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Sample records for active clinical investigation

  1. Histopathological investigation of clinically non-affected perilesional scalp in alopecias detected unexpected spread of disease activities.

    PubMed

    Watanabe-Okada, Emiko; Amagai, Masayuki; Ohyama, Manabu

    2014-09-01

    Histopathological comparison between clinically affected and intact regions in alopecia patients has been considered to facilitate better understanding of the pathophysiology of ongoing disease. Theoretically, adjacent intact regions should provide ideal controls as they should share close histological characteristics, however, to what extent clinically non-affected neighboring regions maintain their pathological integrity has not been fully assessed. The goal of this study is to delineate histopathological characteristics of clinically intact perilesional regions in the patients with various forms of alopecia. Transverse sections of 4-mm punch biopsy at the levels of isthmus and suprabulbar portion were obtained from seemingly unimpaired perilesional scalp of 50 Japanese alopecia patients (16 alopecia areata [AA] multiplex, 19 scarring alopecia [SA], 15 other conditions) and subject to histopathological investigation. Initial screening detected decrease in anagen (anagen : telogen ratio = 82.4:17.6) when compared with previously reported standard hair counts in normal Asian scalp. This finding prompted further investigation. Unexpectedly, 33 (66%) specimens demonstrated some microscopic abnormalities, 10 (62.5%) AA specimens showed increase in telogen ratio, vellus hair count and miniaturization, while perifollicular inflammatory cell infiltration was detected in 5 (26.3%) SA cases. Exclusion of histologically affected specimens yielded average hair count numbers resembling those reported in Koreans, supporting the pathological integrity of selected samples and, more importantly, indicating normal hair counts in east Asians. These findings indicated a less recognized significance of histopathological investigation of clinically non-affected perilesional scalp in alopecias for better assessment of the spread of disease activities, which should enable better management of hair loss conditions. PMID:25156442

  2. Periodontal disease activity: a development strategy for its investigation by means of accurate 3-dimensional clinical measurement.

    PubMed

    Watts, T L; Beards, C f; Ewing, P D; Leeman, S

    1995-03-01

    The central problem in all previous approaches to clinical assessment of periodontal disease activity is the use of unidimensional measurement, which implies a number of unjustifiable assumptions. In addition, the use of unidimensional probing measurement has established that there are several distinct problems of validity and reliability in currently available techniques. The present paper begins with an analysis of these matters, leading to an approach to accurate clinical measurement of periodontitis in 3 dimensions, with the possibility of future development of a valid system for assessing the nature of disease activity. PMID:7790525

  3. Clinical investigation program, fiscal year 1991

    NASA Astrophysics Data System (ADS)

    Schydlower, Manuel

    1992-02-01

    Subject report identifies the research activities conducted at William Beaumont Army Medical Center by investigators who had protocols approved by the Clinical Investigation Committee, the Institutional Review Board, and the Animal Use Committee. This report includes all protocols registered with the Department of Clinical Investigation during FY 1991. All known presentations and publications are also included. The research protocols described were conducted under the provisions of AR 40-38 (Clinical Investigation Program); AR 40-7 (Use of Investigational Drugs in Humans and the Use of Schedule 1 Controlled Substances); AR 70-25 (Usle of Volunteers as Subjects of Research); HSC 40-32 (Management of Clinical Investigation Protocols and Reports); and AR 70-18 (The Use of Animals in DOS programs).

  4. Comparison of the Antibiotic Activities of Daptomycin, Vancomycin, and the Investigational Fluoroquinolone Delafloxacin against Biofilms from Staphylococcus aureus Clinical Isolates

    PubMed Central

    Siala, Wafi; Mingeot-Leclercq, Marie-Paule; Tulkens, Paul M.; Hallin, Marie; Denis, Olivier

    2014-01-01

    Biofilm-related infections remain a scourge. In an in vitro model of biofilms using Staphylococcus aureus reference strains, delafloxacin and daptomycin were found to be the most active among the antibiotics from 8 different pharmacological classes (J. Bauer, W. Siala, P. M. Tulkens, and F. Van Bambeke, Antimicrob. Agents Chemother. 57:2726–2737, 2013, doi:10.1128/AAC.00181-13). In this study, we compared delafloxacin to daptomycin and vancomycin using biofilms produced by 7 clinical strains (S. aureus epidemic clones CC5 and CC8) in order to rationalize the differences observed between the antibiotics and strains. The effects of the antibiotics on bacterial viability (resazurin reduction assay) and biomass (crystal violet staining) were measured and correlated with the proportion of polysaccharides in the matrix, the local microenvironmental pH (micro-pH), and the antibiotic penetration in the biofilm. At clinically meaningful concentrations, delafloxacin, daptomycin, and vancomycin caused a ≥25% reduction in viability against the biofilms formed by 5, 4, and 3 strains, respectively. The antibiotic penetration within the biofilms ranged from 0.6 to 52% for delafloxacin, 0.2 to 10% for daptomycin, and 0.2 to 1% for vancomycin; for delafloxacin, this was inversely related to the polysaccharide proportion in the matrix. Six biofilms were acidic, explaining the high potency of delafloxacin (lower MICs at acidic pH). Norspermidine and norspermine (disassembling the biofilm matrix) drastically increased delafloxacin potency and efficacy (50% reduction in viability for 6 biofilms at clinically meaningful concentrations) in direct correlation with its increased penetration within the biofilm, while they only modestly improved daptomycin efficacy (50% reduction in viability for 2 biofilms) and penetration, and they showed marginal effects with vancomycin. Delafloxacin potency and efficacy against biofilms are benefited by its penetration into the matrix and the local

  5. [Clinical investigation of striatocapsular infarction].

    PubMed

    Tei, H; Uchiyama, S; Maruyama, S

    1993-03-01

    We investigated the clinical profile, etiological factors, neuropsychological features and radiological characteristics of 17 cases of striatocapsular infarction (SCI). SCI was defined as the following CT criteria: the area of infarction included the internal capsule and striatum, the maximum diameter of the lesion exceeded 2.0 cm without cortical involvement. There were 9 men and 8 women with mean age of 58 years. Five patients had lesions mainly involving the caudate head (anterior type) and the other 12 had lesions mainly involving the putamen (lateral type), 6 with left side lesion and 6 with right side lesion. Motor weakness was observed in all patients, and the upper extremities were preferentially involved, while in 9 patients face, upper and lower extremities were simultaneously involved. Etiological investigation revealed that 8 patients were cardioembolic stroke, 2 were artery-to-artery embolism and 2 were MCA stem occlusive disease, while the remaining 5 were undetermined. When compared with patients with lacunar infarction (LI), patients with SCI had significantly more frequent cardioembolic sources (47% vs 17%, p < 0.05) and less frequent hypertension (41% vs 80%, p < 0.01). In acute phase, neuropsychological abnormalities were found in 15 patients. Anterior type patients had psychiatric symptoms such as abulia, depression and agitation, while left lateral type patients had aphasia and right lateral type patients had hemispatial neglect or anosognosia. These symptoms gradually improved, although in most patients subtle abnormalities lasted over chronic phase. In 11 out of 13 patients who underwent SPECT using 99mTc-HMPAO, blood flow was decreased in overlying cerebral cortex besides the infarcted area.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8334792

  6. 76 FR 45577 - Clinical Investigator Training Course

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-29

    ... clinical trials; improve the ] quality of clinical trials; and enhance the safety of trial participants.... Background Clinical trial investigators play a critical role in the development of medical products. They... HUMAN SERVICES Food and Drug Administration Clinical Investigator Training Course AGENCY: Food and...

  7. Clinical investigations in primary care.

    PubMed

    de Souza, Leonardo Cruz; Sarazin, Marie; Goetz, Celine; Dubois, Bruno

    2009-01-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disorder that represents the most common form of dementia. The most prominent feature of AD is the decline in cognitive function, with an early impairment of episodic memory. The memory deficit of an AD patient is characterized by the amnestic syndrome of the medial temporal type. As the disease progresses, the condition often manifests in language disorders, visuospatial deficits and executive dysfunctions. Patients often have neuropsychiatric disturbances, as apathy and psychotic symptoms. Loss of autonomy follows cognitive impairment. The clinical diagnosis of AD is based on a complete medical examination with a neuropsychological evaluation. The FCSRT (free and cued selective reminding test) is recommended for the identification of the amnestic syndrome of the medial temporal type, which is defined by: (1) a very poor free recall and (2) a decreased total recall due to an insufficient effect of cueing. The neuropsychological tests should also assess other cognitive functions that may be perturbed in AD, such as executive functions, praxis, visuospatial capacities and language. Neuroimaging and biological exams (genetics, biomarkers) are of great utility in the evaluation. Other medical, neurological, or psychiatric disorders which could account for the impairment in memory and related symptoms must be always investigated. PMID:19182457

  8. 77 FR 60440 - Clinical Investigator Training Course

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-03

    ... access to electrical outlets. I. Background Clinical trial investigators play a critical role in the... HUMAN SERVICES Food and Drug Administration Clinical Investigator Training Course AGENCY: Food and Drug... are cosponsoring a 3- day training course for clinical investigators on scientific, ethical,...

  9. Reasoning with Linear Orders: Differential Parietal Cortex Activation in Sub-Clinical Depression. An fMRI Investigation in Sub-Clinical Depression and Controls

    PubMed Central

    Hinton, Elanor C.; Wise, Richard G.; Singh, Krish D.; von Hecker, Ulrich

    2015-01-01

    The capacity to learn new information and manipulate it for efficient retrieval has long been studied through reasoning paradigms, which also has applicability to the study of social behavior. Humans can learn about the linear order within groups using reasoning, and the success of such reasoning may vary according to affective state, such as depression. We investigated the neural basis of these latter findings using functional neuroimaging. Using BDI-II criteria, 14 non-depressed (ND) and 12 mildly depressed volunteers took part in a linear-order reasoning task during functional magnetic resonance imaging. The hippocampus, parietal, and prefrontal cortices were activated during the task, in accordance with previous studies. In the learning phase and in the test phase, greater activation of the parietal cortex was found in the depressed group, which may be a compensatory mechanism in order to reach the same behavioral performance as the ND group, or evidence for a different reasoning strategy in the depressed group. PMID:25646078

  10. 75 FR 57472 - Clinical Investigator Training Course

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-21

    ... days in advance. SUPPLEMENTARY INFORMATION: Clinical trial investigators play a critical role in the... HUMAN SERVICES Food and Drug Administration Clinical Investigator Training Course AGENCY: Food and Drug... Programs, in cosponsorship with the Clinical Trials Transformation Initiative (CTTI), is announcing a...

  11. 78 FR 63988 - Clinical Investigator Training Course

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-25

    ... enhance the safety of trial participants. Senior FDA staff will communicate directly with clinical.... Background Clinical trial investigators play a critical role in the development of medical products. They... HUMAN SERVICES Food and Drug Administration Clinical Investigator Training Course AGENCY: Food and...

  12. New generation azole antifungals in clinical investigation.

    PubMed

    Girmenia, Corrado

    2009-09-01

    Considerable progress in treating systemic mycoses has been achieved in the past years through development of new drugs in association with more advanced diagnostic procedures. Here, we review the pharmacological, microbiological and clinical development progress with the so-called 'second generation' triazoles: voriconazole, posaconazole, ravuconazole, isavuconazole and albaconazole. All these drugs exhibit a favourable pharmacokinetic and toxicity profile and possess high activity against resistant and emerging pathogens. However, only voriconazole and posaconazole have been adequately investigated in Phase III studies and have been approved by the regulatory agencies in the treatment and prophylaxis of invasive fungal infections, respectively. On the contrary, ravuconazole, isavuconazole and albaconazole have not been investigated in adequate clinical trials and, in the absence of proper data, the real possibilities of these agents as competitors for the treatment and prevention of invasive mycoses in the clinical setting are still unknown. The drug interactions and the variability in the absorption and/or metabolism of the triazoles, in particular voriconazole and posaconazole, may determine an unpredictable exposure of the pathogens to the antifungal treatments. Literature evidences strongly support the use of therapeutic drug monitoring for these triazoles which may be crucial for the proper management of severe invasive fungal infections. PMID:19678798

  13. A European approach to clinical investigator training.

    PubMed

    Boeynaems, Jean-Marie; Canivet, Cindy; Chan, Anthony; Clarke, Mary J; Cornu, Catherine; Daemen, Esther; Demotes, Jacques; Nys, Katelijne De; Hirst, Barry; Hundt, Ferdinand; Kassai, Behrouz; Kerpel-Fronius, Sandor; Kiessig, Lucy; Klech, Heinrich; Kraehenbuhl, Jean-Pierre; Lafolie, Pierre; Lucht, Martin; Niese, Detlef; Pauli-Magnus, Christiane; Peters, Barbara; Schaltenbrand, Ralf; Stockis, Armel; Stykova, Martina; Verheus, Nicolette; Klingmann, Ingrid

    2013-01-01

    A better education and training of clinical investigators and their teams is one of the factors that could foster the development of clinical research in Europe, a key objective of the Innovative Medicines Initiative (IMI). PharmaTrain (an IMI programme on training in medicines development), and European Clinical Research Infrastructures Network (ECRIN) have joined forces to address this issue. An advisory group composed of representatives of universities, pharmaceutical companies and other organisations met four times between June 2011 and July 2012. This resulted in a position paper proposing a strategy to improve and harmonize clinical investigator training in Europe, and including a detailed syllabus and list of learning outcomes. Major recommendations are the establishment of minimal and mutually recognized certification requirement for investigators throughout the EU and the creation of a European platform to provide a suitable course and examination infrastructure. PMID:24058345

  14. A Data Accounting System for Clinical Investigators

    PubMed Central

    Kashner, T. Michael; Hinson, Robert; Holland, Gloria J.; Mickey, Don D.; Hoffman, Keith; Lind, Lisa; Johnson, Linda D.; Chang, Barbara K.; Golden, Richard M.; Henley, Steven S.

    2007-01-01

    Clinical investigators often preprocess, process, and analyze their data without benefit of formally organized research centers to oversee data management. This article outlines a practical three-file structure to help guide these investigators track and document their data through processing and analyses. The proposed process can be implemented without additional training or specialized software. Thus, it is particularly well suited for research projects with small budgets or limited access to viable research/data coordinating centers. PMID:17460138

  15. Investigation of In Vitro Activity of Five Antifungal Drugs against Dermatophytes Species Isolated from Clinical Samples Using the E-Test Method

    PubMed Central

    Aktas, Ayse Esin; Yigit, Nimet; Aktas, Akin; Gozubuyuk, Sultan Gamze

    2014-01-01

    Objective: Dermatomycosis is an infection with fungi related to the skin: glabrous skin, hair and/or nails. Oral treatment of fungal infections in dermatology has become a preferred modality for the management of these very common conditions. Although there are increasing numbers of antifungals available for treatment of dermatophytes, some cases and relapses have been unresponsive to treatment. The determination of fungus in-vitro antifungal susceptibility has been reported to be important for the ability to eradicate dermatophytes. It is necessary to perform antifungal susceptibility testing of dermatophytes. E-test (AB Biodisk, Sweden) is a rapid, easy-to-perform in-vitro antifungal susceptibility test. The aim of this study was to investigate the susceptibility of the different species of dermatophyte strains isolated clinical specimens to five antifungal agents using the E-test method. Materials and Methods: A total of 66 specimens were collected from the nails, feet, inguinal region, trunk and hands. These strains tested MIC endpoints of E-test for amphotericin B, fluconazole, itraconazole, caspofungin, and ketoconazole were read after 72, and 96 hours incubation for each strain on RPMI 1640 agar. Results: The dermatophytes tested included Trichophyton rubrum 43 (65.1%), Trichophyton mentagrophytes 7 (10.7%), Microsporum canis 5 (7.6%), Trichophyton tonsurans 5 (7.6%), Epidermophyton floccosum 4 (6.0%) and Trichophyton violaceum 2 (3.0%). The most active agent against all dermatophytes species was caspofungin with a minimal inhibitory concentration (MIC) range (μg/mL−1) (0.02–3, 0.032–4, 0.125–0.50, 0.032–2, 0.25–0.50, 0.125–0.50) and it raconazole with an MIC range (μg/mL−1) (0.038–1.5, 0.094–1.5, 1–32, 0.016–0.50, 0.25–0.50, 0.125–0.50). The least active agent was fluconazole with an MIC range (μg/mL−1) (0, 19–48, 2–256, 2–8, 256, 256, 8–24). Conclusion: E-test seems to be an alternative method to MIC

  16. Clinical and Histopathological Investigation of Seborrheic Keratosis

    PubMed Central

    Roh, Nam Kyung; Hahn, Hyung Jin; Lee, Yang Won; Choe, Yong Beom

    2016-01-01

    Background Seborrheic keratosis (SK) is one of the most common epidermal tumors of the skin. However, only a few large-scale clinicohistopathological investigations have been conducted on SK or on the possible correlation between histopathological SK subtype and location. Objective The aim of this study was to analyze the clinical and histopathological features of a relatively large number of cases of diagnosed SK. Methods Two hundred and seventy-one pathology slides of skin tissue from patients with clinically diagnosed SK and 206 cases of biopsy-proven SK were analyzed. The biopsy-proven cases of SK were assessed for histopathological subclassification. The demographic, clinical, and histopathological data of the patients were collected for analysis of associated factors. Results The most frequent histopathological subtype was the acanthotic type, followed by mixed, hyperkeratotic, melanoacanthoma, clonal, irritated, and adenoid types; an unexpectedly high percentage (9.2%) of the melanoacanthoma variant was observed. The adenoid type was more common in sun-exposed sites than in sun-protected sites (p=0.028). Premalignant and malignant entities together represented almost one-quarter (24.2%) of the clinicopathological mismatch cases (i.e., mismatch between the clinical and histopathological diagnoses). Regarding the location of SK development, the frequency of mismatch for the sun-exposed areas was significantly higher than that for sun-protected areas (p=0.043). Conclusion The adenoid type was more common in sun-exposed sites. Biopsy sampling should be performed for lesions situated in sun-exposed areas to exclude other premalignant or malignant diseases. PMID:27081260

  17. 21 CFR 312.70 - Disqualification of a clinical investigator.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Disqualification of a clinical investigator. 312... and Investigators § 312.70 Disqualification of a clinical investigator. (a) If FDA has information indicating that an investigator (including a sponsor-investigator) has repeatedly or deliberately failed...

  18. 21 CFR 312.70 - Disqualification of a clinical investigator.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Disqualification of a clinical investigator. 312... and Investigators § 312.70 Disqualification of a clinical investigator. (a) If FDA has information... writing, or, at the option of the investigator, in an informal conference. If an explanation is...

  19. Clinical Investigation of Benign Asbestos Pleural Effusion

    PubMed Central

    Fujimoto, Nobukazu; Gemba, Kenichi; Aoe, Keisuke; Kato, Katsuya; Yokoyama, Takako; Usami, Ikuji; Onishi, Kazuo; Mizuhashi, Keiichi; Yusa, Toshikazu; Kishimoto, Takumi

    2015-01-01

    There is no detailed information about benign asbestos pleural effusion (BAPE). The aim of the study was to clarify the clinical features of BAPE. The criteria of enrolled patients were as follows: (1) history of asbestos exposure; (2) presence of pleural effusion determined by chest X-ray, CT, and thoracentesis; and (3) the absence of other causes of effusion. Clinical information was retrospectively analysed and the radiological images were reviewed. There were 110 BAPE patients between 1991 and 2012. All were males and the median age at diagnosis was 74 years. The median duration of asbestos exposure and period of latency for disease onset of BAPE were 31 and 48 years, respectively. Mean values of hyaluronic acid, adenosine deaminase, and carcinoembryonic antigen in the pleural fluid were 39,840 ng/mL, 23.9 IU/L, and 1.8 ng/mL, respectively. Pleural plaques were detected in 98 cases (89.1%). Asbestosis was present in 6 (5.5%) cases, rounded atelectasis was detected in 41 (37.3%) cases, and diffuse pleural thickening (DPT) was detected in 30 (27.3%) cases. One case developed lung cancer (LC) before and after BAPE. None of the cases developed malignant pleural mesothelioma (MPM) during the follow-up. PMID:26689234

  20. [CLINICAL INVESTIGATION OF AN EXCESSIVE SLEEPINESS COMPLAINT].

    PubMed

    Evangelista, Elisa; Barateau, Lucie; Dauvilliers, Yves

    2016-06-01

    Excessive sleepiness is a common problem, defined by a complaint of excessive daytime sleepiness almost daily with an inability to stay awake and alert dosing periods at sleep, with episodes of irresistible sleep need or drowsiness or non-intentional sleep, or by a night's sleep time overly extended often associated with sleep inertia. This sleepiness is variable in terms of phenotype and severity to be specified by the out-patient clinic. It is considered to be chronic beyond three months and often responsible for significant functional impairment of school and professional performance, of the accidents and cardiovascular risk. We need to decipher the causes of excessive sleepiness: sleep deprivation, toxic and iatrogenic, psychiatric disorders (including depression), non-psychiatric medical problems (obesity, neurological pathologies...), sleep disorders (as for example the sleep apnea syndrome), and finally the central hypersomnias namely narcolepsy type 1 and 2, idiopathic hypersomnia, and Kleine-Levin syndrome. If careful questioning often towards one of these etiologies, need most of the time a paraclinical balance with a sleep recording to confirm the diagnosis. Patients affected with potential central hypersomnia must be referred to the Sleep Study Centers that have the skills and the appropriate means to achieve this balance sheet. PMID:27538325

  1. Gamete activation: basic knowledge and clinical applications

    PubMed Central

    Tosti, Elisabetta; Ménézo, Yves

    2016-01-01

    Background The first clues to the process of gamete activation date back to nearly 60 years ago. The mutual activation of gametes is a crucial event during fertilization. In the testis and ovaries, spermatozoa and oocytes are in a state of meiotic and metabolic quiescence and require reciprocal signals in order to undergo functional changes that lead to competence for fertilization. First, the oocyte activates sperm by triggering motility, chemoattraction, binding and the acrosome reaction, culminating with the fusion of the two plasma membranes. At the end of this cascade of events, collectively known as sperm capacitation, sperm-induced oocyte activation occurs, generating electrical, morphological and metabolic modifications in the oocyte. Objective and rationale The aim of this review is to provide the current state of knowledge regarding the entire process of gamete activation in selected specific animal models that have contributed to our understanding of fertilization in mammals, including humans. Here we describe in detail the reciprocal induction of the two activation processes, the molecules involved and the mechanisms of cell interaction and signal transduction that ultimately result in successful embryo development and creation of a new individual. Search methods We carried out a literature survey with no restrictions on publication date (from the early 1950s to March 2016) using PubMed/Medline, Google Scholar and Web of Knowledge by utilizing common keywords applied in the field of fertilization and embryo development. We also screened the complete list of references published in the most recent research articles and relevant reviews published in English (both animal and human studies) on the topics investigated. Outcomes Literature on the principal animal models demonstrates that gamete activation is a pre-requisite for successful fertilization, and is a process common to all species studied to date. We provide a detailed description of the dramatic

  2. Understanding clinical investigations in children's endocrinology.

    PubMed

    Davies, Kate; Collin, Jacqueline

    2015-10-01

    Children and young people referred to paediatric endocrinology services present with a wide range of illnesses and disorders varying from minor to life-threatening conditions. This article introduces the role of the children's endocrine nurse in caring for children and families undergoing investigations that are frequently undertaken to identify specific problems associated with pituitary, adrenal and thyroid glands. Although children with endocrine problems may be cared for in specialist centres, they may also present, for other health reasons, in secondary and primary care. In schools some children may need teachers to administer emergency medication. There is a high incidence of children diagnosed with growth hormone deficiency and an even higher incidence of congenital hypothyroidism. These children would benefit from health professionals having a broader understanding of their conditions. This article--the third in the endocrinology nursing series--aims to disseminate information and educate colleagues in children's nursing to raise the profile of children with long-term endocrine conditions. PMID:26448126

  3. The clinical investigator-subject relationship: a contextual approach

    PubMed Central

    2009-01-01

    Background The nature of the relationship between a clinical investigator and a research subject has generated considerable debate because the investigator occupies two distinct roles: clinician and scientist. As a clinician, the investigator has duties to provide the patient with optimal care and undivided loyalty. As a scientist, the investigator has duties to follow the rules, procedures and methods described in the protocol. Results and conclusion In this article, I present a contextual approach to the investigator-subject relationship. The extent of the investigator's duty to provide the patient/subject with clinical care can vary from one situation to the next, as a function of several factors, including: the research design, benefits and risks of the research; the subject's reasonable expectations, motivations, and vulnerabilities; the investigator's ability to benefit the subject; and the investigator's prior relationship with the subject. These and other factors need to be considered when determining the clinical investigator's obligations to provide clinical care to human research subjects. In some research contexts, the investigator has extensive clinical obligations to the patient/subject; in others, the investigator has minimal ones. PMID:19958542

  4. Australian Stringhalt--epidemiological, clinical and neurological investigations.

    PubMed

    Huntington, P J; Jeffcott, L B; Friend, S C; Luff, A R; Finkelstein, D I; Flynn, R J

    1989-07-01

    An investigation of 78 cases of typical Australian Stringhalt from 52 properties in Victoria was carried out from 1985 to 1987. Horses were either examined in the field (n = 52), referred to the Veterinary Clinical Centre (n = 13) or clinical details were obtained verbally (n = 13). In addition 10 cases of false or atypical stringhalt were examined. Detailed soil and pasture analysis was carried out on 14 properties where Australian Stringhalt had occurred. Information was also obtained on epidemiology of the condition from a survey of practitioners. Fifty of the 52 cases examined in the field occurred in horses that were dependent upon poor quality unimproved dry pasture. In all but a few cases, there was no pasture improvement or fertiliser application, leading to the development of weed-dominated pastures, particularly by flatweed, Hypochaeris radicata. The range of clinical signs exhibited by horses with Australian Stringhalt was described and a grading system proposed to classify horses according to severity of signs. Laryngeal abnormalities were present in 10 of 11 cases examined endoscopically and these horses exhibited increased electromyographic (EMG) activity in the long digital extensor muscle at rest and during hindlimb flexion. To a large extent, the EMG changes disappeared and digital extensor muscle atrophy improved in two horses that were monitored to recovery. Deep peroneal nerve conduction studies in four horses with Australian Stringhalt showed a substantial reduction in nerve conduction velocity and when stimulated at 50 Hz were unable to sustain activation of the long digital extensor muscle. EMG and evoked responses appeared to be sensitive indicators of the state of the disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2767028

  5. 76 FR 20575 - Disqualification of a Clinical Investigator

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-13

    ... clinical investigator's disqualification. \\5\\ 63 FR 55873 at 55874, October 19, 1998. We propose to change..., would help to ensure the integrity of clinical trial data and help reduce the risk to human subjects who... example, the final rule at 62 FR 46875, September 5, 1997; clarifying FDA's authority to reach...

  6. Active Spacecraft Potential Control Investigation

    NASA Astrophysics Data System (ADS)

    Torkar, K.; Nakamura, R.; Tajmar, M.; Scharlemann, C.; Jeszenszky, H.; Laky, G.; Fremuth, G.; Escoubet, C. P.; Svenes, K.

    2016-03-01

    In tenuous plasma the floating potential of sunlit spacecraft reaches tens of volts, positive. The corresponding field disturbs measurements of the ambient plasma by electron and ion sensors and can reduce micro-channel plate lifetime in electron detectors owing to large fluxes of attracted photoelectrons. Also the accuracy of electric field measurements may suffer from a high spacecraft potential. The Active Spacecraft Potential Control (ASPOC) neutralizes the spacecraft potential by releasing positive charge produced by indium ion emitters. The method has been successfully applied on other spacecraft such as Cluster and Double Star. Two ASPOC units are present on each spacecraft. Each unit contains four ion emitters, whereby one emitter per instrument is operated at a time. ASPOC for the Magnetospheric Multiscale (MMS) mission includes new developments in the design of the emitters and the electronics. New features include the use of capillaries instead of needles, new materials for the emitters and their internal thermal insulators, an extended voltage and current range of the electronics, both for ion emission and heating purposes, and a more capable control software. This enables lower spacecraft potentials, higher reliability, and a more uniform potential structure in the spacecraft's sheath compared to previous missions. Results from on-ground testing demonstrate compliance with requirements. Model calculations confirm the findings from previous applications that the plasma measurements will not be affected by the beam's space charge. Finally, the various operating modes to adapt to changing boundary conditions are described along with the main data products.

  7. Zirconia abutments and restorations: from laboratory to clinical investigations.

    PubMed

    Ferrari, M; Vichi, A; Zarone, F

    2015-03-01

    In last years the use of zirconia in dentistry has become very popular. Unfortunately, the clinical indications for a dental use of zirconia are not completely clear yet, neither are their limitations. The objective of this review was to evaluate the basic science knowledge on zirconia and to discuss some aspects of the clinical behavior of zirconia-based restorations. In particular, one of the goals was highlighting the possible correlation between in vitro and in vivo studies. The definition of concepts like success, survival and failure was still debated and the correlation between in vitro results and predictability of clinical behavior was investigated. PMID:25576437

  8. Legal issues in human clinical investigation: a primer for physicians.

    PubMed

    Green, A M; Steinmetz, N D

    1997-01-01

    Human clinical investigation plays a central role in contemporary nuclear cardiology. It is a complex expensive endeavor triggering multiple responsibilities not otherwise encountered by physicians in clinical practice. Clinical investigators, drug and device manufacturers, hospitals and universities, governmental agencies, research subjects, patient advocacy groups, and investors all have a legitimate interest in the conduct and the outcome of clinical research. Past abuses of research subjects in many countries including those unknowingly exposed to radioactive isotopes have raised ethical concerns that are now addressed by overlapping laws, regulations, guidelines, and institutional policies that have evolved to guide the research enterprise. The policies underlying this legal and regulatory structure include protection of research subjects, protection of the integrity of research design and research data, and protection of the public and private purse. Knowledge of these laws and regulations is essential for physicians participating in clinical investigations to protect their professional and personal interests. This article reviews legal issues relevant to physicians conducting human clinical trials in the United States. PMID:9456195

  9. 78 FR 55262 - Guidance for Clinical Investigators, Sponsors, and Institutional Review Boards on Investigational...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-10

    ... of subjects and, in Phases 2 and 3 of an investigation, to help assure the quality of the scientific... regulations to a planned clinical investigation. In the Federal Register of October 14, 2010 (75 FR 63189... Institutional Review Boards on Investigational New Drug Applications--Determining Whether Human Research...

  10. Sample sizes in dosage investigational clinical trials: a systematic evaluation.

    PubMed

    Huang, Ji-Han; Su, Qian-Min; Yang, Juan; Lv, Ying-Hua; He, Ying-Chun; Chen, Jun-Chao; Xu, Ling; Wang, Kun; Zheng, Qing-Shan

    2015-01-01

    The main purpose of investigational phase II clinical trials is to explore indications and effective doses. However, as yet, there is no clear rule and no related published literature about the precise suitable sample sizes to be used in phase II clinical trials. To explore this, we searched for clinical trials in the ClinicalTrials.gov registry using the keywords "dose-finding" or "dose-response" and "Phase II". The time span of the search was September 20, 1999, to December 31, 2013. A total of 2103 clinical trials were finally included in our review. Regarding sample sizes, 1,156 clinical trials had <40 participants in each group, accounting for 55.0% of the studies reviewed, and only 17.2% of the studies reviewed had >100 patient cases in a single group. Sample sizes used in parallel study designs tended to be larger than those of crossover designs (median sample size 151 and 37, respectively). In conclusion, in the earlier phases of drug research and development, there are a variety of designs for dosage investigational studies. The sample size of each trial should be comprehensively considered and selected according to the study design and purpose. PMID:25609916

  11. 21 CFR 812.119 - Disqualification of a clinical investigator.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Radiological Health, the Center for Biologics Evaluation and Research, or the Center for Drug Evaluation and... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Disqualification of a clinical investigator. 812.119 Section 812.119 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND......

  12. 21 CFR 812.119 - Disqualification of a clinical investigator.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Radiological Health, the Center for Biologics Evaluation and Research, or the Center for Drug Evaluation and... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Disqualification of a clinical investigator. 812.119 Section 812.119 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND......

