them. In this study, we aimed to characterize the infectious bacteria present in dental waste and waste workers. The dental waste produced over 24 h was collected and waste workers were sampled by swabbing. Isolate resistance profiles were characterized by Vitek ® and PCR and biofilm formation by Congo Red agar, string test and microtitre assay. To assess similarity between the waste and the workers' samples, a random amplified polymorphic DNA test was used. Twenty-eight bacteria were identified as clinically relevant. The most frequent gene was bla TEM present in five Gram-negative micro-organisms, and one bla SHV in Klebsiella pneumoniae. All Pseudomonas aeruginosa were positive to extracellular polymeric substances formation, except one isolated from a worker. Klebsiella pneumoniae had negative results for the string test. Pseudomonas aeruginosa showed better adherence at 25°C after 48 h of incubation and K. pneumonia had the best biofilm formation at the same temperature, after 24 h. The similarity between P. aeruginosa recovered from dental waste and from workers was low, however, it is important to note that a pathogen was found on a worker's hands and that improvements in biosafety are required. Infectious dental waste can contain clinically relevant bacteria with important resistance and biofilm profiles. These micro-organisms could be transmitted to waste workers, other professionals and patients if the principles of biosafety measures are neglected. To our knowledge, no study has ever evaluated the microbial characterization and the potential contamination risk of dental infectious waste and waste handlers. The presence of clinically relevant bacteria in the hands and nasal mucosa of waste workers highlights the need for studies in this field to clarify the risk of these pathogens in dental healthcare services, and to

  16. Locating relevant patient information in electronic health record data using representations of clinical concepts and database structures.

    Science.gov (United States)

    Pan, Xuequn; Cimino, James J

    2014-01-01

    Clinicians and clinical researchers often seek information in electronic health records (EHRs) that are relevant to some concept of interest, such as a disease or finding. The heterogeneous nature of EHRs can complicate retrieval, risking incomplete results. We frame this problem as the presence of two gaps: 1) a gap between clinical concepts and their representations in EHR data and 2) a gap between data representations and their locations within EHR data structures. We bridge these gaps with a knowledge structure that comprises relationships among clinical concepts (including concepts of interest and concepts that may be instantiated in EHR data) and relationships between clinical concepts and the database structures. We make use of available knowledge resources to develop a reproducible, scalable process for creating a knowledge base that can support automated query expansion from a clinical concept to all relevant EHR data.

  17. Prospective early detection of avascular necrosis of the femoral head with MR imaging in high-risk patients: Is it clinically relevant

    International Nuclear Information System (INIS)

    Von Schulthess, G.K.; Binswanger, U.

    1987-01-01

    To evaluate the clinical relevance of early detection of avascular necrosis (AVN) of the femoral head in a high-risk group, the authors performed MR imaging in 16 renal transplant patients receiving prednisone. Imaging was done at 3-month intervals over 8-24 months. Of the 15 patients remaining in the study (one underwent nephrectomy), two have shown clear MR imaging signs of early AVN persisting for 12 months without clinical symptoms. One patient had an abrupt onset of clinically relevant AVN before the second control MR imaging study was done. These results suggest that MR imaging may detect clinically irrelevant AVN, and that even short intervals between examinations may be too long to provide a warning of impending AVN

  18. Clinical relevance of herpes simplex virus viremia in Intensive Care Unit patients.

    Science.gov (United States)

    Lepiller, Q; Sueur, C; Solis, M; Barth, H; Glady, L; Lefebvre, F; Fafi-Kremer, S; Schneider, F; Stoll-Keller, F

    2015-07-01

    To determine the clinical relevance of herpes simplex virus (HSV) viremia episodes in critically ill adult patients. 1556 blood samples obtained for HSV PCR analysis in Intensive Care Unit (ICU) patients over 4 years were retrospectively analyzed, focusing on the comprehensive analysis of 88 HSV-viremic patients. HSV DNA was detected in 11.8% of samples from the ICU. HSV viral loads remained below 5×10(2) copies/ml in 68.2% of patients and exceeded 10(4) copies/ml in 7.9%. Episodes of HSV-viremia correlated with immunosuppressed status and mechanical ventilation in 79.5% and 65.9% of patients, respectively. Only a subset of patients exhibited HSV-related organ damage, including pneumonia and hepatitis (10.2% and 2.3%, respectively). The mortality rate in HSV-viremic patients was not significantly increased compared to the overall mortality rate in the ICU (27.3% vs. 22.9%, p = 0.33). Only patients with high HSV viral loads tended to have a higher, though non-significant, death rate (57.1%, p = 0.14). Our results suggest HSV viremia is common in ICU patients, potentially favored by immunocompromised status and mechanical ventilation. The global impact of HSV-viremia on mortality in the ICU was low. Quantifying HSV DNA may help identifying patients at-risk of severe HSV-induced symptoms. Copyright © 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  19. Molecular Mechanisms of Glutamine Synthetase Mutations that Lead to Clinically Relevant Pathologies.

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    Benedikt Frieg

    2016-02-01

    Full Text Available Glutamine synthetase (GS catalyzes ATP-dependent ligation of ammonia and glutamate to glutamine. Two mutations of human GS (R324C and R341C were connected to congenital glutamine deficiency with severe brain malformations resulting in neonatal death. Another GS mutation (R324S was identified in a neurologically compromised patient. However, the molecular mechanisms underlying the impairment of GS activity by these mutations have remained elusive. Molecular dynamics simulations, free energy calculations, and rigidity analyses suggest that all three mutations influence the first step of GS catalytic cycle. The R324S and R324C mutations deteriorate GS catalytic activity due to loss of direct interactions with ATP. As to R324S, indirect, water-mediated interactions reduce this effect, which may explain the suggested higher GS residual activity. The R341C mutation weakens ATP binding by destabilizing the interacting residue R340 in the apo state of GS. Additionally, the mutation is predicted to result in a significant destabilization of helix H8, which should negatively affect glutamate binding. This prediction was tested in HEK293 cells overexpressing GS by dot-blot analysis: Structural stability of H8 was impaired through mutation of amino acids interacting with R341, as indicated by a loss of masking of an epitope in the glutamate binding pocket for a monoclonal anti-GS antibody by L-methionine-S-sulfoximine; in contrast, cells transfected with wild type GS showed the masking. Our analyses reveal complex molecular effects underlying impaired GS catalytic activity in three clinically relevant mutants. Our findings could stimulate the development of ATP binding-enhancing molecules by which the R324S mutant can be repaired extrinsically.

  20. Effect of ethanol at clinically relevant concentrations on atrial inward rectifier potassium current sensitive to acetylcholine.

    Science.gov (United States)

    Bébarová, Markéta; Matejovič, Peter; Pásek, Michal; Hořáková, Zuzana; Hošek, Jan; Šimurdová, Milena; Šimurda, Jiří

    2016-10-01

    Alcohol intoxication tends to induce arrhythmias, most often the atrial fibrillation. To elucidate arrhythmogenic mechanisms related to alcohol consumption, the effect of ethanol on main components of the ionic membrane current is investigated step by step. Considering limited knowledge, we aimed to examine the effect of clinically relevant concentrations of ethanol (0.8-80 mM) on acetylcholine-sensitive inward rectifier potassium current I K(Ach). Experiments were performed by the whole-cell patch clamp technique at 23 ± 1 °C on isolated rat and guinea-pig atrial myocytes, and on expressed human Kir3.1/3.4 channels. Ethanol induced changes of I K(Ach) in the whole range of concentrations applied; the effect was not voltage dependent. The constitutively active component of I K(Ach) was significantly increased by ethanol with the maximum effect (an increase by ∼100 %) between 8 and 20 mM. The changes were comparable in rat and guinea-pig atrial myocytes and also in expressed human Kir3.1/3.4 channels (i.e., structural correlate of I K(Ach)). In the case of the acetylcholine-induced component of I K(Ach), a dual ethanol effect was apparent with a striking heterogeneity of changes in individual cells. The effect correlated with the current magnitude in control: the current was increased by eth-anol in the cells showing small current in control and vice versa. The average effect peaked at 20 mM ethanol (an increase of the current by ∼20 %). Observed changes of action potential duration agreed well with the voltage clamp data. Ethanol significantly affected both components of I K(Ach) even in concentrations corresponding to light alcohol consumption.

  1. 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.

  2. Functional and clinical relevance of novel and known PCSK1 variants for childhood obesity and glucose metabolism

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    Dennis Löffler

    2017-03-01

    Full Text Available Objective: Variants in Proprotein Convertase Subtilisin/Kexin Type 1 (PCSK1 may be causative for obesity as suggested by monogenic cases and association studies. Here we assessed the functional relevance in experimental studies and the clinical relevance through detailed metabolic phenotyping of newly identified and known PCSK1 variants in children. Results: In 52 obese children selected for elevated proinsulin levels and/or impaired glucose tolerance, we found eight known variants and two novel heterozygous variants (c.1095 + 1G > A and p.S24C by sequencing the PCSK1 gene. Patients with the new variants presented with extreme obesity, impaired glucose tolerance, and PCOS. Functionally, c.1095 + 1G > A caused skipping of exon8 translation and a complete loss of enzymatic activity. The protein was retained within the endoplasmic reticulum (ER causing ER stress. The p.S24C variant had no functional effect on protein size, cell trafficking, or enzymatic activity. The known variants rs6230, rs35753085, and rs725522 in the 5′ end did not affect PCSK1 promoter activity.In clinical association studies in 1673 lean and obese children, we confirmed associations of rs6232 and rs6234 with BMI-SDS and of rs725522 with glucose stimulated insulin secretion and Matsuda index. We did not find the new variants in any other subjects. Conclusions: We identified and functionally characterized two rare novel PCSK1 variants of which c.1095 + 1G > A caused complete loss of protein function. In addition to confirming rs6232 and rs6234 in PCSK1 as polygenic risk variants for childhood obesity, we describe an association of rs725522 with insulin metabolism. Our results support the contribution of PCSK1 variants to obesity predisposition in children. Keywords: PCSK1, PC1/3, Obesity, Children, Prohormone convertase 1/3

  3. Studies Relevent to Catalytic Activation Co & other small Molecules

    Energy Technology Data Exchange (ETDEWEB)

    Ford, Peter C

    2005-02-22

    Detailed annual and triannual reports describing the progress accomplished during the tenure of this grant were filed with the Program Manager for Catalysis at the Office of Basic Energy Sciences. To avoid unnecessary duplication, the present report will provide a brief overview of the research areas that were sponsored by this grant and list the resulting publications and theses based on this DOE supported research. The scientific personnel participating in (and trained by) this grant's research are also listed. Research carried out under this DOE grant was largely concerned with the mechanisms of the homogeneous catalytic and photocatalytic activation of small molecules such as carbon monoxide, dihydrogen and various hydrocarbons. Much of the more recent effort has focused on the dynamics and mechanisms of reactions relevant to substrate carbonylations by homogeneous organometallic catalysts. A wide range of modern investigative techniques were employed, including quantitative fast reaction methodologies such as time-resolved optical (TRO) and time-resolved infrared (TRIR) spectroscopy and stopped flow kinetics. Although somewhat diverse, this research falls within the scope of the long-term objective of applying quantitative techniques to elucidate the dynamics and understand the principles of mechanisms relevant to the selective and efficient catalytic conversions of fundamental feedstocks to higher value materials.

  4. Prevalence of clinically relevant muscle weakness and its association with vitamin D status among older adults in Ecuador.

    Science.gov (United States)

    Orces, Carlos H

    2017-10-01

    Muscle weakness and 25-hydroxyvitamin D (25(OH)D) deficiency have been associated with adverse outcomes among older adults. However, little is known about the relationship between clinically relevant muscle weakness and 25(OH)D levels in Ecuador. To examine the prevalence of muscle weakness and its association with 25(OH)D status among subjects aged 60 years and older in Ecuador. The present study was based on data from 2205 participants in the first National Survey of Health, Wellbeing, and Aging. The Foundation for the National Institute of Health Sarcopenia Project criteria was used to examine muscle weakness prevalence rates. Gender-specific general linear and logistic regression models adjusted for potential confounders were created to compare mean 25(OH)D concentrations and 25(OH)D deficiency across muscle strength categories, respectively. An estimated 32.2% of women and 33.4% of men had evidence of clinically relevant muscle weakness in Ecuador. In general, increased muscle weakness prevalence rates were present among Indigenous, residents in the rural Andes Mountains, underweight subjects, and those with a sedentary lifestyle. Muscle strength was significantly and directly correlated with mean 25(OH)D levels. After controlling for potential confounders, 25(OH)D deficiency prevalence rates were 31 and 43% higher among men and women with muscle weakness than those with normal strength, respectively. One-third of older adults nationwide had evidence of muscle weakness. While the present study found a significant correlation between muscle strength and 25(OH)D concentrations, further research is needed to examine whether optimizing 25(OH)D levels may improve muscle weakness among older adults.

  5. SU-E-T-789: Validation of 3DVH Accuracy On Quantifying Delivery Errors Based On Clinical Relevant DVH Metrics

    International Nuclear Information System (INIS)

    Ma, T; Kumaraswamy, L

    2015-01-01

    Purpose: Detection of treatment delivery errors is important in radiation therapy. However, accurate quantification of delivery errors is also of great importance. This study aims to evaluate the 3DVH software’s ability to accurately quantify delivery errors. Methods: Three VMAT plans (prostate, H&N and brain) were randomly chosen for this study. First, we evaluated whether delivery errors could be detected by gamma evaluation. Conventional per-beam IMRT QA was performed with the ArcCHECK diode detector for the original plans and for the following modified plans: (1) induced dose difference error up to ±4.0% and (2) control point (CP) deletion (3 to 10 CPs were deleted) (3) gantry angle shift error (3 degree uniformly shift). 2D and 3D gamma evaluation were performed for all plans through SNC Patient and 3DVH, respectively. Subsequently, we investigated the accuracy of 3DVH analysis for all cases. This part evaluated, using the Eclipse TPS plans as standard, whether 3DVH accurately can model the changes in clinically relevant metrics caused by the delivery errors. Results: 2D evaluation seemed to be more sensitive to delivery errors. The average differences between ECLIPSE predicted and 3DVH results for each pair of specific DVH constraints were within 2% for all three types of error-induced treatment plans, illustrating the fact that 3DVH is fairly accurate in quantifying the delivery errors. Another interesting observation was that even though the gamma pass rates for the error plans are high, the DVHs showed significant differences between original plan and error-induced plans in both Eclipse and 3DVH analysis. Conclusion: The 3DVH software is shown to accurately quantify the error in delivered dose based on clinically relevant DVH metrics, where a conventional gamma based pre-treatment QA might not necessarily detect

  6. Ultrasonographic Findings of the Gallbladder in Patients with Acute Hepatitis A: Do They Have Clinical Relevance?

    Energy Technology Data Exchange (ETDEWEB)

    An, Ji Young; Kim, Hyoung Jung; Lee, Dong Ho; Lim, Joo Won; Ko, Young Tae; Choi, Bong Keun [Dept. of Radiology, Graduate School of Medicine, Kyung Hee University, Kyung Hee University Medical Center, Seoul (Korea, Republic of)

    2012-06-15

    To determine the association of gallbladder (GB) abnormalities on ultrasonography (US) of patients with acute hepatitis A with demographic, clinical, and biochemical factors, and with other US findings. This retrospective study was approved by our institutional review board, which waived the requirement for informed consent. We retrospectively evaluated 152 consecutive patients with acute hepatitis A who underwent US. The diagnosis of acute hepatitis A was made during acute illness by demonstrating anti- HAV of the IgM class. US images were reviewed simultaneously by two abdominal radiologists and a consensus was reached for GB wall thickening, GB collapse, lymphadenopathy, and hepatic echogenicity. The associations between demographic, clinical, biochemical, and US findings and GB wall thickening or collapse were then assessed. GB wall thickening was present in 123 (81%) and GB collapse in 96 (63%) of the 152 patients. Total bilirubin level and GB collapse differed significantly (p < 0.05) between patients with and without GB wall thickening. Gender ratio, total and peak total bilirubin level, and GB wall thickness differed significantly (p < 0.05) between patients with and without GB collapse. Multivariate analysis showed that GB wall thickening was associated with GB collapse and vice versa. GB wall thickening and GB collapse are common US abnormalities associated with each other in patients with acute hepatitis A. However, GB wall thickening or collapse is not associated with any demographic, clinical, or biochemical factors, or with other US findings, in patients with acute hepatitis A.

  7. Ultrasonographic Findings of the Gallbladder in Patients with Acute Hepatitis A: Do They Have Clinical Relevance?

    International Nuclear Information System (INIS)

    An, Ji Young; Kim, Hyoung Jung; Lee, Dong Ho; Lim, Joo Won; Ko, Young Tae; Choi, Bong Keun

    2012-01-01

    To determine the association of gallbladder (GB) abnormalities on ultrasonography (US) of patients with acute hepatitis A with demographic, clinical, and biochemical factors, and with other US findings. This retrospective study was approved by our institutional review board, which waived the requirement for informed consent. We retrospectively evaluated 152 consecutive patients with acute hepatitis A who underwent US. The diagnosis of acute hepatitis A was made during acute illness by demonstrating anti- HAV of the IgM class. US images were reviewed simultaneously by two abdominal radiologists and a consensus was reached for GB wall thickening, GB collapse, lymphadenopathy, and hepatic echogenicity. The associations between demographic, clinical, biochemical, and US findings and GB wall thickening or collapse were then assessed. GB wall thickening was present in 123 (81%) and GB collapse in 96 (63%) of the 152 patients. Total bilirubin level and GB collapse differed significantly (p < 0.05) between patients with and without GB wall thickening. Gender ratio, total and peak total bilirubin level, and GB wall thickness differed significantly (p < 0.05) between patients with and without GB collapse. Multivariate analysis showed that GB wall thickening was associated with GB collapse and vice versa. GB wall thickening and GB collapse are common US abnormalities associated with each other in patients with acute hepatitis A. However, GB wall thickening or collapse is not associated with any demographic, clinical, or biochemical factors, or with other US findings, in patients with acute hepatitis A.

  8. Clinical relevance of apolipoprotein E genotyping based on a family history of Alzheimer's disease.

    Science.gov (United States)

    Luckhoff, Hilmar K; Brand, Theresa; van Velden, Dawid P; Kidd, Martin; Fisher, Leslie R; van Rensburg, Susan J; Kotze, Maritha J

    2015-01-01

    Having a family history of Alzheimer' s disease (AD) may potentiate cumulative risk associated with phenotypic expression of the ε-4 allele of the apolipoprotein E (APOE) gene. In this study, we compared the genotype distribution and allele frequencies of APOE ε-2 (rs7412) and ε -4 (rs429358) in 537 South African individuals participating in a chronic disease screening program, in order to establish whether AD family history modulates the expression of their dyslipidemic effects. Significant differences in the genotype distribution for APOE ε-2 (p=0.034) as well as APOE ε-4 (p=0.038) were found between study participants with (n=67) and without (n=470) a family history of AD. LDL cholesterol levels were inversely associated with physical activity in the study group with a positive family history of AD (pfamilial hypercholesterolemia, clinical inquiry regarding family history was identified as an important determinant of eligibility for APOE genotyping performed in the context of chronic disease risk management. To our knowledge, this is the first study to demonstrate the modulating influence of AD family history on expression of a dyslipidemic phenotype associated with the APOE ε-4 allele. Our findings provide the scientific rationale supporting a novel clinical application for APOE genotyping as a means of identifying a genetic subgroup of dyslipidemic patients set to derive the greatest benefit from early lifestyle-based interventions aimed at decreasing cumulative risk for cardiovascular disease and prevention of AD later in life.

  9. Clinical relevance of novel Otarine herpesvirus-3 in California sea lions (Zalophus californianus: lymphoma, esophageal ulcers, and strandings

    Directory of Open Access Journals (Sweden)

    Venn-Watson Stephanie

    2012-12-01

    Full Text Available Abstract Herpesviruses have been recognized in marine mammals, but their clinical relevance is not always easy to assess. A novel otarine herpesvirus-3 (OtHV3 was detected in a geriatric California sea lion (Zalophus californianus, and using a newly developed quantitative PCR assay paired with histology, OtHV3 was associated with esophageal ulcers and B cell lymphoblastic lymphoma in this animal. The prevalence and quantities of OtHV3 were then determined among buffy coats from 87 stranded and managed collection sea lions. Stranded sea lions had a higher prevalence of OtHV3 compared to managed collection sea lions (34.9% versus 12.5%; p = 0.04, and among the stranded sea lions, yearlings were most likely to be positive. Future epidemiological studies comparing the presence and viral loads of OtHV3 among a larger population of California sea lions with and without lymphoid neoplasia or esophageal ulcers would help elucidate the relevance of OtHV3-associated pathologies to these groups.

  10. What's New in the Medicine Cabinet?: A Panoramic Review of Clinically Relevant Information for the Busy Dermatologist.

    Science.gov (United States)

    Del Rosso, James Q; Zeichner, Joshua

    2014-01-01

    This article is the first in a periodic series of therapeutic topics with short reviews gleaned from major dermatology meetings, especially Scientific Poster Sessions, and is designed to provide information that may assist the readers in adapting information from the literature to their clinical practice. The topics covered in this issue are discussions of the clinical relevance of newer information about acne pathophysiology, acne in adult women, and topical corticosteroid spray formulations for chronic plaque psoriasis.

  11. Executive function impairments in fibromyalgia syndrome: Relevance of clinical variables and body mass index

    Science.gov (United States)

    2018-01-01

    Background Several investigations suggest the presence of deterioration of executive function in fibromyalgia syndrome (FMS). The study quantified executive functions in patients with FMS. A wide array of functions was assessed, including updating, shifting and inhibition, as well as decision making and mental planning. Moreover, clinical variables were investigated as possible mediators of executive dysfunction, including pain severity, psychiatric comorbidity, medication and body mass index (BMI). Methods Fifty-two FMS patients and 32 healthy controls completed a battery of 14 neuropsychological tests. Clinical interviews were conducted and the McGill Pain Questionnaire, Beck Depression Inventory, State-Trait Anxiety Inventory, Fatigue Severity Scale and Oviedo Quality of Sleep Questionnaire were presented. Results Patients performed poorer than controls on the Letter Number Sequencing, Arithmetic and Similarities subtests of the Wechsler Adult Intelligence Scale, the Spatial Span subtest of the Wechsler Memory Scale, an N-back task, a verbal fluency task, the Ruff Figural Fluency Test, the Inhibition score of the Stroop Test, the Inhibition and Shifting scores of the Five Digits Test, the Key Search Test and the Zoo Map Task. Moreover, patients exhibited less steep learning curves on the Iowa Gambling Task. Among clinical variables, BMI and pain severity explained the largest proportion of performance variance. Conclusions This study demonstrated impairments in executive functions of updating, shifting inhibition, decision making and planning in FMS. While the mediating role of pain in cognitive impairments in FMS had been previously established, the influence of BMI is a novel finding. Overweight and obesity should be considered by FMS researchers, and in the treatment of the condition. PMID:29694417

  12. Executive function impairments in fibromyalgia syndrome: Relevance of clinical variables and body mass index.

    Science.gov (United States)

    Muñoz Ladrón de Guevara, Cristina; Fernández-Serrano, María José; Reyes Del Paso, Gustavo A; Duschek, Stefan

    2018-01-01

    Several investigations suggest the presence of deterioration of executive function in fibromyalgia syndrome (FMS). The study quantified executive functions in patients with FMS. A wide array of functions was assessed, including updating, shifting and inhibition, as well as decision making and mental planning. Moreover, clinical variables were investigated as possible mediators of executive dysfunction, including pain severity, psychiatric comorbidity, medication and body mass index (BMI). Fifty-two FMS patients and 32 healthy controls completed a battery of 14 neuropsychological tests. Clinical interviews were conducted and the McGill Pain Questionnaire, Beck Depression Inventory, State-Trait Anxiety Inventory, Fatigue Severity Scale and Oviedo Quality of Sleep Questionnaire were presented. Patients performed poorer than controls on the Letter Number Sequencing, Arithmetic and Similarities subtests of the Wechsler Adult Intelligence Scale, the Spatial Span subtest of the Wechsler Memory Scale, an N-back task, a verbal fluency task, the Ruff Figural Fluency Test, the Inhibition score of the Stroop Test, the Inhibition and Shifting scores of the Five Digits Test, the Key Search Test and the Zoo Map Task. Moreover, patients exhibited less steep learning curves on the Iowa Gambling Task. Among clinical variables, BMI and pain severity explained the largest proportion of performance variance. This study demonstrated impairments in executive functions of updating, shifting inhibition, decision making and planning in FMS. While the mediating role of pain in cognitive impairments in FMS had been previously established, the influence of BMI is a novel finding. Overweight and obesity should be considered by FMS researchers, and in the treatment of the condition.

  13. Covalent immobilisation of antibodies in Teflon-FEP microfluidic devices for the sensitive quantification of clinically relevant protein biomarkers.

    Science.gov (United States)

    Pivetal, Jeremy; Pereira, Filipa M; Barbosa, Ana I; Castanheira, Ana P; Reis, Nuno M; Edwards, Alexander D

    2017-03-13

    This study reports for the first time the sensitive colorimetric and fluorescence detection of clinically relevant protein biomarkers by sandwich immunoassays using the covalent immobilisation of antibodies onto the fluoropolymer surface inside Teflon®-FEP microfluidic devices. Teflon®-FEP has outstanding optical transparency ideal for high-sensitivity colorimetric and fluorescence bioassays, however this thermoplastic is regarded as chemically inert and very hydrophobic. Covalent immobilisation can offer benefits over passive adsorption to plastic surfaces by allowing better control over antibody density, orientation and analyte binding capacity, and so we tested a range of different and novel covalent immobilisation strategies. We first functionalised the inner surface of a 10-bore, 200 μm internal diameter FEP microcapillary film with high-molecular weight polyvinyl alcohol (PVOH) without changing the outstanding optical transparency of the device delivered by the matched refractive index of FEP and water. Glutaraldehyde immobilisation was compared with the use of photoactivated linkers and NHS-ester crosslinkers for covalently immobilising capture antibodies onto PVOH. Three clinically relevant sandwich ELISAs were tested against the cytokine IL-1β, the myocardial infarct marker cardiac troponin I (cTnI), and the chronic heart failure marker brain natriuretic peptide (BNP). Overall, glutaraldehyde immobilisation was effective for BNP assays, but yielded unacceptable background for IL-1β and cTnI assays caused by direct binding of the biotinylated detection antibody to the modified PVOH surface. We found NHS-ester groups reacted with APTES-treated PVOH coated fluoropolymers. This facilitated a novel method for capture antibody immobilisation onto fluoropolymer devices using a bifunctional NHS-maleimide crosslinker. The density of covalently immobilised capture antibodies achieved using PVOH/APTES/NHS/maleimide approached levels seen with passive adsorption

  14. SU-F-T-345: Quasi-Dead Beams: Clinical Relevance and Implications for Automatic Planning

    Energy Technology Data Exchange (ETDEWEB)

    Price, R; Veltchev, I; Lin, T; Gleason, R; Ma, C [Fox Chase Cancer Center, Philadelphia, PA (United States)

    2016-06-15

    Purpose: Beam direction selection for fixed-beam IMRT planning is typically a manual process. Severe dose-volume limits on critical structures in the thorax often result in atypical selection of beam directions as compared to other body sites. This work demonstrates the potential consequences as well as clinical relevance. Methods: 21 thoracic cases treated with 5–7 beam directions, 6 cases including non-coplanar arrangements, with fractional doses of 150–411cGy were analyzed. Endpoints included per-beam modulation scaling factor (MSF), variation from equal weighting, and delivery QA passing rate. Results: During analysis of patient-specific delivery QA a sub-standard passing rate was found for a single 5-field plan (90.48% of pixels evaluated passing 3% dose, 3mm DTA). During investigation it was found that a single beam demonstrated a MSF of 34.7 and contributed only 2.7% to the mean dose of the target. In addition, the variation from equal weighting for this beam was 17.3% absolute resulting in another beam with a MSF of 4.6 contributing 41.9% to the mean dose to the target; a variation of 21.9% from equal weighting. The average MSF for the remaining 20 cases was 4.0 (SD 1.8) with an average absolute deviation of 2.8% from equal weighting (SD 3.1%). Conclusion: Optimization in commercial treatment planning systems typically results in relatively equally weighted beams. Extreme variation from this can result in excessively high MSFs (very small segments) and potential decreases in agreement between planned and delivered dose distributions. In addition, the resultant beam may contribute minimal dose to the target (quasi-dead beam); a byproduct being increased treatment time and associated localization uncertainties. Potential ramifications exist for automatic planning algorithms should they allow for user-defined beam directions. Additionally, these quasi-dead beams may be embedded in the libraries for model-based systems potentially resulting in inefficient

  15. CLINICAL RELEVANCE OF COEXISTENCE OF DUCTAL CA IN SITU AND INVASIVE DUCTAL CARCINOMA OF BREAST

    Directory of Open Access Journals (Sweden)

    Kirithiga Ramalingam

    2017-06-01

    Full Text Available BACKGROUND There are many studies reported in the literature with respect to the Ductal Carcinoma in Situ (DCIS progressing into Invasive Ductal Carcinoma (IDC of the breast. However, there is hardly any study on the coexistence of both and its clinical significance. The aim of the study is to analyse the clinical and pathological parameters of synchronous DCIS and IDC to predict the prognostic factors. MATERIALS AND METHODS 42 patients with a final pathological diagnosis of synchronous DCIS and IDC diagnosed in 2009-11 were included in the study. Statistical analysis was done using SPSS software utilising the appropriate analytical methods. RESULTS Majority of the patients in this study group presented with early breast cancer (64.3%. Forty eight percent were Her2 subtype (ER, PR negative and HER2/neu-positive and 31% were triple negative. Eighty one percent of the IDC associated histology was Not Otherwise Specified (NOS type. Grade 3 lesions were more common (57%. Recurrence of the disease occurred in 66% of patients during a mean duration of follow up of 3.6 years with predominance of visceral metastasis (51.5%. Recurrence was more common in node positive disease (59.5%, those with lymphovascular emboli (59.5% and perinodal spread (76% on histopathological examination. CONCLUSION Synchronous DCIS and IDC disease entity appears to have an aggressive nature compared to the course of IDC alone entity. Prognostic factors relating to IDC appears to correlate well with recurrence than that of the prognostic factors of DCIS component in such synchronous setting.

  16. Bottom–up protein identifications from microliter quantities of individual human tear samples. Important steps towards clinical relevance.

    Directory of Open Access Journals (Sweden)

    Peter Raus

    2015-12-01

    With 375 confidently identified proteins in the healthy adult tear, the obtained results are comprehensive and in large agreement with previously published observations on pooled samples of multiple patients. We conclude that, to a limited extent, bottom–up tear protein identifications from individual patients may have clinical relevance.

  17. Prognostic Relevance of Immunohistochemical Subclassification of Diffuse Large B-Cell Lymphoma in Two Prospective Phase III Clinical Trials

    NARCIS (Netherlands)

    Rayman, Nazik; Lam, King H.; van der Holt, Bronno; Koss, Clara; Veldhuizen, Dennis; Budel, Leo M.; Mulder, Andries H.; Verdonck, Leo F.; Delwel, Ruud; de Jong, Daphne; van Imhoff, Gustaaf W.; Sonneveld, Pieter

    Purpose: Until now molecular biologic techniques have not been easily used in daily clinical practice to stratify patients for therapeutic purposes. Therefore, we have investigated the prognostic relevance of the immunohistochemical (IHC) germinal center B-cell (GCB) versus non-GCB diffuse large

  18. The Soil Microbiota Harbors a Diversity of Carbapenem-Hydrolyzing β-Lactamases of Potential Clinical Relevance.

    Science.gov (United States)

    Gudeta, Dereje Dadi; Bortolaia, Valeria; Amos, Greg; Wellington, Elizabeth M H; Brandt, Kristian K; Poirel, Laurent; Nielsen, Jesper Boye; Westh, Henrik; Guardabassi, Luca

    2016-01-01

    The origin of carbapenem-hydrolyzing metallo-β-lactamases (MBLs) acquired by clinical bacteria is largely unknown. We investigated the frequency, host range, diversity, and functionality of MBLs in the soil microbiota. Twenty-five soil samples of different types and geographical origins were analyzed by antimicrobial selective culture, followed by phenotypic testing and expression of MBL-encoding genes in Escherichia coli, and whole-genome sequencing of MBL-producing strains was performed. Carbapenemase activity was detected in 29 bacterial isolates from 13 soil samples, leading to identification of seven new MBLs in presumptive Pedobacter roseus (PEDO-1), Pedobacter borealis (PEDO-2), Pedobacter kyungheensis (PEDO-3), Chryseobacterium piscium (CPS-1), Epilithonimonas tenax (ESP-1), Massilia oculi (MSI-1), and Sphingomonas sp. (SPG-1). Carbapenemase production was likely an intrinsic feature in Chryseobacterium and Epilithonimonas, as it occurred in reference strains of different species within these genera. The amino acid identity to MBLs described in clinical bacteria ranged between 40 and 69%. Remarkable features of the new MBLs included prophage integration of the encoding gene (PEDO-1), an unusual amino acid residue at a key position for MBL structure and catalysis (CPS-1), and overlap with a putative OXA β-lactamase (MSI-1). Heterologous expression of PEDO-1, CPS-1, and ESP-1in E. coli significantly increased the MICs of ampicillin, ceftazidime, cefpodoxime, cefoxitin, and meropenem. Our study shows that MBL producers are widespread in soil and include four genera that were previously not known to produce MBLs. The MBLs produced by these bacteria are distantly related to MBLs identified in clinical samples but constitute resistance determinants of clinical relevance if acquired by pathogenic bacteria. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  19. The clinical relevance of the duration of loss of consciousness provoked by tilt testing.

    Science.gov (United States)

    Zyśko, Dorota; Gajek, Jacek; Kozluk, Edward; Agrawal, Anil Kumar; Smereka, Jacek; Checiński, Igor

    2010-04-01

    The authors assessed the relationships between the duration of loss of consciousness (dLOC) during tilt testing-induced syncope (TTS) and demographics, medical history as well as tilt testing results. Previous research focused on the relevance of the type of neurocardiogenic reaction during TTS. The importance of dLOC has not been assessed so far. The study was carried out in 274 patients with suspected neurally mediated syncope and total loss of consciousness during tilt testing. The syncope burden, demographics, and data regarding spontaneous syncope orTTS were compared between group I with dLOC > or =47 seconds and group 2 with dLOC <47 seconds. Medical history revealed that patients in group I had more syncopal spells, more frequent syncope-related traumatic injuries, urine incontinence, jerking movements and typical vasovagal history than in group 2. Moreover, group I patients had more frequently a cardioinhibitory type of reaction and a shorter active phase duration. In addition, they manifested more frequent accompanying cerebral hypoperfusion signs and reproduction of symptoms during TTS than patients in group 2. The loss of consciousness during tilt testing-induced syncope differs in terms of duration among patients with neurally mediated syncope. The dLOC during TTS is associated with medical history and tilt-testing data which confirm the vasovagal aetiology of spontaneous events. The longer dLOC suggests deeper cerebral haemodynamic disturbances during either spontaneous or provoked syncope.

  20. clinical and experimental study

    OpenAIRE

    Tornow, Christoph

    2011-01-01

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

  1. Clinical relevance of precore mutations of hepatitis B virus in chronic liver disease

    Directory of Open Access Journals (Sweden)

    Chaloska-Ivanova Viktorija

    2014-07-01

    Full Text Available Introduction: Hepatitis B is one of the most frequent etiological factors for chronic liver diseases worldwide. Recent studies have suggested the important role of the genetic diversity of the virus on natural course of hepatitis B. Hepatitis B e-antigen negative type of chronic hepatitis is associated with mutations in the precore region and basic core promoter of hepatitis B viral genome. Aim of study was to identify precore mutations in viral genome of patients with chronic hepatitis B and to evaluate clinical patterns of liver disease related to this type of hepatitis B. Methods: Sixty seven patients with hepatitis B were included in the study. In order to evaluate the clinical patterns of chronic liver disease related to hepatitis B viral infection, biochemical and virological investigations were done, as well as a quantification of serum viral load. All patients underwent liver biopsy and semiquantification of necroinflammation and/or fibrosis according to Knodell scoring was done. In the group of e antigen-negative patients, molecular analysis was performed in order to identify presence of mutations in precore region of the virus. Results: Study group was divided in 25 HBeAg-positive and 42 HBeAg-negative subjects. Al anin-aminotransferase activity and level of viral load were higher in HBeAg-positive (p < 0.05, but average age and histology activity index were significantly higher in the HBeAg-negative patients (p < 0.01. Precore mutants were found in 38 of 42 patients with HBeAg-negative hepatitis (90%. Fibrosis was found in 30/38 cases with mutations. Discussion: Mutations in precore region of HBV in HBeAg-negative patients were more prevalent in older age and were associated with higher rate of fibrosis in liver tissue, meaning more advanced stage of the disease. This could be a consequence of longer duration of HBV infection or more severe clinical course of the disease. Conclusion: Our results suggest that precore mutations are

  2. Copper and Anesthesia: Clinical Relevance and Management of Copper Related Disorders

    OpenAIRE

    Langley, Adrian; Dameron, Charles T.

    2013-01-01

    Recent research has implicated abnormal copper homeostasis in the underlying pathophysiology of several clinically important disorders, some of which may be encountered by the anesthetist in daily clinical practice. The purpose of this narrative review is to summarize the physiology and pharmacology of copper, the clinical implications of abnormal copper metabolism, and the subsequent influence of altered copper homeostasis on anesthetic management.

  3. The Swedish Family-Cancer Database: Update, Application to Colorectal Cancer and Clinical Relevance

    Directory of Open Access Journals (Sweden)

    Hemminki Kari

    2005-01-01

    Full Text Available Abstract The Swedish Family-Cancer Database has been used for almost 10 years in the study of familial risks at all common sites. In the present paper we describe some main features of version VI of this Database, assembled in 2004. This update included all Swedes born in 1932 and later (offspring with their biological parents, a total of 10.5 million individuals. Cancer cases were retrieved from the Swedish Cancer Registry from 1958-2002, including over 1.2 million first and multiple primary cancers and in situ tumours. Compared to previous versions, only 6.0% of deceased offspring with a cancer diagnosis lack any parental information. We show one application of the Database in the study of familial risks in colorectal adenocarcinoma, with defined age-group and anatomic site specific analyses. Familial standardized incidence ratios (SIRs were determined for offspring when parents or sibling were diagnosed with colon or rectal cancer. As a novel finding it was shown that risks for siblings were higher than those for offspring of affected parents. The excess risk was limited to colon cancer and particularly to right-sided colon cancer. The SIRs for colon cancer in age matched populations were 2.58 when parents were probands and 3.81 when siblings were probands; for right-sided colon cancer the SIRs were 3.66 and 7.53, respectively. Thus the familial excess (SIR-1.00 was more than two fold higher for right-sided colon cancer. Colon and rectal cancers appeared to be distinguished between high-penetrant and recessive conditions that only affect the colon, whereas low-penetrant familial effects are shared by the two sites. Epidemiological studies can be used to generate clinical estimates for familial risk, conditioned on numbers of affected family members and their ages of onset. Useful risk estimates have been developed for familial breast and prostate cancers. Reliable risk estimates for other cancers should also be seriously considered for

  4. Reduction of cross-reactive carbohydrate determinants in plant foodstuff: elucidation of clinical relevance and implications for allergy diagnosis.

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    Heidi Kaulfürst-Soboll

    Full Text Available BACKGROUND: A longstanding debate in allergy is whether or not specific immunoglobulin-E antibodies (sIgE, recognizing cross-reactive carbohydrate determinants (CCD, are able to elicit clinical symptoms. In pollen and food allergy, ≥20% of patients display in-vitro CCD reactivity based on presence of α1,3-fucose and/or β1,2-xylose residues on N-glycans of plant (xylose/fucose and insect (fucose glycoproteins. Because the allergenicity of tomato glycoallergen Lyc e 2 was ascribed to N-glycan chains alone, this study aimed at evaluating clinical relevance of CCD-reduced foodstuff in patients with carbohydrate-specific IgE (CCD-sIgE. METHODOLOGY/PRINCIPAL FINDINGS: Tomato and/or potato plants with stable reduction of Lyc e 2 (tomato or CCD formation in general were obtained via RNA interference, and gene-silencing was confirmed by immunoblot analyses. Two different CCD-positive patient groups were compared: one with tomato and/or potato food allergy and another with hymenoptera-venom allergy (the latter to distinguish between CCD- and peptide-specific reactions in the food-allergic group. Non-allergic and CCD-negative food-allergic patients served as controls for immunoblot, basophil activation, and ImmunoCAP analyses. Basophil activation tests (BAT revealed that Lyc e 2 is no key player among other tomato (glycoallergens. CCD-positive patients showed decreased (reactivity with CCD-reduced foodstuff, most obvious in the hymenoptera venom-allergic but less in the food-allergic group, suggesting that in-vivo reactivity is primarily based on peptide- and not CCD-sIgE. Peptide epitopes remained unaffected in CCD-reduced plants, because CCD-negative patient sera showed reactivity similar to wild-type. In-house-made ImmunoCAPs, applied to investigate feasibility in routine diagnosis, confirmed BAT results at the sIgE level. CONCLUSIONS/SIGNIFICANCE: CCD-positive hymenoptera venom-allergic patients (control group showed basophil activation despite no

  5. Prospective molecular profiling of canine cancers provides a clinically relevant comparative model for evaluating personalized medicine (PMed trials.

    Directory of Open Access Journals (Sweden)

    Melissa Paoloni

    Full Text Available Molecularly-guided trials (i.e. PMed now seek to aid clinical decision-making by matching cancer targets with therapeutic options. Progress has been hampered by the lack of cancer models that account for individual-to-individual heterogeneity within and across cancer types. Naturally occurring cancers in pet animals are heterogeneous and thus provide an opportunity to answer questions about these PMed strategies and optimize translation to human patients. In order to realize this opportunity, it is now necessary to demonstrate the feasibility of conducting molecularly-guided analysis of tumors from dogs with naturally occurring cancer in a clinically relevant setting.A proof-of-concept study was conducted by the Comparative Oncology Trials Consortium (COTC to determine if tumor collection, prospective molecular profiling, and PMed report generation within 1 week was feasible in dogs. Thirty-one dogs with cancers of varying histologies were enrolled. Twenty-four of 31 samples (77% successfully met all predefined QA/QC criteria and were analyzed via Affymetrix gene expression profiling. A subsequent bioinformatics workflow transformed genomic data into a personalized drug report. Average turnaround from biopsy to report generation was 116 hours (4.8 days. Unsupervised clustering of canine tumor expression data clustered by cancer type, but supervised clustering of tumors based on the personalized drug report clustered by drug class rather than cancer type.Collection and turnaround of high quality canine tumor samples, centralized pathology, analyte generation, array hybridization, and bioinformatic analyses matching gene expression to therapeutic options is achievable in a practical clinical window (<1 week. Clustering data show robust signatures by cancer type but also showed patient-to-patient heterogeneity in drug predictions. This lends further support to the inclusion of a heterogeneous population of dogs with cancer into the preclinical

  6. Novel Paths to Relevance: How Clinical Ethics Committees Promote Ethical Reflection.

    Science.gov (United States)

    Magelssen, Morten; Pedersen, Reidar; Førde, Reidun

    2016-09-01

    How may clinical ethics committees (CECs) inspire ethical reflection among healthcare professionals? How may they deal with organizational ethics issues? In recent years, Norwegian CECs have attempted different activites that stretch or go beyond the standard trio of education, consultation, and policy work. We studied the novel activities of Norwegian CECs by examining annual reports and interviewing CEC members. Through qualitative analysis we identified nine categories of novel CEC activities, which we describe by way of examples. In light of the findings, we argue that some novel working methods may be well suited to promote ethical reflection among clinicians, and that the CEC may be a suitable venue for discussing issues of organizational ethics.

  7. [Formula: see text]The statistical crisis in science: how is it relevant to clinical neuropsychology?