  13. A Qualitative Investigation of Clinical Supervisor Value Conflicts.

    ERIC Educational Resources Information Center

    Veach, Pat McCarthy; Yoon, Eunju; Miranda, Cacy; Ergun, Damla; Tuicomepee, Arunya

    Eighteen clinical supervisors participated in focus groups or an individual interview designed to investigate their personal experiences with value conflicts in supervision. Participants described the types of value conflicts they had experiences and their personal impact, effective and ineffective approaches for addressing these issues, resources…

  14. Investigation of women with postmenopausal uterine bleeding: clinical practice recommendations.

    PubMed

    Munro, Malcolm G

    2014-01-01

    Postmenopausal uterine bleeding is defined as uterine bleeding after permanent cessation of menstruation resulting from loss of ovarian follicular activity. Bleeding can be spontaneous or related to ovarian hormone replacement therapy or to use of selective estrogen receptor modulators (eg, tamoxifen adjuvant therapy for breast carcinoma). Because anovulatory "cycles" with episodes of multimonth amenorrhea frequently precede menopause, no consensus exists regarding the appropriate interval of amenorrhea before an episode of bleeding that allows for the definition of postmenopausal bleeding. The clinician faces the possibility that an underlying malignancy exists, knowing that most often the bleeding comes from a benign source. Formerly, the gold-standard clinical investigation of postmenopausal uterine bleeding was institution-based dilation and curettage, but there now exist office-based methods for the evaluation of women with this complaint. Strategies designed to implement these diagnostic methods must be applied in a balanced way considering the resource utilization issues of overinvestigation and the risk of missing a malignancy with underinvestigation. Consequently, guidelines and recommendations were developed to consider these issues and the diverse spectrum of practitioners who evaluate women with postmenopausal bleeding. The guideline development group determined that, for initial management of spontaneous postmenopausal bleeding, primary assessment may be with either endometrial sampling or transvaginal ultrasonography, allowing patients with an endometrial echo complex thickness of 4 mm or less to be managed expectantly. Guidelines are also provided for patients receiving selective estrogen receptor modulators or hormone replacement therapy, and for an endometrial echo complex with findings consistent with fluid in the endometrial cavity.� PMID:24377427

  15. Investigation of Women with Postmenopausal Uterine Bleeding: Clinical Practice Recommendations

    PubMed Central

    Munro, Malcolm G

    2014-01-01

    Postmenopausal uterine bleeding is defined as uterine bleeding after permanent cessation of menstruation resulting from loss of ovarian follicular activity. Bleeding can be spontaneous or related to ovarian hormone replacement therapy or to use of selective estrogen receptor modulators (eg, tamoxifen adjuvant therapy for breast carcinoma). Because anovulatory “cycles” with episodes of multimonth amenorrhea frequently precede menopause, no consensus exists regarding the appropriate interval of amenorrhea before an episode of bleeding that allows for the definition of postmenopausal bleeding. The clinician faces the possibility that an underlying malignancy exists, knowing that most often the bleeding comes from a benign source. Formerly, the gold-standard clinical investigation of postmenopausal uterine bleeding was institution-based dilation and curettage, but there now exist office-based methods for the evaluation of women with this complaint. Strategies designed to implement these diagnostic methods must be applied in a balanced way considering the resource utilization issues of overinvestigation and the risk of missing a malignancy with underinvestigation. Consequently, guidelines and recommendations were developed to consider these issues and the diverse spectrum of practitioners who evaluate women with postmenopausal bleeding. The guideline development group determined that, for initial management of spontaneous postmenopausal bleeding, primary assessment may be with either endometrial sampling or transvaginal ultrasonography, allowing patients with an endometrial echo complex thickness of 4 mm or less to be managed expectantly. Guidelines are also provided for patients receiving selective estrogen receptor modulators or hormone replacement therapy, and for an endometrial echo complex with findings consistent with fluid in the endometrial cavity. PMID:24377427

  16. A history of the American Society for Clinical Investigation

    PubMed Central

    Howell, Joel D.

    2009-01-01

    One hundred years ago, in 1909, the American Society for Clinical Investigation (ASCI) held its first annual meeting. The founding members based this new society on a revolutionary approach to research that emphasized newer physiological methods. In 1924 the ASCI started a new journal, the Journal of Clinical Investigation. The ASCI has also held an annual meeting almost every year. The society has long debated who could be a member, with discussions about whether members must be physicians, what sorts of research they could do, and the role of women within the society. The ASCI has also grappled with what else the society should do, especially whether it ought to take a stand on policy issues. ASCI history has reflected changing social, political, and economic contexts, including several wars, concerns about the ethics of biomedical research, massive increases in federal research funding, and an increasingly large and specialized medical environment. PMID:19348041

  17. Education of research ethics for clinical investigators with Moodle tool

    PubMed Central

    2013-01-01

    Background In clinical research scientific, legal as well as ethical aspects are important. It is well known that clinical investigators at university hospitals have to undertake their PhD-studies alongside their daily work and reconciling work and study can be challenging. The aim of this project was to create a web based course in clinical research bioethics (5 credits) and to examine whether the method is suitable for teaching bioethics. The course comprised of six modules: an initial examination (to assess knowledge in bioethics), information on research legislation, obtaining permissions from authorities, writing an essay on research ethics, preparing one’s own study protocol, and a final exam. All assignments were designed with an idea of supporting students to reflect on their learning with their own research. Methods 57 PhD-students (medical, nursing and dental sciences) enrolled and 46 completed the course. Course evaluation was done using a questionnaire. The response rate was 78%. Data were analyzed using quantitative methods and qualitative content analysis. Results The course was viewed as useful and technically easy to perform. Students were pleased with the guidance offered. Personal feedback from teachers about students’ own performance was seen advantageous and helped them to appreciate how these aspects could be applied their own studies. The course was also considered valuable for future research projects. Conclusions Ethical issues and legislation of clinical research can be understood more easily when students can reflect the principles upon their own research project. Web based teaching environment is a feasible learning method for clinical investigators. PMID:24330709

  18. Math Activities Using LogoWriter--Investigations.

    ERIC Educational Resources Information Center

    Flewelling, Gary

    This book is one in a series of teacher resource books developed to: (1) rescue students from the clutches of computers that drill and control; and (2) supply teachers with computer activities compatible with a mathematics program that emphasizes investigation, problem solving, creativity, and hypothesis making and testing. This is not a book…

  19. [Clinical application of skin sympathetic nerve activity].

    PubMed

    Iwase, Satoshi

    2009-03-01

    Skin sympathetic nerve activity (SSNA) is microneurographically recorded from the skin nerve fascicle in the peripheral nerves. It is characterized by the following features: 1) irregular, pulse asynchronous, burst activity with respiratory variation, 2) burst activity followed by vasoconstriction and/or sweating, 3) elicited by mental stress and arousal stimuli, e.g., sound, pain, electric stimulation, 4) burst with longer duration as compared with sympathetic outflow to muscles, and 5) burst activity following sudden inspiratory action. It comprises vasoconstrictor (VC) and sudomotor(SM) activity, as well as vasodilator (VD) activity. VC and SM discharge independently, whereas VD is the same activity with different neurotransmission. The VC and SM are differentiated by effector response, e.g., laser Doppler flowmetry and skin potential changes. SSNA function in thermoregulation in the human body; however it is also elicited by mental stress. SSNA is the lowest at thermoneutral ambient temperature (approximately 27 degrees C), and is enhanced in the pressence of ambient warm and cool air. The burst amplitude is well-correlated to both skin blood flow reduction rate or sweat rate change. The clinical application of SSNA comprises the following: 1) clarification of sweating phenomenon, 2) clarification and diagnosis of anhidrosis, 3) clarification and diagnosis of hyperhidrosis, 4) clarification of thermoregulatory function and diagnosis of thermoregulatory disorder, 5) clarification of pathophysiology and diagnosis of vascular diseases, e.g., Raynaud and Buerger diseases. 6) clarification of the relation between cognitive function and SSNA and 7) determination of pharmacological effect attributable to change in neuroeffector responses. PMID:19301594

  20. Modified Activated Carbon to be Used in Clinical Applications

    NASA Astrophysics Data System (ADS)

    Fernando, M. S.; de Silva, W. R. M.; de Silva, K. M. N.

    2014-11-01

    In this study a novel nano composite of hydroxyapatite nano particles impregnated activated carbon (C-HAp), which was synthesized in our own method, was used in iron adsorption studies. The study was conducted in order to investigate the potential of using C-HAp nanocomposite to be used in clinical detoxifications such as acute iron toxicity where the use of Activated carbon (GAC) is not very effective. Adsorption studies were conducted for synthetic solutions of Fe2+, Fe3+ and iron syrup using GAC, C-HAp and neat HAp as adsorbents. According to the results C-HAp nano composite showed improved properties than GAC in adsorbing Fe2+, Fe3+ and also Fe ions in iron syrup solutions. Thus the results of the in-vitro studies of iron adsorption studies indicated the potential of using C-HAp as an alternative to activated carbon in such clinical applications.

  1. Mycoplasma bovis infections in Swiss dairy cattle: a clinical investigation.

    PubMed

    Aebi, Marlis; van den Borne, Bart H P; Raemy, Andreas; Steiner, Adrian; Pilo, Paola; Bodmer, Michèle

    2015-01-01

    Mycoplasma bovis causes mastitis in dairy cows and is associated with pneumonia and polyarthritis in cattle. The present investigation included a retrospective case-control study to identify potential herd-level risk factors for M. bovis associated disease, and a prospective cohort study to evaluate the course of clinical disease in M. bovis infected dairy cattle herds in Switzerland. Eighteen herds with confirmed M. bovis cases were visited twice within an average interval of 75 d. One control herd with no history of clinical mycoplasmosis, matched for herd size, was randomly selected within a 10 km range for each case herd. Animal health data, production data, information on milking and feeding-management, housing and presence of potential stress- factors were collected. Composite quarter milk samples were aseptically collected from all lactating cows and 5% of all animals within each herd were sampled by nasal swabs. Organ samples of culled diseased cows were collected when logistically possible. All samples were analyzed by real-time polymerase chain reaction (PCR). In case herds, incidence risk of pneumonia, arthritis and clinical mastitis prior to the first visit and incidence rates of clinical mastitis and clinical pneumonia between the two visits was estimated. Logistic regression was used to identify potential herd-level risk factors for M. bovis infection. In case herds, incidence risk of M. bovis mastitis prior to the first visit ranged from 2 to 15%, whereas 2 to 35% of the cows suffered from clinical pneumonia within the 12 months prior to the first herd visit. The incidence rates of mycoplasmal mastitis and clinical pneumonia between the two herd visits were low in case herds (0-0.1 per animal year at risk and 0.1-0.6 per animal year at risk, respectively). In the retrospective-case-control study high mean milk production, appropriate stimulation until milk-let-down, fore-stripping, animal movements (cattle shows and trade), presence of stress

  2. NAA TECHNIQUE FOR CLINICAL INVESTIGATION OF MICE IMMUNIZED WITH BOTHROP VENOM

    SciTech Connect

    Zamboni, C. B.; Aguiar, R. O.; Kovacs, L.; Suzuki, M.; Sant'Anna, O. A.

    2009-06-03

    In the present study Neutron Activation Analysis (NAA) technique was used to determine sodium concentration in whole blood of mice immunized with Bothrops venom. With this value it was possible to perform clinical investigation in this animal model using whole blood.

  3. Serious adverse event reporting in investigator-initiated clinical trials.

    PubMed

    Wallace, Sophie; Myles, Paul S; Zeps, Nikolajs; Zalcberg, John R

    2016-04-01

    Reporting adverse events (AEs) and serious AEs (SAEs) are practical steps to ensure safety for volunteers and patients in medical research involving medications, treatments and devices. However, the burden and cost of reporting should be proportionate with the public health benefit of this information. Unfortunately, in Australia there is clear evidence of ever-increasing requirements from sponsors and ethics committees to report AEs and SAEs unnecessarily, leading to a decrease in the uptake of research, particularly less well funded investigator-initiated trials. We believe that individual AE reports to ethics committees serve no useful purpose, because in most cases the study group identity (drug exposure) is not known in studies with blinded treatment arms and their value is limited. Pragmatic, investigator-initiated Phase IV clinical trials of post-marketed drugs or devices are needed to understand their role in everyday clinical practice. In this setting, the workload and costs of systematic, complete reporting of all AEs and SAEs (independent of whether these are treatment-related) is wasteful, and mostly unnecessary. A trial data safety and monitoring committee is in the unique position of being able to review safety information according to the blinded treatment arms of the study. This enables safety data to be analysed appropriately and a summary report provided to the trial steering committee, principal investigators and the relevant ethics committees in a meaningful way. Defined trial endpoints do not need to be reported as safety events (because they are being properly monitored and analysed). PMID:27031396

  4. Arterial disease ulcers, part 1: clinical diagnosis and investigation.

    PubMed

    Weir, Gregory Ralph; Smart, Hiske; van Marle, Jacobus; Cronje, Frans Johannes

    2014-09-01

    Arterial disease (peripheral vascular disease) is the result of narrowing of the blood vessel lumen. The classic clinical signs need to be recognized early before progression to arterial predominant disease and limb ischemia. Arterial ulcers or tissue breakdown can result from trauma, infection, or other etiologies with diabetes, smoking, increasing age, and hypertension the most important risk factors. Diagnostic testing starts with a palpable pulse with special investigation including handheld Doppler for ankle brachial pressure index ratios, segmental duplex leg Doppler waveforms, and more specialized procedures, including transcutaneous oxygen saturation. PMID:25133344

  5. [The Clinical Investigation Centers in France: Whatzat? What for? How does it work?].

    PubMed

    Montagne, O; Le Corvoisier, P

    2008-01-01

    For the last 15 years, French university-affiliated hospitals have dramatically modified how biomedical research is conducted in France. Multidisciplinary and technically complex research projects are increasingly difficult to conduct in clinical units. To ensure quality, good clinical practice, and security, platforms dedicated to clinical research with specific staff have been implanted. These units, called Clinical Investigation Centers (CICs), are open to academic and industrial investigators working in the medical fields involving patients and healthy volunteers. The CICs' activities are always closely related to the university hospital research programs and can also serve as a tool for locally implanted clinical and fundamental research teams (INSERM). Nowadays, clinical research requires specific tools and platforms. To enhance French university hospital research efficiency and provide a more open research environment, all investigators, on-site as well as from other institutions, are invited to use these cohesive research facilities and skills to conduct protocols that are fully adapted to their needs in optimal conditions of professional clinical research. PMID:18401306

  6. Emotion Understanding in Clinically Anxious Children: A Preliminary Investigation

    PubMed Central

    Bender, Patrick K.; Pons, Francisco; Harris, Paul L.; Esbjørn, Barbara H.; Reinholdt-Dunne, Marie L.

    2015-01-01

    Children’s understanding of the nature, origins and consequences of emotions has been intensively investigated over the last 30–40 years. However, few empirical studies have looked at the relation between emotion understanding and anxiety in children and their results are mixed. The aim of the present study was to perform a preliminary investigation of the relationships between emotion understanding, anxiety, emotion dysregulation, and attachment security in clinically anxious children. A sample of 16 clinically anxious children (age 8–12, eight girls/boys) was assessed for emotion understanding (Test of Emotion Comprehension), anxiety (Screening for Child Anxiety Related Emotional Disorders-Revised and Anxiety Disorder Interview Schedule), emotion dysregulation (Difficulties in Emotion Regulation Scale) and attachment security (Security Scale). Children who reported more overall anxiety also reported greater difficulties in regulating their emotions, and were less securely attached to their parents. The results also showed that more specific symptoms of anxiety (i.e., OCD and PTSD) correlated not only with emotion dysregulation and attachment insecurity but also with emotion understanding. Finally, there were interrelations among emotion understanding, attachment security, and emotion dysregulation. The present results provide the first comprehensive evidence for a socio-emotional framework and its relevance to childhood anxiety. PMID:26733909

  7. The US Food and Drug Administration investigational device exemptions (IDE) and clinical investigation of cardiovascular devices: information for the investigator.

    PubMed

    Pritchard, W F; Abel, D B; Karanian, J W

    1999-03-01

    The conduct of a clinical investigation of a medical device to determine the safety and effectiveness of the device is covered by the investigational device exemptions (IDE) regulation. The purpose of IDE regulation is "to encourage, to the extent consistent with the protection of public health and safety and with ethical standards, the discovery and development of useful devices intended for human use, and to that end to maintain optimum freedom for scientific investigators in their pursuit of this purpose" (Federal Food, Drug, and Cosmetic Act). Conducting a clinical investigation may require an approved IDE application. The US Food and Drug Administration encourages early interaction with the agency through the pre-IDE process during the development of a device or technology and during the preparation of an IDE application. This facilitates approval of the IDE application and progression into the clinical investigation. This paper reviews the terminology and applicability of the IDE regulation and the type of study that requires an IDE application to the Food and Drug Administration. The pre-IDE process and the development of an IDE application for a significant risk study of a cardiovascular device are discussed. PMID:10069924

  8. Clinical research: business opportunities for pharmacy-based investigational drug services.

    PubMed

    Marnocha, R M

    1999-02-01

    The application by an academic health center of business principles to the conduct of clinical research is described. Re-engineering of the infrastructure for clinical research at the University of Wisconsin and University of Wisconsin Hospital and Clinics began in 1990 with the creation of the Center for Clinical Trials (CCT) and the restructuring of the investigational drug services (IDS). Strategies to further improve the institution's clinical research activities have been continually assessed and most recently have centered on the adaptation of a business philosophy within the institution's multidisciplinary research infrastructure. Toward that end, the CCT and IDS have introduced basic business principles into operational activities. Four basic business concepts have been implemented: viewing the research protocol as a commodity, seeking payment for services rendered, tracking investments, and assessing performance. It is proposed that incorporation of these basic business concepts is not only compatible with the infrastructure for clinical research but beneficial to that infrastructure. The adaptation of a business mindset is likely to enable an academic health center to reach its clinical research goals. PMID:10030512

  9. [Antimicrobial activity of cefodizime against clinical isolates].

    PubMed

    Suzuki, Y; Ishihara, R; Ishii, Y; Nakazawa, A; Deguchi, K; Matsumoto, Y; Nishinari, C; Nakane, Y; Fukumoto, T

    1996-10-01

    In order to evaluate antimicrobial activity of cefodizime (CDZM), minimum inhibitory concentrations (MICs) of CDZM and control drugs were determined against clinical isolates collected from nation-wide medical institutions and in our laboratory from September to December of 1992 and from September to December of 1995. The results are summarized as follows: 1. Bacterial species with no or few strains resistant to CDZM included Streptococcus pyogenes, Haemophilus influenzae, Citrobacter koseri, Proteus mirabilis and Neisseria gonorrhoeae. The range of MIC values of CDZM against Klebsiella pneumoniae was spread. Other strains, Streptococcus pneumoniae, Moraxella subgenus Branhamella catarrhalis, Escherichia coli, Citrobacter freundii, Enterobacter spp., Serratia marcescens, Proteus vulgaris, Morganella morganii, Providencia spp., Peptostreptococcus spp. and Bacteroides fragilis group were resistant to cephems including CDZM. 2. The MIC90's of CDZM were 0.05 approximately 3.13 micrograms/ml against Streptococcus spp., H. influenzae, M. (B.) catarrhalis, E. coli, Klebsiella spp., P. mirabilis, N. gonorrhoeae and Peptostreptococcus spp. obtained in 1995 that were frequently found in daily treatment of infections. It appears that the effectiveness of CDZM was still relatively high against community-acquired infections. 3. Among H. influenzae isolates included imipenem (IPM)-resistant and norfloxacin (NFLX)-resistant strains. The MIC-range of CDZM against strains collected in 1995 including IPM-resistant and NFLX-resistant strains was < or = 0.025 approximately 0.1 microgram/ml, and MIC90 against these strains was 0.05 microgram/ml. CDZM showed strong antimicrobial activities against H. influenzae strains resistant to carbapenems and new-quinolones. PMID:8986558

  10. 78 FR 13070 - Guidance for Clinical Investigators, Industry, and Food and Drug Administration Staff: Financial...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-26

    ...The Food and Drug Administration (FDA) is announcing the availability of a guidance entitled ``Guidance for Clinical Investigators, Industry, and FDA Staff: Financial Disclosure by Clinical Investigators.'' This guidance is intended to assist clinical investigators, industry, and FDA staff in interpreting and complying with the regulations governing financial disclosure by clinical......

  11. Infarction of the Corpus Callosum: A Retrospective Clinical Investigation

    PubMed Central

    Bai, Yu-meng; Qin, Hua-min; Wu, Xiao-mei; Zhang, Xiao; Jolkkonen, Jukka; Boltze, Johannes; Wang, Su-ping

    2015-01-01

    Objectives The aim of this study was to investigate patients with ischemic infarctions in the territory of the corpus callosum to advance our understanding of this rare stroke subtype by providing comprehensive descriptive and epidemiological data. Methods From January 1, 2010 to June 30, 2014, all cases of acute ischemic stroke diagnosed by clinical manifestation and diffusion weighted imaging in Dalian Municipal Central Hospital were investigated. The patients presenting with corpus callosum infarctions were selected and further allocated into genu and/or body and splenium infarction groups. Proportion, lesion patterns, clinical features, risk factors and etiology of corpus callosum infarction were analyzed. Results Out of 1,629 cases, 59 patients (3.6%) with corpus callosum infarctions were identified by diffusion weighted imaging, including 7 patients who had ischemic lesions restricted to the corpus callosum territory. Thirty six patients had lesions in the splenium (61.0%). Corpus callosum infarction patients suffered from a broad spectrum of symptoms including weakness and/or numbness of the limbs, clumsy speech, and vertigo, which could not be explained by lesions in corpus callosum. A classical callosal disconnection syndrome was found in 2 out of all patients with corpus callosum infarctions. Statistical differences in the risk factor and infarct pattern between the genu and/or body group and splenium group were revealed. Conclusion Corpus callosum infarction and the callosal disconnection syndrome were generally rare. The most susceptible location of ischemic corpus callosum lesion was the splenium. Splenium infarctions were often associated with bilateral cerebral hemisphere involvement (46.2%). The genu and/or body infarctions were associated with atherosclerosis. The most common cause of corpus callosum infarction probably was embolism. PMID:25785450

  12. Geometric investigation of a gaming active device

    NASA Astrophysics Data System (ADS)

    Menna, Fabio; Remondino, Fabio; Battisti, Roberto; Nocerino, Erica

    2011-07-01

    3D imaging systems are widely available and used for surveying, modeling and entertainment applications, but clear statements regarding their characteristics, performances and limitations are still missing. The VDI/VDE and the ASTME57 committees are trying to set some standards but the commercial market is not reacting properly. Since many new users are approaching these 3D recording methodologies, clear statements and information clarifying if a package or system satisfies certain requirements before investing are fundamental for those users who are not really familiar with these technologies. Recently small and portable consumer-grade active sensors came on the market, like TOF rangeimaging cameras or low-cost triangulation-based range sensor. A quite interesting active system was produced by PrimeSense and launched on the market thanks to the Microsoft Xbox project with the name of Kinect. The article reports the geometric investigation of the Kinect active sensors, considering its measurement performances, the accuracy of the retrieved range data and the possibility to use it for 3D modeling application.

  13. 76 FR 70151 - Draft Guidance for Industry, Clinical Investigators, Institutional Review Boards, and Food and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-10

    ...The Food and Drug Administration (FDA) is announcing the availability of the draft guidance entitled ``FDA Decisions for Investigational Device Exemption (IDE) Clinical Investigations.'' This guidance document has been developed to promote the initiation of clinical investigations to evaluate medical devices under FDA's IDE regulations. In an effort to promote timely clinical investigations in......

  14. Dosimetry investigation of MOSFET for clinical IMRT dose verification.

    PubMed

    Deshpande, Sudesh; Kumar, Rajesh; Ghadi, Yogesh; Neharu, R M; Kannan, V

    2013-06-01

    In IMRT, patient-specific dose verification is followed regularly at each centre. Simple and efficient dosimetry techniques play a very important role in routine clinical dosimetry QA. The MOSFET dosimeter offers several advantages over the conventional dosimeters such as its small detector size, immediate readout, immediate reuse, multiple point dose measurements. To use the MOSFET as routine clinical dosimetry system for pre-treatment dose verification in IMRT, a comprehensive set of experiments has been conducted, to investigate its linearity, reproducibility, dose rate effect and angular dependence for 6 MV x-ray beam. The MOSFETs shows a linear response with linearity coefficient of 0.992 for a dose range of 35 cGy to 427 cGy. The reproducibility of the MOSFET was measured by irradiating the MOSFET for ten consecutive irradiations in the dose range of 35 cGy to 427 cGy. The measured reproducibility of MOSFET was found to be within 4% up to 70 cGy and within 1.4% above 70 cGy. The dose rate effect on the MOSFET was investigated in the dose rate range 100 MU/min to 600 MU/min. The response of the MOSFET varies from -1.7% to 2.1%. The angular responses of the MOSFETs were measured at 10 degrees intervals from 90 to 270 degrees in an anticlockwise direction and normalized at gantry angle zero and it was found to be in the range of 0.98 ± 0.014 to 1.01 ± 0.014. The MOSFETs were calibrated in a phantom which was later used for IMRT verification. The measured calibration coefficients were found to be 1 mV/cGy and 2.995 mV/cGy in standard and high sensitivity mode respectively. The MOSFETs were used for pre-treatment dose verification in IMRT. Nine dosimeters were used for each patient to measure the dose in different plane. The average variation between calculated and measured dose at any location was within 3%. Dose verification using MOSFET and IMRT phantom was found to quick and efficient and well suited for a busy radiotherapy

  15. 76 FR 12742 - Guidance for Industry and Food and Drug Administration Staff; Clinical Investigations of Devices...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-08

    ...; Clinical Investigations of Devices Indicated for the Treatment of Urinary Incontinence; Availability AGENCY... Treatment of Urinary Incontinence.'' This guidance document describes FDA's recommendations for clinical investigations of medical devices indicated for the treatment of urinary incontinence. DATES: Submit...

  16. An investigation of nurse educator's perceptions and experiences of undertaking clinical practice.

    PubMed

    Williams, Angela; Taylor, Cathy

    2008-11-01

    Educational policy (DOH, 1999. Making a difference: strengthening the nursing, midwifery and health visiting contribution to health and healthcare. Department of Health, London; UKCC, 1999. Fitness for Practice. United Kingdom Central Council for Nursing, Midwifery and Health Visiting, London; Nursing and Midwifery Council, 2006. Standards to support learning and assessment in practice. Nursing and Midwifery Council, London) and current nursing literature (Griscti, O., Jacono, B., Jacono, J., 2005. The nurse educator's clinical role. Journal of Advanced Nursing 50 (1), 84-92; Owen, S., Ferguson, K., Baguley, I., 2005. The clinical activity of mental health nurse lecturers. Journal of Psychiatric and Mental Health Nursing 12, 310-316), place increasing emphasis on nurse educators undertaking clinical practice to facilitate their clinical confidence and competence. This study investigated nurse educators' perceptions and experiences of undertaking clinical practice. A qualitative design and descriptive, exploratory approach were used. A purposive sample of 11 nurse educators in one nursing department, took part in two focus group interviews, one with 5 and the other with 6 respondents, to identify and discuss their perceptions and experiences of undertaking clinical practice. A process of thematic content analysis revealed three broad themes relating to the meaning and importance of clinical practice, perceived benefits and barriers which are examined and discussed. The paper concludes that despite policy recommendations, barriers highlighted in this study such as insufficient time, heavy workload and a lack of valuing of the clinical role have been raised over the past few decades. The effect of undertaking clinical practice, particularly on the quality of teaching is argued to be valuable armoury in the battle to secure sufficient resources to support engagement in clinical practice. Financial and organisational commitment; valuing of clinical practice and research

  17. 21 CFR 50.51 - Clinical investigations not involving greater than minimal risk.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Clinical investigations not involving greater than... HUMAN SERVICES GENERAL PROTECTION OF HUMAN SUBJECTS Additional Safeguards for Children in Clinical Investigations § 50.51 Clinical investigations not involving greater than minimal risk. Any...

  18. 21 CFR 50.51 - Clinical investigations not involving greater than minimal risk.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 1 2011-04-01 2011-04-01 false Clinical investigations not involving greater than... HUMAN SERVICES GENERAL PROTECTION OF HUMAN SUBJECTS Additional Safeguards for Children in Clinical Investigations § 50.51 Clinical investigations not involving greater than minimal risk. Any...

  19. Miniaturization and globalization of clinical laboratory activities.

    PubMed

    Melo, Murilo R; Clark, Samantha; Barrio, Daniel

    2011-04-01

    Clinical laboratories provide an invaluable service to millions of people around the world in the form of quality diagnostic care. Within the clinical laboratory industry the impetus for change has come from technological development (miniaturization, nanotechnology, and their collective effect on point-of-care testing; POCT) and the increasingly global nature of laboratory services. Potential technological gains in POCT include: the development of bio-sensors, microarrays, genetics and proteomics testing, and enhanced web connectivity. In globalization, prospective opportunities lie in: medical tourism, the migration of healthcare workers, cross-border delivery of testing, and the establishment of accredited laboratories in previously unexplored markets. Accompanying these impressive opportunities are equally imposing challenges. Difficulty transitioning from research to clinical use, poor infrastructure in developing countries, cultural differences and national barriers to global trade are only a few examples. Dealing with the issues presented by globalization and the impact of developing technology on POCT, and on the clinical laboratory services industry in general, will be a daunting task. Despite such concerns, with appropriate countermeasures it will be possible to address the challenges posed. Future laboratory success will be largely dependent on one's ability to adapt in this perpetually shifting landscape. PMID:21175379

  20. Preparing a clinical activities database in plastic surgery using existing information systems.

    PubMed

    Dunn, K; Bazire, N; Housley, L; Shakespeare, P

    1994-11-01

    The collection of data for audit and clinical activity analysis is time consuming. This report outlines a technique by which data held on hospital data systems, such as the PAS and theatre management systems, can be made available to clinical investigators. The saving in time and effort can be enormous. PMID:7598400

  1. Investigative and Clinical Applications of Synthetic Immune Synapses

    PubMed Central

    Milone, Michael C.; Kam, Lance C.

    2012-01-01

    The immune synapse has emerged as a compelling model of cell-cell communication. This interface between a T cell and antigen presenting cell serves as a key point in coordinating the immune response. A distinguishing feature of this interface is that juxtacrine signaling molecules form complex patterns that are defined at micrometer and sub-micrometer scales. Moreover, these patterns are highly dynamic. While cellular and molecular approaches have provided insight into the influence of these patterns on cell-cell signaling, replacing the antigen-presenting cell with a synthetic, micro-/nano-engineered surface promises a new level of sophistication to these studies. Micropatterning of multiple ligands onto a surface, for example, allowed the direct demonstration that T cells can sense and respond to microscale geometry of the immune synapse. Supported lipid bilayers have captured the lateral mobility of natural ligands, allowing insight into this complex property of the cell-cell interface in model systems. Finally, engineered surfaces have allowed the study of forces and mechanosensing in T cell activation, an emerging area of immune cell research. In addition to providing new insight into biophysical principles, investigations into immune synapse function may allow control over ex vivo T cell expansion. Bioreactors based on these concepts may find immediate application in enhancing cellular-based immunotherapy. PMID:22927243

  2. Investigating Nitrogen Pollution: Activities and Models.

    ERIC Educational Resources Information Center

    Green Teacher, 2000

    2000-01-01

    Introduces activities on nitrogen, nitrogen pollution from school commuters, nitrogen response in native and introduced species, and nutrient loading models. These activities help students determine the nitrogen contribution from their parents' cars, test native plant responses to nitrogen, and experiment with the results of removing water from…

  3. Clinical implications of the organizational and activational effects of hormones.

    PubMed

    Diamond, Milton

    2009-05-01

    Debate on the relative contributions of nature and nurture to an individual's gender patterns, sexual orientation and gender identity are reviewed as they appeared to this observer starting from the middle of the last century. Particular attention is given to the organization-activation theory in comparison to what might be called a theory of psychosexual neutrality at birth or rearing consistency theory. The organization-activation theory posits that the nervous system of a developing fetus responds to prenatal androgens so that, at a postnatal time, it will determine how sexual behavior is manifest. How organization-activation was or was not considered among different groups and under which circumstances it is considered is basically understood from the research and comments of different investigators and clinicians. The preponderance of evidence seems to indicate that the theory of organization-activation for the development of sexual behavior is certain for non-human mammals and almost certain for humans. This article also follows up on previous clinical critiques and recommendations and makes some new suggestions. PMID:19446079

  4. Is acuity enough? Other considerations in clinical investigations of visual prostheses.

    PubMed

    Lepri, Bernard P

    2009-06-01

    Visual impairing eye diseases are the major frontier facing ophthalmic research today in light of our rapidly aging population. The visual skills necessary for improving the quality of daily function and life are inextricably linked to these impairing diseases. Both research and reimbursement programs are emphasizing outcome-based results. Is improvement in visual acuity alone enough to improve the function and quality of life of visually impaired persons? This perspective summarizes the types of effectiveness endpoints for clinical investigations of visual prostheses that go beyond visual acuity. The clinical investigation of visual prostheses should include visual function, functional vision and quality of life measures. Specifically, they encompass contrast sensitivity, orientation and mobility, activities of daily living and quality of life assessments. The perspective focuses on the design of clinical trials for visual prostheses and the methods of determining effectiveness above and beyond visual acuity that will yield outcomes that are measured by improved function in the visual world and quality of life. The visually impaired population is the primary consideration in this presentation with particular emphases on retinitis pigmentosa and age-related macular degeneration. Clinical trials for visual prostheses cannot be isolated from the need for medical rehabilitation in order to obtain measurements of effectiveness that produce outcomes/evidence-based success. This approach will facilitate improvement in daily function and quality of life of patients with diseases that cause chronic vision impairment. PMID:19458402

  5. 76 FR 1173 - Draft Guidance for Industry on Electronic Source Documentation in Clinical Investigations...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-07

    ...The Food and Drug Administration (FDA) is announcing the availability of a draft guidance for industry entitled ``Electronic Source Documentation in Clinical Investigations.'' This document provides guidance to sponsors, contract research organizations (CROs), data management centers, and clinical investigators on capturing, using, and archiving electronic data in FDA-regulated clinical......

  6. Clinical applications of in vivo neutron-activation analysis

    SciTech Connect

    Cohn, S.H.