    Science.gov (United States)

    Gelman, Andrew; Geurts, Hilde M

    There is currently increased attention to the statistical (and replication) crisis in science. Biomedicine and social psychology have been at the heart of this crisis, but similar problems are evident in a wide range of fields. We discuss three examples of replication challenges from the field of social psychology and some proposed solutions, and then consider the applicability of these ideas to clinical neuropsychology. In addition to procedural developments such as preregistration and open data and criticism, we recommend that data be collected and analyzed with more recognition that each new study is a part of a learning process. The goal of improving neuropsychological assessment, care, and cure is too important to not take good scientific practice seriously.

  8. Relationship of premenstrual syndrome and premenstrual dysphoric disorder with major depression: relevance to clinical practice.

    Science.gov (United States)

    Padhy, Susanta Kumar; Sarkar, Sidharth; Beherre, Prakash B; Rathi, Rajesh; Panigrahi, Mahima; Patil, Pradeep Sriram

    2015-01-01

    Premenstrual syndrome (PMS), premenstrual dysphoric disorder (PMDD) and depressive disorder are fairly common; symptoms do overlap, often under-identified and under-emphasized, particularly in rural India. The objective was to assess the occurrence of PMS and PMDD in a sample of students and staff of a nursing college and to find their correlation with depression. A prospective cohort study; Tertiary Care Hospital in Rural India (Wardha, Maharashtra); 118 female nursing students or staff aged between 18 and 40 years, who were likely to stay within the institution for the study period. The participants were rated on Penn daily symptom report prospectively for a period of 3-month. Those who scored positive were applied diagnostic and statistical manual of mental disorders, 4(th) edition, text revision (DSM-IV TR) criteria for PMDD; and were applied primary care evaluation of mental disorders depression screening followed by DSM-IV TR criteria for depression. Severity of depression was measured using Hamilton Depression Rating Scale. Main outcome measures were frequency and severity of depression in individuals with PMS and PMDD and their clinical and sociodemographic correlation. The age range of the sample was 18-37 years. Some PMS symptoms were observed in 67%; diagnosis of PMDD in 10%; depressive symptoms in 28% of the sample. 46.4% of those with depressive symptoms had major depression. The diagnosis of major depression was significantly associated with the severity of PMS symptoms as well as the presence of PMDD. Premenstrual syndrome is present in a substantial proportion of young females. Concurrent depression is increased by the severity of PMS symptoms and the presence of PMDD. Gynecologist needs to screen such subjects for depression and refer to mental-health professional early, in routine clinical practice.

  9. The relevance of gastric cancer biomarkers in prognosis and pre- and post- chemotherapy in clinical practice.

    Science.gov (United States)

    Abbas, Muhammad; Habib, Murad; Naveed, Muhammad; Karthik, Kumaragurubaran; Dhama, Kuldeep; Shi, Meiqi; Dingding, Chen

    2017-11-01

    Gastric cancer (GC) is one among the major cancer types, causing human deaths and present noticeable heterogeneity. The incidences and mortality rates are higher in males in comparison to females with a male to female ratio of 2.3:1. A lot of studies have revealed out the molecular basis, pathogenesis, invasion and metastasis related findings of gastric stomach cancer. Present review encompasses the salient information on various biomarkers for the early diagnosis, treatment and prognosis of gastric cancer elaborate the clinical importance of serum tumor markers in patients with this cancer as well as checking the growths, together with epigenetic changes and genetic polymorphisms. A deep and rigorous search was carried out in Pub Med/MEDLINE using specific key words; "gastric cancer", with "tumor marker". Our search yielded 4947 important reports about related topic from books and articles that were published before the end of August 2017. Conclusively, Scientists are utilizing high time and resource to salvage this nemesis which is of global importance and cause health burden. Classical and novel biomarkers are important for treatment as well as pre- and post- diagnosis of GC. Major causes for GC are cigarette smoking, infection by Helicobacter pylori, atrophic gastritis, sex/gender, and high salt intake. Early diagnoses of GC is important for the management, treatment, pathological diagnoses by stage prognosis and metastatic setting; although the treatment outcome proved to be not much fruitful following chemotherapy, and oral medication with oxaliplatin, capecitabine, cisplatin and 5- fluorouracil (5-FU). More research studies and exploring the practical usage of gastric cancer biomarkers in diagnosis, prognosis and pre- and post- chemotherapy in clinical practice for countering gastric cancers would alleviate to some extent the ill health sufferings of humans being caused by this important and common cancerous condition. Copyright © 2017 Elsevier Masson SAS

  10. Self-relevant beauty evaluation: Evidence from an event-related potentials study.

    Science.gov (United States)

    Kong, Fanchang; Zhang, Yan; Tian, Yuan; Fan, Cuiying; Zhou, Zongkui

    2015-03-01

    This study examines the electrophysiological correlates of beauty evaluation when participants performed the self-reference task. About 13 (7 men, 6 women) undergraduates participated in the experiment using event-related potentials. Results showed that the response to self-relevant information was faster compared to other-relevant information and no significant differences for self-relevant relative to mother-relevant information were observed. Both physical and interior beauty words for self-relevant information showed an enhanced late positive component as compared to other-relevant information. Physical beauty for self-relevant information yielded a larger late positive component in contrast to mother-relevant information but not for interior beauty. This study indicates that beauty is specific to the person who judges it though an individual and one's mother may hold similar views of interior beauty.

  11. Clinical relevance of n-isopropyl-(/sup 123/I)p-iodoamphetamine (IMP) SPECT brain imaging

    International Nuclear Information System (INIS)

    Podreka, I.; Holl, K.; Dal Bianco, P.; Goldenberg, G.; Wimberger, D.; Auff, E.; Brucke, T.

    1986-01-01

    SPECT studies of the brain were performed by means of N-isopropyl-(/sup 123/I)p-iodoamphertamine and a double head rotating scintillation camera. Energy spectra showed an increase of scattered radiation proportional to the geometrical resolution of the used Tc-collimators. This is due to the higher lead content and thin septa (septum-penetration of high energy photons of /sup 123/I, scattering in the crystal) of HRES or UHRES collimators. A LEAP collimator (14 mm FWHM resolution in the reconstructed image) is the most suitable one (sufficient resolution - relatively low scatter-fraction) for /sup 123/I labeled tracers. With a multiple window technique scatter correction was performed. The width and position of the scatter windows were estimated in phantom studies. Further steps of data processing (prereconstructional filtering, analytical attenuation compensation), leading to an improvement of the final set of cross sections, are described. Clinical cases (Alzheimers, Huntingtons, Parkinson disease, Moya Moya, stroke and partial complex seizures) and stimulation (acoustic memory tasks, visual stimulations) studies in normal volunteers are presented, and results are compared with PET-data known from recent literature

  12. Enduring relevance: an introduction to the clinical contributions of K. R. Eissler.

    Science.gov (United States)

    Garcia, Emanuel E

    2009-10-01

    The author offers a personal selection and discussion of papers that epitomize the enduring relevance of K. R. Eissler's contributions to psychoanalytic therapy. The innovations of technique embodied by these works (on parameters, schizophrenia, adolescence, cure, fees, and the treatment of the dying patient) reveal a therapeutic approach that is a natural extension of psychoanalytic science: patient-centered, maximally comprehensive, and appropriately flexible.

  13. The Intestinal Microbiome in Infectious Diseases: The Clinical Relevance of a Rapidly Emerging Field

    NARCIS (Netherlands)

    Harris, Vanessa C.; Haak, Bastiaan W.; Boele van Hensbroek, Michaël; Wiersinga, Willem J.

    2017-01-01

    The field of infectious disease is undergoing a paradigm shift as the intestinal microbiome is becoming understood. The aim of this review is to inform infectious disease physicians of the potential relevance of the intestinal microbiome to their practice. We searched Medline using both index and

  14. Clinical Relevance of Trace Bands on Serum Electrophoresis in Patients Without a History of Gammopathy

    Science.gov (United States)

    Gwathmey, TanYa M.; Willis, Monte S.; Tatreau, Jason; Wang, Shaobin; McCudden, Christopher R.

    2015-01-01

    Serum protein electrophoresis (SPE) and immunofixation is commonly used to screen for plasma cell dyscrasias. Interpretation of these tests is qualitative by nature and can yield trace, faint, or scarcely visible immunoglobulin bands (TFS), which can be difficult to classify. Whether these bands should be reported at all is challenging given their unknown clinical significance. In the present study, we retrospectively analyzed 14,036 physician-ordered protein SPE and immunofixation electrophoresis (IFE) tests on serum and urine specimens (from 4,091 patients) during the period of 2000-2010. We found that 17% of all IFE results evaluated for the presence of monoclonal gammopathies (2,389 out of 14,036) contained TFS bands, representing 4.2% (173 out of 4091) of all patients evaluated. Sixty of these patients (42%) had no previous history of gammopathy, and were clinically evaluated over a mean period of up to five years from the original diagnosis of plasma cell pathology. None of these patients had progressed to multiple myeloma, lymphoplasmacytic lymphoma, plasmacytoma, or leukemia. The remaining 82 patients (58%) had a previous history of gammopathy, but had not progressed to any symptomatic plasma cell dyscrasia. Evaluation of these patients was followed for a median period of 4.3 years, with a mean of 21.5 IFE tests per individual. These data suggest that for patients without a previous history of gammopathy, the presence of TFS bands on serum protein electrophoresis does not warrant frequent follow up investigation as commonly practiced. Routine follow up of patients with a prior history of gammopathy, conversely, are warranted and may contribute to overall survival with multiple treatment options now available. For those interpreting IFE results, it may be worth considering these data when composing comments regarding suggested repeat testing frequency by SPE/IFE or alternate test methods. PMID:27683487

  15. Prospective molecular profiling of canine cancers provides a clinically relevant comparative model for evaluating personalized medicine (PMed) trials.

    Science.gov (United States)

    Paoloni, Melissa; Webb, Craig; Mazcko, Christina; Cherba, David; Hendricks, William; Lana, Susan; Ehrhart, E J; Charles, Brad; Fehling, Heather; Kumar, Leena; Vail, David; Henson, Michael; Childress, Michael; Kitchell, Barbara; Kingsley, Christopher; Kim, Seungchan; Neff, Mark; Davis, Barbara; Khanna, Chand; Trent, Jeffrey

    2014-01-01

    Molecularly-guided trials (i.e. PMed) now seek to aid clinical decision-making by matching cancer targets with therapeutic options. Progress has been hampered by the lack of cancer models that account for individual-to-individual heterogeneity within and across cancer types. Naturally occurring cancers in pet animals are heterogeneous and thus provide an opportunity to answer questions about these PMed strategies and optimize translation to human patients. In order to realize this opportunity, it is now necessary to demonstrate the feasibility of conducting molecularly-guided analysis of tumors from dogs with naturally occurring cancer in a clinically relevant setting. A proof-of-concept study was conducted by the Comparative Oncology Trials Consortium (COTC) to determine if tumor collection, prospective molecular profiling, and PMed report generation within 1 week was feasible in dogs. Thirty-one dogs with cancers of varying histologies were enrolled. Twenty-four of 31 samples (77%) successfully met all predefined QA/QC criteria and were analyzed via Affymetrix gene expression profiling. A subsequent bioinformatics workflow transformed genomic data into a personalized drug report. Average turnaround from biopsy to report generation was 116 hours (4.8 days). Unsupervised clustering of canine tumor expression data clustered by cancer type, but supervised clustering of tumors based on the personalized drug report clustered by drug class rather than cancer type. Collection and turnaround of high quality canine tumor samples, centralized pathology, analyte generation, array hybridization, and bioinformatic analyses matching gene expression to therapeutic options is achievable in a practical clinical window (strategies may aid cancer drug development.

  16. A step-by-step guide to systematically identify all relevant animal studies

    Science.gov (United States)

    Leenaars, Marlies; Hooijmans, Carlijn R; van Veggel, Nieky; ter Riet, Gerben; Leeflang, Mariska; Hooft, Lotty; van der Wilt, Gert Jan; Tillema, Alice; Ritskes-Hoitinga, Merel

    2012-01-01

    Before starting a new animal experiment, thorough analysis of previously performed experiments is essential from a scientific as well as from an ethical point of view. The method that is most suitable to carry out such a thorough analysis of the literature is a systematic review (SR). An essential first step in an SR is to search and find all potentially relevant studies. It is important to include all available evidence in an SR to minimize bias and reduce hampered interpretation of experimental outcomes. Despite the recent development of search filters to find animal studies in PubMed and EMBASE, searching for all available animal studies remains a challenge. Available guidelines from the clinical field cannot be copied directly to the situation within animal research, and although there are plenty of books and courses on searching the literature, there is no compact guide available to search and find relevant animal studies. Therefore, in order to facilitate a structured, thorough and transparent search for animal studies (in both preclinical and fundamental science), an easy-to-use, step-by-step guide was prepared and optimized using feedback from scientists in the field of animal experimentation. The step-by-step guide will assist scientists in performing a comprehensive literature search and, consequently, improve the scientific quality of the resulting review and prevent unnecessary animal use in the future. PMID:22037056

  17. The Relevance of (South African) Renaissance Studies | Wright ...

    African Journals Online (AJOL)

    The first is that in South Africa the humanities in general, and Renaissance Studies in particular, are stymied by a lack of strategic thinking from those in the academy. The second is that the humanities, and Renaissance Studies, and Shakespeare, are valid and needed in this country, possibly as never before. Shakespeare ...

  18. Clinical relevance of the bile acid receptor TGR5 in metabolism

    DEFF Research Database (Denmark)

    van Nierop, F Samuel; Scheltema, Matthijs J; Eggink, Hannah M

    2017-01-01

    The bile acid receptor TGR5 (also known as GPBAR1) is a promising target for the development of pharmacological interventions in metabolic diseases, including type 2 diabetes, obesity, and non-alcoholic steatohepatitis. TGR5 is expressed in many metabolically active tissues, but complex enterohep......The bile acid receptor TGR5 (also known as GPBAR1) is a promising target for the development of pharmacological interventions in metabolic diseases, including type 2 diabetes, obesity, and non-alcoholic steatohepatitis. TGR5 is expressed in many metabolically active tissues, but complex...... enterohepatic bile acid cycling limits the exposure of some of these tissues to the receptor ligand. Profound interspecies differences in the biology of bile acids and their receptors in different cells and tissues exist. Data from preclinical studies show promising effects of targeting TGR5 on outcomes...... such as weight loss, glucose metabolism, energy expenditure, and suppression of inflammation. However, clinical studies are scarce. We give a summary of key concepts in bile acid metabolism; outline different downstream effects of TGR5 activation; and review available data on TGR5 activation, with a focus...

  19. Sequence variation of the feline immunodeficiency virus genome and its clinical relevance.

    Science.gov (United States)

    Stickney, A L; Dunowska, M; Cave, N J

    2013-06-08

    The ongoing evolution of feline immunodeficiency virus (FIV) has resulted in the existence of a diverse continuum of viruses. FIV isolates differ with regards to their mutation and replication rates, plasma viral loads, cell tropism and the ability to induce apoptosis. Clinical disease in FIV-infected cats is also inconsistent. Genomic sequence variation of FIV is likely to be responsible for some of the variation in viral behaviour. The specific genetic sequences that influence these key viral properties remain to be determined. With knowledge of the specific key determinants of pathogenicity, there is the potential for veterinarians in the future to apply this information for prognostic purposes. Genomic sequence variation of FIV also presents an obstacle to effective vaccine development. Most challenge studies demonstrate acceptable efficacy of a dual-subtype FIV vaccine (Fel-O-Vax FIV) against FIV infection under experimental settings; however, vaccine efficacy in the field still remains to be proven. It is important that we discover the key determinants of immunity induced by this vaccine; such data would compliment vaccine field efficacy studies and provide the basis to make informed recommendations on its use.

  20. Lab-on-a-brane: A novel physiologically relevant planar arterial model to study transendothelial transport

    Science.gov (United States)

    Budhwani, Karim Ismail

    The tremendous quality of life impact notwithstanding, cardiovascular diseases and Cancer add up to over US$ 700bn each year in financial costs alone. Aging and population growth are expected to further expand the problem space while drug research and development remain expensive. However, preclinical costs can be substantially mitigated by substituting animal models with in vitro devices that accurately model human cardiovascular transport. Here we present a novel physiologically relevant lab-on-a-brane that simulates in vivo pressure, flow, strain, and shear waveforms associated with normal and pathological conditions in large and small blood vessels for studying molecular transport across the endothelial monolayer. The device builds upon previously demonstrated integrated microfluidic loop design by: (a) introducing nanoscale pores in the substrate membrane to enable transmembrane molecular transport, (b) transforming the substrate membrane into a nanofibrous matrix for 3D smooth muscle cell (SMC) tissue culture, (c) integrating electrospinning fabrication methods, (d) engineering an invertible sandwich cell culture device architecture, and (e) devising a healthy co-culture mechanism for human arterial endothelial cell (HAEC) monolayer and multiple layers of human smooth muscle cells (HSMC) to accurately mimic arterial anatomy. Structural and mechanical characterization was conducted using confocal microscopy, SEM, stress/strain analysis, and infrared spectroscopy. Transport was characterized using FITC-Dextran hydraulic permeability protocol. Structure and transport characterization successfully demonstrate device viability as a physiologically relevant arterial mimic for testing transendothelial transport. Thus, our lab-on-a-brane provides a highly effective and efficient, yet considerably inexpensive, physiologically relevant alternative for pharmacokinetic evaluation; possibly reducing animals used in pre-clinical testing, clinical trials cost from false

  1. Clinical relevance of aberrant polypoid nodule scar after endoscopic submucosal dissection

    Science.gov (United States)

    Arantes, Vitor; Uedo, Noriya; Pedrosa, Moises Salgado; Tomita, Yasuhiko

    2016-01-01

    AIM To describe a series of patients with aberrant polypoid nodule scar developed after gastric endoscopic submucosal dissection (ESD), and to discuss its pathogenesis and clinical management. METHODS We reviewed retrospectively the endoscopic database of two academic institutions located in Brazil and Japan and searched for all patients that underwent ESD to manage gastric neoplasms from 2003 to 2015. The criteria for admission in the study were: (1) successful en bloc ESD procedure with R0 and curative resection confirmed histologically; (2) postoperative endoscopic examination with identification of a polypoid nodule scar (PNS) at ESD scar; (3) biopsies of the PNS with hyperplastic or regenerative tissue, reviewed by two independent experienced gastrointestinal pathologists, one from each Institution. Data were examined for patient demographics, Helicobacter pylori status, precise neoplastic lesion location in the stomach, tumor size, histopathological assessment of the ESD specimen, and postoperative information including medical management, endoscopic and histological findings, and clinical outcome. RESULTS A total of 14 patients (10 men/4 women) fulfilled the inclusion criteria and were enrolled in this study. One center contributed with 8 cases out of 60 patients (13.3%) from 2008 to 2015. The second center contributed with 6 cases (1.7%) out of 343 patients from 2003 to 2015. Postoperative endoscopic follow-up revealed similar findings in all patients: A protruded polypoid appearing nodule situated in the center of the ESD scar surrounded by convergence of folds. Biopsies samples were taken from PNS, and histological assessment revealed in all cases regenerative and hyperplastic tissue, without recurrent tumor or dysplasia. Primary neoplastic lesions were located in the antrum in 13 patients and in the angle in one patient. PNS did not develop in any patient after ESD undertaken for tumors located in the corpus, fundus or cardia. All patients have been

  2. The Importance of Integrating Clinical Relevance and Statistical Significance in the Assessment of Quality of Care--Illustrated Using the Swedish Stroke Register.

    Directory of Open Access Journals (Sweden)

    Anita Lindmark

    Full Text Available When profiling hospital performance, quality inicators are commonly evaluated through hospital-specific adjusted means with confidence intervals. When identifying deviations from a norm, large hospitals can have statistically significant results even for clinically irrelevant deviations while important deviations in small hospitals can remain undiscovered. We have used data from the Swedish Stroke Register (Riksstroke to illustrate the properties of a benchmarking method that integrates considerations of both clinical relevance and level of statistical significance.The performance measure used was case-mix adjusted risk of death or dependency in activities of daily living within 3 months after stroke. A hospital was labeled as having outlying performance if its case-mix adjusted risk exceeded a benchmark value with a specified statistical confidence level. The benchmark was expressed relative to the population risk and should reflect the clinically relevant deviation that is to be detected. A simulation study based on Riksstroke patient data from 2008-2009 was performed to investigate the effect of the choice of the statistical confidence level and benchmark value on the diagnostic properties of the method.Simulations were based on 18,309 patients in 76 hospitals. The widely used setting, comparing 95% confidence intervals to the national average, resulted in low sensitivity (0.252 and high specificity (0.991. There were large variations in sensitivity and specificity for different requirements of statistical confidence. Lowering statistical confidence improved sensitivity with a relatively smaller loss of specificity. Variations due to different benchmark values were smaller, especially for sensitivity. This allows the choice of a clinically relevant benchmark to be driven by clinical factors without major concerns about sufficiently reliable evidence.The study emphasizes the importance of combining clinical relevance and level of statistical

  3. The Importance of Integrating Clinical Relevance and Statistical Significance in the Assessment of Quality of Care--Illustrated Using the Swedish Stroke Register.

    Science.gov (United States)

    Lindmark, Anita; van Rompaye, Bart; Goetghebeur, Els; Glader, Eva-Lotta; Eriksson, Marie

    2016-01-01

    When profiling hospital performance, quality inicators are commonly evaluated through hospital-specific adjusted means with confidence intervals. When identifying deviations from a norm, large hospitals can have statistically significant results even for clinically irrelevant deviations while important deviations in small hospitals can remain undiscovered. We have used data from the Swedish Stroke Register (Riksstroke) to illustrate the properties of a benchmarking method that integrates considerations of both clinical relevance and level of statistical significance. The performance measure used was case-mix adjusted risk of death or dependency in activities of daily living within 3 months after stroke. A hospital was labeled as having outlying performance if its case-mix adjusted risk exceeded a benchmark value with a specified statistical confidence level. The benchmark was expressed relative to the population risk and should reflect the clinically relevant deviation that is to be detected. A simulation study based on Riksstroke patient data from 2008-2009 was performed to investigate the effect of the choice of the statistical confidence level and benchmark value on the diagnostic properties of the method. Simulations were based on 18,309 patients in 76 hospitals. The widely used setting, comparing 95% confidence intervals to the national average, resulted in low sensitivity (0.252) and high specificity (0.991). There were large variations in sensitivity and specificity for different requirements of statistical confidence. Lowering statistical confidence improved sensitivity with a relatively smaller loss of specificity. Variations due to different benchmark values were smaller, especially for sensitivity. This allows the choice of a clinically relevant benchmark to be driven by clinical factors without major concerns about sufficiently reliable evidence. The study emphasizes the importance of combining clinical relevance and level of statistical confidence when

  4. Home cage wheel running is an objective and clinically relevant method to assess inflammatory pain in male and female rats

    Science.gov (United States)

    Kandasamy, Ram; Calsbeek, Jonas J.; Morgan, Michael M.

    2016-01-01

    Background The assessment of nociception in preclinical studies is undergoing a transformation from pain-evoked to pain-depressed tests to more closely mimic the effects of clinical pain. Many inflammatory pain-depressed behaviors (reward seeking, locomotion) have been examined, but these tests are limited because of confounds such as stress and difficulties in quantifying behavior. New Method The present study evaluates home cage wheel running as an objective method to assess the magnitude and duration of inflammatory pain in male and female rats. Results Injection of Complete Freund’s Adjuvant (CFA) into the right hindpaw to induce inflammatory pain almost completely inhibited wheel running for 2 days in males and females. Wheel running gradually returned to baseline levels within 12 days despite persistent mechanical hypersensitivity (von Frey test). Comparison with Existing Methods Continuously monitoring home cage wheel running improves on previous studies examining inflammatory pain-depressed wheel running because it is more sensitive to noxious stimuli, avoids the stress of removing the rat from its cage for testing, and provides a complete analysis of the time course for changes in nociception. Conclusions The present data indicate that home cage wheel running is a clinically relevant method to assess inflammatory pain in the rat. The decrease in activity caused by inflammatory pain and subsequent gradual recovery mimics the changes in activity caused by pain in humans. The tendency for pain-depressed wheel running to be greater in female than male rats is consistent with the tendency for women to be at greater risk of chronic pain than men. PMID:26891874

  5. Differential Effectiveness of Clinically-Relevant Analgesics in a Rat Model of Chemotherapy-Induced Mucositis.

    Directory of Open Access Journals (Sweden)

    Alexandra L Whittaker

    Full Text Available Chemotherapy-induced intestinal mucositis is characterized by pain and a pro-inflammatory tissue response. Rat models are frequently used in mucositis disease investigations yet little is known about the presence of pain in these animals, the ability of analgesics to ameliorate the condition, or the effect that analgesic administration may have on study outcomes. This study investigated different classes of analgesics with the aim of determining their analgesic effects and impact on research outcomes of interest in a rat model of mucositis. Female DA rats were allocated to 8 groups to include saline and chemotherapy controls (n = 8. Analgesics included opioid derivatives (buprenorphine; 0.05mg/kg and tramadol 12.5mg/kg and NSAID (carprofen; 15mg/kg in combination with either saline or 5-Fluorouracil (5-FU; 150mg/kg. Research outcome measures included daily clinical parameters, pain score and gut histology. Myeloperoxidase assay was performed to determine gut inflammation. At the dosages employed, all agents had an analgesic effect based on behavioural pain scores. Jejunal myeloperoxidase activity was significantly reduced by buprenorphine and tramadol in comparison to 5-FU control animals (53%, p = 0.0004 and 58%, p = 0.0001. Carprofen had no ameliorating effect on myeloperoxidase levels. None of the agents reduced the histological damage caused by 5-FU administration although tramadol tended to increase villus length even when administered to healthy animals. These data provide evidence that carprofen offers potential as an analgesic in this animal model due to its pain-relieving efficacy and minimal effect on measured parameters. This study also supports further investigation into the mechanism and utility of opioid agents in the treatment of chemotherapy-induced mucositis.

  6. Hypersensitivities for Acetaldehyde and Other Agents among Cancer Cells Null for Clinically Relevant Fanconi Anemia Genes

    OpenAIRE

    Ghosh, Soma; Sur, Surojit; Yerram, Sashidhar R.; Rago, Carlo; Bhunia, Anil K.; Hossain, M. Zulfiquer; Paun, Bogdan C.; Ren, Yunzhao R.; Iacobuzio-Donahue, Christine A.; Azad, Nilofer A.; Kern, Scott E.

    2014-01-01

    Large-magnitude numerical distinctions (>10-fold) among drug responses of genetically contrasting cancers were crucial for guiding the development of some targeted therapies. Similar strategies brought epidemiological clues and prevention goals for genetic diseases. Such numerical guides, however, were incomplete or low magnitude for Fanconi anemia pathway (FANC) gene mutations relevant to cancer in FANC-mutation carriers (heterozygotes). We generated a four-gene FANC-null cancer panel, inclu...

  7. A preliminary study on the relevancy of sustainable building design ...

    African Journals Online (AJOL)

    This preliminary study aims to explore the relationship between sustainable building design paradigms and commercial property depreciation, to assist in the understanding of sustainable building design impact towards commercial building value and rental de employs the qualitative method and analyses valuers' current ...

  8. Dependence and caring in clinical communication: the relevance of attachment and other theories.

    Science.gov (United States)

    Salmon, Peter; Young, Bridget

    2009-03-01

    Clinical relationships are usually asymmetric, being defined by patients' dependence and practitioners' care. Our aims are to: (i) identify literature that can contribute to theory for researching and teaching clinical communication from this perspective; (ii) highlight where theoretical development is needed; and (iii) test the utility of the emerging theory by identifying whether it leads to implications for educational practice. Selective and critical review of research concerned with dependence and caring in clinical and non-clinical relationships. Attachment theory helps to understand patients' need to seek safety in relationships with expert and authoritative practitioners but is of limited help in understanding practitioners' caring. Different theories that formulate practitioners' care as altruistic, rewarded by personal connection or as a contract indicate the potential importance of practitioners' emotions, values and sense of role in understanding their clinical communication. Extending the theoretical grounding of clinical communication can accommodate patients' dependence and practitioners' caring without return to medical paternalism. A broader theoretical base will help educators to address the inherent subjectivity of clinical relationships, and researchers to distinguish scientific questions about how patients and clinicians are from normative questions about how they should be.

  9. Dependence and caring in clinical communication: The relevance of attachment and other theories

    Science.gov (United States)

    Salmon, Peter; Young, Bridget

    2009-01-01

    Objective Clinical relationships are usually asymmetric, being defined by patients’ dependence and practitioners’ care. Our aims are to: (i) identify literature that can contribute to theory for researching and teaching clinical communication from this perspective; (ii) highlight where theoretical development is needed; and (iii) test the utility of the emerging theory by identifying whether it leads to implications for educational practice. Methods Selective and critical review of research concerned with dependence and caring in clinical and non-clinical relationships. Results Attachment theory helps to understand patients’ need to seek safety in relationships with expert and authoritative practitioners but is of limited help in understanding practitioners’ caring. Different theories that formulate practitioners’ care as altruistic, rewarded by personal connection or as a contract indicate the potential importance of practitioners’ emotions, values and sense of role in understanding their clinical communication. Conclusion Extending the theoretical grounding of clinical communication can accommodate patients’ dependence and practitioners’ caring without return to medical paternalism. Practice implications A broader theoretical base will help educators to address the inherent subjectivity of clinical relationships, and researchers to distinguish scientific questions about how patients and clinicians are from normative questions about how they should be. PMID:19157761

  10. Pituitary gland in Bipolar Disorder and Major Depression: Evidence from structural MRI studies: Special Section on "Translational and Neuroscience Studies in Affective Disorders". Section Editor, Maria Nobile MD, PhD. This Section of JAD focuses on the relevance of translational and neuroscience studies in providing a better understanding of the neural basis of affective disorders. The main aim is to briefly summarise relevant research findings in clinical neuroscience with particular regards to specific innovative topics in mood and anxiety disorders.

    Science.gov (United States)

    Delvecchio, G; Altamura, A C; Soares, J C; Brambilla, P

    2017-08-15

    The function of the hypothalamo-pituitary-adrenal axis (HPA) has been widely investigated in mood disorders based on its role in regulating stress response. Particularly, Magnetic Resonance Imaging (MRI) reports have explored pituitary gland (PG) in both bipolar disorder (BD) and major depressive disorder (MDD). In this context, the present review summarizes the results from MRI studies with the final aim of commenting on the presence of common or distinct PG structural alterations between these two disabling illnesses. A bibliographic search on PUBMED of all MRI studies exploring PG volumes in BD and MDD as well as first-degree relatives (RELs) from 2000 up to October 2016 was performed. Following the screening process of the available literature it can be said that a) PG enlargement has been found in both BD and MDD, therefore potentially representing a common neurobiological marker characterizing mood disorders, and b) PG volumes are moderated by age and sex in both illnesses, although the direction and the extent of this moderation are still not fully clear. Few MRI studies with heterogeneous results. These hypotheses must be taken with caution especially because the heterogeneity of the results of the studies reviewed does not allow for a definite answer about the role of PG in affective disorders. Therefore, larger longitudinal studies investigating PG volumes in BD and MDD patients at the early phases of the illness, by considering females and males separately, are needed to further corroborate these findings. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Clinicians' emotional responses and Psychodynamic Diagnostic Manual adult personality disorders: A clinically relevant empirical investigation.

    Science.gov (United States)

    Gazzillo, Francesco; Lingiardi, Vittorio; Del Corno, Franco; Genova, Federica; Bornstein, Robert F; Gordon, Robert M; McWilliams, Nancy

    2015-06-01

    The aim of this study is to explore the relationship between level of personality organization and type of personality disorder as assessed with the categories in the Psychodynamic Diagnostic Manual (PDM; PDM Task Force, 2006) and the emotional responses of treating clinicians. We asked 148 Italian clinicians to assess 1 of their adult patients in treatment for personality disorders with the Psychodiagnostic Chart (PDC; Gordon & Bornstein, 2012) and the Personality Diagnostic Prototype (PDP; Gazzillo, Lingiardi, & Del Corno, 2012) and to complete the Therapist Response Questionnaire (TRQ; Betan, Heim, Zittel-Conklin, & Westen, 2005). The patients' level of overall personality pathology was positively associated with helpless and overwhelmed responses in clinicians and negatively associated with positive emotional responses. A parental and disengaged response was associated with the depressive, anxious, and dependent personality disorders; an exclusively parental response with the phobic personality disorder; and a parental and criticized response with narcissistic disorder. Dissociative disorder evoked a helpless and parental response in the treating clinicians whereas somatizing disorder elicited a disengaged reaction. An overwhelmed and disengaged response was associated with sadistic and masochistic personality disorders, with the latter also associated with a parental and hostile/criticized reaction; an exclusively overwhelmed response with psychopathic patients; and a helpless response with paranoid patients. Finally, patients with histrionic personality disorder evoked an overwhelmed and sexualized response in their clinicians whereas there was no specific emotional reaction associated with the schizoid and the obsessive-compulsive disorders. Clinical implications of these findings were discussed. (c) 2015 APA, all rights reserved).

  12. A pragmatic definition of therapeutic synergy suitable for clinically relevant in vitro multicompound analyses.

    Science.gov (United States)

    Kashif, Muhammad; Andersson, Claes; Åberg, Magnus; Nygren, Peter; Sjöblom, Tobias; Hammerling, Ulf; Larsson, Rolf; Gustafsson, Mats G

    2014-07-01

    For decades, the standard procedure when screening for candidate anticancer drug combinations has been to search for synergy, defined as any positive deviation from trivial cases like when the drugs are regarded as diluted versions of each other (Loewe additivity), independent actions (Bliss independence), or no interaction terms in a response surface model (no interaction). Here, we show that this kind of conventional synergy analysis may be completely misleading when the goal is to detect if there is a promising in vitro therapeutic window. Motivated by this result, and the fact that a drug combination offering a promising therapeutic window seldom is interesting if one of its constituent drugs can provide the same window alone, the largely overlooked concept of therapeutic synergy (TS) is reintroduced. In vitro TS is said to occur when the largest therapeutic window obtained by the best drug combination cannot be achieved by any single drug within the concentration range studied. Using this definition of TS, we introduce a procedure that enables its use in modern massively parallel experiments supported by a statistical omnibus test for TS designed to avoid the multiple testing problem. Finally, we suggest how one may perform TS analysis, via computational predictions of the reference cell responses, when only the target cell responses are available. In conclusion, the conventional error-prone search for promising drug combinations may be improved by replacing conventional (toxicology-rooted) synergy analysis with an analysis focused on (clinically motivated) TS. ©2014 American Association for Cancer Research.

  13. Professor Zalman Makhover. A relevant contributor to early tropopause studies

    Energy Technology Data Exchange (ETDEWEB)

    Antuna, Juan C. [Camagueey Lidar Station, Camagueey (Cuba); Anel, Juan A. [CESAM, Univ. de Aveiro, Campus Univ. de Santiago, Aveiro (Portugal); EPhysLab, Facultade de Ciencias de Ourense, Univ. de Vigo, Ourense (Spain); Sterin, Alexander [Russian Research Inst. for Hydrometeorological Information - World Data Center, Obninsk (Russian Federation); Gimeno, Luis [EPhysLab, Facultade de Ciencias de Ourense, Univ. de Vigo, Ourense (Spain)

    2009-12-15

    We present an assessment of the work of Zalman Meerovich Makhover (1922-99), a leading expert on tropopause studies in the former USSR. Although a much-respected scientist among his peers, his work remains unknown, possibly as a result of much of never having been translated into English. His most important contributions were on the subject of the spatial and temporal structure of the altitude and temperature of the tropopause, as well as its variability over a range of different time scales from annual to daily. We describe the determination of the seasonal features of the tropopause and note his achievements in determining the roles of synoptic conditions and the annual cycle on tropopause characteristics. Recent tropopause research has confirmed much of his earlier work and provided important results for, among other things, stratospheretroposphere exchange processes, climate change indicator studies, and the climatology of aircraft exhaust traces. The legacy of Makhover includes his own research on tropopause phenomena, as well as a synthesis of the numerous studies conducted by former Soviet and other researchers. Here we provide a brief biography, citation data, as well as graphical material taken from his monographs and papers. (orig.)

  14. Chiral drug analysis using mass spectrometric detection relevant to research and practice in clinical and forensic toxicology.

    Science.gov (United States)

    Schwaninger, Andrea E; Meyer, Markus R; Maurer, Hans H

    2012-12-21

    This paper reviews analytical approaches published in 2002-2012 for chiral drug analysis and their relevance in research and practice in the field of clinical and forensic toxicology. Separation systems such as gas chromatography, high performance liquid chromatography, capillary electromigration, and supercritical fluid chromatography, all coupled to mass spectrometry, are discussed. Typical applications are reviewed for relevant chiral analytes such as amphetamines and amphetamine-derived designer drugs, methadone, tramadol, psychotropic and other CNS acting drugs, anticoagulants, cardiovascular drugs, and some other drugs. Usefulness of chiral drug analysis in the interpretation of analytical results in clinical and forensic toxicology is discussed as well. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Perspectives on creating clinically relevant blast models for mild traumatic brain injury and post traumatic stress disorder symptoms

    Directory of Open Access Journals (Sweden)

    Lisa eBrenner

    2012-03-01

    Full Text Available Military personnel are returning from Iraq and Afghanistan and reporting non-specific physical (somatic, behavioral, psychological, and cognitive symptoms. Many of these symptoms are frequently associated with mild traumatic brain injury (mTBI and/or post traumatic stress disorder (PTSD. Despite significant attention and advances in assessment and intervention for these two conditions, challenges persist. To address this, clinically relevant blast models are essential in the full characterization of this type of injury, as well as in the testing and identification of potential treatment strategies. In this publication, existing diagnostic challenges and current treatment practices for mTBI and/or PTSD will be summarized, along with suggestions regarding how what has been learned from existing models of PTSD and traditional mechanism (e.g., non-blast TBI can be used to facilitate the development of clinically relevant blast models.

  16. Caesarean section in a patient with varicella: Anaesthesia considerations and clinical relevance

    Directory of Open Access Journals (Sweden)

    Nandini M Dave

    2007-01-01

    Full Text Available A primigravida with chicken pox was posted for an emergency caesarean section. General anaesthesia was administered. Key issues in anaesthesia management and the clinical implications are discussed.

  17. Effects of acute psychological stress on placebo and nocebo responses in a clinically relevant model of visceroception.

    Science.gov (United States)

    Roderigo, Till; Benson, Sven; Schöls, Margarita; Hetkamp, Madeleine; Schedlowski, Manfred; Enck, Paul; Elsenbruch, Sigrid

    2017-08-01

    There is evidence to suggest a role of emotions in placebo and nocebo effects, but whether acute psychological stress changes the magnitude of placebo or nocebo responses has not been tested. In a clinically relevant model of visceroception, we assessed effects of acute psychological stress on changes in urgency and pain in response to positive or negative treatment suggestions. In 120 healthy volunteers, perceived urge-to-defecate and pain in response to individually calibrated rectal distensions were measured with visual analogue scales during a BASELINE. Participants then underwent the Trier Social Stress Test (N = 60) or a simple cognitive task (control, N = 60) and were randomized to positive (placebo), negative (nocebo), or neutral treatment information regarding intravenous administration of saline. The series of distensions was repeated, and changes in visual analogue scales from BASELINE to TEST were compared between groups using analysis of covariance and planned post hoc tests. Treatment information emerged as a main factor (P effects for both urgency and pain. Effects for urgency were modulated by stress (interaction effect: P stressed groups. For pain, effects of stress emerged for nocebo responses, which were only evident in stressed groups (P = 0.009). This is the first experimental study supporting effects of acute psychological stress on placebo and nocebo responses in visceroception. Results call for mechanistic as well as patient studies to assess how psychological stress shapes patients' treatment expectations and thereby affects health outcomes.

  18. Evaluation of the clinical relevance of anti-annexin-A5 antibodies in Chinese patients with antiphospholipid syndrome.

    Science.gov (United States)

    Zhang, Shulan; Wu, Ziyan; Li, Jing; Wen, Xiaoting; Li, Liubing; Zhang, Wen; Zhao, Jiuliang; Zhang, Fengchun; Li, Yongzhe

    2017-02-01

    A hallmark feature of antiphospholipid syndrome (APS) is the presence of antiphospholipid antibodies (aPLs). Few studies have addressed the clinical relevance of anti-annexin A5 antibodies (aANXA5) in Chinese patients with APS. In this study, we evaluated the clinical performance of aANXA5 in the diagnosis of APS. Sera from 313 subjects were tested, including 170 samples from patients with APS, 104 samples from patients with non-APS diseases as disease controls (DC), and 39 healthy controls (HC). Serum IgG and IgM aANXA5 were determined by ELISA. Overall, the levels of both IgG and IgM aANXA5 were significantly increased in patients with primary APS (PAPS) and APS associated to other diseases (APSAOD) compared with DC and HC. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for IgG and IgM aANXA5 in the diagnosis of APS were 33.5 and 15.3, 99.0 and 99.0, 98.3 and 96.3, and 47.7 and 41.7%, respectively. Significant associations between IgG aANXA5 and arterial thrombotic events (OR, 2.60; 95% CI, 1.44-4.71) and between IgG aANXA5 and venous thrombotic events (OR, 2.80; 95% CI, 1.55-5.06) were identified. No correlations were identified between IgG or IgM aANXA5 and obstetric complications. Our data suggest that aANXA5 could serve as a diagnosis biomarker for patients with APS. More importantly, our data highlighted a potential role of IgG aANXA5 in identifying APS patients with high risk of thrombosis.

  19. A framework to assess the value of application of formal criteria to check clinical relevance in RCTs as part of a benefit assessment strategy.

    Science.gov (United States)

    Vach, Werner; Gladstone, Beryl Primrose

    2016-01-01

    Recently, the topic of assessing clinical relevance on top of statistical significance in the analysis of randomized control trials (RCTs) has got increasing attention, in particular as part of benefit assessments. Several formal criteria to serve this purpose have been published. In this paper, we present a framework to assess the value of the application of such criteria. We propose to quantify the need for the assessment of clinical relevance by the actual risk of having accepted a benefit for a treatment with an irrelevant effect in a successful RCT. We then study how this risk can be controlled by two popular criteria based on comparing the effect estimate or the lower bound of the confidence interval with a given threshold. We further propose to quantify the impact of using formal criteria by considering the expected costs when specifying error-specific costs for each of the three possible types of errors: A benefit may be accepted for a treatment, which is actually inferior, or which is not inferior, but only implies an irrelevant improvement, or a benefit may be rejected for a treatment implying a relevant improvement. This way we can demonstrate that the impact depends on parameters which are typically not explicitly defined in the frame of benefit assessments. Depending on the values of these parameters, formal checks of clinical relevance may imply better decisions on average, but they may also imply more harm than good on average. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Surface Propensity of Atmospherically Relevant Amino Acids Studied by XPS.

    Science.gov (United States)

    Mocellin, Alexandra; Gomes, Anderson Herbert de Abreu; Araújo, Oscar Cardoso; de Brito, Arnaldo Naves; Björneholm, Olle

    2017-04-27

    Amino acids constitute an important fraction of the water-soluble organic nitrogen (WSON) compounds in aerosols and are involved in many processes in the atmosphere. In this work, we applied X-ray photoelectron spectroscopy (XPS) to study aqueous solutions of four amino acids, glycine, alanine, valine, and methionine, in their zwitterionic forms. We found that amino acids with hydrophilic side chains and smaller size, GLY and ALA, tend to stay in the bulk of the liquid, while the hydrophobic and bigger amino acids, VAL and MET, are found to concentrate more on the surface. We found experimental evidence that the amino acids have preferential orientation relative to the surface, with the hydrophobic side chain being closer to the surface than the hydrophilic carboxylate group. The observed amino acid surface propensity has implications in atmospheric science as the surface interactions play a central role in cloud droplet formation, and they should be considered in climate models.

  1. Studies of autoionizing states relevant to dielectronic recombination. Final report

    International Nuclear Information System (INIS)

    Gallagher, T.F.