    1982-01-01

    In vivo neutron activation has opened a new era of both clinical diagnosis and therapy evaluation, and investigation into and modelling of body composition. The techniques are new, but it is already clear that considerable strides can be made in increasing accuracy and precision, increasing the number of elements susceptible to measurement, enhancing uniformity, and reducing the dose required for the measurement. The work presently underway will yield significant data on a variety of environmental contaminants such as Cd. Compositional studies are determining the level of vital constituents such as nitrogen and potassium in both normal subjects and in patients with a variety of metabolic disorders. Therapeutic programs can be assessed while in progress.

  7. In-vivo neutron activation analysis: principles and clinical applications

    SciTech Connect

    Cohn, S.H.

    1982-01-01

    In vivo neutron activation has opened a new era of both clinical diagnosis and therapy evaluation, and investigation into and modelling of body composition. The techniques are new, but it is already clear that considerable strides can be made in increasing accuracy and precision, increasing the number of elements susceptible to measurement, enhancing uniformity, and reducing the dose required for the measurement. The work presently underway will yield significant data on a variety of environmental contaminants such as Cd. Compositional studies are determining the level of vital constituents such as nitrogen and potassium in both normal subjects and in patients with a variety of metabolic disorders. Therapeutic programs can be assessed while in progress. It seems likely that by the end of this century there will have been significant progress with this research tool, and exciting insights obtained into the nature and dynamics of human body composition.

  8. An Investigation Into Supervision During the Clinical Fellowship Year (CFY).

    ERIC Educational Resources Information Center

    Schubert, George W.; Lyngby, Alison M.

    Questionnaires completed by 204 certified speech pathologists and audiologists were analyzed to determine the effectiveness of supervision in the Clinical Fellowship Year (CFY), a practicum for speech pathology and audiology students. Data was collected for the following aspects of the CFY: personal information, information concerning the CFY…

  9. Clinical approval success rates for investigational cancer drugs.

    PubMed

    DiMasi, J A; Reichert, J M; Feldman, L; Malins, A

    2013-09-01

    We examined development risks for new cancer drugs. For the full study period, the estimated clinical approval success rate for cancer compounds was 13.4% (9.9% for the first half of the study period, 19.8% for the second half). Small molecules had a somewhat higher clinical approval success rate than did large molecules (14.3 vs. 11.5%). Compounds studied solely in hematologic indications had markedly higher estimated clinical approval success rates than did compounds studied only in solid tumor indications (36.0 vs. 9.8%). The first, second, and third cancer indications pursued had estimated clinical approval success rates of 9.0, 8.2, and 6.9%, respectively. Success rates of second and third indications were found to be highly dependent on the success or failure of the first indication pursued (54.9 and 42.4%, respectively, for second and third indications if the first indication is a success, but 2.5 and 1.8%, respectively, if the first indication is a failure). PMID:23739536

  10. Artificial oocyte activation: evidence for clinical readiness.

    PubMed

    Ebner, T; Montag, M

    2016-03-01

    Artificial oocyte activation using Ca(2+)ionophores or similar compounds is a widely applied technique in IVF laboratories. This is all the more interesting as most of the agents aiming for intracellular Ca(2+) increase do not result in physiological Ca(2+) oscillations but much rather cause a single Ca(2+) transient. Two observations from mammals may explain why a rather non-physiological single Ca(2+) peak caused by ionophores is sufficient to rescue cycles showing severe male factor infertility, deficient oocyte maturation, developmental problems in humans, or both. On the one hand, it has been shown that it is mainly the initial Ca(2+) rise that drives further downstream events, in particular calcium/calmodulin-dependent protein kinase II (CaMKII) action, and on the other, it is possible that this enzyme remains active even in the absence of Ca(2+). It therefore seems that mammalian oocytes can respond to a wide range of intracellular Ca(2+) signals and have a surprisingly high degree of tolerance for changes in cytosolic Ca(2+). As epigenetic consequences or differences in gene expression have not been studied to date, artificial oocyte activation has to be considered as experimental and should only be applied with a proper indication. PMID:26776820

  11. 21 CFR 312.40 - General requirements for use of an investigational new drug in a clinical investigation.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 false General requirements for use of an investigational new drug in a clinical investigation. 312.40 Section 312.40 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE INVESTIGATIONAL NEW...

  12. 21 CFR 312.40 - General requirements for use of an investigational new drug in a clinical investigation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false General requirements for use of an investigational new drug in a clinical investigation. 312.40 Section 312.40 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE INVESTIGATIONAL NEW...

  13. Acute febrile torticollis in youth: clinical investigation and current management.

    PubMed

    Ouattassi, Naouar; Chmiel, Mohammed; El Kerouiti, Zakaria; Ridal, Mohammed; Alami, Mohammed Nouredine

    2015-01-01

    Acute febrile torticollis in children is a rare and a special clinical picture of variable causes. It may indicate an inflammatory or an infectious pathology affecting any of the anatomical structures of the neck. Treatment is quite clearly defined, and it may be a therapeutic emergency. It is a condition that all ENT specialists must be familiar with since they are most likely to be the first physician to whom such a child is brought. PMID:26328000

  14. Acute febrile torticollis in youth: clinical investigation and current management

    PubMed Central

    Ouattassi, Naouar; Chmiel, Mohammed; Kerouiti, Zakaria El; Ridal, Mohammed; Alami, Mohammed Nouredine

    2015-01-01

    Acute febrile torticollis in children is a rare and a special clinical picture of variable causes. It may indicate an inflammatory or an infectious pathology affecting any of the anatomical structures of the neck. Treatment is quite clearly defined, and it may be a therapeutic emergency. It is a condition that all ENT specialists must be familiar with since they are most likely to be the first physician to whom such a child is brought PMID:26328000

  15. Recovering from Cocaine: Insights from Clinical and Preclinical Investigations

    PubMed Central

    Hanlon, Colleen A.; Beveridge, Thomas J.R.; Porrino, Linda J.

    2013-01-01

    Cocaine remains one of the most addictive substances of abuse and one of the most difficult to treat. Although increasingly sophisticated experimental and technologic advancements in the last several decades have yielded a large body of clinical and preclinical knowledge on the direct effects of cocaine on the brain, we still have a relatively incomplete understanding of the neurobiological processes that occur when drug use is discontinued. The goal of this manuscript is to review both clinical and preclinical data related to abstinence from cocaine and discuss the complementary conclusions that emerge from these different levels of inquiry. This commentary will address observed alterations in neural function, neural structure, and neurotransmitter system regulation that are present in both animal models of cocaine abstinence and data from recovering clinical populations. Although these different levels of inquiry are often challenging to integrate, emerging data discussed in this commentary suggest that from a structural and functional perspective, the preservation of cortical function that is perhaps the most important biomarker associated with extended abstinence from cocaine. PMID:23628740

  16. 21 CFR 50.51 - Clinical investigations not involving greater than minimal risk.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 1 2012-04-01 2012-04-01 false Clinical investigations not involving greater than minimal risk. 50.51 Section 50.51 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... Investigations § 50.51 Clinical investigations not involving greater than minimal risk. Any...

  17. Clinical investigation of speech signal features among patients with schizophrenia

    PubMed Central

    ZHANG, Jing; PAN, Zhongde; GUI, Chao; CUI, Donghong

    2016-01-01

    Background A new area of interest in the search for biomarkers for schizophrenia is the study of the acoustic parameters of speech called 'speech signal features'. Several of these features have been shown to be related to emotional responsiveness, a characteristic that is notably restricted in patients with schizophrenia, particularly those with prominent negative symptoms. Aim Assess the relationship of selected acoustic parameters of speech to the severity of clinical symptoms in patients with chronic schizophrenia and compare these characteristics between patients and matched healthy controls. Methods Ten speech signal features-six prosody features, formant bandwidth and amplitude, and two spectral features-were assessed using 15-minute speech samples obtained by smartphone from 26 inpatients with chronic schizophrenia (at enrollment and 1 week later) and from 30 healthy controls (at enrollment only). Clinical symptoms of the patients were also assessed at baseline and 1 week later using the Positive and Negative Syndrome Scale, the Scale for the Assessment of Negative Symptoms, and the Clinical Global Impression-Schizophrenia scale. Results In the patient group the symptoms were stable over the 1-week interval and the 1-week test-retest reliability of the 10 speech features was good (intraclass correlation coefficients [ICC] ranging from 0.55 to 0.88). Comparison of the speech features between patients and controls found no significant differences in the six prosody features or in the formant bandwidth and amplitude features, but the two spectral features were different: the Mel-frequency cepstral coefficient (MFCC) scores were significantly lower in the patient group than in the control group, and the linear prediction coding (LPC) scores were significantly higher in the patient group than in the control group. Within the patient group, 10 of the 170 associations between the 10 speech features considered and the 17 clinical parameters considered were

  18. Application of ferrokinetic investigation for differential diagnosis in bone marrow hypoplasia and their clinical relevance.

    PubMed

    Gupta, M; Roth, P; Werner, E; Kaltwasser, J P

    1979-02-01

    In this study, erythropoietic activity of bone marrow has been evaluated by ferrokinetics. For that purpose, the data of radioiron disappearance from plasma and its ultimate incorporation in red blood cells after the injection of about 10 muCi of 59Fe tagged autologous plasma, were analysed and fitted to the sum of three exponentials, using a non-linear least square SAAM-25 program on UNIVAC-1108 computer. A function representing time-activity relationship, was constructed. The functional physiological model of iron metabolism, proposed by Cavill and Ricketts, was used to calculate various ferrokinetic parameters in terms of coefficients and exponents of the time-activity function. After identifying the parameters that could be used as indices of erythropoietic activity of bone marrow, the study was repeated in six patients after they had undergone myelostimulative therapy. A distinct correlation was found between ferrokinetic observations and clinical and biochemical findings. It has been demonstrated that in histologically diagnosed cases with bone marrow hypoplasia, a further differentiation between pure aplasia and those with hypoplasia together with ineffective erythropoiesis was possible. This discrimination which is clinically very important, is only possible by means of kinetic investigations. PMID:499222

  19. Numerical Investigation of Plasma Active Flow Control

    NASA Astrophysics Data System (ADS)

    Sun, Baigang; Li, Feng; Zhang, Shanshan; Wang, Jingyu; Zhang, Lijuan; Zhao, Erlei

    2010-12-01

    Based on the theory of EHD (electronhydrodynamic), a simplified volume force model is applied to simulation to analyze the traits of plasma flow control in flow field, in which the cold plasma is generated by a DBD (dielectric-barrier-discharge) actuator. With the para-electric action of volume force in electric field, acceleration characteristics of the plasma flow are investigated for different excitation intensities of RF (radio frequency) power for the actuator. Furthermore, the plasma acceleration leads to an asymmetric distribution of flow field, and hence induces the deflection of jet plume, then results in a significant deflection angle of 6.26° thrust-vectoring effect. It appears that the plasma flow control technology is a new tentative method for the thrust-vectoring control of a space vehicle.

  20. Preliminary Investigation of an Active PLZT Lens

    NASA Technical Reports Server (NTRS)

    Lightsey, W. D.; Peters, B. R.; Reardon, P. J.; Wong, J. K.

    2001-01-01

    The design, analysis and preliminary testing of a prototype Adjustable Focus Optical Correction Lens (AFOCL) is described. The AFOCL is an active optical component composed of solid state lead lanthanum-modified zirconate titanate (PLZT) ferroelectric ceramic with patterned indium tin oxide (ITO) transparent surface electrodes that modulate the refractive index of the PLZT to function as an electro-optic lens. The AFOCL was developed to perform optical re-alignment and wavefront correction to enhance the performance of Ultra-Lightweight Structures and Space Observatories (ULSSO). The AFOCL has potential application as an active optical component within a larger optical system. As such, information from a wavefront sensor would be processed to provide input to the AFOCL to drive the sensed wavefront to the desired shape and location. While offering variable and rapid focussing capability (controlled wavefront manipulation) similar to liquid crystal based spatial light modulators (SLM), the AFOCL offers some potential advantages because it is a solid-state, stationary, low-mass, rugged, and thin optical element that can produce wavefront quality comparable to the solid refractive lens it replaces. The AFOCL acts as a positive or negative lens by producing a parabolic phase-shift in the PLZT material through the application of a controlled voltage potential across the ITO electrodes. To demonstrate the technology, a 4 mm diameter lens was fabricated to produce 5-waves of optical power operating at 2.051 micrometer wavelength. Optical metrology was performed on the device to measure focal length, optical quality, and efficiency for a variety of test configurations. The data was analyzed and compared to theoretical data available from computer-based models of the AFOCL.

  1. Clinical features, investigation and treatment of post-traumatic syringomyelia.

    PubMed Central

    Shannon, N; Symon, L; Logue, V; Cull, D; Kang, J; Kendall, B

    1981-01-01

    Thirteen patients who sustained spinal cord trauma causing persisting disability, developed new symptoms, the chief one of which was severe pain unrelieved by analgesics. The clinical diagnosis of post traumatic syringomyelia was confirmed in each case by means of myelography, as well as endomyelography in seven patients. In every case exploration of the spinal cord syrinx was performed. Ten patients were troubled by severe pain while three patients were mainly subject to altered sensation in the upper limbs. Of the six patients who had initially sustained complete cord transections, three were treated by cord transection and three were treated by syringostomy. The seven patients who sustained incomplete cord lesions were all treated by syringostomy. The patients who initially sustained incomplete sensory motor spinal cord damage had a better symptomatic response to surgery than hose who had sustained a complete spinal cord lesion. The ten patients whose main symptom was severe pain were completely relieved of their symptoms by surgery. Images PMID:7205304

  2. Beecher as Clinical Investigator: Pain and the Placebo Effect.

    PubMed

    Benedetti, Fabrizio

    2016-01-01

    Among the many contributions by Henry Beecher to science and clinical practice, pain and the placebo effect certainly represent two of the most important aspects. On the one hand, Beecher considered the pain experience not only as arising from the peripheral injured tissues, but also as an emotional experience that is capable of modulating the nociceptive input. On the other hand, he analyzed the placebo effect at an unprecedented level for that time. His ideas sparked from his work on wounded soldiers during World War II. In spite of the unusual situation and the lack of sophisticated experimental tools on the battlefield, Beecher succeeded in putting forward several important concepts, and his ideas still pervade modern health care and research. PMID:27499483

  3. 21 CFR 812.119 - Disqualification of a clinical investigator.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ....119 Section 812.119 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... sponsor of the investigation or in any required report, the Center for Devices and Radiological Health, the Center for Biologics Evaluation and Research, or the Center for Drug Evaluation and Research...

  4. Investigation of an Area Health Education Center Clinical Pharmacy Program.

    ERIC Educational Resources Information Center

    Hightower, William L; Yanchick, Victor A.

    1979-01-01

    To investigate the effectiveness of the Area Health Education Center Pharmacy Training Program at the University of Texas, a study was undertaken to determine the amount of time pharmacy externs spend in predefined work categories and to compare them to program objectives. (JMD)

  5. 21 CFR 812.119 - Disqualification of a clinical investigator.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... provide a statement of basis for such determination. (c) Each investigational device exemption (IDE) and... chapter. If a danger to the public health exists, however, the Commissioner shall terminate the IDE... of whether the IDE should be reinstated. (e) If the Commissioner determines, after the...

  6. 21 CFR 812.119 - Disqualification of a clinical investigator.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... provide a statement of basis for such determination. (c) Each investigational device exemption (IDE) and... chapter. If a danger to the public health exists, however, the Commissioner shall terminate the IDE... of whether the IDE should be reinstated. (e) If the Commissioner determines, after the...

  7. A new desensitizing dentifrice--an 8-week clinical investigation.

    PubMed

    Sowinski, J A; Battista, G W; Petrone, M E; Chaknis, P; Zhang, Y P; DeVizio, W; Volpe, A R; Proskin, H M

    2000-01-01

    An 8-week, double-blind, three-way clinical trial compared the dentinal hypersensitivity-reducing effectiveness of a new dentifrice containing 5.0% potassium nitrate and 0.454% stannous fluoride in a silica base (Colgate Sensitive Maximum Strength Toothpaste, Colgate-Palmolive Co.) with a commercially available desensitizing dentifrice containing 5.0% potassium nitrate and 0.243% sodium fluoride in a silica base (Sensodyne Fresh Mint Toothpaste, Block Drug Company, Inc.) and a nondesensitizing dentifrice containing 0.243% sodium fluoride in a silica base (Colgate Winterfresh Gel, Colgate-Palmolive Co.). One hundred nine subjects were stratified into three balanced groups according to gender, age, mean baseline tactile (Yeaple Probe), and thermal (air blast) scores. The test products were randomly assigned to each group with instructions to brush twice daily. Oral examinations with tactile and thermal assessments were repeated after 4 and 8 weeks. The new dentifrice group demonstrated statistically significant improvements in tactile and thermal sensitivity over the two control groups. PMID:11908355

  8. Paracoccidioidomycosis manifesting as oral lesions: clinical, cytological and serological investigation.

    PubMed

    Sposto, M R; Mendes-Giannini, M J; Moraes, R A; Branco, F C; Scully, C

    1994-02-01

    Paracoccidioidomycosis (South American blastomycosis) is a systemic mycosis which can be associated with oral lesions. This study on a group of 14 patients showed oral lesions mainly on the gingival or alveolar mucosa, with pulmonary involvement detectable on chest radiography in most. Microscopic detection of the fungus on a direct smear showed positive results in all 14 patients. Serological investigations including immunodiffusion, counterimmunoelectrophoresis and immunoblot were also positive in 100% of cases. The results suggest that direct smear together with serology may obviate the need for lesional biopsy for the diagnosis of oral paracoccidioidomycosis. PMID:8164159

  9. [Investigation of Pneumocystis jirovecii in clinical specimens by different methods].

    PubMed

    Tekinşen, F Filiz; Koç, A Nedret

    2013-10-01

    Pneumocystis jirovecii causes pneumonia in premature, newborn or malnourished children, as well as in immunocompromised subjects such as chemotherapy receiving, transplant and AIDS patients. Since the mortality and morbidity rates of Pneumocystis pneumonia (PCP) in these patients were high, rapid and accurate diagnosis is important. The aim of this study was to evaluate the diagnostic value of Giemsa staining (GS), direct fluorescent antibody (DFA) assay, (1→3)-β-D-Glucan (BDG) test and real-time polymerase chain reaction (PCR) for the detection of P.jirovecii in clinical specimens. A total of 100 PCP-suspected patients with underlying diseases who were followed-up in outpatient and inpatient clinics of our hospital between December 2008-July 2010 were included in the study. All the patients (66 male, 34 female; mean age: 42.04 years) were under long-term immunosuppressive drug therapy due to their hematological malignancies, kidney transplantation, neutropenia or chronic diseases. Respiratory samples [86 bronchoalveolar lavage (BAL), 8 endotracheal aspirate, 1 nasotracheal aspirate, 3 pleural, 2 lung biopsy samples] obtained from the patients have been studied with GS (Merck, Germany), DFA (Pneumo Cel, Cellabs, Australia) and PCR (primers targeting MSG gene, LightCycler, Roche, USA), while serum samples (n= 100) with BDG (Fungitell, ACC Inc, USA) and PCR methods. In BAL samples two were found positive by GS, DFA and PCR, and six were positive only by PCR, yielding a total positivity in 8 (8%) samples. All of the sera were negative with PCR, however 29 of them were positive (> 80 pg/ml), five were equivocal (61-79 pg/ml) and 66 were negative (< 60 pg/ml) with BDG test. Eight patients with positive results in BAL-PCR were also positive with BDG test. Although the agreement between GS and DFA was high (κ= 1), it was observed as low between PCR and DFA (κ= 0.38), DFA and BDG (κ= 0.07), BAL-PCR and BDG (κ= 0.28). DFA taken as the gold standard, the sensitivity

  10. 77 FR 69632 - Draft Guidance for Industry on Electronic Source Data in Clinical Investigations; Availability

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-20

    ...The Food and Drug Administration (FDA) is announcing the availability of a draft guidance for industry entitled ``Electronic Source Data in Clinical Investigations.'' This document revises and updates the draft guidance entitled ``Electronic Source Documentation in Clinical Investigations.'' This revised draft document provides guidance to sponsors, contract research organizations (CROs), data......

  11. Clinical and laboratory investigation of oral allergy syndrome to grape.

    PubMed

    Falak, Reza; Sankian, Mojtaba; Tehrani, Mohsen; Jabbari Azad, Farahzad; Abolhasani, Ahmad; Varasteh, Abdolreza

    2012-06-01

    Oral allergy syndrome (OAS) is occasionally observed following consumption of raw fruits in allergic adults. Since this phenomenon was commonly reported in Khorasan province of Iran; we intended to check if common diagnostic tests could be applied for differential diagnosis of OAS to grapes.IgE reactivity of 84 patients with OAS to grape and 34 patients with OAS to other fruits were analyzed by in vivo and in vitro methods, and the results were compared with those of controls. The patients underwent skin prick test (SPT) with common allergic pollen extracts as well as grape extract. The specific IgE level to grape proteins was determined by an indirect ELISA. The correlation of SPT results with ELISA and western blotting patterns was checked by statistical methods. The results showed a significant correlation of grape SPT diameters with grape specific IgE levels. Furthermore, a significant association of grape SPT results with IgE immunoreactivity of a 10 kDa grape protein, probably lipid transfer protein (LTP) was prominent. Immunoreactivity of other proteins was linked with mild clinical symptoms. The study showed a significant correlation of grape SPT results with grape total extract, as well as its 10 kDa component's IgE reactivity. The results suggested that OAS to grape should not be considered as a main criterion in diagnosis of grape allergy and a combination of grape SPT results with evaluation of IgE reactivity to grape 10 kDa allergen should be considered to achieve a more reliable grape allergy diagnosis. PMID:22761188

  12. PERSPECTIVE: Is acuity enough? Other considerations in clinical investigations of visual prostheses

    NASA Astrophysics Data System (ADS)

    Lepri, Bernard P.

    2009-06-01

    Visual impairing eye diseases are the major frontier facing ophthalmic research today in light of our rapidly aging population. The visual skills necessary for improving the quality of daily function and life are inextricably linked to these impairing diseases. Both research and reimbursement programs are emphasizing outcome-based results. Is improvement in visual acuity alone enough to improve the function and quality of life of visually impaired persons? This perspective summarizes the types of effectiveness endpoints for clinical investigations of visual prostheses that go beyond visual acuity. The clinical investigation of visual prostheses should include visual function, functional vision and quality of life measures. Specifically, they encompass contrast sensitivity, orientation and mobility, activities of daily living and quality of life assessments. The perspective focuses on the design of clinical trials for visual prostheses and the methods of determining effectiveness above and beyond visual acuity that will yield outcomes that are measured by improved function in the visual world and quality of life. The visually impaired population is the primary consideration in this presentation with particular emphases on retinitis pigmentosa and age-related macular degeneration. Clinical trials for visual prostheses cannot be isolated from the need for medical rehabilitation in order to obtain measurements of effectiveness that produce outcomes/evidence-based success. This approach will facilitate improvement in daily function and quality of life of patients with diseases that cause chronic vision impairment. The views and opinions are those of the author and do not necessarily reflect those of the US Food and Drug Administration, the US Department of Health and Human Services or the Public Health Service.

  13. Clinical investigations of receptive and expressive musical functions after stroke

    PubMed Central

    Rosslau, Ken; Steinwede, Daniel; Schröder, C.; Herholz, Sibylle C.; Lappe, Claudia; Dobel, Christian; Altenmüller, Eckart

    2015-01-01

    There is a long tradition of investigating various disorders of musical abilities after stroke. These impairments, associated with acquired amusia, can be highly selective, affecting only music perception (i.e., receptive abilities/functions) or expression (music production abilities), and some patients report that these may dramatically influence their emotional state. The aim of this study was to systematically test both the melodic and rhythmic domains of music perception and expression in left- and right-sided stroke patients compared to healthy subjects. Music perception was assessed using rhythmic and melodic discrimination tasks, while tests of expressive function involved the vocal or instrumental reproduction of rhythms and melodies. Our approach revealed deficits in receptive and expressive functions in stroke patients, mediated by musical expertise. Those patients who had experienced a short period of musical training in childhood and adolescence performed better in the receptive and expressive subtests compared to those without any previous musical training. While discrimination of specific musical patterns was unimpaired after a left-sided stroke, patients with a right-sided stroke had worse results for fine melodic and rhythmic analysis. In terms of expressive testing, the most consistent results were obtained from a test that required patients to reproduce sung melodies. This implies that the means of investigating production abilities can impact the identification of deficits. PMID:26124731

  14. Clinical investigations of receptive and expressive musical functions after stroke.

    PubMed

    Rosslau, Ken; Steinwede, Daniel; Schröder, C; Herholz, Sibylle C; Lappe, Claudia; Dobel, Christian; Altenmüller, Eckart

    2015-01-01

    There is a long tradition of investigating various disorders of musical abilities after stroke. These impairments, associated with acquired amusia, can be highly selective, affecting only music perception (i.e., receptive abilities/functions) or expression (music production abilities), and some patients report that these may dramatically influence their emotional state. The aim of this study was to systematically test both the melodic and rhythmic domains of music perception and expression in left- and right-sided stroke patients compared to healthy subjects. Music perception was assessed using rhythmic and melodic discrimination tasks, while tests of expressive function involved the vocal or instrumental reproduction of rhythms and melodies. Our approach revealed deficits in receptive and expressive functions in stroke patients, mediated by musical expertise. Those patients who had experienced a short period of musical training in childhood and adolescence performed better in the receptive and expressive subtests compared to those without any previous musical training. While discrimination of specific musical patterns was unimpaired after a left-sided stroke, patients with a right-sided stroke had worse results for fine melodic and rhythmic analysis. In terms of expressive testing, the most consistent results were obtained from a test that required patients to reproduce sung melodies. This implies that the means of investigating production abilities can impact the identification of deficits. PMID:26124731

  15. Hemolytic activity of dermatophytes species isolated from clinical specimens.

    PubMed

    Aktas, E; Yıgıt, N

    2015-03-01

    Hemolytic activity was recently reported for several pathogenic fungal species, such as Aspergillus, Candida, Trichophyton, Penicillium and Fusarium. Based on a number of mechanistic and characterization studies, several fungal hemolysins have been proposed as virulence factors. Hemolysins lyse red blood cells resulting in the release of iron, an important growth factor for microbes especially during infection. The requirement of iron in fungal growth is necessary for metabolic processes and as a catalyst for various biochemical processes. Expression of a hemolytic protein with capabilities to lyse red blood cells has also been suggested to provide a survival strategy for fungi during opportunistic infections. The aims of this study were to investigate the hemolytic activities of dermatophytes species isolated from patients with dermatophytosis. Hair, skin and nail samples of patients were examined with direct microscopy using potassium hydroxide and cultivated on Mycobiotic agar and Sabouraud's dextrose agar. To determine hemolytic activities of dermatophytes species, they were subcultured on Columbia Agar with 5% sheep blood and incubated for 7-14 days at 25°C in aerobic conditions. Media which displayed hemolysis were further incubated for 1-5 days at 37°C to increase hemolytic activity. In this study, 66 dermatophytes strains were isolated from clinical specimens and were identified by six different species: 43 (65.1%) Trichophyton rubrum, 7 (10.7%) Trichophyton mentagrophytes, 5 (7.6%) Microsporum canis, 5 (7.6%) Trichophyton tonsurans, 4 (6.0%) Epidermophyton floccosum and 2 (3.0%) Trichophyton violaceum. Twenty-one T. rubrum strains showed incomplete (alpha) hemolysis and nine T. rubrum strains showed complete (beta) hemolysis, whereas hemolysis was absent in 13 T. rubrum strains. Four T. mentagrophytes strains showed complete hemolysis and three T. tonsurans strains showed incomplete hemolysis. However, M. canis, E. floccosum and T. violaceum species had

  16. Clinical investigations of the therapeutic potential of ayahuasca: rationale and regulatory challenges.

    PubMed

    McKenna, Dennis J

    2004-05-01

    Ayahuasca is a hallucinogenic beverage that is prominent in the ethnomedicine and shamanism of indigenous Amazonian tribes. Its unique pharmacology depends on the oral activity of the hallucinogen, N,N-dimethyltryptamine (DMT), which results from inhibition of monoamine oxidase (MAO) by beta-carboline alkaloids. MAO is the enzyme that normally degrades DMT in the liver and gut. Ayahuasca has long been integrated into mestizo folk medicine in the northwest Amazon. In Brazil, it is used as a sacrament by several syncretic churches. Some of these organizations have incorporated in the United States. The recreational and religious use of ayahuasca in the United States, as well as "ayahuasca tourism" in the Amazon, is increasing. The current legal status of ayahuasca or its source plants in the United States is unclear, although DMT is a Schedule I controlled substance. One ayahuasca church has received favorable rulings in 2 federal courts in response to its petition to the Department of Justice for the right to use ayahuasca under the Religious Freedom Restoration Act. A biomedical study of one of the churches, the Uñiao do Vegetal (UDV), indicated that ayahuasca may have therapeutic applications for the treatment of alcoholism, substance abuse, and possibly other disorders. Clinical studies conducted in Spain have demonstrated that ayahuasca can be used safely in normal healthy adults, but have done little to clarify its potential therapeutic uses. Because of ayahuasca's ill-defined legal status and variable botanical and chemical composition, clinical investigations in the United States, ideally under an approved Investigational New Drug (IND) protocol, are complicated by both regulatory and methodological issues. This article provides an overview of ayahuasca and discusses some of the challenges that must be overcome before it can be clinically investigated in the United States. PMID:15163593

  17. Clinical and morphological investigations on ependymomas and their tissue cultures.

    PubMed

    Casentini, L; Gullotta, F; Möhrer, U

    1981-03-01

    A morphological investigation was carried out on 56 ependymomas cultivated in vitro as short-term cultures in roller tubes. The tumours had been histologically classified as cellular and fibrillary ependymomas, subependymomas, myxopapillary and malignant ependymomas (Table 1). A very good growth was detected in 32 cases, most of them being cellular and malignant ependymomas (Table 2). The prevailing growth pattern was epithelial in type, i.e. proliferating cells forming a carpet. In some cases, in the first stages of growth elongated bipolar cells did appear, but they evolved later as flattened epithelial elements. In four cases, a mixed proliferation of piloid astrocytes and ependymal cells was seen; these tumours were regarded as mixed gliomas. In 46 cases an exact evaluation of the history was possible. Although no correlation could be found between histology and survival time (Table 4), the longest survival was observed in spinal tumours (Table 3). Tumours in children had a slightly worse prognosis in comparison with adults (Table 5). A radical removal of the tumour was generally followed by a longer survival time (Table 6), although the operative procedure employed did not seem to influence the development of recurrences (Table 7). PMID:7219656

  18. Clinical and laboratory investigation of allergy to genetically modified foods.

    PubMed Central

    Bernstein, Jonathan A; Bernstein, I Leonard; Bucchini, Luca; Goldman, Lynn R; Hamilton, Robert G; Lehrer, Samuel; Rubin, Carol; Sampson, Hugh A

    2003-01-01

    Technology has improved the food supply since the first cultivation of crops. Genetic engineering facilitates the transfer of genes among organisms. Generally, only minute amounts of a specific protein need to be expressed to obtain the desired trait. Food allergy affects only individuals with an abnormal immunologic response to food--6% of children and 1.5-2% of adults in the United States. Not all diseases caused by food allergy are mediated by IgE. A number of expert committees have advised the U.S. government and international organizations on risk assessment for allergenicity of food proteins. These committees have created decision trees largely based on assessment of IgE-mediated food allergenicity. Difficulties include the limited availability of allergen-specific IgE antisera from allergic persons as validated source material, the utility of specific IgE assays, limited characterization of food proteins, cross-reactivity between food and other allergens, and modifications of food proteins by processing. StarLink was a corn variety modified to produce a (Italic)Bacillus thuringiensis(/Italic) (Bt) endotoxin, Cry9C. The Centers for Disease Control and Prevention investigated 51 reports of possible adverse reactions to corn that occurred after the announcement that StarLink, allowed for animal feed, was found in the human food supply. Allergic reactions were not confirmed, but tools for postmarket assessment were limited. Workers in agricultural and food preparation facilities have potential inhalation exposure to plant dusts and flours. In 1999, researchers found that migrant health workers can become sensitized to certain Bt spore extracts after exposure to Bt spraying. PMID:12826483

  19. Problem Posing Based on Investigation Activities by University Students

    ERIC Educational Resources Information Center

    da Ponte, Joao Pedro; Henriques, Ana

    2013-01-01

    This paper reports a classroom-based study involving investigation activities in a university numerical analysis course. The study aims to analyse students' mathematical processes and to understand how these activities provide opportunities for problem posing. The investigations were intended to stimulate students in asking questions, to trigger…

  20. 76 FR 20707 - Notice of Possible Shutdown of Investigative Activities

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-13

    ... determined to shut down its investigative activities in the event of the absence of an appropriation. FOR... because of the potential for an absence of an appropriation as of 12:01 a.m. on Saturday, April 9, 2011... shut down its investigative activities for the duration of the absence of appropriation....