    1985-01-01

    Dielectronic recombinaation, the inverse of autoionization, is a process leading to significant power loss in CTR plasmas. Although it is known that dielectronic recombination proceeds via autoionization Rydberg states, few data exist on autoionizing states and how they are affected by conditions found in a CTR plasma. Under this research program we have been using a novel laser excitation technique developed at SRI to study autoionizing states and the perturbing effects of electric fields found in CTR plasmas. We describe experimental investigations of the spectroscopy of autoionizing Rydberg states, the energy analysis of electrons ejected from autoionizing states, autoionizing in electric fields, and the autoionization induced by an electric field. 33 refs., 16 figs

  2. Spectroscopic Studies of Molecular Systems relevant in Astrobiology

    Science.gov (United States)

    Fornaro, Teresa

    2016-01-01

    In the Astrobiology context, the study of the physico-chemical interactions involving "building blocks of life" in plausible prebiotic and space-like conditions is fundamental to shed light on the processes that led to emergence of life on Earth as well as to molecular chemical evolution in space. In this PhD Thesis, such issues have been addressed both experimentally and computationally by employing vibrational spectroscopy, which has shown to be an effective tool to investigate the variety of intermolecular interactions that play a key role in self-assembling mechanisms of nucleic acid components and their binding to mineral surfaces. In particular, in order to dissect the contributions of the different interactions to the overall spectroscopic signals and shed light on the intricate experimental data, feasible computational protocols have been developed for the characterization of the spectroscopic properties of such complex systems. This study has been carried out through a multi-step strategy, starting the investigation from the spectroscopic properties of the isolated nucleobases, then studying the perturbation induced by the interaction with another molecule (molecular dimers), towards condensed phases like the molecular solid, up to the case of nucleic acid components adsorbed on minerals. A proper modeling of these weakly bound molecular systems has required, firstly, a validation of dispersion-corrected Density Functional Theory methods for simulating anharmonic vibrational properties. The isolated nucleobases and some of their dimers have been used as benchmark set for identifying a general, reliable and effective computational procedure based on fully anharmonic quantum mechanical computations of the vibrational wavenumbers and infrared intensities within the generalized second order vibrational perturbation theory (GVPT2) approach, combined with the cost-effective dispersion-corrected density functional B3LYP-D3, in conjunction with basis sets of

  3. Consideration of a new definition of clinically relevant myocardial infarction after coronary revascularization: an expert consensus document from the Society for Cardiovascular Angiography and Interventions (SCAI).

    Science.gov (United States)

    Moussa, Issam D; Klein, Lloyd W; Shah, Binita; Mehran, Roxana; Mack, Michael J; Brilakis, Emmanouil S; Reilly, John P; Zoghbi, Gilbert; Holper, Elizabeth; Stone, Gregg W

    2014-01-01

    Numerous definitions have been proposed for the diagnosis of myocardial infarction (MI) after coronary revascularization. The universal definition for MI designates post procedural biomarker thresholds for defining percutaneous coronary intervention (PCI)-related MI (type 4a) and coronary artery bypass grafting (CABG)-related MI (type 5) which are of uncertain prognostic importance. In addition, for both MI types cTn is recommended as the biomarker of choice, the prognostic significance of which is less well validated than CK-MB. Widespread adoption of a MI definition not clearly linked to subsequent adverse events such as mortality or heart failure may have serious consequences for the appropriate assessment of devices and therapies, may affect clinical care pathways, and may result in misinterpretation of physician competence. Rather than employing an MI definition sensitive for small degrees of myonecrosis (the occurrence of which, based on contemporary large-scale studies, are unlikely to have important clinical consequences), it is instead recommended that a threshold level of biomarker elevation which has been strongly linked to subsequent adverse events in clinical studies be used to define a "clinically relevant MI." The present document introduces a new definition for "clinically relevant MI" after coronary revascularization (PCI or CABG) which is applicable for use in clinical trials, patient care, and quality outcomes assessment. Copyright © 2013 Wiley Periodicals, Inc.

  4. Study of relevant parameters of GEM-based detectors

    CERN Document Server

    Croci, Gabriele; Sauli, Fabio; Ragazzi, S

    2007-01-01

    The Gas Electron Multiplier consist of a thin Kapton insulating (50 $\\mu$m) foil copper-clad on both sides and perforated by a high density, regular matrix of holes (around 100 per square millimeter). Typically the distance between holes (pitch) is 140 $\\mu$m and diameters of about 70 $\\mu$m. The mesh is realised by conventional photolitographic methods as used for the fabrication of multi-layer board. Upon application of a potential difference between the GEM electrodes, a high dipole field develops in the holes focusing the field lines between the drift electrode and the readout element. Electron drift along the channel and the charge is amplified by a factor that depends on the field density and the length of the channel. Owing to their excellent position resolution and rate capability GEM-based detector are very suitable to be used in different applications: from the high energy physics to the medical field. The GEM temporal and rate gain stability was studied and it was discovered that the gain variation...

  5. The clinical relevance of advanced artificial feedback in the control of a multi-functional myoelectric prosthesis.

    Science.gov (United States)

    Markovic, Marko; Schweisfurth, Meike A; Engels, Leonard F; Bentz, Tashina; Wüstefeld, Daniela; Farina, Dario; Dosen, Strahinja

    2018-03-27

    -loop control does not improve the performance, it could be beneficial as it seems to improve the subjective experience. Therefore, in this study we demonstrate, for the first time, the relevance of an advanced, multi-variable feedback interface for dexterous, multi-functional prosthesis control in a clinically relevant setting.

  6. Clinical Relevance and Predictive Value of Damage Biomarkers of Drug-Induced Kidney Injury.

    Science.gov (United States)

    Kane-Gill, Sandra L; Smithburger, Pamela L; Kashani, Kianoush; Kellum, John A; Frazee, Erin

    2017-11-01

    Nephrotoxin exposure accounts for up to one-fourth of acute kidney injury episodes in hospitalized patients, and the associated consequences are as severe as acute kidney injury due to other etiologies. As the use of nephrotoxic agents represents one of the few modifiable risk factors for acute kidney injury, clinicians must be able to identify patients at high risk for drug-induced kidney injury rapidly. Recently, significant advancements have been made in the field of biomarker utilization for the prediction and detection of acute kidney injury. Such biomarkers may have a role both for detection of drug-induced kidney disease and implementation of preventative and therapeutic strategies designed to mitigate injury. In this article, basic principles of renal biomarker use in practice are summarized, and the existing evidence for six markers specifically used to detect drug-induced kidney injury are outlined, including liver-type fatty acid binding protein, neutrophil gelatinase-associated lipocalin, tissue inhibitor of metalloproteinase-2 times insulin-like growth factor-binding protein 7 ([TIMP-2]·[IGFBP7]), kidney injury molecule-1 and N-acetyl-β-D-glucosaminidase. The results of the literature search for these six kidney damage biomarkers identified 29 unique articles with none detected for liver-type fatty acid binding protein and [TIMP-2]·[IGFBP7]. For three biomarkers, kidney injury molecule-1, neutrophil gelatinase-associated lipocalin and N-acetyl-β-D-glucosaminidase, the majority of the studies suggest utility in clinical practice. While many questions need to be answered to clearly articulate the use of biomarkers to predict drug-induced kidney disease, current data are promising.

  7. Rectal microbicides: clinically relevant approach to the design of rectal specific placebo formulations

    Directory of Open Access Journals (Sweden)

    Dezzutti Charlene

    2011-03-01

    Full Text Available Abstract Background The objective of this study is to identify the critical formulation parameters controlling distribution and function for the rectal administration of microbicides in humans. Four placebo formulations were designed with a wide range of hydrophilic characteristics (aqueous to lipid and rheological properties (Newtonian, shear thinning, thermal sensitive and thixotropic. Aqueous formulations using typical polymers to control viscosity were iso-osmotic and buffered to pH 7. Lipid formulations were developed from lipid solvent/lipid gelling agent binary mixtures. Testing included pharmaceutical function and stability as well as in vitro and in vivo toxicity. Results The aqueous fluid placebo, based on poloxamer, was fluid at room temperature, thickened and became shear thinning at 37°C. The aqueous gel placebo used carbopol as the gelling agent, was shear thinning at room temperature and showed a typical decrease in viscosity with an increase in temperature. The lipid fluid placebo, myristyl myristate in isopropyl myristate, was relatively thin and temperature independent. The lipid gel placebo, glyceryl stearate and PEG-75 stearate in caprylic/capric triglycerides, was also shear thinning at both room temperature and 37°C but with significant time dependency or thixotropy. All formulations showed no rectal irritation in rabbits and were non-toxic using an ex vivo rectal explant model. Conclusions Four placebo formulations ranging from fluid to gel in aqueous and lipid formats with a range of rheological properties were developed, tested, scaled-up, manufactured under cGMP conditions and enrolled in a formal stability program. Clinical testing of these formulations as placebos will serve as the basis for further microbicide formulation development with drug-containing products.

  8. Towards studies of organizational behaviour with greater local relevance

    Directory of Open Access Journals (Sweden)

    Peter B. Smith

    2007-12-01

    Full Text Available Theories of organizational behaviour mostly originated in North America. In testing their applicability elsewhere, attention must be given to differences in local environments and inthe values of local employees. Within Latin America, the prevalence of high collectivism and power distance are particularly important. Employees’ attachment to their organization has been shown to differ within collectivistic cultures. The argument is illustrated by two Latin American studies. Firstly, the ways in which managers handle work events within Mexico, Colombia, Brazil, Chile and Argentina are compared. Secondly, cross-national work problems of employees from these countries are surveyed. The results emphasize the need to take account of variability within the region, and the need to use measures that capture locally important issues. -- Las teorías del comportamiento organizacional se han originado principalmente en Américadel Norte. Al probar su aplicabilidad en otras regiones culturales, debe prestarse atención a las diferencias en los ambientes y en los valores de los empleados locales. Dentro de Latinoamérica, la prevalencia de altos niveles de colectivismo y distancia al poder es particularmenteimportante. En ese sentido, se ha demostrado que el apego de los empleados hacia su organización difiere dentro de las culturas colectivistas. El argumento se ilustra por dosestudios latinoamericanos. En el primero, se compara la forma en que los gerentes manejan los eventos laborales dentro de México, Colombia, Brasil, Chile y Argentina. En el segundo,se examinan los problemas laborales transnacionales de los empleados de estos países. Los resultados enfatizan la necesidad de utilizar medidas que capturen aspectos localmente importantes.

  9. Cellular recovery kinetic studies relevant to combined-modality research and therapy

    International Nuclear Information System (INIS)

    Dethlefsen, L.A.

    1979-01-01

    The relevance of cellular recovery kinetics to combined-modality therapy is evaluated within the framework of an idealized experimental flow chart and published adriamycin data. Within this context, limitations for both experimental design and data interpretations are discussed. The effects of adriamycin have been documented extensively at the molecular and cellular level and its interactions with x-irradiation have been studied, both in vitro and in vivo. The limited in vivo results suggest that the end results of a given protocol correlate with cellular recovery kinetics; however, definitive experiments simply have not been done. For example, no one has used single-dose drug and irradiation data to predict the outcome and then confirm or refute the prediction even in a relatively simple 2-dose drug + 2-dose drug + 2-dose x-ray protocol. Thus, at this time, the extent of the correlations between cellular recovery kinetics and clinical response for either normal or malignant tissues is not known and the possible relevance of such studies cannot be discounted

  10. Elements determination of clinical relevance in biological tissues Dmdmdx/J dystrophic mice strains investigated by NAA

    International Nuclear Information System (INIS)

    Metairon, Sabrina

    2012-01-01

    In this work the determination of chemistry elements in biological tissues (whole blood, bones and organs) of dystrophic mice, used as animal model of Duchenne Muscular Dystrophy (DMD), was performed using analytical nuclear technique. The aim of this work was to determine reference values of elements of clinical (Ca, Cl, K, Mg, Na) and nutritional (Br and S) relevance in whole blood, tibia, quadriceps and hearts from Dmdmdx/J (10 males and 10 females) dystrophic mice and C57BL/6J (10 males) control group mice, using Neutron Activation Analysis technique (NAA). To show in more details the alterations that this disease may cause in these biological tissues, correlations matrixes of the DMD mdx /J mouse strain were generated and compared with C57BL/6J control group. For this study 119 samples of biological tissue were irradiated in the IEA-R1 nuclear reactor at IPEN (Sao Paulo, Brazil). The concentrations of these elements in biological tissues of Dmd mdx /J and C57B/6J mice are the first indicative interval for reference values. Moreover, the alteration in some correlation coefficients data among the elements in the health status and in the diseased status indicates a connection between these elements in whole blood, tibia, quadriceps and heart. These results may help the researchers to evaluate the efficiency of new treatments and to compare the advantages of different treatment approaches before performing tests in patients with muscular dystrophy. (author)

  11. Clinical aspects and relevance of molecular diagnosis in late mucocutaneous leishmaniasis patients in Paraná, Brazil

    Directory of Open Access Journals (Sweden)

    Andréa Thomaz-Soccol

    2011-06-01

    Full Text Available The aim of the present work was to study the clinical aspects and relevance of molecular diagnosis in late mucocutaneous leishmaniasis patients in Parana, Brazil. Twenty one suspected cases of mucocutaneous leishmaniasis (MCL in patients from the endemic areas of leishmaniasis were assessed. Different methods used in diagnosing the disease and the polymerase chain reaction (PCR technique were compared in order to establish the sensitivity of each method. Out of the 21 patients analyzed, 14.3% presented other etiologies such as vasculitis, syphilis, and paracoccidioidomycosis, with all tests negative for leishmaniasis. Out of the remaining 15 patients, 6.7% cases were confirmed for leishmaniasis by direct examination; 46.67% were positive for culture, which allowed isolating and identifying the parasite and - with the PCR technique - it was possible to diagnose 100% MCL patients for all the three repetitions of exams. The PCR optimized for the present work proved to be an auxiliary method for diagnosing leishmaniasis applicable in the patients carrying MCL due to Leishmania (Viannia braziliensis and did not need culture to be performed, resulting in a faster diagnosis.

  12. Long noncoding RNA HOTAIR is relevant to cellular proliferation, invasiveness, and clinical relapse in small-cell lung cancer

    International Nuclear Information System (INIS)

    Ono, Hiroshi; Motoi, Noriko; Nagano, Hiroko; Miyauchi, Eisaku; Ushijima, Masaru; Matsuura, Masaaki; Okumura, Sakae; Nishio, Makoto; Hirose, Tetsuro; Inase, Naohiko; Ishikawa, Yuichi

    2014-01-01

    Small-cell lung cancer (SCLC) is a subtype of lung cancer with poor prognosis. To identify accurate predictive biomarkers and effective therapeutic modalities, we focus on a long noncoding RNA, Hox transcript antisense intergenic RNA (HOTAIR), and investigated its expression, cellular functions, and clinical relevance in SCLC. In this study, HOTAIR expression was assessed in 35 surgical SCLC samples and 10 SCLC cell lines. The efficacy of knockdown of HOTAIR by siRNA transfection was evaluated in SBC-3 cells in vitro, and the gene expression was analyzed using microarray. HOTAIR was expressed highly in pure, rather than combined, SCLC (P = 0.012), that the subgroup with high expression had significantly more pure SCLC (P = 0.04), more lymphatic invasion (P = 0.03) and more relapse (P = 0.04) than the low-expression subgroup. The knockdown of HOTAIR in SBC-3 cells led to decreased proliferation activity and decreased invasiveness in vitro. Gene expression analysis indicated that depletion of HOTAIR resulted in upregulation of cell adhesion-related genes such as ASTN1, PCDHA1, and mucin production-related genes such as MUC5AC, and downregulation of genes involved in neuronal growth and signal transduction including NTM and PTK2B. Our results suggest that HOTAIR has an oncogenic role in SCLC and could be a prognostic biomarker and therapeutic target

  13. Exploring internal features of 16S rRNA gene for identification of clinically relevant species of the genus Streptococcus

    Science.gov (United States)

    2011-01-01

    Background Streptococcus is an economically important genus as a number of species belonging to this genus are human and animal pathogens. The genus has been divided into different groups based on 16S rRNA gene sequence similarity. The variability observed among the members of these groups is low and it is difficult to distinguish them. The present study was taken up to explore 16S rRNA gene sequence to develop methods that can be used for preliminary identification and can supplement the existing methods for identification of clinically-relevant isolates of the genus Streptococcus. Methods 16S rRNA gene sequences belonging to the isolates of S. dysgalactiae, S. equi, S. pyogenes, S. agalactiae, S. bovis, S. gallolyticus, S. mutans, S. sobrinus, S. mitis, S. pneumoniae, S. thermophilus and S. anginosus were analyzed with the purpose to define genetic variability within each species to generate a phylogenetic framework, to identify species-specific signatures and in-silico restriction enzyme analysis. Results The framework based analysis was used to segregate Streptococcus spp. previously identified upto genus level. This segregation was validated using species-specific signatures and in-silico restriction enzyme analysis. 43 uncharacterized Streptococcus spp. could be identified using this approach. Conclusions The markers generated exploring 16S rRNA gene sequences provided useful tool that can be further used for identification of different species of the genus Streptococcus. PMID:21702978

  14. Faith healing in paediatrics: what do we know about its relevance to clinical practice?

    Science.gov (United States)

    Baverstock, A; Finlay, F

    2012-05-01

    There is widespread use of complementary or alternative medicine among adults and children. Families may use faith healing alongside conventional medicine or as an alternative. In their clinical practice, professionals should be aware of this and need to consider asking patients and their families about complementary or alternative medicine use, including faith healing. © 2011 Blackwell Publishing Ltd.

  15. Frailty and sarcopenia: From theory to clinical implementation and public health relevance.

    Science.gov (United States)

    Cesari, Matteo; Nobili, Alessandro; Vitale, Giovanni

    2016-11-01

    The sustainability of healthcare systems is threatened by the increasing (absolute and relative) number of older persons referring to clinical services. Such global phenomenon is questioning the traditional paradigms of medicine, pushing towards the need of new criteria at the basis of clinical decision algorithms. In this context, frailty has been advocated as a geriatric condition potentially capable of overcoming the weakness of chronological age in the identification of individuals requiring adapted care due to their increased vulnerability to stressors. Interestingly, frailty poses itself beyond the concept of nosological conditions due to the difficulties at correctly framing traditional diseases in the complex and heterogeneous scenario of elders. Thus, frailty may play a key role in public health policies for promoting integrated care towards biologically aged individuals, currently presenting multiple unmet clinical needs. At the same time, the term frailty has also been frequently used in the literature for framing a physical condition of risk for (mainly functional) negative endpoints. The combination of such physical impairment with an organ-specific phenotype (e.g., the age-related skeletal muscle decline or sarcopenia) may determine the assumptions for the development of a clinical condition to be used as potential target for ad hoc interventions against physical disability. In the present article, we present the background of frailty and sarcopenia, and discuss their potentialities for reshaping current clinical and research practice in order to promote holistic approach to older patients, solicit personalization of care, and develop new targets for innovative interventions. Copyright © 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  16. Clinically relevant diagnostic research in primary care: the example of B-type natriuretic peptides in the detection of heart failure.

    Science.gov (United States)

    Kelder, Johannes C; Rutten, Frans H; Hoes, Arno W

    2009-02-01

    With the emergence of novel diagnostic tests, e.g. point-of-care tests, clinically relevant empirical evidence is needed to assess whether such a test should be used in daily practice. With the example of the value of B-type natriuretic peptides (BNP) in the diagnostic assessment of suspected heart failure, we will discuss the major methodological issues crucial in diagnostic research; most notably the choice of the study population and the data analysis with a multivariable approach. BNP have been studied extensively in the emergency care setting, and also several studies in the primary care are available. The usefulness of this test when applied in combination with other readily available tests is still not adequately addressed in the relevant patient domain, i.e. those who are clinically suspected of heart failure by their GP. Future diagnostic research in primary care should be targeted much more at answering the clinically relevant question 'Is it useful to add this (new) test to the other tests I usually perform, including history taking and physical examination, in patients I suspect of having a certain disease'.

  17. Investigation of critical inter-related factors affecting the efficacy of pulsed light for inactivating clinically relevant bacterial pathogens.

    Science.gov (United States)

    Farrell, H P; Garvey, M; Cormican, M; Laffey, J G; Rowan, N J

    2010-05-01

    diminish survival compared to similarly treated bacteria inoculated and enumerated on nonselective agar plates. Critical inter-related factors affecting the effective and repeatable in vitro decontamination performance of PL were identified during this study that will aid further development of this athermal process technology for applications in health care and in industry. Very rapid reductions (c. 7 log(10) CFU cm(-2) within discharge energy of 20 J for all tested clinically relevant bacteria under study when treated at 8 cm distance from xenon light source. While no resistant flora is expected to develop for treatment of microbial pathogens on two-dimensional surfaces, careful consideration of scale up factors such as design and operational usage of this PL technique will be required to assure operator safety. Findings and conclusions derived from this study will enable further development and optimization of this decontamination technique in health care and in food preparation settings, and will advance the field of nonthermal processing technologies.

  18. Patient-reported symptoms during radiotherapy. Clinically relevant symptom burden in patients treated with palliative and curative intent

    Energy Technology Data Exchange (ETDEWEB)

    Koerner, Philipp [Universitaetsklinikum Wuerzburg, Interdisziplinaeres Zentrum Palliativmedizin, Wuerzburg (Germany); Universitaetsklinikum Wuerzburg, Klinik und Poliklinik fuer Strahlentherapie, Wuerzburg (Germany); Ehrmann, Katja [Universitaetsklinikum Wuerzburg, Medizinische Psychologie und Psychotherapie, Medizinische Soziologie und Rehabilitationswissenschaften, Wuerzburg (Germany); Hartmannsgruber, Johann [Praxis Landshut, Kinderzahnheilkunde, Landshut (Germany); Metz, Michaela; Steigerwald, Sabrina; Flentje, Michael [Universitaetsklinikum Wuerzburg, Klinik und Poliklinik fuer Strahlentherapie, Wuerzburg (Germany); Oorschot, Birgitt van [Universitaetsklinikum Wuerzburg, Interdisziplinaeres Zentrum Palliativmedizin, Wuerzburg (Germany)

    2017-07-15

    The benefits of patient-reported symptom assessment combined with integrated palliative care are well documented. This study assessed the symptom burden of palliative and curative-intent radiation oncology patients. Prior to first consultation and at the end of RT, all adult cancer patients planned to receive fractionated percutaneous radiotherapy (RT) were asked to answer the Edmonton Symptom Assessment Scale (ESAS; nine symptoms from 0 = no symptoms to 10 = worst possible symptoms). Mean values were used for curative vs. palliative and pre-post comparisons, and the clinical relevance was evaluated (symptom values ≥ 4). Of 163 participating patients, 151 patients (90.9%) completed both surveys (116 curative and 35 palliative patients). Before beginning RT, 88.6% of palliative and 72.3% of curative patients showed at least one clinically relevant symptom. Curative patients most frequently named decreased general wellbeing (38.6%), followed by tiredness (35.0%), anxiety (32.4%), depression (30.0%), pain (26.3%), lack of appetite (23.5%), dyspnea (17.8%), drowsiness (8.0%) and nausea (6.1%). Palliative patients most frequently named decreased general wellbeing (62.8%), followed by pain (62.8%), tiredness (60.0%), lack of appetite (40.0%), anxiety (38.0%), depression (33.3%), dyspnea (28.5%), drowsiness (25.7%) and nausea (14.2%). At the end of RT, the proportion of curative and palliative patients with a clinically relevant symptom had increased significantly to 79.8 and 91.4%, respectively; whereas the proportion of patients reporting clinically relevant pain had decreased significantly (42.8 vs. 62.8%, respectively). Palliative patients had significantly increased tiredness. Curative patients reported significant increases in pain, tiredness, nausea, drowsiness, lack of appetite and restrictions in general wellbeing. Assessment of patient-reported symptoms was successfully realized in radiation oncology routine. Overall, both groups showed a high symptom burden

  19. The clinical relevance of cell-based therapy for the treatment of stress urinary incontinence

    DEFF Research Database (Denmark)

    Gräs, Søren; Lose, Gunnar

    2011-01-01

    or progenitor cells presents an alternative approach, which aims at repairing the anatomical components of the urethral continence mechanism. In vitro expanded progenitor cells isolated from muscle biopsies have been most intensely investigated, and both preclinical trials and a few clinical trials have......Stress urinary incontinence is a common disorder affecting the quality of life for millions of women worldwide. Effective surgical procedures involving synthetic permanent meshes exist, but significant short- and long-term complications occur. Cell-based therapy using autologous stem cells...... provided proof of concept for the idea. An initial enthusiasm caused by positive results from early clinical trials has been dampened by the recognition of scientific irregularities. At the same time, the safety issue for cell-based therapy has been highlighted by the appearance of new and comprehensive...

  20. The default network and self-generated thought: component processes, dynamic control, and clinical relevance

    Science.gov (United States)

    Andrews-Hanna, Jessica R.; Smallwood, Jonathan; Spreng, R. Nathan

    2014-01-01

    Though only a decade has elapsed since the default network was first emphasized as being a large-scale brain system, recent years have brought great insight into the network’s adaptive functions. A growing theme highlights the default network as playing a key role in internally-directed—or self-generated—thought. Here, we synthesize recent findings from cognitive science, neuroscience, and clinical psychology to focus attention on two emerging topics as current and future directions surrounding the default network. First, we present evidence that self-generated thought is a multi-faceted construct whose component processes are supported by different subsystems within the network. Second, we highlight the dynamic nature of the default network, emphasizing its interaction with executive control systems when regulating aspects of internal thought. We conclude by discussing clinical implications of disruptions to the integrity of the network, and consider disorders when thought content becomes polarized or network interactions become disrupted or imbalanced. PMID:24502540

  1. Phylogeny of the Clinically Relevant Species of the Emerging Fungus Trichoderma and Their Antifungal Susceptibilities

    Science.gov (United States)

    Sandoval-Denis, Marcelo; Sutton, Deanna A.; Cano-Lira, José F.; Fothergill, Annette W.; Wiederhold, Nathan P.; Guarro, Josep

    2014-01-01

    A set of 73 isolates of the emerging fungus Trichoderma isolated from human and animal clinical specimens were characterized morphologically and molecularly using a multilocus sequence analysis that included the internal transcribed spacer (ITS) regions of the nuclear ribosomal DNA and fragments of the translation elongation factor 1 alpha (Tef1), endochitinase CHI18-5 (Chi18-5), and actin 1 (Act1) genes. The most frequent species was Trichoderma longibrachiatum (26%), followed by Trichoderma citrinoviride (18%), the Hypocrea lixii/Trichoderma harzianum species complex (15%), the newly described species Trichoderma bissettii (12%), and Trichoderma orientale (11%). The most common anatomical sites of isolation in human clinical specimens were the respiratory tract (40%), followed by deep tissue (30%) and superficial tissues (26%), while all the animal-associated isolates were obtained from superficial tissue samples. Susceptibilities of the isolates to eight antifungal drugs in vitro showed mostly high MICs, except for voriconazole and the echinocandins. PMID:24719448

  2. Lack of clinical relevance in routine final subcultures of radiometrically negative BACTEC blood culture vials

    International Nuclear Information System (INIS)

    Plorde, J.J.; Carlson, L.G.; Dau, M.E.

    1982-01-01

    During a 38-month period, 10,106 blood specimens were received in the laboratory for culture. These were inoculated into 26,424 vials and processed using the BACTEC radiometric detection system. Of these vials, 1,914 were eventually found to be microbiologically positive. Isolates from 836 vials were judged to be contaminants. In the remaining 1,078 vials, growth was first detected visually or radiometrically in 1,062 and by final subculture in 16. Growth from these sixteen bottles represented 12 clinically significant bacteremic episodes in as many patients. In nine of these episodes, other culture vials from the same patient were positive radiometrically. Therefore, 358 of 361 (99.2%) bacteremic episodes were detected without the benefit of routine final subcultures. The three patients whose bacteremia was missed were diagnosed clinically and placed on appropriate therapy prior to the detection of the bacteremias by final subculture

  3. Spectrometric determination of clinically relevant fatty acids in the blood serum

    Science.gov (United States)

    Kalinin, A. V.; Krasheninnikov, V. N.; Sviridov, A. P.; Titov, V. N.

    2017-01-01

    The content of fatty acid (FA) triglycerides in food and biological media is predicting traditionally using gas and liquid chromatographic methods. Named techniques aren't available for clinical labs due to their complexity. So, our objective was to develop the method and apparatus for rapid assay of a few clinically important FA as the saturated palmitic, mono unsaturated oleic and others in serum using near infrared spectrometer. As a result, the applicability of the FT spectrometer in the wavelength range of 0.9 -1.8 μ to analyze these FA in serum without sample preparation was confirmed. Besides, measurement specifications were determined and a correlations of the absorption spectra and contents of total triglycerides and cholesterol, palmitic, oleic, linoleic and arachidonic FA in serum were established

  4. Clinical relevance of changes in bone metabolism in inflammatory bowel disease

    Science.gov (United States)

    Miheller, Pal; Lőrinczy, Katalin; Lakatos, Peter Laszlo

    2010-01-01

    Low bone mineral density is an established, frequent, but often neglected complication in patients with inflammatory bowel disease (IBD). Data regarding the diagnosis, therapy and follow-up of low bone mass in IBD has been partially extrapolated from postmenopausal osteoporosis; however, the pathophysiology of bone loss is altered in young patients with IBD. Fracture, a disabling complication, is the most important clinical outcome of low bone mass. Estimation of fracture risk in IBD is difficult. Numerous risk factors have to be considered, and these factors should be weighed properly to help in the identification of the appropriate patients for screening. In this editorial, the authors aim to highlight the most important clinical aspects of the epidemiology, prevention, diagnosis and treatment of IBD-related bone loss. PMID:21105186

  5. Conditional conservatism and value relevance of financial reporting: A study in view of converging accounting standards

    NARCIS (Netherlands)

    Thijssen, Maximiliaan Willem Pierre; Iatridis, George Emmanuel

    2016-01-01

    This study examines the relationship between conditional conservatism and value relevance in the EU and US. Specifically, it investigates whether this relationship differs under US GAAP and IFRS compliance. In addition, this study examines the trend in value relevance, conditional conservatism and

  6. The relevance of clinical balance assessment tools to differentiate balance deficits

    OpenAIRE

    Mancini, Martina; Horak, Fay B

    2010-01-01

    Control of balance is complex and involves maintaining postures, facilitating movement, and recovering equilibrium. Balance control consists of controlling the body center of mass over its limits of stability. Clinical balance assessment can help assess fall risk and/or determine the underlying reasons for balance disorders. Most functional balance assessment scales assess fall risk and the need for balance rehabilitation but do not differentiate types of balance deficits. A system approach t...

  7. The role of neuropsychology in UK pediatric HIV care: Relevance to clinical practice and research.

    Science.gov (United States)

    Freeman, Anita

    2017-11-01

    There has been a dramatic improvement in the survival of children with perinatally-acquired HIV (PHIV) following the introduction of effective treatment in 1990s. The care for children living with PHIV is now focused on more accurately understanding the effects of both HIV and HIV treatment on the developing body and brain. An evaluation of current HIV neuroimaging, and neurocognitive research, when combined with clinical experience in the area of HIV, could help to inform United Kingdom (UK) PHIV service provision. This paper argues that an understanding from a neuropsychological perspective will help these young people to optimize their health, quality of life, and future functioning. The aim of the paper is to bring together research and clinical understanding of HIV and its treatment effects on the developing brain, together with an understanding of other potential neurological risk factors. It is argued here that there is a need for targeted neuropsychology assessment and preventative interventions, supported by clinical and preliminary research on the neurocognitive effects of HIV and its treatments.

  8. Cato Guldberg and Peter Waage, the history of the Law of Mass Action, and its relevance to clinical pharmacology.

    Science.gov (United States)

    Ferner, Robin E; Aronson, Jeffrey K

    2016-01-01

    We have traced the historical link between the Law of Mass Action and clinical pharmacology. The Law evolved from the work of the French chemist Claude Louis Berthollet, was first formulated by Cato Guldberg and Peter Waage in 1864 and later clarified by the Dutch chemist Jacobus van 't Hoff in 1877. It has profoundly influenced our qualitative and quantitative understanding of a number of physiological and pharmacological phenomena. According to the Law of Mass Action, the velocity of a chemical reaction depends on the concentrations of the reactants. At equilibrium the concentrations of the chemicals involved bear a constant relation to each other, described by the equilibrium constant, K. The Law of Mass Action is relevant to various physiological and pharmacological concepts, including concentration-effect curves, dose-response curves, and ligand-receptor binding curves, all of which are important in describing the pharmacological actions of medications, the Langmuir adsorption isotherm, which describes the binding of medications to proteins, activation curves for transmembrane ion transport, enzyme inhibition and the Henderson-Hasselbalch equation, which describes the relation between pH, as a measure of acidity and the concentrations of the contributory acids and bases. Guldberg and Waage recognized the importance of dynamic equilibrium, while others failed to do so. Their ideas, over 150 years old, are embedded in and still relevant to clinical pharmacology. Here we explain the ideas and in a subsequent paper show how they are relevant to understanding adverse drug reactions. © 2015 The British Pharmacological Society.

  9. The relevance of clinical ethnography: reflections on 10 years of a cultural consultation service.

    Science.gov (United States)

    Dominicé Dao, Melissa; Inglin, Sophie; Vilpert, Sarah; Hudelson, Patricia

    2018-01-11

    Training health professionals in culturally sensitive medical interviewing has been widely promoted as a strategy for improving intercultural communication and for helping clinicians to consider patients' social and cultural contexts and improve patient outcomes. Clinical ethnography encourages clinicians to explore the patient's explanatory model of illness, recourse to traditional and alternative healing practices, healthcare expectations and social context, and to use this information to negotiate a mutually acceptable treatment plan. However, while clinical ethnographic interviewing skills can be successfully taught and learned, the "real-world" context of medical practice may impose barriers to such patient-centered interviewing. Creating opportunities for role modeling and critical reflection may help overcome some of these barriers, and contribute to improved intercultural communication in healthcare. We report and reflect on a retrospective analysis of 10 years experience with a "cultural consultation service" (CCS) whose aim is to provide direct support to clinicians who encounter intercultural difficulties and to model the usefulness of clinical ethnographic interviewing for patient care. We analyzed 236 cultural consultation requests in order to identify key patient, provider and consultation characteristics, as well as the cross cultural communication challenges that motivate health care professionals to request a cultural consultation. In addition, we interviewed 51 clinicians about their experience and satisfaction with the CCS. Requests for cultural consultations tended to involve patient care situations with complex social, cultural and medical issues. All patients had a migration background, two-thirds spoke French less than fluently. In over half the cases, patients had a high degree of social vulnerability, compromising illness management. Effective communication was hindered by language barriers and undetected or underestimated patient

  10. Tumor hypoxia at the micro-regional level: clinical relevance and predictive value of exogenous and endogenous hypoxic cell markers

    International Nuclear Information System (INIS)

    Bussink, Johan; Kaanders, Johannes H.A.M.; Kogel, Albert J. van der

    2003-01-01

    selection of treatment strategies for individual patients. This requires testing of these markers in prospective randomized clinical trials comparing standard treatment against experimental treatments targeting the relevant microregional constituent

  11. Comprehensive genomic profiling of 295 cases of clinically advanced urothelial carcinoma of the urinary bladder reveals a high frequency of clinically relevant genomic alterations.

    Science.gov (United States)

    Ross, Jeffrey S; Wang, Kai; Khaira, Depinder; Ali, Siraj M; Fisher, Huge A G; Mian, Badar; Nazeer, Tipu; Elvin, Julia A; Palma, Norma; Yelensky, Roman; Lipson, Doron; Miller, Vincent A; Stephens, Philip J; Subbiah, Vivek; Pal, Sumanta K

    2016-03-01

    In the current study, the authors present a comprehensive genomic profile (CGP)-based study of advanced urothelial carcinoma (UC) designed to detect clinically relevant genomic alterations (CRGAs). DNA was extracted from 40 µm of formalin-fixed, paraffin-embedded sections from 295 consecutive cases of recurrent/metastatic UC. CGP was performed on hybridization-captured, adaptor ligation-based libraries to a mean coverage depth of 688X for all coding exons of 236 cancer-related genes plus 47 introns from 19 genes frequently rearranged in cancer, using process-matched normal control samples as a reference. CRGAs were defined as GAs linked to drugs on the market or currently under evaluation in mechanism-driven clinical trials. All 295 patients assessed were classified with high-grade (International Society of Urological Pathology classification) and advanced stage (stage III/IV American Joint Committee on Cancer) disease, and 294 of 295 patients (99.7%) had at least 1 GA on CGP with a mean of 6.4 GAs per UC (61% substitutions/insertions/deletions, 37% copy number alterations, and 2% fusions). Furthermore, 275 patients (93%) had at least 1 CRGA involving 75 individual genes with a mean of 2.6 CRGAs per UC. The most common CRGAs involved cyclin-dependent kinase inhibitor 2A (CDKN2A) (34%), fibroblast growth factor receptor 3 (FGFR3) (21%), phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) (20%), and ERBB2 (17%). FGFR3 GAs were diverse types and included 10% fusions. ERBB2 GAs were equally divided between amplifications and substitutions. ERBB2 substitutions were predominantly within the extracellular domain and were highly enriched in patients with micropapillary UC (38% of 32 cases vs 5% of 263 nonmicropapillary UC cases; PCancer 2016;122:702-711. © 2015 American Cancer Society. © 2015 American Cancer Society.

  12. Guidance on assessing the methodological and reporting quality of toxicologically relevant studies: A scoping review.

    Science.gov (United States)

    Samuel, Gbeminiyi O; Hoffmann, Sebastian; Wright, Robert A; Lalu, Manoj Mathew; Patlewicz, Grace; Becker, Richard A; DeGeorge, George L; Fergusson, Dean; Hartung, Thomas; Lewis, R Jeffrey; Stephens, Martin L

    2016-01-01

    Assessments of methodological and reporting quality are critical to adequately judging the credibility of a study's conclusions and to gauging its potential reproducibility. To aid those seeking to assess the methodological or reporting quality of studies relevant to toxicology, we conducted a scoping review of the available guidance with respect to four types of studies: in vivo and in vitro, (quantitative) structure-activity relationships ([Q]SARs), physico-chemical, and human observational studies. Our aims were to identify the available guidance in this diverse literature, briefly summarize each document, and distill the common elements of these documents for each study type. In general, we found considerable guidance for in vivo and human studies, but only one paper addressed in vitro studies exclusively. The guidance for (Q)SAR studies and physico-chemical studies was scant but authoritative. There was substantial overlap across guidance documents in the proposed criteria for both methodological and reporting quality. Some guidance documents address toxicology research directly, whereas others address preclinical research generally or clinical research and therefore may not be fully applicable to the toxicology context without some translation. Another challenge is the degree to which assessments of methodological quality in toxicology should focus on risk of bias - as in clinical medicine and healthcare - or be broadened to include other quality measures, such as confirming the identity of test substances prior to exposure. Our review is intended primarily for those in toxicology and risk assessment seeking an entry point into the extensive and diverse literature on methodological and reporting quality applicable to their work. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  13. Relevancia de la anatomía humana en el ejercicio de la medicina de asistencia primaria y en el estudio de las asignaturas de segundo ciclo de la licenciatura en medicina Relevance of Gross Human Anatomy in health primary care and in clinical disciplines of medical studies

    Directory of Open Access Journals (Sweden)

    Blanca Mompeó

    2003-03-01

    Full Text Available El objetivo de este trabajo fue conocer la relevancia y la necesidad que de conocimientos en Anatomía macroscópica tenían los médicos de asistencia primaria y los alumnos del segundo ciclo de la licenciatura en Medicina. También nos interesó saber cual era su opinión sobre esta disciplina del curriculum médico. Para ello, médicos de asistencia primaria de los Centros de Salud de la provincia de las Palmas y alumnos de 6º curso de la Licenciatura en Medicina de la U.L.P.G.C., cumplimentaron un cuestionario en el que se valoraron los aspectos referidos. Ambos grupos consideraron que la Anatomía era fundamental para la exploración física y para la interpretación de técnicas de imagen. Los conocimientos más necesarios a la hora de su aplicación a la práctica y al estudio de las asignaturas clínicas fueron los de sistema nervioso y aparato locomotor. Modificarían la docencia que recibieron, incrementando el número de clases prácticas y dándole un mayor enfoque clínico. Los tres objetivos fundamentales de aprendizaje propuestos por los profesionales en ejercicio fueron: 1. Conocer las estructuras anatómicas y relaciones entre ellas 2. Reconocer estructuras anatómicas mediante técnicas de imagen y 3. Ser capaz de describir las bases anatómicas de la patología.The aim of this work was to highlight the relevance and necessity about gross anatomy knowledge had on family physicians and clinical-courses medical students. We also wanted to know their suggestions about the discipline Human Anatomy in Medical studies. To obtain our objective, physicians of Health Centres in Las Palmas and last-year medical students of U.L.P.G.C. were asked to fill a questionnaire. In this questionnaire the referred items were considered. The data obtained showed that both groups thought that Gross Anatomy was fundamental in the physical exploration and the image techniques interpretation. They considered that anatomical knowledge more necessary for

  14. Cisplatin Resistant Spheroids Model Clinically Relevant Survival Mechanisms in Ovarian Tumors.

    Directory of Open Access Journals (Sweden)

    Winyoo Chowanadisai

    Full Text Available The majority of ovarian tumors eventually recur in a drug resistant form. Using cisplatin sensitive and resistant cell lines assembled into 3D spheroids we profiled gene expression and identified candidate mechanisms and biological pathways associated with cisplatin resistance. OVCAR-8 human ovarian carcinoma cells were exposed to sub-lethal concentrations of cisplatin to create a matched cisplatin-resistant cell line, OVCAR-8R. Genome-wide gene expression profiling of sensitive and resistant ovarian cancer spheroids identified 3,331 significantly differentially expressed probesets coding for 3,139 distinct protein-coding genes (Fc >2, FDR < 0.05 (S2 Table. Despite significant expression changes in some transporters including MDR1, cisplatin resistance was not associated with differences in intracellular cisplatin concentration. Cisplatin resistant cells were significantly enriched for a mesenchymal gene expression signature. OVCAR-8R resistance derived gene sets were significantly more biased to patients with shorter survival. From the most differentially expressed genes, we derived a 17-gene expression signature that identifies ovarian cancer patients with shorter overall survival in three independent datasets. We propose that the use of cisplatin resistant cell lines in 3D spheroid models is a viable approach to gain insight into resistance mechanisms relevant to ovarian tumors in patients. Our data support the emerging concept that ovarian cancers can acquire drug resistance through an epithelial-to-mesenchymal transition.