  1. Fecal Calprotectin and Clinical Disease Activity in Pediatric Ulcerative Colitis

    PubMed Central

    Kolho, Kaija-Leena; Turner, Dan

    2013-01-01

    Objective. To explore fecal calprotectin levels in pediatric ulcerative colitis (UC) in relation with the validated clinical activity index PUCAI. Methods. This study included all 37 children (median age 14 years) with UC who had calprotectin measured (PhiCal ELISA Test) by the time of PUCAI assessment at the Children's Hospital of Helsinki in a total of 62 visits. Calprotectin values <100 μg/g of stool were considered as normal. The best cut-off value of each measure to predict 3-month clinical outcome was derived by maximizing sensitivity and specificity. Results. In clinically active disease (PUCAI ≥ 10), calprotectin was elevated in 29/32 patients (91% sensitivity). When in clinical remission, 26% (8/30) of the children had normal calprotectin but 7 (23%) had an exceedingly high level (>1000 μg/g). The best cut-off value for calprotectin for predicting poor outcome was 800 μg/g (sensitivity 73%, specificity 72%; area under the ROC curve being 0.71 (95%CI 0.57–0.85)) and for the PUCAI best cut-off values >10 (sensitivity 62%, specificity 64%; area under the ROC curve 0.714 (95%CI 0.58–0.85)). Conclusion. The clinical relevance of somewhat elevated calprotectin during clinical remission in pediatric UC is not known and, until further evidence accumulates, does not indicate therapy escalation. PMID:23533791

  2. Antifungal Activity of Bee Venom and Sweet Bee Venom against Clinically Isolated Candida albicans

    PubMed Central

    Lee, Seung-Bae

    2016-01-01

    Objectives: The purpose of this study was to investigate the antifungal effect of bee venom (BV) and sweet bee venom (SBV) against Candida albicans (C. albicans) clinical isolates. Methods: In this study, BV and SBV were examined for antifungal activities against the Korean Collection for Type Cultures (KCTC) strain and 10 clinical isolates of C. albicans. The disk diffusion method was used to measure the antifungal activity and minimum inhibitory concentration (MIC) assays were performed by using a broth microdilution method. Also, a killing curve assay was conducted to investigate the kinetics of the anti- fungal action. Results: BV and SBV showed antifungal activity against 10 clinical isolates of C. albicans that were cultured from blood and the vagina by using disk diffusion method. The MIC values obtained for clinical isolates by using the broth microdilution method varied from 62.5 μg/ mL to 125 μg/mL for BV and from 15.63 μg/mL to 62.5 μg/mL for SBV. In the killing-curve assay, SBV behaved as amphotericin B, which was used as positive control, did. The antifungal efficacy of SBV was much higher than that of BV. Conclusion: BV and SBV showed antifungal activity against C. albicans clinical strains that were isolated from blood and the vagina. Especially, SBV might be a candidate for a new antifungal agent against C. albicans clinical isolates. PMID:27280049

  3. Exploring Patient Activation in the Clinic: Measurement from Three Perspectives

    ERIC Educational Resources Information Center

    Ledford, Christy J. W.; Ledford, Christopher C.; Childress, Marc A.

    2013-01-01

    Objective. To further conceptualize and operationalize patient activation (PA), using measures from patient, physician, and researcher perspectives. Data Source/Study Setting. Multimethod observation in 2010 within a family medicine clinic. Study Design. Part of an intervention with 130 patients with type 2 diabetes, this observational study…

  4. Active Interventions in Clinical Practice: Contributions of Gestalt Therapy.

    ERIC Educational Resources Information Center

    Lammert, Marilyn; Dolan, Mary M.

    1983-01-01

    Describes two dimensions of Gestalt therapy that can enhance clinical practice--orientation to the present and active-experimental style--and examines them in relation to some traditional principles of practice. Gestalt theory offers a method of discovery that is a combination of phenomenology and behaviorism. (JAC)

  5. Applying active learning to assertion classification of concepts in clinical text.

    PubMed

    Chen, Yukun; Mani, Subramani; Xu, Hua

    2012-04-01

    Supervised machine learning methods for clinical natural language processing (NLP) research require a large number of annotated samples, which are very expensive to build because of the involvement of physicians. Active learning, an approach that actively samples from a large pool, provides an alternative solution. Its major goal in classification is to reduce the annotation effort while maintaining the quality of the predictive model. However, few studies have investigated its uses in clinical NLP. This paper reports an application of active learning to a clinical text classification task: to determine the assertion status of clinical concepts. The annotated corpus for the assertion classification task in the 2010 i2b2/VA Clinical NLP Challenge was used in this study. We implemented several existing and newly developed active learning algorithms and assessed their uses. The outcome is reported in the global ALC score, based on the Area under the average Learning Curve of the AUC (Area Under the Curve) score. Results showed that when the same number of annotated samples was used, active learning strategies could generate better classification models (best ALC-0.7715) than the passive learning method (random sampling) (ALC-0.7411). Moreover, to achieve the same classification performance, active learning strategies required fewer samples than the random sampling method. For example, to achieve an AUC of 0.79, the random sampling method used 32 samples, while our best active learning algorithm required only 12 samples, a reduction of 62.5% in manual annotation effort. PMID:22127105

  6. 78 FR 35937 - Food and Drug Administration Decisions for Investigational Device Exemption Clinical...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-14

    ... for Investigational Device Exemption (IDE) Clinical Investigations.'' This guidance document was... investigations to evaluate medical devices under FDA's IDE regulations. The guidance was also intended to provide... IDE and to provide a general explanation of the reasons for those decisions. This guidance has...

  7. 78 FR 52932 - Guidance for Institutional Review Boards, Clinical Investigators, and Sponsors: Institutional...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-27

    ....fda.gov/ScienceResearch/SpecialTopics/RunningClinicalTrials/GuidancesInformationSheetsandNotices... Investigators, Adequacy of Research Sites, and the Determination of Whether an Investigational New Drug... Qualifications of Investigators, Adequacy of Research Sites, and the Determination of Whether an IND/IDE...

  8. 76 FR 50484 - Draft Guidance for Industry, Clinical Investigators, and Food and Drug Administration Staff...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-15

    ... Food and Drug Administration Staff; Design Considerations for Pivotal Clinical Investigations for... and Drug Administration (FDA) is announcing the availability of the draft guidance entitled ``Design... study design principles relevant to the development of medical device clinical studies that can be...

  9. Clinical and arthroscopic findings in recreationally active patients

    PubMed Central

    2010-01-01

    Objective To examine the diagnostic accuracy of standard clinical tests for the shoulder in recreational athletes with activity related pain. Design Cohort study with index test of clinical examination and reference standard of arthroscopy. Setting Sports Medicine clinic in Sheffield, U.K. Participants 101 recreational athletes (82 male, 19 female; mean age 40.8 ± 14.6 years) over a six year period. Interventions Bilateral evaluation of movements of the shoulder followed by standardized shoulder tests, formulation of clinical diagnosis and shoulder arthroscopy conducted by the same surgeon. Main Outcome Measurements Sensitivity, specificity, likelihood ratio for a positive test and over-all accuracy of clinical examination was examined retrospectively and compared with arthroscopy. Results Isolated pathology was rare, most patients (72%) having more than one injury recorded. O'Brien's clinical test had a mediocre sensitivity (64%) and over-all accuracy (54%) for diagnosing SLAP lesions. Hawkins test and Jobe's test had the highest but still not impressive over-all accuracy (67%) and sensitivity (67%) for rotator cuff pathology respectively. External and internal impingement tests showed similar levels of accuracy. When a positive test was observed in one of a combination of shoulder tests used for diagnosing SLAP lesions or rotator cuff disease, sensitivity increased substantially whilst specificity decreased. Conclusions The diagnostic accuracy of isolated standard shoulder tests in recreational athletes was over-all very poor, potentially due to the majority of athletes (71%) having concomitant shoulder injuries. Most likely, this means that many of these injuries are missed in general practice and treatment is therefore delayed. Clinical examination of the shoulder should involve a combination of clinical tests in order to identify likely intra articular pathology which may warrant referral to specialist for surgery. PMID:20157421

  10. Practising Active Science with Child Refugees: A Clinical Perspective

    ERIC Educational Resources Information Center

    Perrier, Frédéric

    2004-01-01

    In this paper, pilot sessions in Rwanda and Nepal are analysed to evaluate the therapeutic benefit of active science for traumatised child refugees. The nature of the activities, choice of tools, organisation of the sessions, group size, and the role of the educators are investigated. Despite the lack of quantitative assessment, practical…

  11. 76 FR 80948 - Draft Guidance for Industry, Clinical Investigators, Institutional Review Boards, and Food and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-27

    ..., November, 10, 2011 (76 FR 70151). In the notice, FDA requested comments on the draft guidance that has been... (76 FR 70151), FDA published a notice announcing the availability of the draft guidance entitled ``FDA... Investigational Device Exemption (IDE) Clinical Investigations; Extension of Comment Period AGENCY: Food and...

  12. Consensus-based recommendations for investigating clinical heterogeneity in systematic reviews

    PubMed Central

    2013-01-01

    Background Critics of systematic reviews have argued that these studies often fail to inform clinical decision making because their results are far too general, that the data are sparse, such that findings cannot be applied to individual patients or for other decision making. While there is some consensus on methods for investigating statistical and methodological heterogeneity, little attention has been paid to clinical aspects of heterogeneity. Clinical heterogeneity, true effect heterogeneity, can be defined as variability among studies in the participants, the types or timing of outcome measurements, and the intervention characteristics. The objective of this project was to develop recommendations for investigating clinical heterogeneity in systematic reviews. Methods We used a modified Delphi technique with three phases: (1) pre-meeting item generation; (2) face-to-face consensus meeting in the form of a modified Delphi process; and (3) post-meeting feedback. We identified and invited potential participants with expertise in systematic review methodology, systematic review reporting, or statistical aspects of meta-analyses, or those who published papers on clinical heterogeneity. Results Between April and June of 2011, we conducted phone calls with participants. In June 2011 we held the face-to-face focus group meeting in Ann Arbor, Michigan. First, we agreed upon a definition of clinical heterogeneity: Variations in the treatment effect that are due to differences in clinically related characteristics. Next, we discussed and generated recommendations in the following 12 categories related to investigating clinical heterogeneity: the systematic review team, planning investigations, rationale for choice of variables, types of clinical variables, the role of statistical heterogeneity, the use of plotting and visual aids, dealing with outlier studies, the number of investigations or variables, the role of the best evidence synthesis, types of statistical methods

  13. Clinical Investigation of the Dopaminergic System with PET and FLUORINE-18-FLUORO-L-DOPA.

    NASA Astrophysics Data System (ADS)

    Oakes, Terrence Rayford

    1995-01-01

    Positron Emission Tomography (PET) is a tool that provides quantitative physiological information. It is valuable both in a clinical environment, where information is sought for an individual, and in a research environment, to answer more fundamental questions about physiology and disease states. PET is particularly attractive compared to other nuclear medicine imaging techniques in cases where the anatomical regions of interest are small or when true metabolic rate constants are required. One example with both of these requirements is the investigation of Parkinson's Disease, which is characterized as a presynaptic motor function deficit affecting the striatum. As dopaminergic neurons die, the ability of the striatum to affect motor function decreases. The extent of functional neuronal damage in the small sub-structures may be ascertained by measuring the ability of the caudate and putamen to trap and store dopamine, a neurotransmitter. PET is able to utilize a tracer of dopamine activity, ^ {18}F- scL-DOPA, to quantitate the viability of the striatum. This thesis work deals with implementing and optimizing the many different elements that compose a PET study of the dopaminergic system, including: radioisotope production; conversion of aqueous ^{18}F ^-into [^ {18}F]-F2; synthesis of ^{18}F- scL -DOPA; details of the PET scan itself; measurements to estimate the radiation dosimetry; accurate measurement of a plasma input function; and the quantitation of dopaminergic activity in normal human subjects as well as in Parkinson's Disease patients.

  14. Investigations of fungal secondary metabolites with potential anticancer activity.

    PubMed

    Balde, ElHadj Saidou; Andolfi, Anna; Bruyère, Céline; Cimmino, Alessio; Lamoral-Theys, Delphine; Vurro, Maurizio; Damme, Marc Van; Altomare, Claudio; Mathieu, Véronique; Kiss, Robert; Evidente, Antonio

    2010-05-28

    Fourteen metabolites, isolated from phytopathogenic and toxigenic fungi, were evaluated for their in vitro antigrowth activity for six distinct cancer cell lines, using the MTT colorimetric assay. Bislongiquinolide (1) and dihydrotrichodimerol (5), which belong to the bisorbicillinoid structural class, displayed significant growth inhibitory activity against the six cancer cell lines studied, while the remaining compounds displayed weak or no activity. The data show that 1 and 5 have similar growth inhibitory activities with respect to those cancer cell lines that display certain levels of resistance to pro-apoptotic stimuli or those that are sensitive to apoptosis. Quantitative videomicroscopy analysis revealed that 1 and 5 exert their antiproliferative effect through cytostatic and not cytotoxic activity. The preliminary results from the current study have stimulated further structure-activity investigations with respect to the growth inhibitory activity of compounds belonging to the bisorbicillinoid group. PMID:20415482

  15. Activity-based costing for clinical paths. An example to improve clinical cost & efficiency.

    PubMed

    Asadi, M J; Baltz, W A

    1996-01-01

    How much does this medical service or surgical procedure cost the hospital to provide? What is the most efficient clinical pathway that maximizes the quality of patient care while minimizing costs? More and more hospitals are discovering that they don't have solid answers to these critically important questions. In an age of managed care and capitation, however, it is imperative for management to know if the patient care services they provide are making or losing money-and by how much. This article discusses how a powerful new tool called activity-based costing (ABC) can be used to help hospitals accurately determine patient care costs. We show how to build a model that combines both clinical and financial data to measure how efficiently the operation allocates human, material and capital resources to provide its services. The modeling approach described in this article can be used to better analyze a wide range of important operational and financial issues, including: How to efficiently allocate resources, and what resources will be needed as patient demand changes-ideal for operational management and planning; How efficiently activities and processes are performed to meet patient needs-effective for measuring performance and improving quality; Determining clinical pathway profitability-essential for understanding where you're making or losing money; Cycle time, throughput and the impact of resource capacity constraints-critical for meeting patient demand; Costs of idle capacity-important for using resources more efficiently. We will illustrate with an example how this modeling technique can be used to develop and implement efficient clinical pathways. PMID:8982988

  16. [Standard Cancer Therapy Are Established by the Investigator-Initiated Post-Marketing Clinical Trials, Not by the Indication-Directed Clinical Trials].

    PubMed

    Shimada, Yasuhiro

    2016-04-01

    The financial supports for investigator-initiated post-marketing clinical trial in clinical oncology are reduced after scandals related to the other fields of clinical trials in Japan. These clinical trials are the essential final steps of clinical development in newer cancer therapy, which should be conducted in the investigator-initiated clinical trial groups with well-organized infrastructure and continuous financial supports. The present problems are discussed and summarized. Future perspectives with the national viewpoints needed to be included the idea of "health technology assessment". PMID:27220797

  17. FFCD-1004 Clinical Trial: Impact of Cytidine Deaminase Activity on Clinical Outcome in Gemcitabine-Monotherapy Treated Patients

    PubMed Central

    Serdjebi, Cindy; Gagnière, Johan; Desramé, Jérôme; Fein, Francine; Guimbaud, Rosine; François, Eric; André, Thierry; Seitz, Jean-François; Montérymard, Carole; Arsene, Dominique; Volet, Julien; Abakar-Mahamat, Abakar; Lecomte, Thierry; Guerin-Meyer, Véronique; Legoux, Jean-Louis; Deplanque, Gaël; Guillet, Pierre; Ciccolini, Joseph; Lepage, Côme; Dahan, Laetitia

    2015-01-01

    Purpose Because cytidine deaminase (CDA) is the key enzyme in gemcitabine metabolism, numerous studies have attempted to investigate impact of CDA status (i.e. genotype or phenotype) on clinical outcome. To date, data are still controversial because none of these studies has fully investigated genotype-phenotype CDA status, pharmacokinetics and clinical outcome relationships in gemcitabine-treated patients. Besides, most patients were treated with gemcitabine associated with other drugs, thus adding a confounding factor. We performed a multicenter prospective clinical trial in gemcitabine-treated patients which aimed at investigating the link between CDA deficiency on the occurrence of severe toxicities and on pharmacokinetics, and studying CDA genotype-phenotype relationships. Experimental design One hundred twenty patients with resected pancreatic adenocarcinoma eligible for adjuvant gemcitabine monotherapy were enrolled in this study promoted and managed by the Fédération Francophone de Cancérologie Digestive. Toxicities were graded according to National Cancer Institute’s Common Terminology Criteria for Adverse Events Version 4. They were considered severe for grade ≥ 3, and early when occurring during the first eight weeks of treatment. CDA status was evaluated using a double approach: genotyping for 79A>C and functional testing. Therapeutic drug monitoring of gemcitabine and its metabolite were performed on the first course of gemcitabine. Results Five patients out of 120 (i.e., 4.6%) were found to be CDA deficient (i.e., CDA activity <1.3 U/mg), and only one among them experienced early severe hematological toxicity. There was no statistically significant difference in CDA activity between patients experiencing hematological severe toxicities (28.44%) and patients who tolerated the treatment (71.56%). CDA genetic analysis failed in evidencing an impact in terms of toxicities or in CDA activity. Regarding pharmacokinetics, a wide inter

  18. Ankylosing spondylitis functional and activity indices in clinical practice

    PubMed Central

    Popescu, C; Trandafir, M; Bădică, AM; Morar, F; Predeţeanu, D

    2014-01-01

    Background: Clinicians have at hand several indices to evaluate disease activity and functionality in ankylosing spondylitis (AS), in order to evaluate the prognostic and the treatment of AS patients. Objectives: to examine the relationship between functional and activity scores in AS; to note whether disease activity is associated with any clinical or laboratory variables. Methods: the study included AS patients, classified according to the revised New York criteria; data recorded: demographics, disease duration, type of articular involvement, HLA B27 presence, history of uveitis, calculation of BASFI, BASDAI and ASDASCRP, quantification of inflammation markers. Results: 50 AS patients; ASDASCRP correlated significantly (p < 0.001) with BASFI (r = 811), BASDAI (r = 0.810) and with erythrocyte sedimentation rate (ESR; r = 0.505); HLA B27 positive patients had a median BASDAI 5 times higher than HLA B27 negative patients (p = 0.033); compared with patients with strictly axial disease form, patients with axial and peripheral disease had a median ESR 3 times higher (p = 0.042) and a median BASDAI 2 times higher (p = 0.050). Conclusions: functional and activity AS indices are strongly correlated in assessing disease severity; inflammation and HLA B27 can predict the high value of these indices; axial and peripheral disease pattern is associated with higher disease activity. PMID:24653763

  19. Experimental investigation of active machine tool vibration control

    NASA Astrophysics Data System (ADS)

    Rojas, J.; Liang, Chen; Geng, Zheng J.

    1996-05-01

    The successful vibration reduction of machine tools during machining process can improve productivity, increase quality, and reduce tool wear. This paper will present our initial investigation in the application of smart material technologies in machine tool vibration control using magnetostrictive actuators and electrorheological elastomer dampers on an industrial Sheldon horizontal lathe. The dynamics of the machining process are first studied, which reveals the complexity in the machine tool vibration response and the challenge to the active control techniques. The active control experiment shows encouraging results. The use of electrorheological elastomer damping device for active/passive vibration control provides significant vibration reduction in the high frequency range and great improvement in the workpiece surface finishing. The research presented in this paper demonstrates that the combination of active and active/passive vibration control techniques is very promising for successful machine tool vibration control.

  20. Bacterial vectors for active immunotherapy reach clinical and industrial stages

    PubMed Central

    Le Gouëllec, Audrey; Chauchet, Xavier; Polack, Benoit; Buffat, Laurent; Toussaint, Bertrand

    2012-01-01

    Active immunotherapy based on live attenuated bacterial vectors has matured in terms of industrial development and develops through a combination of three phenomena. First, active immunotherapy that stimulates an antigen-specific cytotoxic T-cell immune response has become a reality after several years of work. Second, there is still a need to identify vectors that can deliver antigens to the cytosol of antigen-presenting cells in vivo. Third, the recent progress in the understanding of bacterial lifestyle and in developing genetic engineering tools has enabled the design of bioengineered bugs that are capable of delivering antigens. Here, we review the mechanisms by which clinical bacterial vectors deliver antigens into the cytosol of antigen-presenting cells and summarize the development strategy of the three identified firms in this field. PMID:22894945

  1. Worksite Physical Activity Intervention for Ambulatory Clinic Nursing Staff.

    PubMed

    Tucker, Sharon; Farrington, Michele; Lanningham-Foster, Lorraine M; Clark, M Kathleen; Dawson, Cindy; Quinn, Geralyn J; Laffoon, Trudy; Perkhounkova, Yelena

    2016-07-01

    Health behaviors, including physical activity (PA), of registered nurses (RNs) and medical assistants (MAs) are suboptimal but may improve with worksite programs. Using a repeated-measures crossover design, the authors explored if integrating a 6-month worksite non-exercise activity thermogenesis (NEAT) intervention, with and without personalized health coaching via text messaging into workflow could positively affect sedentary time, PA, and body composition of nursing staff without jeopardizing work productivity. Two ambulatory clinics were randomly assigned to an environmental NEAT intervention plus a mobile text message coaching for either the first 3 months (early texting group, n = 27) or the last 3 months (delayed texting group, n = 13), with baseline 3-month and 6-month measurements. Sedentary and PA levels, fat mass, and weight improved for both groups, significantly only for the early text group. Productivity did not decline for either group. This worksite intervention is feasible and may benefit nursing staff. PMID:27143144

  2. A phenomenological investigation into the role of the clinical nurse specialist.

    PubMed

    Bousfield, C

    1997-02-01

    This research study adopts a phenomenological approach to investigate how a group of clinical nurse specialists think and experience their role. It reviews the literature on the clinical nurse specialist from 1943, when Frances Reiter first coined the phrase "nurse clinician', to the present time, when individuals are committed to a range of initiatives aimed at improving the quality of the British National Health Service and patient care. The study investigates and analyses their views and conveys the personal meaning of clinical nurse specialists' "lived experience' in the role. Findings of the study suggest that clinical nurse specialists are experienced practitioners who strive to be in positions in which they influence patient care and utilize advanced knowledge, expertise and leadership skills in a multidisciplinary environment. The literature proposes that for the role to be recognized and accepted individuals need to be educated at an advanced level, demonstrate practice based in research and have a firm base as a specialist in nursing. The findings clearly suggest that while the role of the clinical nurse specialist can be influenced in a positive manner by the organization and guided by the individual, it is important to acknowledge that the role is in a transitional phase. Finally, the research suggests the importance of establishing a clear role definition in a creative and supportive environment allowing for autonomy, professional growth and the development of individuals as clinically competent nurse specialists. PMID:9043997

  3. Human subject protection; foreign clinical studies not conducted under an investigational new drug application. Final rule.

    PubMed

    2008-04-28

    The Food and Drug Administration (FDA) is amending its regulations on acceptance of foreign clinical studies not conducted under an investigational new drug application (IND) (non-IND foreign clinical studies) as support for an IND or application for marketing approval for a drug or biological product. The final rule replaces the requirement that these studies be conducted in accordance with ethical principles stated in the Declaration of Helsinki (Declaration) issued by the World Medical Association (WMA), specifically the 1989 version (1989 Declaration), with a requirement that the studies be conducted in accordance with good clinical practice (GCP), including review and approval by an independent ethics committee (IEC). The final rule updates the standards for the acceptance of foreign clinical studies not conducted under an IND and helps ensure the protection of human subjects and the quality and integrity of data obtained from these studies. PMID:18567164

  4. [Investigation of the antibacterial activity of faropenem against Streptococcus pneumoniae].

    PubMed

    Hanaki, H; Inaba, Y; Hiramatsu, K

    1999-09-01

    We evaluated the antibacterial activity of faropenem against penicillin-susceptible Streptococcus pneumoniae (PSSP) and penicillin-resistant S. pneumoniae (PRSP). It was shown that the minimum inhibitory concentrations against 90% of the clinically isolated strains (MIC90) of faropenem, penicillin G, cefaclor, cefcapene, and cefditoren against PSSP were 0.032, 0.063, 2, 0.25, and 0.125 micrograms/ml, respectively. While those against PRSP were 0.5, 2, > 128, 1, and 1 micrograms/ml, respectively. Furthermore, we evaluated the bactericidal activity, at the level of 1/4, 1, and 4 MIC, of faropenem and the above four reference antibacterial agents against PSSP and PRSP. Against PSSP No. 127, a sensitive strain to both penicillin G and cefcapene, faropenem showed almost the same bactericidal activity as those of reference agents. Against PSSP No. 108, a penicillin-susceptible and cephem-resistant strain, and PRSP No. 57, a resistant strain to both of penicillin and cephem, faropenem of 1 MIC showed bactericidal activity, but reference agents needed 4 MIC to show bactericidal activity. PMID:10746191

  5. Tools to investigate how interprofessional education activities link to competencies

    PubMed Central

    West, Courtney; Veronin, Michael; Landry, Karen; Kurz, Terri; Watzak, Bree; Quiram, Barbara; Graham, Lori

    2015-01-01

    Integrating interprofessional education (IPE) activities and curricular components in health professions education has been emphasized recently by the inclusion of accreditation standards across disciplines. The Interprofessional Education Collaborative (IPEC) established IPE competencies in 2009, but evaluating how activities link to competencies has not been investigated in depth. The purpose of this project is to investigate how well two IPE activities align with IPEC competencies. To evaluate how our IPE activities met IPEC competencies, we developed a checklist and an observation instrument. A brief description of each is included as well as the outcomes. We analyzed Disaster Day, a simulation exercise that includes participants from Nursing, Medicine, and Pharmacy, and Interprofessional Healthcare Ethics (IPHCE), a course that introduced medical, nursing, and pharmacy students to ethical issues using didactic sessions and case discussions. While both activities appeared to facilitate the development of IPE competencies, Disaster Day aligned more with IPEC competencies than the IPHCE course and appears to be a more comprehensive way of addressing IPEC competencies. However, offering one IPE activity or curricular element is not sufficient. Having several IPE options available, utilizing the tools we developed to map the IPE curriculum and evaluating competency coverage is recommended. PMID:26208707

  6. Virtual clinical trials using inserted pathology in clinical images: investigation of assumptions for local glandularity and noise

    NASA Astrophysics Data System (ADS)

    Rashidnasab, Alaleh; Elangovan, Premkumar; Mackenzie, Alistair; Dance, David R.; Young, Kenneth C.; Bosmans, Hilde; Wells, Kevin

    2015-03-01

    Virtual clinical trials have been proposed as a viable alternative to clinical trials for testing and comparing the performance of breast imaging systems. One of the main simulation methodologies used in virtual trials employs clinical images of patients in which simulated models of cancer are inserted using a physics-based template multiplication technique. The purpose of this work is to investigate two assumptions commonly considered in this simulation approach: Firstly, given the absence of useful depth information in a clinical situation, an average measure of the local breast glandularity is commonly used as an estimate of the breast composition at the insertion site; secondly, it is also assumed that any change in the relative noise in the image at the insertion site, after insertion of a mass, is negligible. In order to test the validity of these assumptions, spheres representing idealised masses and anthropomorphic computational breast phantoms with perfect prior knowledge of local tissue composition and distribution were used. Results from several region of interest (ROI) insertions demonstrated a lack of variation obtained in contrast with insertion depth using the template multiplication insertion method as compared to the true depth-wise variation contrast values obtained from voxel replacement in a heterogeneous phantom. It was also found that the amount of noise is underestimated by insertion of spherical masses using template multiplication method by 8% - 29% compared to voxel replacement for the test conditions. This resulted in up to 12% variation in contrast-to-noise-ratio (CNR) values between template multiplication and voxel replacement methods.

  7. Template protocol for clinical trials investigating vaccines—Focus on safety elements☆

    PubMed Central

    Bonhoeffer, Jan; Imoukhuede, Egeruan B.; Aldrovandi, Grace; Bachtiar, Novilia S.; Chan, Eng-Soon; Chang, Soju; Chen, Robert T.; Fernandopulle, Rohini; Goldenthal, Karen L.; Heffelfinger, James D.; Hossain, Shah; Jevaji, Indira; Khamesipour, Ali; Kochhar, Sonali; Makhene, Mamodikoe; Malkin, Elissa; Nalin, David; Prevots, Rebecca; Ramasamy, Ranjan; Sellers, Sarah; Vekemans, Johan; Walker, Kenneth B.; Wilson, Pam; Wong, Virginia; Zaman, Khalequz; Heininger, Ulrich

    2015-01-01

    This document is intended as a guide to the protocol development for trials of prophylactic vaccines. The template may serve phases I–IV clinical trials protocol development to include safety relevant information as required by the regulatory authorities and as deemed useful by the investigators. This document may also be helpful for future site strengthening efforts. PMID:23499603

  8. 21 CFR 50.54 - Clinical investigations not otherwise approvable that present an opportunity to understand...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 1 2011-04-01 2011-04-01 false Clinical investigations not otherwise approvable... or welfare of children. 50.54 Section 50.54 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT... alleviation of a serious problem affecting the health or welfare of children; and (b) The Commissioner of...

  9. 78 FR 60291 - Investigational Device Exemptions for Early Feasibility Medical Device Clinical Studies...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-01

    ...The Food and Drug Administration (FDA) is announcing the availability of the guidance entitled ``Investigational Device Exemptions (IDEs) for Early Feasibility Medical Device Clinical Studies, Including Certain First in Human (FIH) Studies.'' Through the approaches announced in this guidance, FDA intends to facilitate early feasibility studies of medical devices, using appropriate risk......

  10. Investigating Invariant Item Ordering in Personality and Clinical Scales: Some Empirical Findings and a Discussion

    ERIC Educational Resources Information Center

    Meijer, Rob R.; Egberink, Iris J. L.

    2012-01-01

    In recent studies, different methods were proposed to investigate invariant item ordering (IIO), but practical IIO research is an unexploited field in questionnaire construction and evaluation. In the present study, the authors explored the usefulness of different IIO methods to analyze personality scales and clinical scales. From the authors'…

  11. Infantile Autism. A Clinical and Phenomenological-Anthropological Investigation Taking Language as the Guide.

    ERIC Educational Resources Information Center

    Bosch, Gerhard

    A clinical and phenomenological-anthropological investigation taking language as the guide, the study of infantile autism concentrates upon an analysis of the idiosyncratic language of autistic children and of what is revealed by the way they use it. Following the presentation of very detailed case histories of five of the autistic children…

  12. 76 FR 32367 - Draft Guidance for Clinical Investigators, Industry, and FDA Staff: Financial Disclosure by...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-06

    ... notice that appeared in the Federal Register of May 24, 2011 (76 FR 30175). The document announced the...-0002, 301-796-9148. SUPPLEMENTARY INFORMATION: In FR Doc. 2011-12623, appearing on page 30175, in the... HUMAN SERVICES Food and Drug Administration Draft Guidance for Clinical Investigators, Industry, and...

  13. Template protocol for clinical trials investigating vaccines--focus on safety elements.

    PubMed

    Bonhoeffer, Jan; Imoukhuede, Egeruan B; Aldrovandi, Grace; Bachtiar, Novilia S; Chan, Eng-Soon; Chang, Soju; Chen, Robert T; Fernandopulle, Rohini; Goldenthal, Karen L; Heffelfinger, James D; Hossain, Shah; Jevaji, Indira; Khamesipour, Ali; Kochhar, Sonali; Makhene, Mamodikoe; Malkin, Elissa; Nalin, David; Prevots, Rebecca; Ramasamy, Ranjan; Sellers, Sarah; Vekemans, Johan; Walker, Kenneth B; Wilson, Pam; Wong, Virginia; Zaman, Khalequz; Heininger, Ulrich

    2013-11-12

    This document is intended as a guide to the protocol development for trials of prophylactic vaccines. The template may serve phases I-IV clinical trials protocol development to include safety relevant information as required by the regulatory authorities and as deemed useful by the investigators. This document may also be helpful for future site strengthening efforts. PMID:23499603

  14. 21 CFR 50.54 - Clinical investigations not otherwise approvable that present an opportunity to understand...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Clinical investigations not otherwise approvable that present an opportunity to understand, prevent, or alleviate a serious problem affecting the health... opportunity to understand, prevent, or alleviate a serious problem affecting the health or welfare of...

  15. 78 FR 12937 - Additional Safeguards for Children in Clinical Investigations of Food and Drug Administration...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-26

    ... burdensome to institutions, IRBs, and the process of clinical investigation (66 FR 20589 at 20591). The... VIII. Federalism IX. References I. Background In the Federal Register of April 24, 2001 (66 FR 20589... interim rule (66 FR 20589), including the Food and Drug Administration Modernization Act of 1997...

  16. Using Hermeneutic Phenomenology to Investigate How Experienced Practitioners Learn to Communicate Clinical Reasoning

    ERIC Educational Resources Information Center

    Ajjawi, Rola; Higgs, Joy

    2007-01-01

    This paper is primarily targeted at doctoral students and other researchers considering using hermeneutic phenomenology as a research strategy. We present interpretive paradigm research designed to investigate how experienced practitioners learn to communicate their clinical reasoning in professional practice. Twelve experienced physiotherapy…

  17. 78 FR 57395 - Guidance for Industry on Electronic Source Data in Clinical Investigations; Availability

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-18

    ... ``Electronic Source Data in Clinical Investigations.'' This document provides guidance to sponsors, contract... accurate and complete data. In the Federal Register of November 20, 2012 (77 FR 69632), FDA issued a draft... FR 76049)). Most of the comments sought clarification on the topics discussed in the guidance....