  15. The ICSD-3 and DSM-5 guidelines for diagnosing narcolepsy: clinical relevance and practicality.

    Science.gov (United States)

    Ruoff, Chad; Rye, David

    2016-07-20

    Narcolepsy is a chronic neurological disease manifesting as difficulty with maintaining continuous wake and sleep. Clinical presentation varies but requires excessive daytime sleepiness (EDS) occurring alone or together with features of rapid-eye movement (REM) sleep dissociation (e.g., cataplexy, hypnagogic/hypnopompic hallucinations, sleep paralysis), and disrupted nighttime sleep. Narcolepsy with cataplexy is associated with reductions of cerebrospinal fluid (CSF) hypocretin due to destruction of hypocretin peptide-producing neurons in the hypothalamus in individuals with a specific genetic predisposition. Updated diagnostic criteria include the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) and International Classification of Sleep Disorders Third Edition (ICSD-3). DSM-5 criteria require EDS in association with any one of the following: (1) cataplexy; (2) CSF hypocretin deficiency; (3) REM sleep latency ≤15 minutes on nocturnal polysomnography (PSG); or (4) mean sleep latency ≤8 minutes on multiple sleep latency testing (MSLT) with ≥2 sleep-onset REM-sleep periods (SOREMPs). ICSD-3 relies more upon objective data in addition to EDS, somewhat complicating the diagnostic criteria: 1) cataplexy and either positive MSLT/PSG findings or CSF hypocretin deficiency; (2) MSLT criteria similar to DSM-5 except that a SOREMP on PSG may count as one of the SOREMPs required on MSLT; and (3) distinct division of narcolepsy into type 1, which requires the presence of cataplexy or documented CSF hypocretin deficiency, and type 2, where cataplexy is absent, and CSF hypocretin levels are either normal or undocumented. We discuss limitations of these criteria such as variability in clinical presentation of cataplexy, particularly when cataplexy may be ambiguous, as well as by age; multiple and/or invasive CSF diagnostic test requirements; and lack of normative diagnostic test data (e.g., MSLT) in certain populations. While ICSD-3 criteria

  16. Exhaled nitric oxide measure using multiple flows in clinically relevant subgroups of COPD

    DEFF Research Database (Denmark)

    Roberts, Nassim Bazeghi; Gerds, Thomas A; Budtz-Jørgensen, Esben

    2011-01-01

    Although there is widespread interest in fractional exhaled nitric oxide (FeNO) as a non-invasive, time and cost effective biomarker for assessing airway inflammation in chronic obstructive pulmonary disease (COPD), its usefulness is still controversial. We examined the FeNO levels in clinically...... (Caw). All patients had spirometry, assessment of symptoms with questionnaires and low-dose CT scan as well as assessment of weight and body composition. We examined the following subgroups of COPD: Patients with 1) Severe emphysema, 2) Chronic bronchitis, 3) Frequent exacerbations, 4) Loss of lean...

  17. Biologically effective dose distribution based on the linear quadratic model and its clinical relevance

    International Nuclear Information System (INIS)

    Lee, Steve P.; Leu, Min Y.; Smathers, James B.; McBride, William H.; Parker, Robert G.; Withers, H. Rodney

    1995-01-01

    Purpose: Radiotherapy plans based on physical dose distributions do not necessarily entirely reflect the biological effects under various fractionation schemes. Over the past decade, the linear-quadratic (LQ) model has emerged as a convenient tool to quantify biological effects for radiotherapy. In this work, we set out to construct a mechanism to display biologically oriented dose distribution based on the LQ model. Methods and Materials: A computer program that converts a physical dose distribution calculated by a commercially available treatment planning system to a biologically effective dose (BED) distribution has been developed and verified against theoretical calculations. This software accepts a user's input of biological parameters for each structure of interest (linear and quadratic dose-response and repopulation kinetic parameters), as well as treatment scheme factors (number of fractions, fractional dose, and treatment time). It then presents a two-dimensional BED display in conjunction with anatomical structures. Furthermore, to facilitate clinicians' intuitive comparison with conventional fractionation regimen, a conversion of BED to normalized isoeffective dose (NID) is also allowed. Results: Two sample cases serve to illustrate the application of our tool in clinical practice. (a) For an orthogonal wedged pair of x-ray beams treating a maxillary sinus tumor, the biological effect at the ipsilateral mandible can be quantified, thus illustrates the so-called 'double-trouble' effects very well. (b) For a typical four-field, evenly weighted prostate treatment using 10 MV x-rays, physical dosimetry predicts a comparable dose at the femoral necks between an alternate two-fields/day and four-fields/day schups. However, our BED display reveals an approximate 21% higher BED for the two-fields/day scheme. This excessive dose to the femoral necks can be eliminated if the treatment is delivered with a 3:2 (anterio-posterior/posterio-anterior (AP

  18. Cancer Genome Interpreter annotates the biological and clinical relevance of tumor alterations.

    Science.gov (United States)

    Tamborero, David; Rubio-Perez, Carlota; Deu-Pons, Jordi; Schroeder, Michael P; Vivancos, Ana; Rovira, Ana; Tusquets, Ignasi; Albanell, Joan; Rodon, Jordi; Tabernero, Josep; de Torres, Carmen; Dienstmann, Rodrigo; Gonzalez-Perez, Abel; Lopez-Bigas, Nuria

    2018-03-28

    While tumor genome sequencing has become widely available in clinical and research settings, the interpretation of tumor somatic variants remains an important bottleneck. Here we present the Cancer Genome Interpreter, a versatile platform that automates the interpretation of newly sequenced cancer genomes, annotating the potential of alterations detected in tumors to act as drivers and their possible effect on treatment response. The results are organized in different levels of evidence according to current knowledge, which we envision can support a broad range of oncology use cases. The resource is publicly available at http://www.cancergenomeinterpreter.org .

  19. LEFT VENTRICULAR ROTATION, TWIST AND UNTWIST: PHYSIOLOGICAL ROLE AND CLINICAL RELEVANCE

    Directory of Open Access Journals (Sweden)

    E. N. Pavlyukova

    2015-09-01

    Full Text Available The helical ventricular myocardial band of Torrent-Guasp is a new concept, which provides strong grounds for reconciliation of some important aspects in cardiovascular medicine. Oblique fiber orientation provides left ventricular rotation, which in addition to radial thickening and longitudinal shortening, is predicted as an essential component of the effective left ventricular pumping. Left ventricular rotation can be measured in clinical practice noninvasively using echocardiography and this provides new opportunities for the assessment of different aspects of left ventricular mechanical function.

  20. [Clinical relevance of ESR1 circulating mutations detection in hormone receptor positive metastatic breast cancer].

    Science.gov (United States)

    Clatot, Florian; Perdrix, Anne; Sefrioui, David; Sarafan-Vasseur, Nasrin; Di Fiore, Frédéric

    2018-01-01

    If hormone therapy is a key treatment for hormone receptor positive advanced breast cancers, secondary resistance occurs as a rule. Recently, acquired alterations of the ESR1 gene have been identified as a mechanism of resistance on aromatase inhibitor (AI) treatment. The selective pressure by AI exposure during the metastatic setting triggers the emergence of ESR1 activating mutations. In that context, the "liquid biopsy" concept has been used to detect this molecular resistance before progression. Thus, the ESR1 circulating mutation detection will soon be used in daily practice to help monitoring patients on AI treatment and provide an early change for specific therapies that still have to be determined in prospective clinical trials. This review will present the acquired ESR1 mutations, as well as the methods used for their detection in blood and the potential clinical impact of this approach for hormone receptor positive breast cancer management. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  1. Clinically Relevant Pharmacological Strategies That Reverse MDMA-Induced Brain Hyperthermia Potentiated by Social Interaction.

    Science.gov (United States)

    Kiyatkin, Eugene A; Ren, Suelynn; Wakabayashi, Ken T; Baumann, Michael H; Shaham, Yavin

    2016-01-01

    MDMA-induced hyperthermia is highly variable, unpredictable, and greatly potentiated by the social and environmental conditions of recreational drug use. Current strategies to treat pathological MDMA-induced hyperthermia in humans are palliative and marginally effective, and there are no specific pharmacological treatments to counteract this potentially life-threatening condition. Here, we tested the efficacy of mixed adrenoceptor blockers carvedilol and labetalol, and the atypical antipsychotic clozapine, in reversing MDMA-induced brain and body hyperthermia. We injected rats with a moderate non-toxic dose of MDMA (9 mg/kg) during social interaction, and we administered potential treatment drugs after the development of robust hyperthermia (>2.5 °C), thus mimicking the clinical situation of acute MDMA intoxication. Brain temperature was our primary focus, but we also simultaneously recorded temperatures from the deep temporal muscle and skin, allowing us to determine the basic physiological mechanisms of the treatment drug action. Carvedilol was modestly effective in attenuating MDMA-induced hyperthermia by moderately inhibiting skin vasoconstriction, and labetalol was ineffective. In contrast, clozapine induced a marked and immediate reversal of MDMA-induced hyperthermia via inhibition of brain metabolic activation and blockade of skin vasoconstriction. Our findings suggest that clozapine, and related centrally acting drugs, might be highly effective for reversing MDMA-induced brain and body hyperthermia in emergency clinical situations, with possible life-saving results.

  2. Clinical relevance of copy number profiling in oral and oropharyngeal squamous cell carcinoma

    Science.gov (United States)

    van Kempen, Pauline M W; Noorlag, Rob; Braunius, Weibel W; Moelans, Cathy B; Rifi, Widad; Savola, Suvi; Koole, Ronald; Grolman, Wilko; van Es, Robert J J; Willems, Stefan M

    2015-01-01

    Current conventional treatment modalities in head and neck squamous cell carcinoma (HNSCC) are nonselective and have shown to cause serious side effects. Unraveling the molecular profiles of head and neck cancer may enable promising clinical applications that pave the road for personalized cancer treatment. We examined copy number status in 36 common oncogenes and tumor suppressor genes in a cohort of 191 oropharyngeal squamous cell carcinomas (OPSCC) and 164 oral cavity squamous cell carcinomas (OSCC) using multiplex ligation probe amplification. Copy number status was correlated with human papillomavirus (HPV) status in OPSCC, with occult lymph node status in OSCC and with patient survival. The 11q13 region showed gain or amplifications in 59% of HPV-negative OPSCC, whereas this amplification was almost absent in HPV-positive OPSCC. Additionally, in clinically lymph node-negative OSCC (Stage I–II), gain of the 11q13 region was significantly correlated with occult lymph node metastases with a negative predictive value of 81%. Multivariate survival analysis revealed a significantly decreased disease-free survival in both HPV-negative and HPV-positive OPSCC with a gain of Wnt-induced secreted protein-1. Gain of CCND1 showed to be an independent predictor for worse survival in OSCC. These results show that copy number aberrations, mainly of the 11q13 region, may be important predictors and prognosticators which allow for stratifying patients for personalized treatment of HNSCC. PMID:26194878

  3. Clinical relevance of copy number profiling in oral and oropharyngeal squamous cell carcinoma

    International Nuclear Information System (INIS)

    Kempen, Pauline M W van; Noorlag, Rob; Braunius, Weibel W; Moelans, Cathy B; Rifi, Widad; Savola, Suvi; Koole, Ronald; Grolman, Wilko; Es, Robert J J van; Willems, Stefan M

    2015-01-01

    Current conventional treatment modalities in head and neck squamous cell carcinoma (HNSCC) are nonselective and have shown to cause serious side effects. Unraveling the molecular profiles of head and neck cancer may enable promising clinical applications that pave the road for personalized cancer treatment. We examined copy number status in 36 common oncogenes and tumor suppressor genes in a cohort of 191 oropharyngeal squamous cell carcinomas (OPSCC) and 164 oral cavity squamous cell carcinomas (OSCC) using multiplex ligation probe amplification. Copy number status was correlated with human papillomavirus (HPV) status in OPSCC, with occult lymph node status in OSCC and with patient survival. The 11q13 region showed gain or amplifications in 59% of HPV-negative OPSCC, whereas this amplification was almost absent in HPV-positive OPSCC. Additionally, in clinically lymph node-negative OSCC (Stage I–II), gain of the 11q13 region was significantly correlated with occult lymph node metastases with a negative predictive value of 81%. Multivariate survival analysis revealed a significantly decreased disease-free survival in both HPV-negative and HPV-positive OPSCC with a gain of Wnt-induced secreted protein-1. Gain of CCND1 showed to be an independent predictor for worse survival in OSCC. These results show that copy number aberrations, mainly of the 11q13 region, may be important predictors and prognosticators which allow for stratifying patients for personalized treatment of HNSCC

  4. Clinical relevance of epigenetics in the onset and management of type 2 diabetes mellitus

    Science.gov (United States)

    Sommese, Linda; Zullo, Alberto; Mancini, Francesco Paolo; Fabbricini, Rossella; Soricelli, Andrea; Napoli, Claudio

    2017-01-01

    ABSTRACT Epigenetics is involved in the altered expression of gene networks that underlie insulin resistance and insufficiency. Major genes controlling β-cell differentiation and function, such as PAX4, PDX1, and GLP1 receptor, are epigenetically controlled. Epigenetics can cause insulin resistance through immunomediated pro-inflammatory actions related to several factors, such as NF-kB, osteopontin, and Toll-like receptors. Hereafter, we provide a critical and comprehensive summary on this topic with a particular emphasis on translational and clinical aspects. We discuss the effect of epigenetics on β-cell regeneration for cell replacement therapy, the emerging bioinformatics approaches for analyzing the epigenetic contribution to type 2 diabetes mellitus (T2DM), the epigenetic core of the transgenerational inheritance hypothesis in T2DM, and the epigenetic clinical trials on T2DM. Therefore, prevention or reversion of the epigenetic changes occurring during T2DM development may reduce the individual and societal burden of the disease. PMID:28059593

  5. PROFOUND AND SEXUALLY DIMORPHIC EFFECTS OF CLINICALLY-RELEVANT LOW DOSE SCATTER IRRADIATION ON THE BRAIN AND BEHAVIOR

    Directory of Open Access Journals (Sweden)

    Anna eKovalchuk

    2016-06-01

    Full Text Available Irradiated cells can signal damage and distress to both close and distant neighbors that have not been directly exposed to the radiation (naïve bystanders. While studies have shown that such bystander effects occur in the shielded brain of animals upon body irradiation, their mechanism remains unexplored. Observed effects may be caused by some blood-borne factors; however they may also be explained, at least in part, by very small direct doses received by the brain that result from scatter or leakage. In order to establish the roles of low doses of scatter irradiation in the brain response, we developed a new model for scatter irradiation analysis whereby one rat was irradiated directly at the liver and the second rat was placed adjacent to the first and received a scatter dose to its body and brain. This work focuses specifically on the response of the latter rat brain to the low scatter irradiation dose. Here, we provide the first experimental evidence that very low, clinically relevant doses of scatter irradiation alter gene expression, induce changes in dendritic morphology, and lead to behavioral deficits in exposed animals. The results showed that exposure to radiation doses as low as 0.115 cGy caused changes in gene expression and reduced spine density, dendritic complexity, and dendritic length in the prefrontal cortex tissues of females, but not males. In the hippocampus, radiation altered neuroanatomical organization in males, but not in females. Moreover, low dose radiation caused behavioral deficits in the exposed animals. This is the first study to show that low dose scatter irradiation influences the brain and behavior in a sex-specific way.

  6. FCγ Chimeric Receptor-Engineered T Cells: Methodology, Advantages, Limitations, and Clinical Relevance

    Directory of Open Access Journals (Sweden)

    Giuseppe Sconocchia

    2017-04-01

    Full Text Available For many years, disappointing results have been generated by many investigations, which have utilized a variety of immunologic strategies to enhance the ability of a patient’s immune system to recognize and eliminate malignant cells. However, in recent years, immunotherapy has been used successfully for the treatment of hematologic and solid malignancies. The impressive clinical responses observed in many types of cancer have convinced even the most skeptical clinical oncologists that a patient’s immune system can recognize and reject his tumor if appropriate strategies are implemented. The success immunotherapy is due to the development of at least three therapeutic strategies. They include tumor-associated antigen (TAA-specific monoclonal antibodies (mAbs, T cell checkpoint blockade, and TAA-specific chimeric antigen receptors (CARs T cell-based immunotherapy. However, the full realization of the therapeutic potential of these approaches requires the development of strategies to counteract and overcome some limitations. They include off-target toxicity and mechanisms of cancer immune evasion, which obstacle the successful clinical application of mAbs and CAR T cell-based immunotherapies. Thus, we and others have developed the Fc gamma chimeric receptors (Fcγ-CRs-based strategy. Like CARs, Fcγ-CRs are composed of an intracellular tail resulting from the fusion of a co-stimulatory molecule with the T cell receptor ζ chain. In contrast, the extracellular CAR single-chain variable fragment (scFv, which recognizes the targeted TAA, has been replaced with the extracellular portion of the FcγRIIIA (CD16. Fcγ-CR T cells have a few intriguing features. First, given in combination with mAbs, Fcγ-CR T cells mediate anticancer activity in vitro and in vivo by an antibody-mediated cellular cytotoxicity mechanism. Second, CD16-CR T cells can target multiple cancer types provided that TAA-specific mAbs with the appropriate specificity are available

  7. Clinical relevance of hemoglobin level in cervical cancer patients administered definitive radiotherapy

    International Nuclear Information System (INIS)

    Serkies, Krystyna; Badzio, Andrzej; Jassem, Jacek

    2006-01-01

    The prognostic impact of pretreatment hemoglobin (Hb) level and its changes during definitive radiotherapy was evaluated by univariate and multivariate analysis in the group of 453 FIGO IB-IIIB cervical cancer patients. Pretreatment anemia (Hb 12 g/dl; p∼0.001). Baseline Hb =12 g/dl was also associated with longer disease-free survival and improved local control. Declining Hb level during radiotherapy predicted for impaired 5-year disease-free survival and local control probability. In multivariate analysis, low pretreatment Hb level remained associated with worse overall and disease-free survival, whereas adverse impact of declining Hb level on outcome was not observed. With regard to other clinical factors, stage and tumor extension (uni- or bilateral parametrium involvement for Stage III) were the only independent determinants of prognosis

  8. Naturally occurring BRCA2 alternative mRNA splicing events in clinically relevant samples

    DEFF Research Database (Denmark)

    Fackenthal, James D; Yoshimatsu, Toshio; Zhang, Bifeng

    2016-01-01

    patterns and thereby disrupt gene function. mRNA analyses are therefore among the tests used to interpret the clinical significance of some genetic variants. However, these could be confounded by the appearance of naturally occurring alternative transcripts unrelated to germline sequence variation...... to characterise the spectrum of naturally occurring BRCA2 mRNA alternate-splicing events. METHODS: mRNA was prepared from several blood and breast tissue-derived cells and cell lines by contributing ENIGMA laboratories. cDNA representing BRCA2 alternate splice sites was amplified and visualised using capillary...... or agarose gel electrophoresis, followed by sequencing. RESULTS: We demonstrate the existence of 24 different BRCA2 mRNA alternate-splicing events in lymphoblastoid cell lines and both breast cancer and non-cancerous breast cell lines. CONCLUSIONS: These naturally occurring alternate-splicing events...

  9. Evaluating glymphatic pathway function utilizing clinically relevant intrathecal infusion of CSF tracer.

    Science.gov (United States)

    Yang, Lijun; Kress, Benjamin T; Weber, Harris J; Thiyagarajan, Meenakshisundaram; Wang, Baozhi; Deane, Rashid; Benveniste, Helene; Iliff, Jeffrey J; Nedergaard, Maiken

    2013-05-01

    Neurodegenerative diseases such as Alzheimer's are associated with the aggregation of endogenous peptides and proteins that contribute to neuronal dysfunction and loss. The glymphatic system, a brain-wide perivascular pathway along which cerebrospinal fluid (CSF) and interstitial fluid (ISF) rapidly exchange, has recently been identified as a key contributor to the clearance of interstitial solutes from the brain, including amyloid β. These findings suggest that measuring changes in glymphatic pathway function may be an important prognostic for evaluating neurodegenerative disease susceptibility or progression. However, no clinically acceptable approach to evaluate glymphatic pathway function in humans has yet been developed. Time-sequenced ex vivo fluorescence imaging of coronal rat and mouse brain slices was performed at 30-180 min following intrathecal infusion of CSF tracer (Texas Red- dextran-3, MW 3 kD; FITC- dextran-500, MW 500 kD) into the cisterna magna or lumbar spine. Tracer influx into different brain regions (cortex, white matter, subcortical structures, and hippocampus) in rat was quantified to map the movement of CSF tracer following infusion along both routes, and to determine whether glymphatic pathway function could be evaluated after lumbar intrathecal infusion. Following lumbar intrathecal infusions, small molecular weight TR-d3 entered the brain along perivascular pathways and exchanged broadly with the brain ISF, consistent with the initial characterization of the glymphatic pathway in mice. Large molecular weight FITC-d500 remained confined to the perivascular spaces. Lumbar intrathecal infusions exhibited a reduced and delayed peak parenchymal fluorescence intensity compared to intracisternal infusions. Lumbar intrathecal contrast delivery is a clinically useful approach that could be used in conjunction with dynamic contrast enhanced MRI nuclear imaging to assess glymphatic pathway function in humans.

  10. Clinical relevance of voltage-gated potassium channel–complex antibodies in children.

    Science.gov (United States)

    Hacohen, Yael; Singh, Rahul; Rossi, Meghan; Lang, Bethan; Hemingway, Cheryl; Lim, Ming; Vincent, Angela

    2015-09-15

    To assess the clinical and immunologic findings in children with voltage-gated potassium channel (VGKC)-complex antibodies (Abs). Thirty-nine of 363 sera, referred from 2 pediatric centers from 2007 to 2013, had been reported positive (.100 pM) for VGKC-complex Abs. Medical records were reviewed retrospectively and the patients’ condition was independently classified as inflammatory (n 5 159) or noninflammatory (n 5 204). Positive sera (.100 pM) were tested/retested for the VGKC complex Ab–positive complex proteins LGI1 and CASPR2, screened for binding to live hippocampal neurons, and 12 high-titer sera (.400 pM) tested by radioimmunoassay for binding to VGKC Kv1 subunits with or without intracellular postsynaptic density proteins. VGKC-complex Abs were found in 39 children, including 20% of encephalopathies and 7.6% of other conditions (p 5 0.001). Thirty children had inflammatory conditions and 9 had noninflammatory etiologies but titers.400 pM (n512) were found only in inflammatory diseases (p , 0.0001). Four sera, including from 2 children with coexisting NMDA receptor Abs and one with Guillain-Barré syndrome and Abs to both LGI1 and CASPR2, bound to hippocampal neurons. None of the sera bound detectably to VGKC Kv1 subunits on live HEK cells, but 4 of 12 .400 pM sera immunoprecipitated VGKC Kv1 subunits, with or without postsynaptic densities, extracted from transfected cells. Positive VGKC-complex Abs cannot be taken to indicate a specific clinical syndrome in children, but appear to be a nonspecific biomarker of inflammatory neurologic diseases, particularly of encephalopathy. Some of the Abs may bind to intracellular epitopes on the VGKC subunits, or to the intracellular interacting proteins, but in many the targets remain undefined.

  11. Cost-effective multiplexing before capture allows screening of 25 000 clinically relevant SNPs in childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Wesolowska, Agata; Dalgaard, M. D.; Borst, L.