  18. 21 CFR 50.54 - Clinical investigations not otherwise approvable that present an opportunity to understand...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 1 2013-04-01 2013-04-01 false Clinical investigations not otherwise approvable that present an opportunity to understand, prevent, or alleviate a serious problem affecting the health or welfare of children. 50.54 Section 50.54 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL...

  19. Evaluation of Clinical Biomaterial Surface Effects on T Lymphocyte Activation

    PubMed Central

    Rodriguez, Analiz; Anderson, James M.

    2009-01-01

    Previous in vitro studies in our laboratory have shown that lymphocytes can influence macrophage adhesion and fusion on biomaterial surfaces. However, few studies have evaluated how material adherent macrophages can influence lymphocyte behavior, specifically T cells. In this study, we cultured human peripheral blood mononuclear cells from healthy donors on three synthetic non-biodegradable biomedical polymers: Elasthane 80A (PEU), Silicone rubber (SR), or polyethylene terephthalate (PET) and tissue culture polystyrene (TCPS). Upregulation of T cell surface activation markers (CD69 and CD25), lymphocyte proliferation, and interleukin-2 (IL-2) and interferon-γ (IFNγ) concentrations were evaluated by flow cytometry, carboxy-fluorescein diacetate, succinimydyl ester (CFSE) incorporation, and multiplex cytokine immunoassay, respectively, to assess T cell activation. Following 3 and 7 days of culture, CD4+ helper T cells from cultures of any of the material groups did not express the activation markers CD69 and CD25 and lymphocyte proliferation was not present. IL-2 and IFNγ levels were produced, but dependent on donor. These data indicate that T cells are not activated in response to clinically relevant synthetic biomaterials. The data also suggest that lymphocyte subsets exclusive of T cells are the source of the lymphokines, IL-2 and IFN-γ, in certain donors. PMID:19172618

  20. An Initial Investigation of Active Galaxies in RESOLVE and ECO

    NASA Astrophysics Data System (ADS)

    Norman, Dara J.; Kannappan, Sheila; Bittner, Ashley; Yarber, Aara'L.; Hoversten, Erik A.; Stark, David; RESOLVE Team

    2016-01-01

    The volume-limited REsolved Spectroscopy Of a Local VolumE (RESOLVE) survey and its complementary Environmental COntext (ECO) catalog are dominated by low mass, gas-rich galaxies, as is typical of the bulk of large-scale structure in the local universe. These surveys, therefore, provide an excellent opportunity to investigate the complete large-scale environments of low-redshift AGN and nuclear starbursts in such galaxies, in order to search for external triggering, examine activity in relation to gas supply, and investigate the role of feedback. By data-mining multi-wavelength catalogs that use varied techniques, we identify known AGN in RESOLVE and ECO, including a population of gas-dominated low-mass galaxies. We take advantage of these surveys' multi-wavelength supporting data to investigate triggering, feedback, and the roles of environment and gas supply in this initial sample of active galaxies. Because biases in standard AGN candidate selection techniques (e.g. BPT, X-ray luminosity) make them individually poor selectors of AGN activity in star-forming and low mass (<10^10 Msun) host galaxies, we also seek to improve the identification of nuclear activity in such galaxies via combined analysis of star formation and AGN signatures. RESOLVE is supported by NSF grant AST-0955368

  1. Presentation and clinical investigation of mitochondrial respiratory chain disease. A study of 51 patients.

    PubMed

    Jackson, M J; Schaefer, J A; Johnson, M A; Morris, A A; Turnbull, D M; Bindoff, L A

    1995-04-01

    Defects of the mitochondrial respiratory chain are associated with a great variety of clinical disorders. Whilst recognition of these conditions is increasing, the need for sophisticated biochemical and molecular studies has tended to limit both their investigation and diagnosis to a few specialist centres. Using a group of 51 patients with histochemically, biochemically and/or genetically defined respiratory chain defects, we have examined both the clinical heterogeneity of these disorders and how they may be investigated most effectively in non-specialist centres. We evaluated the use of the following routinely available clinical investigations--fasting intermediary metabolites (lactate, pyruvate, ketone bodies, etc.) in blood and cerebrospinal fluid, serum creatine kinase estimation, EMG, EEG, CT, MRI and histological/histochemical muscle biopsy analysis. Our studies show that, in addition to well-recognized syndromes (e.g. chronic progressive external ophthalmoplegia, mitochondrial encephalopathy lactic acidosis and stroke like episodes, and myoclonus epilepsy with ragged red-fibres, a significant number of patients present with non-specific encephalopathic disorders. Furthermore, even within those categories of respiratory chain disease which have been genetically defined, a wide variation of presenting symptoms and signs were found. Where there was initial doubt concerning the diagnosis, the following clinical features were helpful in suggesting respiratory chain disease: ophthalmoplegia; a maternal pattern of inheritance; the presence of myopathy or deafness in association with encephalopathy. Of the clinical investigations we assessed, elevated lactate in blood or cerebrospinal fluid and low density lesions in the basal ganglia were helpful in identifying patients with respiratory chain dysfunction. Histochemical analysis of muscle was, however, the single most useful investigation being diagnostic in patients with chronic progressive external

  2. Investigation of Antiulcer and Antioxidant Activity of Moclobemide in Rats

    PubMed Central

    Albayrak, Abdulmecit; Alp, Hamit H.; Suleyman, Halis

    2015-01-01

    Objective: Even though there are many drugs for the treatment of gastric ulcers, these drugs sometimes cannot succeed. Since the 1950s, antidepressant drugs have been used for several non-psychiatric indications. Many antidepressant drugs have been shown experimentally to produce antiulcer activity in various ulcer models. Moclobemide is an antidepressant drug which inhibits monoamine oxidase-A (MAO) enzyme selectively. When it is compared to the classic antidepressants drugs, moclobemide is the first choice in depression treatment because of its effectiveness and less side effects. This study aimed to investigate the antiulcer effects of moclobemide and to determine its relationship with antioxidant mechanisms in rat gastric tissue. Materials and Methods: The antiulcer activities of 10, 20, 40, 80, 150 mg/kg moclobemide and 20 mg/kg famotidine have been investigated on indomethacin-induced ulcers in rats, and the results have been compared with that of the control group. Results: Moclobemide decreased the indomethacin-induced ulcers significantly at all doses used. While used doses of moclobemide increased the glutathione (GSH), nitric oxide (NO) level and superoxide dismutase (SOD) activity, it decreased the malondialdehyde (MDA) level and myeloperoxidase (MPO) activity in stomach tissue when compared to the control group. Conclusion: It is determined that an antidepressant drug, moclobemide is a potent anti-ulcer agent. Inhibition of toxic oxidant radicals and activation of antioxidant mechanisms play a role in its anti-ulcer effect mechanisms. PMID:25745343

  3. Students' Performance in Investigative Activity and Their Understanding of Activity Aims

    ERIC Educational Resources Information Center

    Gomes, Alessandro Damasio Trani; Borges, A. Tarciso; Justi, Rosaria

    2008-01-01

    This study investigates the relationship between the students' understanding of the aims of an investigative activity and their performance when conducting it. One hundred and eighty-one year nine students from a public middle school in Brazil took part in the study. Students working in pairs were asked to investigate two problems using a…

  4. Functional and clinical aspects of the B-cell-activating factor (BAFF): a narrative review.

    PubMed

    Lied, G A; Berstad, A

    2011-01-01

    B-cell-activating factor (BAFF) influences peripheral B-cell survival, maturation and immunoglobulin class-switch recombination and has a range of potential clinical implications. Biological functions of BAFF and its relevance in various clinical disorders including currently investigated BAFF-targeting therapies are reviewed and discussed based on PubMed search of relevant articles. Serum levels of BAFF are increased in autoimmune diseases including autoimmune hepatitis and primary biliary cirrhosis where BAFF concentrations are related to titres of autoantibodies and disease progression. Increased BAFF levels are found in synovial, bronchoalveolar and gut lavage fluids, suggesting local class switching and immunoglobulin production. Clinical relevance and diagnostic potential of BAFF are also noted in patients with allergic diseases, malignancies and infections including hepatitis C virus. BAFF antagonists are promising new therapeutic agents, currently being tried in B-cell-related autoimmune diseases. Serum level of BAFF may indicate disease mechanisms and the degree of activity. Determination of BAFF in different body compartments like synovium, airways and gut may also have clinical implications. Results of ongoing clinical trials with BAFF antagonists are eagerly awaited. PMID:21128997

  5. Strategies for promoting physical activity in clinical practice.

    PubMed

    Sallis, Robert; Franklin, Barry; Joy, Liz; Ross, Robert; Sabgir, David; Stone, James

    2015-01-01

    The time has come for healthcare systems to take an active role in the promotion of physical activity (PA). The connection between PA and health has been clearly established and exercise should be viewed as a cost effective medication that is universally prescribed as a first line treatment for virtually every chronic disease. While there are potential risks associated with exercise, these can be minimized with a proper approach and are far outweighed by the benefits. Key to promoting PA in the clinical setting is the use of a PA Vital Sign in which every patient's exercise habits are assessed and recorded in their medical record. Those not meeting the recommended 150min per week of moderate intensity PA should be encouraged to increase their PA levels with a proper exercise prescription. We can improve compliance by assessing our patient's barriers to being more active and employing new and evolving technology like accelerometers and smart phones applications, along with various websites and programs that have proven efficacy. PMID:25459975

  6. Pre-Clinical Rheumatoid Arthritis: Identification, Evaluation and Future Directions for Investigation

    PubMed Central

    Deane, Kevin D.; Norris, Jill M.; Holers, V. Michael

    2010-01-01

    Synopsis Rheumatoid arthritis (RA) likely develops in several phases, beginning with genetic risk, followed by asymptomatic autoimmunity, then finally, clinically-apparent disease. Investigating the phases of disease that exist prior to the onset of symptoms - i.e. the pre-clinical period of RA – will lead to understanding of the important relationships between genetic and environmental factors that may lead to disease, as well as allow for the development of predictive models for disease, and ultimately preventive strategies for RA. PMID:20510231

  7. [THE RESULTS OF CLINICAL AND PSYCHOPATHOLOGICAL AND PSYCHOLOGICAL DIAGNOSTIC INVESTIGATIONS EMPLOYEES OF FINANCIAL INSTITUTIONS WHICH WERE IDENTIFIED NEUROTIC DISORDERS].

    PubMed

    Solovyova, M

    2014-12-01

    The article presents the results of the clinical and psychopathological and psychological diagnostic, investigations mental health employees of financial institutions, description and analysis of clinical forms identified disorders. PMID:26638468

  8. Investigations on the sporicidal and fungicidal activity of disinfectants.

    PubMed

    Lensing, H H; Oei, H L

    1985-12-01

    The sporicidal and fungicidal activity of disinfectants was studied in a suspension test. Glutaraldehyde 4%, sodium-dichloroisocyanurate-dihydrate (2400 ppm active chlorine) and peracetic acid 0.25% demonstrated after 30 min of exposure at 20 degrees C in the presence of 4% horse serum a clear activity against spores of Bacillus cereus. Under the same conditions formaldehyde 4% and glutaraldehyde 2% were also found to be sporicidal, but only after a longer time of exposure. Spores of Bacillus anthracis and B. cereus appeared to be comparably resistant against the investigated disinfectants, whereas conidiospores of Aspergillus fumigatus and Aspergillus niger were less resistant. Of the micro-organisms tested Candida albicans proved to be slightest resistant, while spores of Bacillus subtilis were found the most resistant. PMID:3938146

  9. Effect of Low-Level Laser Therapy on Orthodontic Tooth Movement: A Clinical Investigation

    PubMed Central

    Dalaie, Kazem; Kharazifard, Mohammad Javad; Mahdian, Mina; Bayat, Mehrdad

    2015-01-01

    Objectives: One major drawback of orthodontic treatment is its long duration due to slow tooth movement and the pain at the onset of treatment following application of forces. There is controversy regarding the efficacy of laser for decreasing the treatment time and pain of orthodontic treatment. The purpose of this study was to investigate the effect of low level diode laser on the rate of orthodontic tooth movement and the associated pain. Materials and Methods: In this double blind randomized controlled clinical trial, 12 orthodontic patients referring to Shahid Beheshti School of Dentistry for first premolar extraction were randomly selected and allocated to gallium aluminum-arsenide laser (GA-AL-AS diode laser, 880 nm, 100 mW, 5 j/cm2, 8 points, 80 seconds, continuous mode) or control group. The patients initially underwent leveling and alignment using the sectional system. Force (150 gr) was applied to each canine tooth via sectional closing loops. The loops were activated every month. The rate of tooth movement and pain were monitored over the treatment period and recorded on days 1, 3, 7, 30, 33, 37, 60, 63 and 67. Two-way ANOVA was used for comparison of groups. Results: There was no significant difference in terms of tooth movement and pain scores between the irradiated and non-irradiated sides at any time point (P>0.05). Conclusion: Although laser enhanced orthodontic tooth movement in the upper jaw, we failed to provide solid evidence to support the efficacy of laser for expediting tooth movement or reducing the associated pain. PMID:26622279

  10. Present status of clinical deployment of glucokinase activators.

    PubMed

    Nakamura, Akinobu; Terauchi, Yasuo

    2015-03-01

    Glucokinase is one of four members of the hexokinase family of enzymes. Its expression is limited to the major organs (such as the pancreas, liver, brain and the gastrointestinal tract) that are thought to have an integrated role in glucose sensing. In the liver, phosphorylation of glucose by glucokinase promotes glycogen synthesis, whereas in the β-cells, it results in insulin release. Studies of glucokinase-linked genetically-modified mice and mutations in humans have illustrated the important roles played by glucokinase in whole-body glucose homeostasis, and suggest that the use of pharmacological agents that augment glucokinase activity could represent a viable treatment strategy in patients with type 2 diabetes. Since 2003, many glucokinase activators (GKAs) have been developed, and their ability to lower the blood glucose has been shown in several animal models of type 2 diabetes. Also, we and others have shown in mouse models that GKAs also have the effect of stimulating the proliferation of β-cells. However, the results of recent phase II trials have shown that GKAs lose their efficacy within several months of use, and that their use is associated with a high incidence of hypoglycemia; furthermore, patients treated with GKAs frequently developed dyslipidemia. A better understanding of the role of glucokinase in metabolic effects is required to resolve several issues identified in clinical trials. PMID:25802718

  11. [Clinical investigation on target value of T>MIC in carbapenems].

    PubMed

    Mikamo, Hiroshige; Yamagishi, Yuka; Tanaka, Kaori; Watanabe, Kunitomo

    2008-04-01

    There have been few clinical reports on pharmacokinetics-pharmacodynamics (PK-PD) theory, although many basic or fundamental researches on appropriate use for the antimicrobials based on the PK-PD theory have been performed. We evaluated the target T>MIC values on meropenem and biapenem which have been obtained by basic researches. While we investigated whether the target T>MIC values were also useful for anaerobic infections. Clinical and bacteriological efficacies of meropenem and biapenem were about 70% in T>MIC over 25% or over 80% in T>MIC over 30%. When monomicrobial infections by anaerobes were occurred as abscesses, there have been no correlation between target T>MIC values and clinical effect. When polymicrobial infections between aerobes and anaerobes were occurred, we have achieved over 90% clinical efficacy when over 20% T>MIC values. These results supported the data by Craig, W. A. and Drusano, G. L. The regimen based on PK-PD theory would be useful in clinical practice including against anaerobic infections. PMID:18669417

  12. Electrochemical Impedance Spectroscopy Investigation on the Clinical Lifetime of ProTaper Rotary File System

    PubMed Central

    Pirvu, Cristian; Demetrescu, Ioana

    2014-01-01

    The main objective of the current paper is to show that electrochemical impedance spectroscopy (EIS) could be a method for evaluating and predicting of ProTaper rotary file system clinical lifespan. This particular aspect of everyday use of the endodontic files is of great importance in each dental practice and has profound clinical implications. The method used for quantification resides in the electrochemical impedance spectroscopy theory and has in its main focus the characteristics of the surface titanium oxide layer. This electrochemical technique has been adapted successfully to identify the quality of the Ni-Ti files oxide layer. The modification of this protective layer induces changes in corrosion behavior of the alloy modifying the impedance value of the file. In order to assess the method, 14 ProTaper sets utilized on different patients in a dental clinic have been submitted for testing using EIS. The information obtained in regard to the surface oxide layer has offered an indication of use and proves that the said layer evolves with each clinical application. The novelty of this research is related to an electrochemical technique successfully adapted for Ni-Ti file investigation and correlation with surface and clinical aspects. PMID:24605336

  13. Drilling to investigate processes in active tectonics and magmatism

    NASA Astrophysics Data System (ADS)

    Shervais, J.; Evans, J.; Toy, V.; Kirkpatrick, J.; Clarke, A.; Eichelberger, J.

    2014-12-01

    Coordinated drilling efforts are an important method to investigate active tectonics and magmatic processes related to faults and volcanoes. The US National Science Foundation (NSF) recently sponsored a series of workshops to define the nature of future continental drilling efforts. As part of this series, we convened a workshop to explore how continental scientific drilling can be used to better understand active tectonic and magmatic processes. The workshop, held in Park City, Utah, in May 2013, was attended by 41 investigators from seven countries. Participants were asked to define compelling scientific justifications for examining problems that can be addressed by coordinated programs of continental scientific drilling and related site investigations. They were also asked to evaluate a wide range of proposed drilling projects, based on white papers submitted prior to the workshop. Participants working on faults and fault zone processes highlighted two overarching topics with exciting potential for future scientific drilling research: (1) the seismic cycle and (2) the mechanics and architecture of fault zones. Recommended projects target fundamental mechanical processes and controls on faulting, and range from induced earthquakes and earthquake initiation to investigations of detachment fault mechanics and fluid flow in fault zones. Participants working on active volcanism identified five themes: the volcano eruption cycle; eruption sustainability, near-field stresses, and system recovery; eruption hazards; verification of geophysical models; and interactions with other Earth systems. Recommended projects address problems that are transferrable to other volcanic systems, such as improved methods for identifying eruption history and constraining the rheological structure of shallow caldera regions. Participants working on chemical geodynamics identified four major themes: large igneous provinces (LIPs), ocean islands, continental hotspot tracks and rifts, and

  14. Investigating the physiology of brain activation with MRI

    NASA Astrophysics Data System (ADS)

    Buxton, Richard B.; Uludag, Kamil; Dubowitz, David J.

    2004-04-01

    Functional magnetic resonance imaging (fMRI) has become a powerful tool for investigating the working human brain based on the blood oxygenation level dependent (BOLD) effect on the MR signal. However, despite the widespread use of fMRI techniques for mapping brain activation, the basic physiological mechanisms underlying the observed signal changes are still poorly understood. Arterial spin labeling (ASL) techniques, which measure cerebral blood flow (CBF) and the BOLD effect simultaneously, provide a useful tool for investigating these physiological questions. In this paper, recent results of studies manipulating the baseline CBF both pharmacologically and physiologically will be discussed. These data are consistent with a feed-forward mechanism of neurovascular coupling, and suggest that the CBF change itself may be a more robust reflection of neural activity changes than the BOLD effect. Consistent with these data, a new thermodynamic hypothesis is proposed for the physiological function of CBF regulation: maintenance of the [O2]/[CO2] concentration ratio at the mitochondria in order to preserve the free energy available from oxidative metabolism. A kinetic model based on this hypothesis provides a reasonable quantitative description of the CBF changes associated with neural activity and altered blood gases (CO2 and O2).

  15. Activity of quinolones against gram-positive cocci: clinical features.

    PubMed

    Giamarellou, H

    1995-01-01

    The potential role of the commercially available fluoroquinolones in the treatment of Gram-positive infections is discussed on the basis of data obtained from animal experiments and clinical trials. In respiratory tract infections, and particularly in community-acquired pneumonia, it is evident that the presently available quinolones cannot be prescribed empirically as first-line therapy because of their borderline activity against Streptococcus pneumoniae and anaerobes. Reports of pneumococcal seeding in other tissues during quinolone therapy render their administration a debatable issue. Experience in endocarditis is limited to the use of ciprofloxacin plus rifampicin in intravenous drug users with right-sided Staphylococcus aureus endocarditis. Patients with staphylococcal osteomyelitis are included among cases of other bone infections. In noncontrolled studies ciprofloxacin, ofloxacin and pefloxacin attained a staphylococcal eradication rate ranging from 70 to 100%, while the addition of rifampicin has been proven to reduce the emergence of resistant mutants during therapy. In soft tissue and skin structure infections that also involve Gram-negative bacteria, ciprofloxacin and ofloxacin eradicated 72.6 and 89% of staphylococci, respectively; however, the presence of diabetes or vascular disease compromised the success of treatment. In staphylococcal peritonitis complicating continuous ambulatory peritoneal dialysis, results with ciprofloxacin given intravenously or intraperitoneally were promising. In infections in neutropenic hosts, success of prophylaxis or therapy is still not clear, since colonisation and breakthrough bacteraemias with viridans streptococci and staphylococci have been reported. Furthermore, therapeutic results are compromised by the low response rate in Gram-positive infections. Despite the reported clinical efficacy of the newer fluoroquinolones, physicians should be alerted to the emergence of staphylococci resistant to fluoroquinolones

  16. Optical Tools to Investigate Cellular Activity in the Intestinal Wall

    PubMed Central

    Boesmans, Werend; Hao, Marlene M; Berghe, Pieter Vanden

    2015-01-01

    Live imaging has become an essential tool to investigate the coordinated activity and output of cellular networks. Within the last decade, 2 Nobel prizes have been awarded to recognize innovations in the field of imaging: one for the discovery, use, and optimization of the green fluorescent protein (2008) and the second for the development of super-resolved fluorescence microscopy (2014). New advances in both optogenetics and microscopy now enable researchers to record and manipulate activity from specific populations of cells with better contrast and resolution, at higher speeds, and deeper into live tissues. In this review, we will discuss some of the recent developments in microscope technology and in the synthesis of fluorescent probes, both synthetic and genetically encoded. We focus on how live imaging of cellular physiology has progressed our understanding of the control of gastrointestinal motility, and we discuss the hurdles to overcome in order to apply the novel tools in the field of neurogastroenterology and motility. PMID:26130630

  17. AN ULTRAVIOLET INVESTIGATION OF ACTIVITY ON EXOPLANET HOST STARS

    SciTech Connect

    Shkolnik, Evgenya L.

    2013-03-20

    Using the far-UV (FUV) and near-UV (NUV) photometry from the NASA Galaxy Evolution Explorer (GALEX), we searched for evidence of increased stellar activity due to tidal and/or magnetic star-planet interactions (SPI) in the 272 known FGK planetary hosts observed by GALEX. With the increased sensitivity of GALEX, we are able probe systems with lower activity levels and at larger distances than what has been done to date with X-ray satellites. We compared samples of stars with close-in planets (a < 0.1 AU) to those with far-out planets (a > 0.5 AU) and looked for correlations of excess activity with other system parameters. This statistical investigation found no clear correlations with a, M{sub p} , or M{sub p} /a, in contrast to some X-ray and Ca II studies. However, there is tentative evidence (at a level of 1.8{sigma}) that stars with radial-velocity-(RV)-detected close-in planets are more FUV-active than stars with far-out planets, in agreement with several published X-ray and Ca II results. The case is strengthened to a level of significance to 2.3{sigma} when transit-detected close-in planets are included. This is most likely because the RV-selected sample of stars is significantly less active than the field population of comparable stars, while the transit-selected sample is similarly active. Given the factor of 2-3 scatter in fractional FUV luminosity for a given stellar effective temperature, it is necessary to conduct a time-resolved study of the planet hosts in order to better characterize their UV variability and generate a firmer statistical result.

  18. Investigation of some biologic activities of Swertia longifolia Boiss

    PubMed Central

    Hajimehdipoor, H.; Esmaeili, S.; Shekarchi, M.; Emrarian, T.; Naghibi, F.

    2013-01-01

    Swertia species are widespread in Eastern and Southern Asian countries and used in traditional medicine as anti-pyretic, analgesic, gastro and liver tonic. Among different species, only Swertia longifolia grows in Iran. In this investigation, antioxidant, cytotoxic and acetylcholinesterase inhibitory activities of S. longifolia have been studied. Aerial parts and roots of the plant were collected, dried and extracted with methanol 80% (total extract). Different extracts of the plant were obtained using hexane, chloroform, ethyl acetate, methanol, methanol:water (1:1) and water, respectively. Cytotoxic activity was determined by MTT assay on MDBK, HepG2, MCF7, HT29 and A549 cell lines. Antioxidant activity was measured by 2,2-diphenyl-1-picryl hydrazyl (DPPH) free radicals and acetylcholinesterase inhibitory (AChEI) effect was evaluated based on Ellman’s method in 96-well microplates.The results showed no cytotoxicity of the plant extracts on MDBK, HepG2, MCF7, HT29 and A549 cell lines up to 100 μg/ml. All samples showed radical scavenging activity but methanol extract of aerial parts and ethyl acetate extract of the roots showed the highest effects.Total extract of the roots showed higher AChEI activity than the aerial parts. Among different extracts, chloroform and ethyl acetate extracts of the roots and chloroform and methanol:water extracts of the aerial parts were more potent in AChEI assay. It is concluded that aerial parts and roots of the plant are rich in antioxidant agents with no cytotoxicity on selected cell lines up to 100 μg/ml. Moreover, since antioxidant and AChEI activity of compounds play an important role in the treatment of Alzheimer’s disorder, this plant might be a potential candidate for isolation of antioxidant and AChEI compounds which could be used as supportive treatment of Alzheimer’s disease. PMID:24082894

  19. Antimicrobial Activity of Solithromycin against Clinical Isolates of Legionella pneumophila Serogroup 1

    PubMed Central

    Mallegol, Julia; Fernandes, Prabhavathi

    2014-01-01

    The activity of solithromycin was evaluated against clinical Legionella pneumophila serogroup 1 (Lp1) isolates (n = 196) collected in Ontario, Canada, from 1980 to 2011. Its in vitro activity was compared to that of azithromycin (AZM) using the broth microdilution method. Solithromycin had a MIC50 of ≤0.015 μg/ml and a MIC90 of 0.031 μg/ml, making its activity at least 8-fold to 32-fold higher than that of AZM (MIC50 and MIC90, 0.125 μg/ml and 1 μg/ml, respectively). Ninety-nine percent of the isolates had MICs for solithromycin ranging from ≤0.015 μg/ml to 0.031 μg/ml, whereas 83.6% of the isolates showed MICs for AZM ranging from 0.062 μg/ml to 0.25 μg/ml. Interestingly, 96.7% (30 out of 31 clinical isolates) identified with higher AZM MICs (0.5 μg/ml to 2 μg/ml) belonged to the clinically prevalent sequence type 1. To investigate the intracellular activity of solithromycin, in vitro invasion assays were also performed against a subset of representative Lp1 isolates internalized within human lung epithelial cells. Solithromycin and AZM both inhibited growth of all intracellular Lp1 isolates at 1× or 8× MICs, displaying bacteriostatic effects, as would be expected with protein synthesis inhibitor rather than bactericidal activity. Solithromycin demonstrated the highest in vitro and intracellular potency against all Lp1 isolates compared to AZM. Given the rapid spread of resistance mechanisms among respiratory pathogens and the reported treatment failures in legionellosis, the development of this new fluoroketolide, already in phase 3 oral clinical studies, constitutes a promising alternative option for the treatment of legionellosis. PMID:24277019

  20. 78 FR 13067 - Agency Information Collection Activities: Proposed Collection; Comment Request; Foreign Clinical...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-26

    ... clinical trial, totaling 37,920 hours (32 x 1,185). FDA estimates the burden of this collection of... Collection; Comment Request; Foreign Clinical Studies Not Conducted Under an Investigational New Drug... contained in FDA's regulations on foreign clinical studies not conducted under an investigational new...

  1. Browser Based Platform in Maintaining Clinical Activities - Use of The iPads in Head and Neck Clinics

    NASA Astrophysics Data System (ADS)

    Yang, W. Y.; Moore, J.; Quon, H.; Evans, K.; Sharabi, A.; Herman, J.; Hacker-Prietz, A.; McNutt, T.

    2014-03-01

    Purpose: Incompatibility between documentation and clinical workflow causes physician resistance in organized data collection, which in turn complicates the use of data in patient care improvement. To resolve the gap, we developed an iPad compatible in situ browser-based platform that integrates clinical activity with data collection and analysis presentation. The ability to perform in-clinic activities and monitor decision making using the iPad was evaluated. Methods: A browser-based platform that can exchange and present analysed data from the MOSAIQ database was developed in situ, the iPads were distributed in head and neck clinics to present the browser for clinical activities, data collection and assessment monitoring. Performance of the iPads for in-clinic activities was observed. Results: All in-clinic documentation activities can be performed without workstation computers. Accessing patient record and previous assessments was significantly faster without having to open the MOSAIQ application. Patient assessments can be completed with the physician facing the patient. Graphical presentation of toxicity progression and patient radiation plans to the patient can be performed in single interface without patient leaving the seating area. Updates in patient treatment status and medical history were presented in real time without having to move paper charts around. Conclusions: The iPad can be used in clinical activities independent of computer workstations. Improvements in clinical workflow can be critical in reducing physician resistance in data maintenance. Using the iPad in providing real-time quality monitoring is intuitive to both providers and patients.

  2. Electroencephalogram associations to cognitive performance in clinically active nurses.

    PubMed

    Lees, Ty; Khushaba, Rami; Lal, Sara

    2016-07-01

    Cognitive impairment is traditionally identified via cognitive screening tools that have limited ability in detecting early or transitional stages of impairment. The dynamic nature of physiological variables such as the electroencephalogram (EEG) may provide alternate means for detecting these transitions. However, previous research examining EEG and cognitive performance is largely confined to samples with diagnosed cognitive impairments, and research examining non-impaired, and occupation specific samples, is limited. The present study aimed to investigate the associations between frontal pole and central EEG and cognitive performance in a sample of male and female nurses, and to determine the significance of these associations. Fifty seven nurses participated in the study, in which two lead bipolar EEG was recorded at positions Fp1 (frontal polar), Fp2, C3 (central) and C4 during a baseline and an active phase involving the common neuropsychological Stroop test. Participants' cognitive performance was assessed using the mini-mental state exam (MMSE) and Cognistat screening tools. Significant correlations between EEG beta activity and the outcome of MMSE and Cognistat were revealed, where an increased beta activity was associated to an increased global cognitive performance. Additionally, domain specific cognitive performance was also significantly associated to various EEG variables. The study identified potential EEG biomarkers for global and domain specific cognitive performance, and provides initial groundwork for the development of future EEG based biomarkers for detection of cognitive pathologies. PMID:27244262

  3. LDEF meteoroid and debris special investigation group investigations and activities at the Johnson Space Center

    NASA Technical Reports Server (NTRS)

    See, Thomas H.; Warren, Jack L.; Zolensky, Michael E.; Sapp, Clyde A.; Bernhard, Ronald P.; Dardano, Claire B.

    1995-01-01

    Since the return of the Long Duration Exposure Facility (LDEF) in January, 1990, members of the Meteoroid and Debris Special Investigation Group (M&D SIG) at the Johnson Space Center (JSC) in Houston, Texas have been examining LDEF hardware in an effort to expand the knowledge base regarding the low-Earth orbit (LEO) particulate environment. In addition to the various investigative activities, JSC is also the location of the general Meteoroid & Debris database. This publicly accessible database contains information obtained from the various M&D SIG investigations, as well as limited data obtained by individual LDEF Principal Investigators. LDEF exposed approximately 130 m(exp 2) of surface area to the LEO particulate environment, approximately 15.4 m(exp 2) of which was occupied by structural frame components (i.e., longerons and intercoastals) of the spacecraft. The data reported here was obtained as a result of detailed scans of LDEF intercoastals, 68 of which reside at JSC. The limited amount of data presently available on the A0178 thermal control blankets was reported last year and will not be reiterated here. The data presented here are limited to measurements of crater diameters and their frequency of occurrence (i.e., flux).

  4. LDEF meteoroid and debris special investigation group investigations and activities at the Johnson Space Center

    NASA Astrophysics Data System (ADS)

    See, Thomas H.; Warren, Jack L.; Zolensky, Michael E.; Sapp, Clyde A.; Bernhard, Ronald P.; Dardano, Claire B.

    1995-02-01

    Since the return of the Long Duration Exposure Facility (LDEF) in January, 1990, members of the Meteoroid and Debris Special Investigation Group (M&D SIG) at the Johnson Space Center (JSC) in Houston, Texas have been examining LDEF hardware in an effort to expand the knowledge base regarding the low-Earth orbit (LEO) particulate environment. In addition to the various investigative activities, JSC is also the location of the general Meteoroid & Debris database. This publicly accessible database contains information obtained from the various M&D SIG investigations, as well as limited data obtained by individual LDEF Principal Investigators. LDEF exposed approximately 130 m(exp 2) of surface area to the LEO particulate environment, approximately 15.4 m(exp 2) of which was occupied by structural frame components (i.e., longerons and intercoastals) of the spacecraft. The data reported here was obtained as a result of detailed scans of LDEF intercoastals, 68 of which reside at JSC. The limited amount of data presently available on the A0178 thermal control blankets was reported last year and will not be reiterated here. The data presented here are limited to measurements of crater diameters and their frequency of occurrence (i.e., flux).