    2011-01-01

    designed a cost-effective, high-throughput capture assay of â¼25â000 clinically relevant SNPs, and demonstrated that multiple samples can be tagged and pooled before genome capture in targeted enrichment with a sufficient sequencing depth for genotyping. This multiplexed, targeted sequencing method allows...... exploration of the impact of pharmacogenetics on efficacy and toxicity in childhood ALL treatment, which will be of importance for personalized chemotherapy.Leukemia advance online publication, 18 March 2011; doi:10.1038/leu.2011.32....

  12. Overexpression of caveolin-1 in lymphoblastoid TK6 cells enhances proliferation after irradiation with clinically relevant doses

    Energy Technology Data Exchange (ETDEWEB)

    Barzan, David; Maier, Patrick; Wenz, Frederik; Herskind, Carsten [Dept. of Radiation Oncology, Univ. Medical Center Mannheim, Univ. of Heidelberg, Mannheim (Germany); Zeller, W. Jens [Pharmacology of Cancer Treatment, German Cancer Research Center, Heidelberg (Germany)

    2010-02-15

    Background and Purpose: The transmembrane protein caveolin-1 (CAV1) is an essential component of caveolae, small membrane invaginations involved in vesicle formation. CAV1 plays a role in signal transduction, tumor suppression and oncogene transformation. Previous studies with CAV1 knockout mice and CAV1 knockdown in pancreatic tumor cells implicated CAV1 in mediating radioresistance. The aim of this work was to test the effect of CAV1 overexpression after irradiation in human cells lacking endogenous CAV1 expression. Material and Methods: Human CAV1 was overexpressed in lymphoblastoid TK6 cells (TK6-wt) using a eukaryotic expression plasmid, pCI-CAV1, or a lentiviral SIN (self-inactivating) vector, HR'SIN-CAV1. CAV1 expression was verified in TK6 cells with Western blot analysis or intracellular FACS (fluorescence-activated cell sorting) staining. The effect of CAV1 on proliferation kinetics after irradiation of TK6 cells was measured with a growth assay. Results: TK6-wt showed no detectable endogenous CAV1 expression. Lentivirally mediated transduction with HR'SIN-CAV1 (TK6-CAV1) resulted in a considerably stronger CAV1 expression in comparison to TK6 cells electroporated with pCI-CAV1. Intracellular FACS analysis showed that 90% of transduced cells expressed CAV1. CAV1 enhanced early proliferation of TK6 cells after irradiation with a dose of 2 Gy, whereas proliferation of unirradiated cells was not affected. CAV1 also protected cells after irradiation with 4 Gy. This radioprotective effect was supported by a reduction of radiation-induced apoptosis. Conclusion: A model system for expression of exogenous CAV1 by stable lentiviral transduction of TK6 cells was established. Functional assays demonstrated enhanced early proliferation by CAV1 expression in TK6 cells after irradiation with clinically relevant doses supporting the role of CAV1 as a prosurvival factor. (orig.)

  13. Overexpression of caveolin-1 in lymphoblastoid TK6 cells enhances proliferation after irradiation with clinically relevant doses

    International Nuclear Information System (INIS)

    Barzan, David; Maier, Patrick; Wenz, Frederik; Herskind, Carsten; Zeller, W. Jens

    2010-01-01

    Background and Purpose: The transmembrane protein caveolin-1 (CAV1) is an essential component of caveolae, small membrane invaginations involved in vesicle formation. CAV1 plays a role in signal transduction, tumor suppression and oncogene transformation. Previous studies with CAV1 knockout mice and CAV1 knockdown in pancreatic tumor cells implicated CAV1 in mediating radioresistance. The aim of this work was to test the effect of CAV1 overexpression after irradiation in human cells lacking endogenous CAV1 expression. Material and Methods: Human CAV1 was overexpressed in lymphoblastoid TK6 cells (TK6-wt) using a eukaryotic expression plasmid, pCI-CAV1, or a lentiviral SIN (self-inactivating) vector, HR'SIN-CAV1. CAV1 expression was verified in TK6 cells with Western blot analysis or intracellular FACS (fluorescence-activated cell sorting) staining. The effect of CAV1 on proliferation kinetics after irradiation of TK6 cells was measured with a growth assay. Results: TK6-wt showed no detectable endogenous CAV1 expression. Lentivirally mediated transduction with HR'SIN-CAV1 (TK6-CAV1) resulted in a considerably stronger CAV1 expression in comparison to TK6 cells electroporated with pCI-CAV1. Intracellular FACS analysis showed that 90% of transduced cells expressed CAV1. CAV1 enhanced early proliferation of TK6 cells after irradiation with a dose of 2 Gy, whereas proliferation of unirradiated cells was not affected. CAV1 also protected cells after irradiation with 4 Gy. This radioprotective effect was supported by a reduction of radiation-induced apoptosis. Conclusion: A model system for expression of exogenous CAV1 by stable lentiviral transduction of TK6 cells was established. Functional assays demonstrated enhanced early proliferation by CAV1 expression in TK6 cells after irradiation with clinically relevant doses supporting the role of CAV1 as a prosurvival factor. (orig.)

  14. Clinical and immunological relevance of anti-neuronal antibodies in celiac disease with neurological manifestations

    Science.gov (United States)

    Caio, Giacomo; Giorgio, Roberto De; Venturi, Alessandro; Giancola, Fiorella; Latorre, Rocco; Boschetti, Elisa; Serra, Mauro; Ruggeri, Eugenio; Volta, Umberto

    2015-01-01

    Aim: To assess anti-neuronal antibodies (NA) prevalence and their correlation with neurological disorders and bowel habits in celiac disease (CD) patients. Background: Neurological manifestations are estimated to occur in about 10% of celiac disease patients and NA to central nervous system (CNS) and enteric nervous system (ENS) are found in a significant proportion of them. Little is known about the clinical and immunological features in CD patients with neurological manifestations. Patients and methods: NA to CNS and ENS were investigated in 106 CD patients and in 60 controls with autoimmune disorders by indirect immunofluorescence on rat / primate cerebellar cortex and intestinal (small and large bowel) sections. Results: IgG NA to CNS (titer 1:50 - 1:400) were positive in 23 celiacs (21%), being more frequently detected in those with neurological disorders that in those without neurological dysfunction (49% vs. 8%, P 1:200 had severe constipation. Only one patient with cerebellar ataxia and intestinal sub-occlusion was positive for NA to CNS and ENS. NA to CNS and ENS were found in 7% and 5% of controls, respectively. Conclusion: In CD the positivity of NA to CNS can be regarded as a marker of neurological manifestations. High titer NA to ENS are associated with severe constipation. The demonstration of NA to CNS and ENS suggests an immune-mediated pathogenesis leading to central neural impairment as well as gut dysfunction (hence constipation), respectively. PMID:25926940

  15. Distinct characteristics of mandibular bone collagen relative to long bone collagen: relevance to clinical dentistry.

    Science.gov (United States)

    Matsuura, Takashi; Tokutomi, Kentaro; Sasaki, Michiko; Katafuchi, Michitsuna; Mizumachi, Emiri; Sato, Hironobu

    2014-01-01

    Bone undergoes constant remodeling throughout life. The cellular and biochemical mechanisms of bone remodeling vary in a region-specific manner. There are a number of notable differences between the mandible and long bones, including developmental origin, osteogenic potential of mesenchymal stem cells, and the rate of bone turnover. Collagen, the most abundant matrix protein in bone, is responsible for determining the relative strength of particular bones. Posttranslational modifications of collagen, such as intermolecular crosslinking and lysine hydroxylation, are the most essential determinants of bone strength, although the amount of collagen is also important. In comparison to long bones, the mandible has greater collagen content, a lower amount of mature crosslinks, and a lower extent of lysine hydroxylation. The great abundance of immature crosslinks in mandibular collagen suggests that there is a lower rate of cross-link maturation. This means that mandibular collagen is relatively immature and thus more readily undergoes degradation and turnover. The greater rate of remodeling in mandibular collagen likely renders more flexibility to the bone and leaves it more suited to constant exercise. As reviewed here, it is important in clinical dentistry to understand the distinctive features of the bones of the jaw.

  16. Distinct Characteristics of Mandibular Bone Collagen Relative to Long Bone Collagen: Relevance to Clinical Dentistry

    Directory of Open Access Journals (Sweden)

    Takashi Matsuura

    2014-01-01

    Full Text Available Bone undergoes constant remodeling throughout life. The cellular and biochemical mechanisms of bone remodeling vary in a region-specific manner. There are a number of notable differences between the mandible and long bones, including developmental origin, osteogenic potential of mesenchymal stem cells, and the rate of bone turnover. Collagen, the most abundant matrix protein in bone, is responsible for determining the relative strength of particular bones. Posttranslational modifications of collagen, such as intermolecular crosslinking and lysine hydroxylation, are the most essential determinants of bone strength, although the amount of collagen is also important. In comparison to long bones, the mandible has greater collagen content, a lower amount of mature crosslinks, and a lower extent of lysine hydroxylation. The great abundance of immature crosslinks in mandibular collagen suggests that there is a lower rate of cross-link maturation. This means that mandibular collagen is relatively immature and thus more readily undergoes degradation and turnover. The greater rate of remodeling in mandibular collagen likely renders more flexibility to the bone and leaves it more suited to constant exercise. As reviewed here, it is important in clinical dentistry to understand the distinctive features of the bones of the jaw.

  17. Matching donor to recipient in liver transplantation: Relevance in clinical practice.

    Science.gov (United States)

    Reddy, Mettu Srinivas; Varghese, Joy; Venkataraman, Jayanthi; Rela, Mohamed

    2013-11-27

    Achieving optimum outcomes after liver transplantation requires an understanding of the interaction between donor, graft and recipient factors. Within the cohort of patients waiting for a transplant, better matching of the donor organ to the recipient will improve transplant outcomes and benefit the overall waiting list by minimizing graft failure and need for re-transplantation. A PubMed search was conducted to identify published literature investigating the effects of donor factors such as age, gender, ethnicity, viral serology; graft factors such as size and quality, recipient factors such as age, size, gender and transplant factors such as major or minor blood group incompatibility and immunological factors. We also report technical and therapeutic modifications that can be used to manage donor-recipient mismatch identified from literature and the authors' clinical experience. Multiple donor and recipient factors impact graft survival after liver transplantation. Appropriate matching based on donor-organ-recipient variables, modification of surgical technique and innovative peri-transplant strategies can increase the donor pool by utilizing grafts from marginal donors that are traditionally turned down.

  18. Strategy for the maximization of clinically relevant information from hepatitis C virus, RT-PCR quantification.

    LENUS (Irish Health Repository)

    Levis, J

    2012-02-03

    BACKGROUND: The increasing clinical application of viral load assays for monitoring viral infections has been an incentive for the development of standardized tests for the hepatitis C virus. OBJECTIVE: To develop a simple model for the prediction of baseline viral load in individuals infected with the hepatitis C virus. METHODOLOGY: Viral load quantification of each patient\\'s first sample was assessed by RT-PCR-ELISA using the Roche MONITOR assay in triplicate. Genotype of the infecting virus was identified by reverse line probe hybridization, using amplicons resulting from the qualitative HCV Roche AMPLICOR assay. RESULTS: Retrospective evaluation of first quantitative values suggested that 82.4% (n=168\\/204) of individuals had a viral load between 4.3 and 6.7 log(10) viral copies per ml. A few patients (3.4%; n=7\\/204) have a serum viremia less than the lower limit of the linear range of the RT-PCR assay. Subsequent, prospective evaluation of hepatitis C viral load of all new patients using a model based on the dynamic range of viral load in the retrospective group correctly predicted the dynamic range in 75.9% (n=33\\/54). CONCLUSION: The dynamic range of hepatitis C viremia extends beyond the linear range of the Roche MONITOR assay. Accurate determination of serum viremia is substantially improved by dilution of specimens prior to quantification.

  19. Microbiological Features and Clinical Relevance of New Species of the Genus Mycobacterium

    Science.gov (United States)

    2014-01-01

    SUMMARY Nontuberculous mycobacteria (NTM) are present in the environment, mainly in water, and are occasionally responsible for opportunistic infections in humans. Despite the fact that NTM are characterized by a moderate pathogenicity, the diseases caused by NTM at various body sites are increasing on a worldwide level. Among over 150 officially recognized NTM species, only two or three dozen are familiar to clinicians, and even to most microbiologists. In this paper, approximately 50 new species described in the last 8 years are reviewed, and their role in human infections is assessed on the basis of reported clinical cases. The small number of reports concerning most of the “new” mycobacterial species is responsible for the widespread conviction that they are very rare. Their role is actually largely underestimated, mainly because they often remain unrecognized and misidentified. Aiming to minimize such bias, emphasis has been placed on more common identification pitfalls. Together with new NTM, new members of the Mycobacterium tuberculosis complex described in the last few years are also an object of the present review. PMID:25278573

  20. The relevance of 'mixed anxiety and depression' as a diagnostic category in clinical practice.

    Science.gov (United States)

    Möller, Hans-Jürgen; Bandelow, Borwin; Volz, Hans-Peter; Barnikol, Utako Birgit; Seifritz, Erich; Kasper, Siegfried

    2016-12-01

    According to ICD-10 criteria, mixed anxiety and depressive disorder (MADD) is characterized by co-occurring, subsyndromal symptoms of anxiety and depression, severe enough to justify a psychiatric diagnosis, but neither of which are clearly predominant. MADD appears to be very common, particularly in primary care, although prevalence estimates vary, often depending on the diagnostic criteria applied. It has been associated with similarly pronounced distress, impairment of daily living skills, and reduced health-related quality of life as fully syndromal depression and anxiety. Although about half of the patients affected remit within a year, non-remitting patients are at a high risk of transition to a fully syndromal psychiatric disorder. The validity and clinical usefulness of MADD as a diagnostic category are under debate. It has not been included in the recently released DSM-5 since the proposed diagnostic criteria turned out to be not sufficiently reliable. Moreover, reviewers have disputed the justification of MADD based on divergent results regarding its prevalence and course, diagnostic stability over time, and nosological inconsistencies between subthreshold and threshold presentations of anxiety and depressive disorders. We review the evidence in favor and against MADD and argue that it should be included into classification systems as a diagnostic category because it may enable patients to gain access to appropriate treatment early. This may help to reduce patients' distress, prevent exacerbation to a more serious psychiatric disorder, and ultimately reduce the societal costs of this very common condition.

  1. Duplex investigations in children: Are clinical signs in children with venous disorders relevant?

    Science.gov (United States)

    Birgitte Maessen-Visch, M; Smeets, L; van Vleuten, C

    2015-12-01

    Ultra sound colored duplex sonography is the preferred method in diagnosing chronic venous disease. Data in children on incidence, indications, and results are lacking. From the total of 9180 duplex investigations performed in our hospital from 2009 to 2012, data on indication and results of the investigation as well as patient characteristics were evaluated retrospectively for the proportion of pediatric patients. Duplex investigations were performed 49 times in 38 children (6-18 years), with an average of 1.3 times (1-6 times) per child. Forty percent showed abnormalities: 17 times deep venous thrombosis was suspected; deep venous thrombosis was objectified in 18%. In the 21 investigations performed for varicosis-related complaints, varicose veins or venous malformations were objectified in 57%. Edema was never a symptom of chronic venous disease. Duplex investigation is not often performed in children. In children with established deep venous thrombosis, a family history with deep venous thrombosis is common. In general, edema was not seen in children with varicose veins and, therefore, does not seem a reliable clinical sign at young age. © The Author(s) 2014.

  2. Exploring the information and communication technology competence and confidence of nursing students and their perception of its relevance to clinical practice.

    Science.gov (United States)

    Levett-Jones, Tracy; Kenny, Raelene; Van der Riet, Pamela; Hazelton, Michael; Kable, Ashley; Bourgeois, Sharon; Luxford, Yoni

    2009-08-01

    This paper profiles a study that explored nursing students' information and communication technology competence and confidence. It presents selected findings that focus on students' attitudes towards information and communication technology as an educational methodology and their perceptions of its relevance to clinical practice. Information and communication technology is integral to contemporary nursing practice. Development of these skills is important to ensure that graduates are 'work ready' and adequately prepared to practice in increasingly technological healthcare environments. This was a mixed methods study. Students (n=971) from three Australian universities were surveyed using an instrument designed specifically for the study, and 24 students participated in focus groups. The focus group data revealed that a number of students were resistant to the use of information and communication technology as an educational methodology and lacked the requisite skills and confidence to engage successfully with this educational approach. Survey results indicated that 26 per cent of students were unsure about the relevance of information and communication technology to clinical practice and only 50 per cent felt 'very confident' using a computer. While the importance of information and communication technology to student's learning and to their preparedness for practice has been established, it is evident that students' motivation is influenced by their level of confidence and competence, and their understanding of the relevance of information and communication technology to their future careers.

  3. Clinical relevance of the effects of reach-to-grasp training using trunk restraint in individuals with hemiparesis poststroke: A systematic review.

    Science.gov (United States)

    Greisberger, Andrea; Aviv, Hanna; Garbade, Sven F; Diermayr, Gudrun

    2016-04-28

    To evaluate the evidence for, and clinical relevance of, immediate and long-term effects of trunk restraint during reach-to-grasp training poststroke on movement patterns and functional abilities within the framework of the International Classification of Functioning, Disability and Health. PubMed, Web of Science, CINAHL, Embase, PEDro, Cochrane Library (publication dates January 1985 to March 2015). Randomized controlled trials comparing training using trunk restraint with any other exercise training. Data were extracted by one researcher and checked by two other researchers. The Cochrane Collaboration's tool for assessing risk of bias and the Physiotherapy Evidence Database scale were used by two researchers to assess study quality and risk of bias. Eight studies met the inclusion criteria. Five studies found better recovery of movement patterns (trunk displacement, elbow extension, and/or shoulder flexion - body function/structure) at post-test in the experimental compared with the control groups. Functional abilities (activity/participation) improved more in the experimental groups in 3 studies at post-test. Long-term effects were found in one study after 4 weeks. Trunk restraint has immediate and some long-term effects in adults with chronic stroke. However, these effects are not consistently clinically relevant when referring to minimal detectable change or minimal clinically important difference values.

  4. Clinical relevancy and determinants of potential drug–drug interactions in chronic kidney disease patients: results from a retrospective analysis

    Directory of Open Access Journals (Sweden)

    Saleem A

    2017-02-01

    Full Text Available Ahsan Saleem,1,2 Imran Masood,1 Tahir Mehmood Khan3 1Department of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, Pakistan; 2Pharmacy Services Department, Integrated Medical Center, The Aga Khan University Hospital, Lahore, Pakistan; 3School of Pharmacy, Monash University, Sunway Campus, Selangor, Malaysia Background: Chronic kidney disease (CKD alters the pharmacokinetic and pharmacodynamic responses of various renally excreted drugs and increases the risk of drug-related problems, such as drug–drug interactions.Objectives: To assess the pattern, determinants, and clinical relevancy of potential drug–drug interactions (pDDIs in CKD patients.Materials and methods: This study retrospectively reviewed medical charts of all CKD patients admitted in the nephrology unit of a tertiary care hospital in Pakistan from January 2013 to December 2014. The Micromedex Drug-Reax® system was used to screen patient profiles for pDDIs, and IBM SPSS version 20 was used to carry out statistical analysis.Results: We evaluated 209 medical charts and found pDDIs in nearly 78.5% CKD patients. Overall, 541 pDDIs were observed, of which, nearly 60.8% patients had moderate, 41.1% had minor, 27.8% had major, and 13.4% had contraindicated interactions. Among those interactions, 49.4% had good evidence, 44.0% had fair, 6.3% had excellent evidence, and 35.5% interactions had delayed onset of action. The potential adverse outcomes of pDDIs included postural hypotension, QT prolongation, ceftriaxone–calcium precipitation, cardiac arrhythmias, and reduction in therapeutic effectiveness. The occurrence of pDDIs was found strongly associated with the age of <60 years, number of prescribed medicines ≥5, hypertension, and the lengthy hospitalization of patients.Conclusion: The occurrence of pDDIs was high in CKD patients. It was observed that CKD patients with an older age, higher number of prescribed medicines, lengthy hospitalization, and hypertension were at

  5. Comprehensive genomic analysis of Oesophageal Squamous Cell Carcinoma reveals clinical relevance

    DEFF Research Database (Denmark)

    Du, Peina; Huang, Peide; Huang, Xuanlin

    2017-01-01

    Oesophageal carcinoma is the fourth leading cause of cancer-related death in China, and more than 90% of these tumours are oesophageal squamous cell carcinoma (ESCC). Although several ESCC genomic sequencing studies have identified mutated somatic genes, the number of samples in each study...

  6. Clinically relevant doses of lidocaine and bupivacaine do not impair cutaneous wound healing in mice.

    Science.gov (United States)

    Waite, A; Gilliver, S C; Masterson, G R; Hardman, M J; Ashcroft, G S

    2010-06-01

    Lidocaine and bupivacaine are commonly infiltrated into surgical cutaneous wounds to provide local anaesthesia after surgical procedures. However, very little is known about their effects on cutaneous wound healing. If an inhibitory effect is demonstrated, then the balance between the benefits of postoperative local anaesthesia and the negatives of impaired cutaneous wound healing may affect the decision to use local anaesthesia or not. Furthermore, if a difference in the rate of healing of lidocaine- and bupivacaine-treated cutaneous wounds is revealed, or if an inhibitory effect is found to be dose-dependent, then this may well influence the choice of agent and its concentration for clinical use. Immediately before incisional wounding, we administered lidocaine and bupivacaine intradermally to adult female mice, some of which had been ovariectomized to act as a model of post-menopausal women (like post-menopausal women, ovariectomized mice heal wounds poorly, with increased proteolysis and inflammation). Day 3 wound tissue was analysed histologically and tested for expression of inflammatory and proteolytic factors. On day 3 post-wounding, wound areas and extent of re-epithelialization were comparable between the control and local anaesthetic-treated animals, in both intact and ovariectomized groups. Both tested drugs significantly increased wound activity of the degradative enzyme matrix metalloproteinase-2 relative to controls, while lidocaine also increased wound neutrophil numbers. Although lidocaine and bupivacaine influenced local inflammatory and proteolytic factors, they did not impair the rate of healing in either of two well-established models (mimicking normal human wound healing and impaired age-r