  5. A clinical trial of active hearing protection for orchestral musicians.

    PubMed

    O'Brien, Ian; Driscoll, Tim; Williams, Warwick; Ackermann, Bronwen

    2014-01-01

    Orchestral musicians-an at-risk group for noise-induced hearing loss-have consistently reported great difficulty using hearing protection while performing or rehearsing, even when using earplugs specifically designed for musicians. A recent innovation in this field has been electronic earplugs that claim to deliver very high quality sound and only attenuate when sound levels become excessive. This study investigated these claims, aiming to determine whether professional orchestral musicians were able to use these devices and whether they were preferred to existing earplugs. Initially clinical and laboratory testing was carried out on the devices, indicating some spectral alteration of processed sound occurred, however claims of attenuation properties were validated. Following this, 26 orchestral musicians used the devices during rehearsals and performances for at least four weeks, providing feedback throughout this period. While musicians preferred the devices to previous earplugs, they identified issues including difficulty with orchestral balance, perception of dynamics and quality of sound provided by the devices. Results indicate these earplugs are a very positive step towards a usable hearing conservation tool for orchestral musicians to use in conjunction with other risk mitigation measures. PMID:24433326

  6. Clinical application of transcriptional activators of bile salt transporters☆

    PubMed Central

    Baghdasaryan, Anna; Chiba, Peter; Trauner, Michael

    2014-01-01

    Hepatobiliary bile salt (BS) transporters are critical determinants of BS homeostasis controlling intracellular concentrations of BSs and their enterohepatic circulation. Genetic or acquired dysfunction of specific transport systems causes intrahepatic and systemic retention of potentially cytotoxic BSs, which, in high concentrations, may disturb integrity of cell membranes and subcellular organelles resulting in cell death, inflammation and fibrosis. Transcriptional regulation of canalicular BS efflux through bile salt export pump (BSEP), basolateral elimination through organic solute transporters alpha and beta (OSTα/OSTβ) as well as inhibition of hepatocellular BS uptake through basolateral Na+-taurocholate cotransporting polypeptide (NTCP) represent critical steps in protection from hepatocellular BS overload and can be targeted therapeutically. In this article, we review the potential clinical implications of the major BS transporters BSEP, OSTα/OSTβ and NTCP in the pathogenesis of hereditary and acquired cholestatic syndromes, provide an overview on transcriptional control of these transporters by the key regulatory nuclear receptors and discuss the potential therapeutic role of novel transcriptional activators of BS transporters in cholestasis. PMID:24333169

  7. Active control: an investigation method for combustion instabilities

    NASA Astrophysics Data System (ADS)

    Poinsot, T.; Yip, B.; Veynante, D.; Trouvé, A.; Samaniego, J. M.; Candel, S.

    1992-07-01

    Closed-loop active control methods and their application to combustion instabilities are discussed. In these methods the instability development is impeded with a feedback control loop: the signal provided by a sensor monitoring the flame or pressure oscillations is processed and sent back to actuators mounted on the combustor or on the feeding system. Different active control systems tested on a non-premixed multiple-flame turbulent combustor are described. These systems can suppress all unstable plane modes of oscillation (i.e. low frequency modes). The active instability control (AIC) also constitutes an original and powerful technique for studies of mechanisms leading to instability or resulting from the instability. Two basic applications of this kind are described. In the first case the flame is initially controlled with AIC, the feedback loop is then switched off and the growth of the instability is analysed through high speed Schlieren cinematography and simultaneous sound pressure and reaction rate measurements. Three phases are identified during th growth of the oscillations: (1) a linear phase where acoustic waves induce a flapping motion of the flame sheets without interaction between sheets, (2) a modulation phase, where flame sheets interact randomly and (3) a nonlinear phase where the flame sheets are broken and a limit cycle is reached. In the second case we investigate different types of flame extinctions associated with combustion instability. It is shown that pressure oscillations may lead to partial or total extinctions. Extinctions occur in various forms but usually follow a rapid growth of pressure oscillations. The flame is extinguished during the modulation phase observed in the initiation experiments. In these studies devoted to transient instability phenomena, the control system constitutes a unique investigation tool because it is difficult to obtain the same information by other means. Implications for modelling and prediction of

  8. Seal Investigations of an Active Clearance Control System Concept

    NASA Technical Reports Server (NTRS)

    Steinetz, Bruce M.; Taylor, Shawn; Oswald, Jay; DeCastro, Jonathan A.

    2006-01-01

    In an effort to improve upon current thermal active clearance control methods, a first generation, fast-acting mechanically actuated, active clearance control system has been designed and installed into a non-rotating test rig. In order to harvest the benefit of tighter blade tip clearances, low-leakage seals are required for the actuated carrier segments of the seal shroud to prevent excessive leakage of compressor discharge (P3) cooling air. The test rig was designed and fabricated to facilitate the evaluation of these types of seals, identify seal leakage sources, and test other active clearance control system concepts. The objective of this paper is to present both experimental and analytical investigations into the nature of the face-seal to seal-carrier interface. Finite element analyses were used to examine face seal contact pressures and edge-loading under multiple loading conditions, varied E-seal positions and two new face seal heights. The analyses indicated that moving the E-seal inward radially and reducing face seal height would lead to more uniform contact conditions between the face seal and the carriers. Lab testing confirmed that moving the balance diameter inward radially caused a decrease in overall system leakage.

  9. Understanding the investigators: a qualitative study investigating the barriers and enablers to the implementation of local investigator-initiated clinical trials in Ethiopia

    PubMed Central

    Franzen, Samuel R P; Chandler, Clare; Enquselassie, Fikre; Siribaddana, Sisira; Atashili, Julius; Angus, Brian; Lang, Trudie

    2013-01-01

    Objectives Clinical trials provide ‘gold standard’ evidence for policy, but insufficient locally relevant trials are conducted in low-income and middle-income countries. Local investigator-initiated trials could generate highly relevant data for national governments, but information is lacking on how to facilitate them. We aimed to identify barriers and enablers to investigator-initiated trials in Ethiopia to inform and direct capacity strengthening initiatives. Design Exploratory, qualitative study comprising of in-depth interviews (n=7) and focus group discussions (n=3). Setting Fieldwork took place in Ethiopia during March 2011. Participants Local health researchers with previous experiences of clinical trials or stakeholders with an interest in trials were recruited through snowball sampling (n=20). Outcome measures Detailed discussion notes were analysed using thematic coding analysis and key themes were identified. Results All participants perceived investigator-initiated trials as important for generating local evidence. System and organisational barriers included: limited funding allocation, weak regulatory and administrative systems, few learning opportunities, limited human and material capacity and poor incentives for conducting research. Operational hurdles were symptomatic of these barriers. Lack of awareness, confidence and motivation to undertake trials were important individual barriers. Training, knowledge sharing and experience exchange were key enablers to trial conduct and collaboration was unanimously regarded as important for improving capacity. Conclusions Barriers to trial conduct were found at individual, operational, organisational and system levels. These findings indicate that to increase locally led trial conduct in Ethiopia, system wide changes are needed to create a more receptive and enabling research environment. Crucially, the creation of research networks between potential trial groups could provide much needed practical

  10. Using thermographic cameras to investigate eye temperature and clinical severity in depression

    NASA Astrophysics Data System (ADS)

    Maller, Jerome J.; George, Shefin Sam; Viswanathan, Rekha Puzhavakkathumadom; Fitzgerald, Paul B.; Junor, Paul

    2016-02-01

    Previous studies suggest that altered corneal temperature may be a feature of schizophrenia, but the association between major depressive disorder (MDD) and corneal temperature has yet to be assessed. The aim of this study is to investigate whether eye temperature is different among MDD patients than among healthy individuals. We used a thermographic camera to measure and compare the temperature profile across the corneas of 16 patients with MDD and 16 age- and sex-matched healthy subjects. We found that the average corneal temperature between the two groups did not differ statistically, although clinical severity correlated positively with right corneal temperature. Corneal temperature may be an indicator of clinical severity in psychiatric disorders, including depression.

  11. Investigation of cytotoxic activity in four stachys species from iran.

    PubMed

    Khanavi, Mahnaz; Manayi, Azadeh; Lotfi, Mahnaz; Abbasi, Rofeyde; Majdzadeh, Maryam; Ostad, Seyed Nasser

    2012-01-01

    The aerial parts of Stachys laxa Boiss. and Buhse. from Siah-bishe in Mazandaran province, Stachys trinervis Aitch. and Hemsl. from Karaj in Alborz province, Stachys subaphylla Rech. F. and Stachys turcomanica Trautv. from Golestan province have been collected in May 2008. Total extracts were obtained through MeOH/H2O (80/20) and then partitioned between CHCl3, EtOAc and MeOH. These fractions and total extracts have been investigated for in-vitro cytotoxic activity against the colon carcinoma (HT-29), colorectal adenocarcinoma (Caco-2), breast ductal carcinoma (T47D) and Swiss mouse embryo fibroblast (NIH 3T3) cell lines using MTT assay (3-(4,5-di methyl thiazol-2-yl)-2,5-di phenyltetrazolium bromide). At each cell line, doses of 3.125, 6.25, 12.5, 25, 100, 200, 400 and 800 µg/mL in 1% (v/v) DMSO of all samples were tested. Ethyl acetate and chloroform fractions of Stachys laxa against proliferation of T47D and HT-29 cell lines and chloroform fraction of Stachys subaphylla and Stachys subaphylla ethyl acetate fraction toward T47D cell line exhibited highest cytotoxic activity (IC50 < 50 µg/mL). Ethyl acetate and chloroform fractions of Stachys turcomanica against HT-29 cell line, except methanol fraction of Stachys subaphylla, the other extrcts on T47D cell line, represented moderate cytotoxic activity (IC50 < 70 µg/mL). All fractions of S. trinervis demonstrated no effective cytotoxic activity. IC50 values confirmed that the growth and proliferation of HT-29 and T47D cells were most affected by chloroform and ethyl acetate fractions of Stachys laxa and Stachys turcomanica due to their nonpolar compounds. PMID:24250483

  12. Clinical Investigations in Mathematics Education. Thematic Addresses from the Fourth National Conference on Diagnostic and Prescriptive Mathematics.

    ERIC Educational Resources Information Center

    Speer, William R.

    Five invitational addresses presented at the Fourth National Conference of the Research Council for Diagnostic and Prescriptive Mathematics are included in this document. "The Nature of the Clinical Investigation" (Romberg and Uprichard) discusses the validity of clinical investigations and suggests guidelines for conducting such studies of…

  13. Modified Active Site Coordination in a Clinical Mutant of Sulfite Oxidase

    SciTech Connect

    Doonan, C.J.; Wilson, H.L.; Rajagopalan, K.V.; Garrett, R.M.; Bennett, B.; Prince, R.C.; George, G.N.

    2009-06-02

    The molybdenum site of the Arginine 160 {yields} Glutamine clinical mutant of the physiologically vital enzyme sulfite oxidase has been investigated by a combination of X-ray absorption spectroscopy and density functional theory calculations. We conclude that the mutant enzyme has a six-coordinate pseudo-octahedral active site with coordination of Glutamine O{sup {epsilon}} to molybdenum. This contrasts with the wild-type enzyme which is five-coordinate with approximately square-based pyramidal geometry. This difference in the structure of the molybdenum site explains many of the properties of the mutant enzyme which have previously been reported.

  14. Serotonin content of platelets in inflammatory rheumatic diseases. Correlation with clinical activity.

    PubMed

    Zeller, J; Weissbarth, E; Baruth, B; Mielke, H; Deicher, H

    1983-04-01

    Significantly decreased platelet serotonin contents were measured in rheumatoid arthritis, systemic lupus erythematosus (SLE), progressive systemic sclerosis, and mixed connective tissue disease. An inverse relationship between platelet serotonin levels and clinical disease activity was observed in both rheumatoid arthritis and systemic lupus erythematosus. SLE patients with multiple organ involvement showed the lowest platelet serotonin values. No correlation was observed between platelet serotonin contents and nonsteroidal antiinflammatory drug treatment, presence of circulating platelet reactive IgG, or the amount of circulating immune complexes. The results are interpreted as indicating platelet release occurring in vivo during inflammatory episodes of the rheumatic disorders investigated. PMID:6838676

  15. Sustaining the Clinical and Translational Research Workforce: Training and Empowering the Next Generation of Investigators.

    PubMed

    Yin, Helen L; Gabrilove, Janice; Jackson, Rebecca; Sweeney, Carol; Fair, Alecia M; Toto, Robert

    2015-07-01

    There is mounting concern that clinician-scientists are a vanishing species and that the pipeline for clinical and translational research (CTR) investigators is in jeopardy. For the majority of current junior CTR investigators, the career path involves first obtaining a National Institutes of Health (NIH)-funded K-type career development award, particularly K08 and K23, and subsequently an NIH R01. This transition, popularly referred to as K2R, is a major hurdle with a low success rate and gaps in funding. In this Perspective, the authors identify factors that facilitate K2R transition and important aspects of increasing and sustaining the pipeline of CTR investigators. They also highlight significant differences in success rates of women and those underrepresented in biomedical research. Early career exposure to research methodology, protected time, multidisciplinary mentoring, and institutional "culture shift" are important for fostering and rewarding team science. Mentoring is the single most important contributor to K2R success, and emerging evidence suggests that formal mentor training and team mentoring are effective. Leadership training can empower junior investigators to thrive as independent CTR investigators. Future research should focus on delineating the difference between essential and supplemental factors to achieve this transition, and mentoring methods that foster success, including those that promote K2R transition of women and those underrepresented in biomedical research. The Clinical and Translational Science Awards National Consortium is well positioned to test existing models aimed at shortening the time frame, increasing the rate of K2R transition, and identifying strategies that improve success. PMID:26414054

  16. Sustaining the Clinical Translational Research Workforce: Training and Empowering the Next Generation of Investigators

    PubMed Central

    Yin, Helen L.; Gabrilove, Janice; Jackson, Rebecca; Sweeney, Carol; Fair, Alecia M.; Toto, Robert

    2015-01-01

    There is mounting concern that clinician scientists are a vanishing species, and that the pipeline for clinical translational research (CTR) investigators is in jeopardy. For the majority of current junior CTR investigators, the career path involves first obtaining a National Institutes of Health (NIH) funded K-type career development award, particularly K08 and K23, and subsequently an NIH R01. This transition, popularly referred to as K2R, is a major hurdle with a low success rate and gaps in funding. In this Perspective, the authors identify factors that facilitate K2R transition and important aspects of increasing and sustaining the pipeline of CTR investigators. They also highlight significant differences in success rates of women and those underrepresented in biomedical research. Early career exposure to research methodology, protected time, multidisciplinary mentoring, and institutional “culture shift” are important for fostering and rewarding team science. Mentoring is the single most important contributor to K2R success, and emerging evidence suggests that formal mentor training and team mentoring are effective. Leadership training can empower junior investigators to thrive as independent CTR investigators. Future research should focus on delineating the difference between essential and supplemental factors to achieve this transition, and mentoring methods that foster success, including those that promote K2R transition of women and those underrepresented in biomedical research. The Clinical Translational Science Awards National Consortium is well positioned to test existing models aimed at shortening the timeframe, increasing the rate of K2R transition, and identifying strategies that improve success. PMID:26414054

  17. The Effects of Sex Steroids on Spatial Performance: A Review and an Experimental Clinical Investigation.

    ERIC Educational Resources Information Center

    Liben, Lynn S.; Susman, Elizabeth J.; Finkelstein, Jordan W.; Chinchilli, Vernon M.; Kunselman, Susan; Schwab, Jacqueline; Dubas, Judith Semon; Demers, Laurence M.; Lookingbill, Georgia; D'Arcangelo, M. Rose; Krogh, Holleen R.; Kulin, Howard E.

    2002-01-01

    Investigated the relationship between sex hormones and spatial performance among adolescents treated with sex steroids for delayed puberty. Found that spatial performance varied according to gender but did not vary with levels of actively circulating sex steroids. Reviewed physiological mechanisms, developmental periods, and past empirical work…

  18. In vitro activities of polycationic peptides alone and in combination with clinically used antimicrobial agents against Rhodococcus equi.

    PubMed

    Giacometti, A; Cirioni, O; Ancarani, F; Del Prete, M S; Fortuna, M; Scalise, G

    1999-08-01

    The in vitro activities of magainin II, nisin, and ranalexin alone and in combination with other antimicrobial agents against six clinical isolates of Rhodococcus equi were investigated by MIC and time-kill studies. All isolates were more susceptible to nisin. A positive interaction was observed when the peptides were combined with ampicillin, ceftriaxone, rifabutin, rifampin, azithromycin, clarithromycin, and vancomycin. PMID:10428947

  19. Quality investigation of hydroxyprogesterone caproate active pharmaceutical ingredient and injection

    PubMed Central

    Chollet, John L.; Jozwiakowski, Michael J.

    2012-01-01

    The purpose of this study was to investigate the quality of hydroxyprogesterone caproate (HPC) active pharmaceutical ingredient (API) sources that may be used by compounding pharmacies, compared to the FDA-approved source of the API; and to investigate the quality of HPC injection samples obtained from compounding pharmacies in the US, compared to the FDA-approved product (Makena®). Samples of API were obtained from every source confirmed to be an original manufacturer of the drug for human use, which were all companies in China that were not registered with FDA. Eight of the ten API samples (80%) did not meet the impurity specifications required by FDA for the API used in the approved product. One API sample was found to not be HPC at all; additional laboratory testing showed that it was glucose. Thirty samples of HPC injection obtained from com pounding pharmacies throughout the US were also tested, and eight of these samples (27%) failed to meet the potency requirement listed in the USP monograph for HPC injection and/or the HPLC assay. Sixteen of the thirty injection samples (53%) exceeded the impurity limit setforthe FDA-approved drug product. These results confirm the inconsistency of compounded HPC Injections and suggest that the risk-benefit ratio of using an unapproved compounded preparation, when an FDA-approved drug product is available, is not favorable. PMID:22329865

  20. Missed Opportunities for TB Investigation in Primary Care Clinics in South Africa: Experience from the XTEND Trial

    PubMed Central

    Chihota, Violet N.; Ginindza, Sibuse; McCarthy, Kerrigan; Grant, Alison D.; Churchyard, Gavin; Fielding, Katherine

    2015-01-01

    Setting 40 primary health clinics (PHCs) in four provinces in South Africa, June 2012 –February 2013. Objective To determine whether health care worker (HCW) practice in investigating people with TB symptoms was altered when the initial test for TB was changed from smear microscopy to Xpert MTB/RIF. Design Cross-sectional substudy at clinics participating in a pragmatic cluster randomised trial, Xpert for TB: Evaluating a New Diagnostic "XTEND", which evaluated the effect of Xpert MTB/RIF implementation in South Africa. Methods Consecutive adults exiting PHCs reporting at least one TB symptom (defined as any of cough, weight loss, night sweats and fever) were enrolled. The main outcome was the proportion who self-reported having sputum requested by HCW during the clinic encounter just completed. Results 3604 adults exiting PHCs (1676 in Xpert arm, 1928 in microscopy arm) were enrolled (median age 38 years, 71.4% female, 38.8% reported being HIV-positive, 70% reported cough). For 1267 participants (35.2%) the main reason for attending the clinic was TB symptom(s). Overall 2130/3604 (59.1%) said they reported their symptom(s) to HCW. 22.7% (818/3604) reported having been asked to give sputum for TB investigation. Though participants in the Xpert vs. microscopy arm were more likely to have sputum requested by HCW, this was not significantly different: overall (26.0% [436/1676] vs 19.8% [382/1928]; adjusted prevalence ratio [aPR] 1.31, [95% CI 0.78–2.20]) and when restricted to those presenting at clinics due to symptoms (49.1% [260/530] vs 29.9% [220/737]; aPR 1.38 [0.89–2.13]) and those reporting being HIV-positive (29.4% [190/647] vs 20.8% [156/749]; aPR 1.38[0.88–2.16]). Those attending clinic due to TB symptoms, were more likely to have sputum requested if they had increasing number of symptoms; longer duration of cough, unintentional weight loss and night sweats and if they reported symptoms to HCW. Conclusions A large proportion of people exiting PHCs

  1. Anti-tumor activity of calcitriol: pre-clinical and clinical studies.

    PubMed

    Trump, Donald L; Hershberger, Pamela A; Bernardi, Ronald J; Ahmed, Sharmilla; Muindi, Josephia; Fakih, Marwan; Yu, Wei-Dong; Johnson, Candace S

    2004-05-01

    1,25-Dihydroxycholecalciferol (calcitriol) is recognized widely for its effects on bone and mineral metabolism. Epidemiological data suggest that low Vitamin D levels may play a role in the genesis of prostate cancer and perhaps other tumors. Calcitriol is a potent anti-proliferative agent in a wide variety of malignant cell types. In prostate, breast, colorectal, head/neck and lung cancer as well as lymphoma, leukemia and myeloma model systems calcitriol has significant anti-tumor activity in vitro and in vivo. Calcitriol effects are associated with an increase in G0/G1 arrest, induction of apoptosis and differentiation, modulation of expression of growth factor receptors. Glucocorticoids potentiate the anti-tumor effect of calcitriol and decrease calcitriol-induced hypercalcemia. Calcitriol potentiates the antitumor effects of many cytotoxic agents and inhibits motility and invasiveness of tumor cells and formation of new blood vessels. Phase I and II trials of calcitriol either alone or in combination with carboplatin, taxanes or dexamethasone have been initiated in patients with androgen dependent and independent prostate cancer and advanced cancer. Data indicate that high-dose calcitriol is feasible on an intermittent schedule, no dose-limiting toxicity has been encountered and optimal dose and schedule are being delineated. Clinical responses have been seen with the combination of high dose calcitriol+dexamethasone in androgen independent prostate cancer (AIPC) and apparent potentiation of the antitumor effects of docetaxel have been seen in AIPC. These results demonstrate that high intermittent doses of calcitriol can be administered to patients without toxicity, that the MTD is yet to be determined and that calcitriol has potential as an anti-cancer agent. PMID:15225831

  2. Project Zero Delay: a process for accelerating the activation of cancer clinical trials.

    PubMed

    Kurzrock, Razelle; Pilat, Susan; Bartolazzi, Marcel; Sanders, Dwana; Van Wart Hood, Jill; Tucker, Stanley D; Webster, Kevin; Mallamaci, Michael A; Strand, Steven; Babcock, Eileen; Bast, Robert C

    2009-09-10

    Drug development in cancer research is lengthy and expensive. One of the rate-limiting steps is the initiation of first-in-human (phase I) trials. Three to 6 months can elapse between investigational new drug (IND) approval by the US Food and Drug Administration and the entry of a first patient. Issues related to patient participation have been well analyzed, but the administrative processes relevant to implementing clinical trials have received less attention. While industry and academia often partner for the performance of phase I studies, their administrative processes are generally performed independently, and their timelines driven by different priorities: safety reviews, clinical operations, regulatory submissions, and contracting of clinical delivery vendors for industry; contracts, budgets, and institutional review board approval for academia. Both processes converge on US Food and Drug Administration approval of an IND. In the context of a strategic alliance between M. D. Anderson Cancer Center and AstraZeneca Pharmaceuticals LP, a concerted effort has been made to eliminate delays in implementing clinical trials. These efforts focused on close communications, identifying and matching key timelines, alignment of priorities, and tackling administrative processes in parallel, rather than sequentially. In a recent, first-in-human trial, the study was activated and the first patient identified in 46 days from completion of the final study protocol and about 48 hours after final US Food and Drug Administration IND approval, reducing the overall timeline by about 3 months, while meeting all clinical good practice guidelines. Eliminating administrative delays can accelerate the evaluation of new drugs without compromising patient safety or the quality of clinical research. PMID:19652061

  3. Tractography Activation Patterns in Dorsolateral Prefrontal Cortex Suggest Better Clinical Responses in OCD DBS

    PubMed Central

    Hartmann, Christian J.; Lujan, J. Luis; Chaturvedi, Ashutosh; Goodman, Wayne K.; Okun, Michael S.; McIntyre, Cameron C.; Haq, Ihtsham U.

    2016-01-01

    Background: Medication resistant obsessive-compulsive disorder (OCD) patients can be successfully treated with Deep Brain Stimulation (DBS) which targets the anterior limb of the internal capsule (ALIC) and the nucleus accumbens (NA). Growing evidence suggests that in patients who respond to DBS, axonal fiber bundles surrounding the electrode are activated, but it is currently unknown which discrete pathways are critical for optimal benefit. Our aim was to identify axonal pathways mediating clinical effects of ALIC-NA DBS. Methods: We created computational models of ALIC-NA DBS to simulate the activation of fiber tracts and to identify connected cerebral regions. The pattern of activated axons and their cortical targets was investigated in six OCD patients who underwent ALIC-NA DBS. Results: Modulation of the right anterior middle frontal gyrus (dorsolateral prefrontal cortex) was associated with an excellent response. In contrast, non-responders showed high activation in the orbital part of the right inferior frontal gyrus (lateral orbitofrontal cortex/anterior ventrolateral prefrontal cortex). Factor analysis followed by step-wise linear regression indicated that YBOCS improvement was inversely associated with factors that were predominantly determined by gray matter activation results. Discussion: Our findings support the hypothesis that optimal therapeutic results are associated with the activation of distinct fiber pathways. This suggests that in DBS for OCD, focused stimulation of specific fiber pathways, which would allow for stimulation with lower amplitudes, may be superior to activation of a wide array of pathways, typically associated with higher stimulation amplitudes. PMID:26834544

  4. An Investigation of Activity Profiles of Older Adults

    PubMed Central

    Putnam, Michelle; Lee, Yung Soo; Greenfield, Jennifer C.; Inoue, Megumi; Chen, Huajuan

    2014-01-01

    Objectives. In this study, we advance knowledge about activity engagement by considering many activities simultaneously to identify profiles of activity among older adults. Further, we use cross-sectional data to explore factors associated with activity profiles and prospective data to explore activity profiles and well-being outcomes. Method. We used the core survey data from the years 2008 and 2010, as well as the 2009 Health and Retirement Study Consumption and Activities Mail Survey (HRS CAMS). The HRS CAMS includes information on types and amounts of activities. We used factor analysis and latent class analysis to identify activity profiles and regression analyses to assess antecedents and outcomes associated with activity profiles. Results. We identified 5 activity profiles: Low Activity, Moderate Activity, High Activity, Working, and Physically Active. These profiles varied in amount and type of activities. Demographic and health factors were related to profiles. Activity profiles were subsequently associated with self-rated health and depression symptoms. Discussion. The use of a 5-level categorical activity profile variable may allow more complex analyses of activity that capture the “whole person.” There is clearly a vulnerable group of low-activity individuals as well as a High Activity group that may represent the “active ageing” vision. PMID:24526690

  5. Direct-detection EPID dosimetry: investigation of a potential clinical configuration for IMRT verification.

    PubMed

    Vial, Philip; Gustafsson, Helen; Oliver, Lyn; Baldock, Clive; Greer, Peter B

    2009-12-01

    The routine use of electronic portal imaging devices (EPIDs) as dosimeters for radiotherapy quality assurance is complicated by the non-water equivalence of the EPID's dose response. A commercial EPID modified to a direct-detection configuration was previously demonstrated to provide water-equivalent dose response with d(max) solid water build-up and 10 cm solid water backscatter. Clinical implementation of the direct EPID (dEPID) requires a design that maintains the water-equivalent dose response, can be incorporated onto existing EPID support arms and maintains sufficient image quality for clinical imaging. This study investigated the dEPID dose response with different configurations of build-up and backscatter using varying thickness of solid water and copper. Field size output factors and beam profiles measured with the dEPID were compared with ionization chamber measurements of dose in water for both 6 MV and 18 MV. The dEPID configured with d(max) solid water build-up and no backscatter (except for the support arm) was within 1.5% of dose in water data for both energies. The dEPID was maintained in this configuration for clinical dosimetry and image quality studies. Close agreement between the dEPID and treatment planning system was obtained for an IMRT field with 98.4% of pixels within the field meeting a gamma criterion of 3% and 3 mm. The reduced sensitivity of the dEPID resulted in a poorer image quality based on quantitative (contrast-to-noise ratio) and qualitative (anthropomorphic phantom) studies. However, clinically useful images were obtained with the dEPID using typical treatment field doses. The dEPID is a water-equivalent dosimeter that can be implemented with minimal modifications to the standard commercial EPID design. The proposed dEPID design greatly simplifies the verification of IMRT dose delivery. PMID:19904032

  6. Direct-detection EPID dosimetry: investigation of a potential clinical configuration for IMRT verification

    NASA Astrophysics Data System (ADS)

    Vial, Philip; Gustafsson, Helen; Oliver, Lyn; Baldock, Clive; Greer, Peter B.

    2009-12-01

    The routine use of electronic portal imaging devices (EPIDs) as dosimeters for radiotherapy quality assurance is complicated by the non-water equivalence of the EPID's dose response. A commercial EPID modified to a direct-detection configuration was previously demonstrated to provide water-equivalent dose response with dmax solid water build-up and 10 cm solid water backscatter. Clinical implementation of the direct EPID (dEPID) requires a design that maintains the water-equivalent dose response, can be incorporated onto existing EPID support arms and maintains sufficient image quality for clinical imaging. This study investigated the dEPID dose response with different configurations of build-up and backscatter using varying thickness of solid water and copper. Field size output factors and beam profiles measured with the dEPID were compared with ionization chamber measurements of dose in water for both 6 MV and 18 MV. The dEPID configured with dmax solid water build-up and no backscatter (except for the support arm) was within 1.5% of dose in water data for both energies. The dEPID was maintained in this configuration for clinical dosimetry and image quality studies. Close agreement between the dEPID and treatment planning system was obtained for an IMRT field with 98.4% of pixels within the field meeting a gamma criterion of 3% and 3 mm. The reduced sensitivity of the dEPID resulted in a poorer image quality based on quantitative (contrast-to-noise ratio) and qualitative (anthropomorphic phantom) studies. However, clinically useful images were obtained with the dEPID using typical treatment field doses. The dEPID is a water-equivalent dosimeter that can be implemented with minimal modifications to the standard commercial EPID design. The proposed dEPID design greatly simplifies the verification of IMRT dose delivery.

  7. The Clinically Tested Gardos Channel Inhibitor Senicapoc Exhibits Antimalarial Activity

    PubMed Central

    Tubman, Venée N.; Mejia, Pedro; Shmukler, Boris E.; Bei, Amy K.; Alper, Seth L.; Mitchell, James R.

    2015-01-01

    Senicapoc, a Gardos channel inhibitor, prevented erythrocyte dehydration in clinical trials of patients with sickle cell disease. We tested the hypothesis that senicapoc-induced blockade of the Gardos channel inhibits Plasmodium growth. Senicapoc inhibited in vitro growth of human and primate plasmodia during the clinical blood stage. Senicapoc treatment suppressed P. yoelii parasitemia in vivo in C57BL/6 mice. The reassuring safety and biochemical profile of senicapoc encourage its use in antimalarial development. PMID:26459896

  8. Genome-wide investigation of schizophrenia associated plasma Ndel1 enzyme activity.

    PubMed

    Gadelha, Ary; Coleman, Jonathan; Breen, Gerome; Mazzoti, Diego Robles; Yonamine, Camila M; Pellegrino, Renata; Ota, Vanessa Kiyomi; Belangero, Sintia Iole; Glessner, Joseph; Sleiman, Patrick; Hakonarson, Hakon; Hayashi, Mirian A F; Bressan, Rodrigo A

    2016-04-01

    Ndel1 is a DISC1-interacting oligopeptidase that cleaves in vitro neuropeptides as neurotensin and bradykinin, and which has been associated with both neuronal migration and neurite outgrowth. We previously reported that plasma Ndel1 enzyme activity is lower in patients with schizophrenia (SCZ) compared to healthy controls (HCs). To our knowledge, no previous study has investigated the genetic factors associated with the plasma Ndel1 enzyme activity. In the current analyses, samples from 83 SCZ patients and 92 control subjects that were assayed for plasma Ndel1 enzyme activity were genotyped on Illumina Omni Express arrays. A genetic relationship matrix using genome-wide information was then used for ancestry correction, and association statistics were calculated genome-wide. Ndel1 enzyme activity was significantly lower in patients with SCZ (t=4.9; p<0.001) and was found to be associated with CAMK1D, MAGI2, CCDC25, and GABGR3, at a level of suggestive significance (p<10(-6)), independent of the clinical status. Then, we performed a model to investigate the observed differences for case/control measures. 2 SNPs at region 1p22.2 reached the p<10(-7) level. ZFPM2 and MAD1L1 were the only two genes with more than one hit at 10(-6) order of p value. Therefore, Ndel1 enzyme activity is a complex trait influenced by many different genetic variants that may contribute to SCZ physiopathology. PMID:26851141

  9. Investigate the Child's Scientific Activities on Practical Child's Activity Books for the Kindergarten's Children

    ERIC Educational Resources Information Center

    Aldarabah, Intisar Turki; Al-Mouhtadi, Reham

    2015-01-01

    This research aimed to investigate the extent to which the interactive international curriculum is included in the "Child's Scientific Activities" issued by the Ministry of Education in Jordan, for the kindergarten stage according to the global criterion (NRC). In order to answer the study questions, an instrument was developed to…

  10. Clinical Relevance of Telomere Status and Telomerase Activity in Colorectal Cancer

    PubMed Central

    Fernández-Marcelo, Tamara; Sánchez-Pernaute, Andrés; Pascua, Irene; De Juan, Carmen; Head, Jacqueline; Torres-García, Antonio-José; Iniesta, Pilar

    2016-01-01

    The role of telomeres and telomerase in colorectal cancer (CRC) is well established as the major driving force in generating chromosomal instability. However, their potential as prognostic markers remains unclear. We investigated the outcome implications of telomeres and telomerase in this tumour type. We considered telomere length (TL), ratio of telomere length in cancer to non-cancer tissue (T/N ratio), telomerase activity and TERT levels; their relation with clinical variables and their role as prognostic markers. We analyzed 132 CRCs and paired non-cancer tissues. Kaplan-Meier curves for disease-free survival were calculated for TL, T/N ratio, telomerase activity and TERT levels. Overall, tumours had shorter telomeres than non-tumour tissues (P < 0.001) and more than 80% of CRCs displayed telomerase activity. Telomere lengths of non-tumour tissues and CRCs were positively correlated (P < 0.001). Considering telomere status and clinical variables, the lowest degree of telomere shortening was shown by tumours located in the rectum (P = 0.021). Regarding prognosis studies, patients with tumours showing a mean TL < 6.35 Kb experienced a significantly better clinical evolution (P < 0.001) and none of them with the highest degree of tumour telomere shortening relapsed during the follow-up period (P = 0.043). The mean TL in CRCs emerged as an independent prognostic factor in the Cox analysis (P = 0.017). Telomerase-positive activity was identified as a marker that confers a trend toward a poor prognosis. In CRC, our results support the use of telomere status as an independent prognostic factor. Telomere status may contribute to explaining the different molecular identities of this tumour type. PMID:26913901

  11. Anxiety and depression in rheumatoid arthritis: an epidemiologic survey and investigation of clinical correlates in Iranian population.

    PubMed

    Jamshidi, Ahmad-Reza; Banihashemi, Arash Tehrani; Paragomi, Pedram; Hasanzadeh, Maryam; Barghamdi, Mozhgan; Ghoroghi, Shima

    2016-08-01

    Psychiatric disorders occur in a considerable proportion of patients with rheumatoid arthritis (RA). This study was conducted in order to evaluate the prevalence of anxiety and depression in Iranian RA patients. In the cross sectional study, 414 RA patients were enrolled prospectively during a period of 6 months from RA clinic of Rheumatology Research Center. Beck's and Cattell's inventories were applied to investigate depression and anxiety in RA patients. RA activity was measured by Disease Activity Score and patients' disability was assessed by Health Assessment Questionnaire. Levels of pain perception were stratified based on Visual Analog Scale. The prevalence of depression was 63.6 % and anxiety was in 84.1 % among RA patients. Mixed anxiety and depression was detected in 60.2 % of the study population. Functional disability was significantly associated with severity of depressive and anxiety symptoms (p < 0.001); however there was no association between disease activity and depression or anxiety (p = 0.420). There was weak correlation between disease activity score and functional disability (Spearman's rho = 0.33; p < 0.01). Severe levels of depression and anxiety were associated with higher levels of pain perception (p < 0.001). Our study stressed the impact of depressive and anxiety symptoms in functional disability and pain perception of RA patients. Our results point out the multidisciplinary management of RA. PMID:27193469

  12. Anticandidal activity of medicinal plants and Pseudomonas aeruginosa strains of clinical specimens.

    PubMed

    Bora, Limpon

    2016-04-01

    This study was designed to investigate the in vitro anticandidal activity of some medicinal plants and Pseudomonas aeruginosa strains against Candida species. The antifungal activity of methanolic extracts of five medicinal plants, namely, Cinnamomum porrectum, Lippia nudiflora, Cestrum nocturnum, Trachyspermum ammi, and Sida carpinifolia were studied. The medicinal characteristics of these plants were compared with commercially used antibiotics. The antimicrobial assay was done by agar well diffusion and the broth dilution method. Among the plants used, T. ammi and C. nocturnum were found to be more potent than the others. Twenty P. aeruginosa strains were isolated from various clinical specimens. The total inhibitions obtained were found to be 47%, 38%, and 36% in blood agar, whereas in Sabouraud dextrose agar (SDA) the inhibitions were 57%, 48%, and 37%, respectively. PMID:25592881

  13. Cluster Active Archive products and multipoint magnetospheric investigations

    NASA Astrophysics Data System (ADS)

    Perry, C.; Laakso, H.; Taylor, M.; Escoubet, P.

    2007-12-01

    The four-satellite Cluster mission investigates the small-scale structures (in three dimensions) of the Earth's plasma environment, such as those involved in the interaction between the solar wind and the magnetospheric plasma, in global magnetotail dynamics, in cross-tail currents, and in the formation and dynamics of the neutral line and of plasmoids. The Cluster Active Archive CAA (http://caa.estec.esa.int/) contains the entire set of Cluster high resolution data and other allied products in a standard format. The CAA currently has data from most of the Cluster instruments for at least the first three years of operations (2001-2003). The coverage and range of products is being continually improved with more than 200 datasets available from each spacecraft including high-resolution magnetic & electric DC fields and wave spectra; full 3D electron & ion distributions from a few eV to hundreds of keV; and various ancillary & browse products to help with spacecraft and event location. The data archived are (1) publicly accessible, (2) of the best quality achievable with the given resources, and (3) suitable for science use and publication by both the Cluster and broader scientific community. The presentation contains examples of user friendly services of the CAA for searching and accessing these data and ancillary products and of online capabilities of the system.

  14. Preliminary investigations of active pixel sensors in Nuclear Medicine imaging

    NASA Astrophysics Data System (ADS)

    Ott, Robert; Evans, Noel; Evans, Phil; Osmond, J.; Clark, A.; Turchetta, R.

    2009-06-01

    Three CMOS active pixel sensors have been investigated for their application to Nuclear Medicine imaging. Startracker with 525×525 25 μm square pixels has been coupled via a fibre optic stud to a 2 mm thick segmented CsI(Tl) crystal. Imaging tests were performed using 99mTc sources, which emit 140 keV gamma rays. The system was interfaced to a PC via FPGA-based DAQ and optical link enabling imaging rates of 10 f/s. System noise was measured to be >100e and it was shown that the majority of this noise was fixed pattern in nature. The intrinsic spatial resolution was measured to be ˜80 μm and the system spatial resolution measured with a slit was ˜450 μm. The second sensor, On Pixel Intelligent CMOS (OPIC), had 64×72 40 μm pixels and was used to evaluate noise characteristics and to develop a method of differentiation between fixed pattern and statistical noise. The third sensor, Vanilla, had 520×520 25 μm pixels and a measured system noise of ˜25e. This sensor was coupled directly to the segmented phosphor. Imaging results show that even at this lower level of noise the signal from 140 keV gamma rays is small as the light from the phosphor is spread over a large number of pixels. Suggestions for the 'ideal' sensor are made.

  15. In vitro antimicrobial activity of five essential oils on multidrug resistant Gram-negative clinical isolates

    PubMed Central

    Sakkas, Hercules; Gousia, Panagiota; Economou, Vangelis; Sakkas, Vassilios; Petsios, Stefanos; Papadopoulou, Chrissanthy

    2016-01-01

    Aim/Background: The emergence of drug-resistant pathogens has drawn attention on medicinal plants for potential antimicrobial properties. The objective of the present study was the investigation of the antimicrobial activity of five plant essential oils on multidrug resistant Gram-negative bacteria. Materials and Methods: Basil, chamomile blue, origanum, thyme, and tea tree oil were tested against clinical isolates of Acinetobacter baumannii (n = 6), Escherichia coli (n = 4), Klebsiella pneumoniae (n = 7), and Pseudomonas aeruginosa (n = 5) using the broth macrodilution method. Results: The tested essential oils produced variable antibacterial effect, while Chamomile blue oil demonstrated no antibacterial activity. Origanum, Thyme, and Basil oils were ineffective on P. aeruginosa isolates. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration values ranged from 0.12% to 1.50% (v/v) for tea tree oil, 0.25-4% (v/v) for origanum and thyme oil, 0.50% to >4% for basil oil and >4% for chamomile blue oil. Compared to literature data on reference strains, the reported MIC values were different by 2SD, denoting less successful antimicrobial activity against multidrug resistant isolates. Conclusions: The antimicrobial activities of the essential oils are influenced by the strain origin (wild, reference, drug sensitive, or resistant) and it should be taken into consideration whenever investigating the plants’ potential for developing new antimicrobials. PMID:27366345

  16. Clinical value of fecal calprotectin in determining disease activity of ulcerative colitis

    PubMed Central

    Xiang, Jun-Ying; Ouyang, Qin; Li, Guo-Dong; Xiao, Nan-Ping

    2008-01-01

    AIM: To investigate possibility and clinical application of fecal calprotectin in determining disease activity of ulcerative colitis (UC). METHODS: The enzyme-linked immunosorbent assay (ELISA) was used to measure the concentrations of calprotectin in feces obtained from 66 patients with UC and 20 controls. C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), acid glycoprotein (AGP) were also measured and were compared with calprotectin in determining disease activity of UC. The disease activity of UC was also determined by the Sutherland criteria. RESULTS: The fecal calprotectin concentration in the patients with active UC was significantly higher than that in the inactive UC and in the controls (402.16 ± 48.0 μg/g vs 35.93 ± 3.39 μg/g, 11.5 ± 3.42 μg/g, P < 0.01). The fecal calprotectin concentration in the inactive UC group was significantly higher than that in the control group (P < 0.05). A significant difference was also found in the patients with active UC of mild, moderate and severe degrees. The area under the curve of the receiver operating characteristics (AUCROC) was 0.975, 0.740, 0.692 and 0.737 for fecal calprotectin, CRP, ESR and AGP, respectively. There was a strong correlation between the fecal calprotectin concentration and the endoscopic gradings for UC (r = 0.866, P < 0.001). CONCLUSION: Calprotectin in the patient’s feces can reflect the disease activity of UC and can be used as a rational fecal marker for intestinal inflammation in clinical practice. This kind of marker is relatively precise, simple and noninvasive when compared with other commonly-used markers such as CRP, ESR and AGP. PMID:18176961

  17. Developing Clinical Competency in Crisis Event Management: An Integrated Simulation Problem-Based Learning Activity

    ERIC Educational Resources Information Center

    Liaw, S. Y.; Chen, F. G.; Klainin, P.; Brammer, J.; O'Brien, A.; Samarasekera, D. D.

    2010-01-01

    This study aimed to evaluate the integration of a simulation based learning activity on nursing students' clinical crisis management performance in a problem-based learning (PBL) curriculum. It was hypothesized that the clinical performance of first year nursing students who participated in a simulated learning activity during the PBL session…

  18. Peering into the Pharmaceutical “Pipeline”: Investigational Drugs, Clinical Trials, and Industry Priorities

    PubMed Central

    Cottingham, Marci D.; Kalbaugh, Corey A.

    2014-01-01

    In spite of a growing literature on pharmaceuticalization, little is known about the pharmaceutical industry’s investments in research and development (R&D). Information about the drugs being developed can provide important context for existing case studies detailing the expanding – and often problematic – role of pharmaceuticals in society. To access the pharmaceutical industry’s pipeline, we constructed a database of drugs for which pharmaceutical companies reported initiating clinical trials over a five-year period (July 2006-June 2011), capturing 2,477 different drugs in 4,182 clinical trials. Comparing drugs in the pipeline that target diseases in high-income and low-income countries, we found that the number of drugs for diseases prevalent in high-income countries was 3.46 times higher than drugs for diseases prevalent in low-income countries. We also found that the plurality of drugs in the pipeline were being developed to treat cancers (26.2%). Interpreting our findings through the lens of pharmaceuticalization, we illustrate how investigating the entire drug development pipeline provides important information about patterns of pharmaceuticalization that are invisible when only marketed drugs are considered. PMID:25159693

  19. Connecting clinical and experimental investigations of awareness in traumatic brain injury.

    PubMed

    Dockree, Paul M; O'Connell, Redmond G; Robertson, Ian H

    2015-01-01

    Questionnaire-based demonstrations of impaired self-awareness (SA) after traumatic brain injury (TBI) are not always supported by experimental studies of in-the-moment or online awareness. This chapter begins by describing the clinical phenomenon of impaired SA, how it is measured, and why its interdependency with mechanisms of online awareness may provide the scaffolding from which appraisals of cognitive functioning can be accurately revised following a brain injury. We review research that has measured unawareness of errors in routine action in TBI patients and propose more rigorous methodological approaches to studying the emergent properties of awareness with greater clarity in the laboratory. We discuss how neuropsychological and electrophysiologic studies are beginning to inform our understanding of impaired error processing in TBI patients and we highlight recent theory proposing that online metacognitive processes accumulate evidence of erroneous responses in a graded fashion. Neural signals with amplitudes that scale with the strength of accruing evidence and peak latencies that mark the threshold at which awareness emerges represent important neural mechanisms to examine the breakdown of error awareness after brain injury. We also discuss how errors can be investigated in relation to different sources of evidence that contribute to aware experiences after brain injury. Finally, we explore conditions beyond error signaling, and how different "objects of insight" that require retrospective and prospective judgments of confidence need to be examined in relation to the clinical phenomenon of impaired SA. PMID:25701904

  20. BASF studies: epidemiological and clinical investigations on dioxin-exposed chemical workers.

    PubMed

    Zober, A; Messerer, P; Ott, M G

    First in 1953 and again later in 1988, BASF Aktiengesellschaft, Ludwigshafen, Germany, faced production-related dioxin contamination problems. In both situations, the immediate actions were efforts to limit the potential for employee exposure. In 1953, after a reactor accident, the production of trichlorophenol was stopped and extensive clean-up and demolition work was undertaken. In 1988, major technical improvements were made to an extrusion blending process and the flame retardants were changed to substances that chemically should not be dioxin precursors. The health experience of the potentially exposed populations has been followed extensively in both situations. Five recent epidemiological investigations: a long-term mortality follow-up, a morbidity study, a clinical laboratory study, and a chromosome study of persons from the 1953 accident cohort, as well as immunological studies of employees assigned to the extrusion operations, are discussed. In addition, considerable dioxin biomonitoring data from blood lipids for both populations are summarized. PMID:9508734

  1. An Investigation of Factors Influencing Nurses' Clinical Decision-Making Skills.

    PubMed

    Wu, Min; Yang, Jinqiu; Liu, Lingying; Ye, Benlan

    2016-08-01

    This study aims to investigate the influencing factors on nurses' clinical decision-making (CDM) skills. A cross-sectional nonexperimental research design was conducted in the medical, surgical, and emergency departments of two university hospitals, between May and June 2014. We used a quantile regression method to identify the influencing factors across different quantiles of the CDM skills distribution and compared the results with the corresponding ordinary least squares (OLS) estimates. Our findings revealed that nurses were best at the skills of managing oneself. Educational level, experience, and the total structural empowerment had significant positive impacts on nurses' CDM skills, while the nurse-patient relationship, patient care and interaction, formal empowerment, and information empowerment were negatively correlated with nurses' CDM skills. These variables explained no more than 30% of the variance in nurses' CDM skills and mainly explained the lower quantiles of nurses' CDM skills distribution. PMID:26906246

  2. Progress in defining clinically meaningful changes for clinical trials in nonrenal manifestations of SLE disease activity.

    PubMed

    Choi, Chan-Bum; Liang, Matthew H; Bae, Sang-Cheol

    2016-01-01

    Since the 2002 Dusseldorf meeting, one new agent, Benlysta, has been approved by the US Food and Drug Administration for systemic lupus erythematosus. Experiences from the field in conducting trials of all the agents tested during this period have provided valuable practical insights. There has been incremental progress in defining the minimal clinically important difference (MCID) of key disease manifestations and the view is largely that of the health care providers and not that of the person suffering the disease. This basic methodological work on the MCID should improve the efficiency and the clinical relevance of future trials and their design. PMID:26732314

  3. Similar barriers and facilitators to physical activity across different clinical groups experiencing lower limb spasticity.

    PubMed

    Hundza, Sandra; Quartly, Caroline; Kim, Jasmine M; Dunnett, James; Dobrinsky, Jill; Loots, Iris; Choy, Kim; Chow, Brayley; Hampshire, Alexis; Temple, Viviene A

    2016-07-01

    Purpose Given the importance of physical activity in maintaining health and wellness, an improved understanding of physical activity patterns across different clinical populations is required. This study examines the facilitators for, and barriers to, participation in physical activity across multiple contexts for three clinical groups with chronic lower limb spasticity (individuals with stroke, multiple sclerosis and incomplete spinal cord injury). Method This cross-sectional study employed quantitative measures for spasticity, ankle range of motion, pain, falls, cognition, mobility, and physical activity as well as qualitative semi-structured interviews. Results There were similar impairments in body functions and structures and limitations in activities across the clinical groups. These impairments and limitations negatively impacted participation in physical activity, which was low. Environmental and personal factors exacerbated or mitigated the limiting effects of body functions and structures and activities on physical activity in many areas of life. Conclusions In this population, participation in physical activity includes activities such as housework which are different than what is typically considered as physical activity. Further, the presence of similar barriers and facilitators across the groups suggests that support and services to promote valued forms of physical activity could be organised and delivered based on limitations in mobility and functioning rather than clinical diagnosis. Implications for rehabilitation Physical activity is of utmost importance in maintaining health and wellness in clinical populations. This research highlights the desired and actual physical activity for these populations can look different than what may traditionally be considered as physical activity (e.g. housework is not typically considered participation physical activity). Therefore, rehabilitation interventions need to be directly designed to enhance clients

  4. ROSAT investigation of flaring and activity on Prox Cen

    NASA Technical Reports Server (NTRS)

    Haisch, Bernhard

    1993-01-01

    The objective of this program was to investigate with high sensitivity the low-level flare activity which may underlie coronal heating. This was done. The ROSAT observations of Prox Cen were scheduled for 50 ks spread out from 26 Feb. - 10 Mar. 1992. Unfortunately because of spacecraft problems many of these pointings turned out to contain no useful data or extremely truncated valid data sets. Considerable time was spent trying to determine which of the data would be scientifically useful and which would not. Fortunately, several developments took place to augment the original data in such a way that the scientific goal of advancing the study of flaring and variability was able to be achieved after all. These are as follows: (1) a second round of ROSAT observations was carried out in Feb. 1993 which only came to the attention of the PI in Apr. 1993 when a new data tape arrived; (2) simultaneous IUE observations were requested and obtained; (3) data from the UK WFC are available via the collaboration with Dr. G. Bromage; and (4) the 'cleaned-up' original data set was found to include one major flare and 2 moderate flares. Because of the problems with the original data set, the unexpected acquisition of new data only two months ago, and the availability of IUE and WFC data, an article on Prox Cen for publication is not ready at this time. Such an article is being developed and can be completed as part of ongoing ROSAT research efforts on stellar coronae and flaring.

  5. 21 CFR 50.52 - Clinical investigations involving greater than minimal risk but presenting the prospect of direct...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... subjects. Any clinical investigation within the scope described in §§ 50.1 and 56.101 of this chapter in which more than minimal risk to children is presented by an intervention or procedure that holds out...

  6. Hydrodynamics and rheology of active liquid crystals: a numerical investigation.

    PubMed

    Marenduzzo, D; Orlandini, E; Yeomans, J M

    2007-03-16

    We report numerical studies of the hydrodynamics and rheology of an active liquid crystal. We confirm the existence of a transition between a passive and an active phase, with spontaneous flow in steady state. We explore how the velocity profile changes with activity, and we point out the difference in behavior for flow-aligning and tumbling materials. We find that an active material can thicken or thin under a flow, or even exhibit both behaviors as the forcing changes. PMID:17501095

  7. Clinically Available Medicines Demonstrating Anti-Toxoplasma Activity

    PubMed Central

    Neville, Andrew J.; Zach, Sydney J.; Wang, Xiaofang; Larson, Joshua J.; Judge, Abigail K.; Davis, Lisa A.; Vennerstrom, Jonathan L.

    2015-01-01

    Toxoplasma gondii is an apicomplexan parasite of humans and other mammals, including livestock and companion animals. While chemotherapeutic regimens, including pyrimethamine and sulfadiazine regimens, ameliorate acute or recrudescent disease such as toxoplasmic encephalitis or ocular toxoplasmosis, these drugs are often toxic to the host. Moreover, no approved options are available to treat infected women who are pregnant. Lastly, no drug regimen has shown the ability to eradicate the chronic stage of infection, which is characterized by chemoresistant intracellular cysts that persist for the life of the host. In an effort to promote additional chemotherapeutic options, we now evaluate clinically available drugs that have shown efficacy in disease models but which lack clinical case reports. Ideally, less-toxic treatments for the acute disease can be identified and developed, with an additional goal of cyst clearance from human and animal hosts. PMID:26392504

  8. Clinically Available Medicines Demonstrating Anti-Toxoplasma Activity.

    PubMed

    Neville, Andrew J; Zach, Sydney J; Wang, Xiaofang; Larson, Joshua J; Judge, Abigail K; Davis, Lisa A; Vennerstrom, Jonathan L; Davis, Paul H

    2015-12-01

    Toxoplasma gondii is an apicomplexan parasite of humans and other mammals, including livestock and companion animals. While chemotherapeutic regimens, including pyrimethamine and sulfadiazine regimens, ameliorate acute or recrudescent disease such as toxoplasmic encephalitis or ocular toxoplasmosis, these drugs are often toxic to the host. Moreover, no approved options are available to treat infected women who are pregnant. Lastly, no drug regimen has shown the ability to eradicate the chronic stage of infection, which is characterized by chemoresistant intracellular cysts that persist for the life of the host. In an effort to promote additional chemotherapeutic options, we now evaluate clinically available drugs that have shown efficacy in disease models but which lack clinical case reports. Ideally, less-toxic treatments for the acute disease can be identified and developed, with an additional goal of cyst clearance from human and animal hosts. PMID:26392504

  9. In vitro activity of terbinafine against clinical isolates of dermatophytes.

    PubMed

    Arzeni, D; Barchiesi, F; Compagnucci, P; Cellini, A; Simonetti, O; Offidani, A M; Scalise, G

    1998-08-01

    A broth macrodilution method following the recommendations established by the National Committee for Clinical Laboratory Standards was employed for testing terbinafine against 20 clinical isolates of dermatophytes belonging to seven species. The minimal inhibitory concentrations resulting in either 80% or 100% inhibition of growth, compared to growth in drug-free control tubes, ranged from

  10. Clinical and Pathological Findings in Green Turtles (Chelonia mydas) from Gladstone, Queensland: Investigations of a Stranding Epidemic.

    PubMed

    Flint, Mark; Eden, Paul A; Limpus, Colin J; Owen, Helen; Gaus, Caroline; Mills, Paul C

    2015-06-01

    An investigation into the health of green turtles was undertaken near Gladstone, Queensland, in response to a dramatic increase in stranding numbers in the first half of 2011. A total of 56 live turtles were subject to clinical examination and blood sampling for routine blood profiles, and 12 deceased turtles underwent a thorough necropsy examination. This population of green turtles was found to be in poor body condition and a range of infectious and non-infectious conditions were identified in the unhealthy turtles, including hepato-renal insufficiency (up to 81%, 27/33 based on clinical pathology), cachexia (92%, 11/12), parasitism (75%, 9/12), cardiopulmonary anomalies (42%, 5/12), gastroenteritis (25%, 3/12), masses (25%, 3/12) and mechanical impediments (17%, 2/12 based on necropsy). Overall, there was no evidence to indicate a unifying disease as a primary cause of the mass mortality. Recent adverse weather events, historic regional contamination and nearby industrial activities are discussed as potential causative factors. PMID:25256011

  11. Investigation of a portable performance measurement system for neurologic screening in clinics.

    PubMed

    Kondraske, George V; Mulukutla, Rahul; Stewart, R Malcolm

    2006-01-01

    Motivated by the need for clinical screening for early detection of neurologic disease, a prototype portable instrument dubbed the human performance multimeter (HPMM) was developed. The HPMM is based on a set of lab-based performance capacity tests developed and evaluated over the last two decades. We attempted to integrate selected functionality of a set of modular lab-based instruments into a single, small package. In the present study, a 4th generation prototype was developed and evaluated for usability, measurement repeatability, and preliminary measurement validity. Five performance capacity tests (upper extremity coordination, isometric grip strength, simple response speed, rapid alternating movement, and steadiness/tremor) were administered to twenty healthy adult volunteers. Short-term reliability was investigated using a test-retest protocol. Most measures were found to possess good test-retest reliability (r>0.75). Preliminary validity was investigated by comparing results to those obtained with non-portable devices that served as models for the HPMM. Results were in good agreement with those instruments. It is concluded that measures of good fidelity can be obtained with this type of instrument. PMID:17946212

  12. In-vitro activity of cationic peptides alone and in combination with clinically used antimicrobial agents against Pseudomonas aeruginosa.

    PubMed

    Giacometti, A; Cirioni, O; Barchiesi, F; Fortuna, M; Scalise, G

    1999-11-01

    The in-vitro activity of cecropin P1, indolicidin, magainin II, nisin and ranalexin alone and in combination with nine clinically used antimicrobial agents was investigated against a control strain, Pseudomonas aeruginosa ATCC 27853 and 40 clinical isolates of P. aeruginosa. Antimicrobial activities were measured by MIC, MBC and viable count. In the combination study, the clinically used antibiotics were used at concentrations close to their mean serum level in humans in order to establish the clinical relevance of the results. To select peptide-resistant mutants, P. aeruginosa ATCC 27853 was treated with consecutive cycles of exposure to each peptide at 1 x MIC. The peptides had a varied range of inhibitory values: all isolates were more susceptible to cecropin P1, while ranalexin showed the lowest activity. Nevertheless, synergy was observed when the peptides were combined with polymyxin E and clarithromycin. Consecutive exposures to each peptide at 1 x MIC resulted in the selection of stable resistant mutants. Cationic peptides might be valuable as new antimicrobial agents. Our findings show that they are effective against P. aeruginosa, and that their activity is enhanced when they are combined with clinically used antimicrobial agents, particularly with polymyxin E and clarithromycin. PMID:10552980

  13. The delayed sleep phase syndrome: clinical and investigative findings in 14 subjects.

    PubMed

    Alvarez, B; Dahlitz, M J; Vignau, J; Parkes, J D

    1992-08-01

    Fourteen subjects are described in whom a clinical diagnosis of the delayed sleep phase syndrome was made. The condition is multi-factorial, dependent on lifestyle, mood and personality, as well as on familial factors but no single factor in isolation is sufficient to explain the delay in sleep timing. Refusal to attend school may be important in some instances but will not explain cases with delayed age of onset. In half the subjects the delay in sleep phase started in childhood or adolescence. The syndrome causes severe disruption to education, work and family life. Polysomnography, motor activity monitoring of rest-activity cycles, plasma melatonin profiles and urinary melatonin metabolite excretion are normal. Different patterns of sleep phase delay seen in the syndrome include stable, progressive, irregular and non-24 hour sleep-wake cycles. These patterns may result from different social and other Zeitgebers ("time-markers", for example sunrise, sunset) in the normal environment. Treatment by forced sleep-wake phase advance or with melatonin resulted in a partial sleep-phase advance but this was not maintained on stopping treatment. PMID:1527536

  14. Association between activities related to routes of infection and clinical manifestations of melioidosis.

    PubMed

    Lim, C; Peacock, S J; Limmathurotsakul, D

    2016-01-01

    We sought associations between route of infection by Burkholderia pseudomallei and clinical manifestations in 330 cases of melioidosis in northeast Thailand using bivariate multivariable logistic regression models. Activities related to skin inoculation were negatively associated with bacteraemia, activities related to ingestion were associated with bacteraemia, and activities related to inhalation were associated with pneumonia. Our study suggests that route of infection is one of the factors related to clinical manifestations of melioidosis. PMID:26417852

  15. Association between activities related to routes of infection and clinical manifestations of melioidosis

    PubMed Central

    Lim, C.; Peacock, S.J.; Limmathurotsakul, D.

    2016-01-01

    We sought associations between route of infection by Burkholderia pseudomallei and clinical manifestations in 330 cases of melioidosis in northeast Thailand using bivariate multivariable logistic regression models. Activities related to skin inoculation were negatively associated with bacteraemia, activities related to ingestion were associated with bacteraemia, and activities related to inhalation were associated with pneumonia. Our study suggests that route of infection is one of the factors related to clinical manifestations of melioidosis. PMID:26417852

  16. VSL#3 induces and maintains short-term clinical response in patients with active microscopic colitis: a two-phase randomised clinical trial

    PubMed Central

    Rohatgi, Sarika; Ahuja, Vineet; Makharia, Govind K; Rai, Tarun; Das, Prasenjit; Dattagupta, Siddharth; Mishra, Veena; Garg, Sushil Kumar

    2015-01-01

    Background The probiotic mixture VSL#3 has proven efficacious in inflammatory bowel diseases and irritable bowel syndrome; however, its efficacy in microscopic colitis (MC) is being investigated. Objective To evaluate the safety and efficacy of a multistrain probiotic, VSL#3, in inducing clinical remission and achieving clinical response, as compared with mesalamine, in patients with active MC. Methods A randomised, open labelled study comparing the efficacy of 900 billion colony-forming units/day of VSL#3 (group (Gp) A) or 1.6 g of mesalamine/day (Gp B) for 8 weeks in 30 patients with MC was conducted. After a washout period of 2 weeks, Gp B received 8 weeks of VSL#3 and Gp A was off medication for the next 8 weeks. The primary end points were clinical remission and clinical response at 8 weeks. Results Of 30 patients, 15 were randomised in each arm. 11 patients in Gp A and 13 patients in Gp B completed 8 weeks of treatment. 5 (46%) of 11 patients in Gp A and 1 (8%) of 13 patients in Gp B attained clinical remission (p=0.022). Clinical response was seen in Gp A, as evidenced by a lower stool weight (377.6±104.5 g) as compared with Gp B (507±168.2 g; p=0.03). VSL#3 was effective in maintaining clinical response up to 10 weeks, even after discontinuation of therapy. Secondary end points like stool parameters, histology and well-being improved in both treatment groups. Conclusions The probiotic VSL#3 was found to offer the benefit of inducing as well as maintaining short-term clinical response in patients with active MC. Trial registration number The clinical trial is registered with CLINICAL TRIAL REGISTRY INDIA; http://ctri.nic.in, CTRI No. “CTRI/2008/091/000086” (registered on: 23/06/2008). PMID:26462271

  17. [The 12th amendment to the German Drug Law. Chances and obstacles for investigator-initiated clinical trials].

    PubMed

    Dreier, G; Marx, C; Schmoor, C; Maier-Lenz, H

    2005-04-01

    The European Union's so called Clinical Trials Directive 2001/20/EC was implemented in national law in Germany in August 2004, leading to the 12th amendment of the German Drug Law (Arzneimittelgesetz). The directive is intended to harmonize the clinical trial's regulatory environment across the European Union and to improve protection of human subjects. It lays down the principles and guidelines of Good Clinical Practice (GCP). As the regulation applies to all clinical trials on medicinal products for human use, and as only non-interventional studies are excluded, academic, investigator-initiated clinical trials will also have to comply with the EU clinical trials directive implemented in the German Drug Law. In an investigator-initiated trial in which the investigator takes the responsibility of a sponsor, the investigator-sponsor must take total legal and financial responsibility for the clinical trial. Since publicly funded clinical trials make a large contribution to improved care, concern has been expressed that non-commercial research projects will be reduced and the vital medical research conducted at academic institutions curtailed. Nonetheless GCP ensures a valid study design, qualified data management, analysis and monitoring of the trial and thereby promotes more valid data and protection of study participants. The trials are more likely to lead to reliable results leading to new therapies, strategies or a better understanding of diseases. What is needed, therefore, is an increase in public funding and the establishment of clinical trial units/organizations associated with the universities or hospitals where independent researchers have the possibility to obtain theoretical advice and practical help, professional training and support. In the end, the directive may serve as a stimulus to build a better national research environment and to promote public funding, and may lead to fewer but more valid clinical trials. PMID:15830256

  18. Microenvironmental influence on pre-clinical activity of polo-like kinase inhibition in multiple myeloma: implications for clinical translation.

    PubMed

    McMillin, Douglas W; Delmore, Jake; Negri, Joseph; Ooi, Melissa; Klippel, Steffen; Miduturu, Chandrasekhar V; Gray, Nathanael S; Richardson, Paul G; Anderson, Kenneth C; Kung, Andrew L; Mitsiades, Constantine S

    2011-01-01

    Polo-like kinases (PLKs) play an important role in cell cycle progression, checkpoint control and mitosis. The high mitotic index and chromosomal instability of advanced cancers suggest that PLK inhibitors may be an attractive therapeutic option for presently incurable advanced neoplasias with systemic involvement, such as multiple myeloma (MM). We studied the PLK 1, 2, 3 inhibitor BI 2536 and observed potent (IC50<40 nM) and rapid (commitment to cell death <24 hrs) in vitro activity against MM cells in isolation, as well as in vivo activity against a traditional subcutaneous xenograft mouse model. Tumor cells in MM patients, however, don't exist in isolation, but reside in and interact with the bone microenvironment. Therefore conventional in vitro and in vivo preclinical assays don't take into account how interactions between MM cells and the bone microenvironment can potentially confer drug resistance. To probe this question, we performed tumor cell compartment-specific bioluminescence imaging assays to compare the preclinical anti-MM activity of BI 2536 in vitro in the presence vs. absence of stromal cells or osteoclasts. We observed that the presence of these bone marrow non-malignant cells led to decreased anti-MM activity of BI 2536. We further validated these results in an orthotopic in vivo mouse model of diffuse MM bone lesions where tumor cells interact with non-malignant cells of the bone microenvironment. We again observed that BI 2536 had decreased activity in this in vivo model of tumor-bone microenvironment interactions highlighting that, despite BI 2536's promising activity in conventional assays, its lack of activity in microenvironmental models raises concerns for its clinical development for MM. More broadly, preclinical drug testing in the absence of relevant tumor microenvironment interactions may overestimate potential clinical activity, thus explaining at least in part the gap between preclinical vs. clinical efficacy in MM and other cancers

  19. Preclinical and clinical investigations of mood stabilizers for Huntington's disease: what have we learned?

    PubMed

    Scheuing, Lisa; Chiu, Chi-Tso; Liao, Hsiao-Mei; Linares, Gabriel R; Chuang, De-Maw

    2014-01-01

    Huntington's disease (HD) is a lethal, autosomal dominant neurodegenerative disorder caused by CAG repeat expansions at exon 1 of the huntingtin (Htt) gene, which encodes for a mutant huntingtin protein (mHtt). Prominent symptoms of HD include motor dysfunction, characterized by chorea; psychiatric disturbances such as mood and personality changes; and cognitive decline that may lead to dementia. Pathologically multiple complex processes and pathways are involved in the development of HD, including selective loss of neurons in the striatum and cortex, dysregulation of cellular autophagy, mitochondrial dysfunction, decreased neurotrophic and growth factor levels, and aberrant regulation of gene expression and epigenetic patterns. No cure for HD presently exists, nor are there drugs that can halt the progression of this devastating disease. Therefore, the need to discover neuroprotective modalities to combat HD is critical. In basic and preclinical studies using cellular and animal HD models, the mood stabilizers lithium and valproic acid (VPA) have shown multiple beneficial effects, including behavioral and motor improvement, enhanced neuroprotection, and lifespan extension. Recent studies in transgenic HD mice support the notion that combined lithium/VPA treatment is more effective than treatment with either drug alone. In humans, several clinical studies of HD patients found that lithium treatment improved mood, and that VPA treatment both stabilized mood and moderately reduced chorea. In contrast, other studies observed that the hallmark features of HD were unaffected by treatment with either lithium or VPA. The current review discusses preclinical and clinical investigations of the beneficial effects of lithium and VPA on HD pathophysiology. PMID:25285035

  20. Preclinical and Clinical Investigations of Mood Stabilizers for Huntington's Disease: What Have We Learned?

    PubMed Central

    Scheuing, Lisa; Chiu, Chi-Tso; Liao, Hsiao-Mei; Linares, Gabriel R.; Chuang, De-Maw

    2014-01-01

    Huntington's disease (HD) is a lethal, autosomal dominant neurodegenerative disorder caused by CAG repeat expansions at exon 1 of the huntingtin (Htt) gene, which encodes for a mutant huntingtin protein (mHtt). Prominent symptoms of HD include motor dysfunction, characterized by chorea; psychiatric disturbances such as mood and personality changes; and cognitive decline that may lead to dementia. Pathologically multiple complex processes and pathways are involved in the development of HD, including selective loss of neurons in the striatum and cortex, dysregulation of cellular autophagy, mitochondrial dysfunction, decreased neurotrophic and growth factor levels, and aberrant regulation of gene expression and epigenetic patterns. No cure for HD presently exists, nor are there drugs that can halt the progression of this devastating disease. Therefore, the need to discover neuroprotective modalities to combat HD is critical. In basic and preclinical studies using cellular and animal HD models, the mood stabilizers lithium and valproic acid (VPA) have shown multiple beneficial effects, including behavioral and motor improvement, enhanced neuroprotection, and lifespan extension. Recent studies in transgenic HD mice support the notion that combined lithium/VPA treatment is more effective than treatment with either drug alone. In humans, several clinical studies of HD patients found that lithium treatment improved mood, and that VPA treatment both stabilized mood and moderately reduced chorea. In contrast, other studies observed that the hallmark features of HD were unaffected by treatment with either lithium or VPA. The current review discusses preclinical and clinical investigations of the beneficial effects of lithium and VPA on HD pathophysiology. PMID:25285035

  1. Investigation of the clinical potential of scattering foil free electron beams

    NASA Astrophysics Data System (ADS)

    Eldib, Ahmed; Jin, Lihui; Li, Jinsheng; Ma, C.-M. Charlie

    2014-02-01

    Electron beam therapy has been an important radiation therapy modality for many decades. Studies have been conducted recently for more efficient and advanced delivery of electron beam radiation therapy. X-ray contamination is a common problem that exists with all of the advanced electron beam therapy techniques such as Bolus Electron conformal therapy, segmented electron conformal therapy, and modulated electron arc therapy. X-ray contamination could add some limitations to the advancement and clinical utility of those electron modalities. It was previously shown in the literature that the scattering foil is one of the major accelerator parts contributing to the generation of bremsstrahlung photons. Thus, in this work we investigate the dosimetric characteristics of scattering foil free (SFF) electron beams and the feasibility of using those beams for breast cancer boosts. The SFF electron beams were modeled and simulated using the Monte Carlo method. CT scans of six previously treated breast patients were used for the treatment plan generation utilizing our in-house Monte Carlo-based treatment planning system. Electron boost plans with conventional beams and the SFF beams were generated, respectively, for all patients. A significant reduction of the photon component was observed with the removal of the primary scattering foil for beam energies higher than 12 MeV. Flatness was greatly affected but the difference in flatness between conventional and SFF beams was much reduced for small cone sizes, which were often used clinically for breast boosts. It was found that the SFF electron beams could deliver high-quality dose distributions as conventional electron beams for boost treatments of the breast with an added advantage of a further reduced dose to the lung and the heart.

  2. Childhood pyogenic meningitis: clinical and investigative indicators of etiology and outcome.

    PubMed

    Johnson, Abdul-Wahab B R; Adedoyin, Olanrewaju T; Abdul-Karim, Aishat A; Olanrewaju, Abdul-Waheed I

    2007-08-01

    The relevant parameters of 71 consecutive pediatric admissions for pyogenic meningitis at the University of Ilorin Teaching Hospital, Ilorin, Nigeria, were analyzed to identify possible clinical and nonmicrobiologic investigative clues of disease etiology and mortality. Cerebrospinal fluid (CSF) was Gram-smear positive (GSP) in 41 (57.6%) of the 71 cases. Twenty-three (56.1%) had Gram-positive cocci (GPC), 14 (34.2%) Gram-negative bacilli (GNB) and three (7.3%) Gram-negative diplococci (GND). The respective mean ages of GPC, GNB and GND cases were 4.49 +/- 5.3, 3.06 +/- 4.8 and 4.47 +/-4.9 years. Streptococcus pneumoniae accounted for 22 (78.6%) of the 28 CSF isolates (p=0.00), Haemophilus influenzae for two (7.1%) cases and Neisseria meningitides in one (3.5%). Anemia was significantly more common among GSP cases (p=0.04), as was convulsion among those with GNB-positive smears (p=0.03) and a bulging fontanelle in the Gram-smear-negative category. Otherwise, the prevalence and resolution times of the other clinical parameters were comparable across the etiological categories. There were 30 deaths (42.3%) among which GNB-positive cases had significantly shorter stay (p=0.045). Mortality was significantly higher in those with an abnormal respiratory rhythm at admission (p=0.04), purulent/turbid CSF (p=0.03), CSF protein of >150 mg/dl (p=0.02) and glucose <1 mg/dl (p=0.047). Our findings highlight the inherent limitations of predicting the etiology of pediatric meningitides from the clinical parameters as well as the poor prognostic import of respiratory dysrhythmia and a profoundly deranged CSF protein and glucose. The etiological burden of GPC/S. pneumoniae in childhood meningitides in sub-Saharan Africa, the propensity of GNB/H. influenzae for quick fatality and the need for the relevant preventive vaccines are expounded in the discussion. PMID:17722674

  3. Childhood pyogenic meningitis: clinical and investigative indicators of etiology and outcome.

    PubMed Central

    Johnson, Abdul-Wahab B. R.; Adedoyin, Olanrewaju T.; Abdul-Karim, Aishat A.; Olanrewaju, Abdul-Waheed I.

    2007-01-01

    The relevant parameters of 71 consecutive pediatric admissions for pyogenic meningitis at the University of Ilorin Teaching Hospital, Ilorin, Nigeria, were analyzed to identify possible clinical and nonmicrobiologic investigative clues of disease etiology and mortality. Cerebrospinal fluid (CSF) was Gram-smear positive (GSP) in 41 (57.6%) of the 71 cases. Twenty-three (56.1%) had Gram-positive cocci (GPC), 14 (34.2%) Gram-negative bacilli (GNB) and three (7.3%) Gram-negative diplococci (GND). The respective mean ages of GPC, GNB and GND cases were 4.49 +/- 5.3, 3.06 +/- 4.8 and 4.47 +/-4.9 years. Streptococcus pneumoniae accounted for 22 (78.6%) of the 28 CSF isolates (p=0.00), Haemophilus influenzae for two (7.1%) cases and Neisseria meningitides in one (3.5%). Anemia was significantly more common among GSP cases (p=0.04), as was convulsion among those with GNB-positive smears (p=0.03) and a bulging fontanelle in the Gram-smear-negative category. Otherwise, the prevalence and resolution times of the other clinical parameters were comparable across the etiological categories. There were 30 deaths (42.3%) among which GNB-positive cases had significantly shorter stay (p=0.045). Mortality was significantly higher in those with an abnormal respiratory rhythm at admission (p=0.04), purulent/turbid CSF (p=0.03), CSF protein of >150 mg/dl (p=0.02) and glucose <1 mg/dl (p=0.047). Our findings highlight the inherent limitations of predicting the etiology of pediatric meningitides from the clinical parameters as well as the poor prognostic import of respiratory dysrhythmia and a profoundly deranged CSF protein and glucose. The etiological burden of GPC/S. pneumoniae in childhood meningitides in sub-Saharan Africa, the propensity of GNB/H. influenzae for quick fatality and the need for the relevant preventive vaccines are expounded in the discussion. PMID:17722674

  4. Altered relationships between age and functional brain activation in adolescents at clinical high risk for psychosis.

    PubMed

    Karlsgodt, Katherine H; van Erp, Theo G M; Bearden, Carrie E; Cannon, Tyrone D

    2014-01-30

    Schizophrenia is considered a neurodevelopmental disorder, but whether the adolescent period, proximal to onset, is associated with aberrant development in individuals at clinical high risk (CHR) for psychosis is incompletely understood. While abnormal gray and white matter development has been observed, alterations in functional neuroimaging (fMRI) parameters during adolescence as related to conversion to psychosis have not yet been investigated. Twenty CHR individuals and 19 typically developing controls (TDC), (ages 14-21), were recruited from the Center for Assessment and Prevention of Prodromal States (CAPPS) at UCLA. Participants performed a Sternberg-style verbal working memory (WMem) task during fMRI and data were analyzed using a cross-sectional design to test the hypothesis that there is a deviant developmental trajectory in WMem associated neural circuitry in those at risk for psychosis. Eight of the CHR adolescents converted to psychosis within 2 years of initial assessment. A voxel-wise regression examining the relationship between age and activation revealed a significant group-by-age interaction. TDC showed a negative association between age and functional activation in the WMem circuitry while CHR adolescents showed a positive association. Moreover, CHR patients who later converted to overt psychosis showed a distinct pattern of abnormal age-associated activation in the frontal cortex relative to controls, while non-converters showed a more diffuse posterior pattern. Finding that age related variation in baseline patterns of neural activity differentiate individuals who subsequently convert to psychosis from healthy subjects suggests that these differences are likely to be clinically relevant. PMID:24144510

  5. Therapeutic Role of Rifaximin in Inflammatory Bowel Disease: Clinical Implication of Human Pregnane X Receptor Activation

    PubMed Central

    Cheng, Jie; Shah, Yatrik M.; Ma, Xiaochao; Pang, Xiaoyan; Tanaka, Toshiya; Kodama, Tatsuhiko; Krausz, Kristopher W.

    2010-01-01

    Human pregnane X receptor (PXR) has been implicated in the pathogenesis of inflammatory bowel disease (IBD). Rifaximin, a human PXR activator, is in clinical trials for treatment of IBD and has demonstrated efficacy in Crohn's disease and active ulcerative colitis. In the current study, the protective and therapeutic role of rifaximin in IBD and its respective mechanism were investigated. PXR-humanized (hPXR), wild-type, and Pxr-null mice were treated with rifaximin in the dextran sulfate sodium (DSS)-induced and trinitrobenzene sulfonic acid (TNBS)-induced IBD models to determine the protective function of human PXR activation in IBD. The therapeutic role of rifaximin was further evaluated in DSS-treated hPXR and Pxr-null mice. Results demonstrated that preadministration of rifaximin ameliorated the clinical hallmarks of colitis in DSS- and TNBS-treated hPXR mice as determined by body weight loss and assessment of diarrhea, rectal bleeding, colon length, and histology. In addition, higher survival rates and recovery from colitis symptoms were observed in hPXR mice, but not in Pxr-null mice, when rifaximin was administered after the onset of symptoms. Nuclear factor κB (NF-κB) target genes were markedly down-regulated in hPXR mice by rifaximin treatment. In vitro NF-κB reporter assays demonstrated inhibition of NF-κB activity after rifaximin treatment in colon-derived cell lines expressing hPXR. These findings demonstrated the preventive and therapeutic role of rifaximin on IBD through human PXR-mediated inhibition of the NF-κB signaling cascade, thus suggesting that human PXR may be an effective target for the treatment of IBD. PMID:20627999

  6. [Non-commercial clinical trials--who will be the legal sponsor? Sponsorship of investigator-initiated clinical trials according to the German Drug Law].

    PubMed

    Benninger-Döring, G; Boos, J

    2006-07-01

    Non-commercial clinical trials may be of great benefit to the patients concerned. The 12th amendment to the German Drug Law (AMG) changed legal liability of the initiators of investigator-initiated clinical trials with extensive consequences for traditional project leaders. The central point under discussion is the sponsor's responsibility according to the AMG. Presently leading management divisions of university hospitals and universities are developing proceedings to assume sponsor responsibility by institutions (institutional sponsorship), which should enable investigator-initiated clinical trials to be conducted according to legal requirements in the future. Detailed problems and special questions can only be resolved in a single-minded fashion, and if necessary political processes should be catalyzed. PMID:16763801

  7. Insights and clinical questions about the active surveillance of low-risk papillary thyroid microcarcinomas [Review].

    PubMed

    Ito, Yasuhiro; Oda, Hitomi; Miyauchi, Akira

    2016-04-25

    Over 20 years ago, two Japanese institutions initiated an active surveillance policy for papillary microcarcinomas (PMCs) without high-risk features (such as clinical lymph node and distant metastases) and suspected trachea or recurrent laryngeal nerve invasion. Since the most recent American Thyroid Association (ATA) guidelines adopt active surveillance as a therapy option for low-risk PMCs, the number of institutions worldwide carrying out this policy can be expected to increase. However, before adopting an active surveillance strategy, some important clinical questions must be considered. In this review, conceivable clinical questions with our answers based on the present accumulation of low-risk PMC surveillance data are presented. PMID:26632168

  8. Peer assisted learning in the clinical setting: an activity systems analysis.

    PubMed

    Bennett, Deirdre; O'Flynn, Siun; Kelly, Martina

    2015-08-01

    Peer assisted learning (PAL) is a common feature of medical education. Understanding of PAL has been based on processes and outcomes in controlled settings, such as clinical skills labs. PAL in the clinical setting, a complex learning environment, requires fresh evaluation. Socio-cultural theory is proposed as a means to understand educational interventions in ways that are practical and meaningful. We describe the evaluation of a PAL intervention, introduced to support students' transition into full time clinical attachments, using activity theory and activity systems analysis (ASA). Our research question was How does PAL transfer to the clinical environment? Junior students on their first clinical attachments undertook a weekly same-level, reciprocal PAL activity. Qualitative data was collected after each session, and focus groups (n = 3) were held on completion. Data was analysed using ASA. ASA revealed two competing activity systems on clinical attachment; Learning from Experts, which students saw as the primary function of the attachment and Learning with Peers, the PAL intervention. The latter took time from the first and was in tension with it. Tensions arose from student beliefs about how learning takes place in clinical settings, and the importance of social relationships, leading to variable engagement with PAL. Differing perspectives within the group were opportunities for expansive learning. PAL in the clinical environment presents challenges specific to that context. Using ASA helped to describe student activity on clinical attachment and to highlight tensions and contradictions relating PAL in that setting. Planning learning opportunities on clinical placements, must take account of how students learn in workplaces, and the complexity of the multiple competing activity systems related to learning and social activities. PMID:25269766

  9. Investigating the Jack the Ripper Case: Engaging Students in a Criminal Investigations Class through Active Learning

    ERIC Educational Resources Information Center

    Gutierrez, Daniel; Kazmi, Syed

    2010-01-01

    The present study examines the utilization of a class project involving the Jack the Ripper murders. Students enrolled in a criminal investigations class were required to investigate the five canonical murders associated with the infamous serial killer known as Jack the Ripper and the murders that occurred in London during 1888. This paper…

  10. Investigations of the use of bioavailability data to adjust occupational exposure limits for active pharmaceutical ingredients.

    PubMed

    Naumann, Bruce D; Weideman, Patricia A; Sarangapani, Ramesh; Hu, Shu-Cheih; Dixit, Rakesh; Sargent, Edward V

    2009-11-01

    Occupational exposure limits (OELs) for active pharmaceutical ingredients have traditionally been established using no-observed-adverse-effect levels derived from clinical studies employing po and iv routes of administration and by applying default uncertainty factors or chemical-specific adjustment factors. However, exposure by the inhalation or dermal route is more relevant in terms of occupational safety. In this investigation, to explore new methods for route-to-route extrapolation, the bioavailability of MK-0679, a leukotriene D(4) receptor antagonist, was compared following iv, po, intranasal (in), or intratracheal (it) administration. The relative bioavailability of MK-0679 was iv congruent with it > po congruent with in. Bioavailability correction factors (BCFs) of 2.0 and 0.6 were derived from these data to adjust a hypothetical OEL of 0.1 mg/m(3) for MK-0679 with particle sizes of 10 and 50 mum, respectively. These BCFs were used to adjust the OEL established using po clinical data, to reflect the differences in bioavailability following deposition in different regions of the respiratory tract. To further investigate how bioavailability data could be used in setting OELs, a preliminary pharmacokinetic (PK) model was developed to describe the time course of plasma concentrations using the data from the route comparison study. An inhalation study was then performed to test the validity of using either empirical data or modeling approaches to derive BCFs when setting OELs. These investigations demonstrated how the use of route-specific PK data could reduce some of the uncertainties associated with route-to-route extrapolation and allow for improved precision and quantitative adjustments when establishing OELs. Further investigations are needed to better understand the factors responsible for differences in systemic uptake following deposition in different regions of the respiratory tract and how these can be generalized across different classes of soluble

  11. 25 CFR 900.196 - Do covered services include the conduct of clinical studies and investigations and the provision...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... studies and investigations and the provision of emergency services, including the operation of emergency motor vehicles? 900.196 Section 900.196 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR... Claims § 900.196 Do covered services include the conduct of clinical studies and investigations and...

  12. 25 CFR 900.196 - Do covered services include the conduct of clinical studies and investigations and the provision...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... studies and investigations and the provision of emergency services, including the operation of emergency motor vehicles? 900.196 Section 900.196 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR... Claims § 900.196 Do covered services include the conduct of clinical studies and investigations and...

  13. 25 CFR 900.196 - Do covered services include the conduct of clinical studies and investigations and the provision...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... studies and investigations and the provision of emergency services, including the operation of emergency motor vehicles? 900.196 Section 900.196 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR... Claims § 900.196 Do covered services include the conduct of clinical studies and investigations and...

  14. 25 CFR 900.196 - Do covered services include the conduct of clinical studies and investigations and the provision...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... studies and investigations and the provision of emergency services, including the operation of emergency motor vehicles? 900.196 Section 900.196 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR... Claims § 900.196 Do covered services include the conduct of clinical studies and investigations and...

  15. 25 CFR 900.196 - Do covered services include the conduct of clinical studies and investigations and the provision...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... studies and investigations and the provision of emergency services, including the operation of emergency motor vehicles? 900.196 Section 900.196 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR... Claims § 900.196 Do covered services include the conduct of clinical studies and investigations and...

  16. Clinical study on thermography, as modern investigation method for Candida-associated denture stomatitis.

    PubMed

    Iosif, Laura; Preoteasa, Cristina Teodora; Murariu-Măgureanu, Cătălina; Preoteasa, Elena

    2016-01-01

    Candida-associated denture stomatitis is an infectious inflammatory condition of the oral mucosa, with frequent recurrences. The aim of this study was to assess the use of infrared thermography as investigation method for Candida-associated denture stomatitis (as inflammatory disorder of the maxillary denture bearing area), by comparing disease and non-disease groups. An observational study was conducted on maxillary edentulous patients treated by acrylic dentures, with and without Candida-associated denture stomatitis. Diagnostic test methods used were clinical examination for denture stomatitis and conventional microbiological culture method for oral candidiasis. Thermography analysis of the maxillary denture bearing area was made using the ThermaCAM PM350 infrared camera (Inframetrics, Flir Systems) and ThermaGram Pro 95 software, data being acquired by usage of standard protocol of thermographic registrations. The sample included 52 patients, 21 with and 31 without Candida-associated denture stomatitis. The temperature of the maxillary mucosa corresponding to the denture bearing area was found to be statistically significantly higher in Candida-associated denture stomatitis (mean 36.20°C), compared to healthy oral mucosa (mean 34.85°C). The thermal threshold value of 35.44°C was identified as best differentiating a pathological from normal state of the maxillary mucosa corresponding to the denture bearing area. In conclusion, infrared thermography, a rapid non-invasive investigation method, has the premises to bring valuable data in inflammatory disorders of the maxillary denture bearing area, as Candida-associated denture stomatitis that may be used for screening, diagnostic or monitoring purposes. PMID:27151707

  17. Automation of o-dianisidine assay for ceruloplasmin activity analyses: usefulness of investigation in Wilson's disease and in hepatic encephalopathy.

    PubMed

    Siotto, Mariacristina; Pasqualetti, Patrizio; Marano, Massimo; Squitti, Rosanna

    2014-10-01

    Ceruloplasmin (Cp) is a serum ferroxidase that plays an essential role in iron metabolism. It is routinely tested by immunoturbidimetric assays that quantify the concentration of the protein both in its active and inactive forms. Cp activity is generally analyzed manually; the process is time-consuming, has a limited repeatability, and is not suitable for a clinical setting. To overcome these inconveniences, we have set the automation of the o-dianisidine Cp activity assay on a Cobas Mira Plus apparatus. The automation was rapid and repeatable, and the data were provided in terms of IU/L. The assay was adapted for human sera and showed a good precision [coefficient of variation (CV) 3.7 %] and low limit of detection (LoD 11.58 IU/L). The simultaneous analysis of Cp concentration and activity in the same run allowed us to calculate the Cp-specific activity that provides a better index of the overall Cp status. To test the usefulness of this automation, we tested this assay on 104 healthy volunteers and 36 patients with Wilson's disease, hepatic encephalopathy, and chronic liver disease. Cp activity and specific activity distinguished better patients between groups with respect to Cp concentration alone, and providing support for the clinical investigation of neurological diseases in which liver failure is one of the clinical hallmarks. PMID:24663495

  18. Complement activation by Coccidioides immitis: in vitro and clinical studies.

    PubMed Central

    Galgiani, J N; Yam, P; Petz, L D; Williams, P L; Stevens, D A

    1980-01-01

    Mycelial- or spherule-phase derivatives of Coccidioides immitis caused a decrease in vitro of total hemolytic complement in serum from a nonsensitized person. Activation involved both classic and alternative pathways as shown by deprssion of hemolytic C4 and by generation of products of activation of components C3, C4, and factor B. In addition, functional complement activity or immunoreactive levels of complement components or both were measured in 23 patients with self-limited or disseminated coccidioidomycosis. Low total hemolytic complement was found in nine, usually during the early phase of primary illness, and was transient. Hemolytic C4 was low, and the effect of inulin to decrease complement levels was blunted, suggested both classic and alternative pathways may be deficient. However, associated depression of immunoreactive levels of components assayed (C3, C4, C5, factor B, and properdin) was not consistently found. This disparity raises the possibility of enhanced in vitro inactivation analogous to activation by immune complexes. Images Fig. 2 PMID:6901703

  19. Clinical and genetic investigation of families with type II Waardenburg syndrome.

    PubMed

    Chen, Yong; Yang, Fuwei; Zheng, Hexin; Zhou, Jianda; Zhu, Ganghua; Hu, Peng; Wu, Weijing

    2016-03-01

    The present study aimed to investigate the molecular pathology of Waardenburg syndrome type II in three families, in order to provide genetic diagnosis and hereditary counseling for family members. Relevant clinical examinations were conducted on the probands of the three pedigrees. Peripheral blood samples of the probands and related family members were collected and genomic DNA was extracted. The coding sequences of paired box 3 (PAX3), microphthalmia‑associated transcription factor (MITF), sex‑determining region Y‑box 10 (SOX10) and snail family zinc finger 2 (SNAI2) were analyzed by polymerase chain reaction and DNA sequencing. The heterozygous mutation, c.649_651delAGA in exon 7 of the MITF gene was detected in the proband and all patients of pedigree 1; however, no pathological mutation of the relevant genes (MITF, SNAI2, SOX10 or PAX3) was detected in pedigrees 2 and 3. The heterozygous mutation c.649_651delAGA in exon 7 of the MITF gene is therefore considered the disease‑causing mutation in pedigree 1. However, there are novel disease‑causing genes in Waardenburg syndrome type II, which require further research. PMID:26781036

  20. Clinical and genetic investigation of families with type II Waardenburg syndrome

    PubMed Central

    CHEN, YONG; YANG, FUWEI; ZHENG, HEXIN; ZHOU, JIANDA; ZHU, GANGHUA; HU, PENG; WU, WEIJING

    2016-01-01

    The present study aimed to investigate the molecular pathology of Waardenburg syndrome type II in three families, in order to provide genetic diagnosis and hereditary counseling for family members. Relevant clinical examinations were conducted on the probands of the three pedigrees. Peripheral blood samples of the probands and related family members were collected and genomic DNA was extracted. The coding sequences of paired box 3 (PAX3), microphthalmia-associated transcription factor (MITF), sex-determining region Y-box 10 (SOX10) and snail family zinc finger 2 (SNAI2) were analyzed by polymerase chain reaction and DNA sequencing. The heterozygous mutation, c.649_651delAGA in exon 7 of the MITF gene was detected in the proband and all patients of pedigree 1; however, no pathological mutation of the relevant genes (MITF, SNAI2, SOX10 or PAX3) was detected in pedigrees 2 and 3. The heterozygous mutation c.649_651delAGA in exon 7 of the MITF gene is therefore considered the disease-causing mutation in pedigree 1. However, there are novel disease-causing genes in Waardenburg syndrome type II, which require further research. PMID:26781036

  1. Polythelia: simple atavistic remnant or a suspicious clinical sign for investigation?

    PubMed

    Galli-Tsinopoulou, Assimina; Stergidou, Dorothea

    2014-03-01

    Supernumerary nipples (or polythelia) usually appear along the embryonic milk lines or in other sites including the back, thigh, vulva, neck etc. The frequency of polythelia ranges from 0.2% to 5.6%. Despite the plethora of published cases concerning its association with other congenital malformations or syndromes with different patterns of inheritance, polythelia still remains a controversial and theoretical issue. Although most reports describe a link between supernumerary nipples and kidney/urinary tract anomalies, a potential relationship with other congenital anomalies or malignancies has also been speculated. Additionally, polythelia has been associated with genodermatoses, thus being related with an increased malignant potential, as well as with an increased risk for solid tumors such as renal adenocarcinoma, testicular cancer, prostate cancer, and urinary bladder carcinoma. The fact that the Scaramanga (ska) mutant mice presented with ectopic breast tissue imply that misregulation of the neuregulin-3 signaling pathway may be critical in the occurrence of polythelia. This is an attempt to review existing literature in order to (a) draw reliable conclusions whether polythelia is a manifestation of simple atavism or may be associated with concomitant severe conditions needing further investigation and/or management, (b) elucidate its aetiology and (c) establish appropriate clinical and laboratory approach. PMID:24716395

  2. A Clinical Trial to Investigate the Effect of Cynatine HNS on Hair and Nail Parameters

    PubMed Central

    Veghte, Robert H.

    2014-01-01

    Objective. A new, novel product, Cynatine HNS, was evaluated for its effects as a supplement for improving various aspects of hair and nails in a randomized, double-blind, placebo-controlled clinical trial. Methods. A total of 50 females were included and randomized into two groups. The active group (n = 25) received 2 capsules containing Cynatine HNS, comprised of Cynatine brand keratin (500 mg) plus vitamins and minerals, per day, and the placebo group (n = 25) received 2 identical capsules of maltodextrin per day for 90 days. End points for hair loss, hair growth, hair strength, amino acid composition, and hair luster were measured. End points were also measured for nail strength and the appearance of nails. Results. The results show that subjects taking Cynatine HNS showed statistically significant improvements in their hair and nails when compared to placebo. Conclusion. Cynatine HNS is an effective supplement for improving hair and nails in 90 days or less. EudraCT number is 2014-002645-22. PMID:25386609

  3. An Investigation of Implicit Active Contours for Scientific Image Segmentation

    SciTech Connect

    Weeratunga, S K; Kamath, C

    2003-10-29

    The use of partial differential equations in image processing has become an active area of research in the last few years. In particular, active contours are being used for image segmentation, either explicitly as snakes, or implicitly through the level set approach. In this paper, we consider the use of the implicit active contour approach for segmenting scientific images of pollen grains obtained using a scanning electron microscope. Our goal is to better understand the pros and cons of these techniques and to compare them with the traditional approaches such as the Canny and SUSAN edge detectors. The preliminary results of our study show that the level set method is computationally expensive and requires the setting of several different parameters. However, it results in closed contours, which may be useful in separating objects from the background in an image.

  4. STRUCTURE-ACTIVITY RELATIONSHIP STUIDES AND THEIR ROLE IN PREDICTING AND INVESTIGATING CHEMICAL TOXICITY

    EPA Science Inventory

    Structure-Activity Relationship Studies and their Role in Predicting and Investigating Chemical Toxicity

    Structure-activity relationships (SAR) represent attempts to generalize chemical information relative to biological activity for the twin purposes of generating insigh...

  5. Investigating the Clinical Usefulness of the Social Responsiveness Scale (SRS) in a Tertiary Level, Autism Spectrum Disorder Specific Assessment Clinic

    ERIC Educational Resources Information Center

    Aldridge, Fiona J.; Gibbs, Vicki M.; Schmidhofer, Katherine; Williams, Megan

    2012-01-01

    The Social Responsiveness Scale (SRS; Constantino and Gruber in Social Responsiveness Scale (SRS). Western Psychological Services, Los Angeles, 2005) is a commonly used screening tool for identifying children with possible autism spectrum disorder (ASD). This study investigated the relationship between SRS scores and eventual diagnostic outcome…

  6. An investigation of the impact of selected prereading activities on student content learning through laboratory activities

    NASA Astrophysics Data System (ADS)

    Kass, Jesse (Shaya)

    This study investigated whether two prereading activities impacted student learning from hands-on science activities. The study was based on constructivist learning theory. Based on the work of Piaget, it was hypothesized that students who activated prior knowledge would learn more from the activities. Based on the work of Vygotsky it was hypothesized that students who talk more and write more would learn more from the activity. The K-W-L chart and anticipation guide strategies were used with eighth grade students at Graves Middle School in Whittier, California before learning about levers and convection currents. D. M. Ogle (1986) created the three-column K-W-L chart to have students activate prior knowledge. In the first column, the students write what they already know about a subject, in the second column, the students write what they want to know about the subject, and the students complete the third column after learning about a subject by writing answers to the questions that they asked in the second column. Duffelmeyer (1994) created the anticipation guide based on Herber's (1978) reasoning guide. In the anticipation guide, the teacher creates three or four sentences that convey the major ideas of the topic and the students either agree or disagree with the statements. After learning about the topic, students revisit their answers and decide if they were correct or incorrect and they must defend their choices. This research used the Solomon (1947) four-square design and compared both the experimental groups to a control group that simply discussed the concepts before completing the activity. The research showed no significant difference between the control group and either of the treatment groups. The reasons for the lack of significant differences are considered. It was hypothesized that since the students were unfamiliar with the prereading activities and did not have much experience with using either writing-to-learn or talking-to-learn strategies, the

  7. Activity restriction in mild COPD: a challenging clinical problem.

    PubMed

    O'Donnell, Denis E; Gebke, Kevin B

    2014-01-01

    Dyspnea, exercise intolerance, and activity restriction are already apparent in mild chronic obstructive pulmonary disease (COPD). However, patients may not seek medical help until their symptoms become troublesome and persistent and significant respiratory impairment is already present; as a consequence, further sustained physical inactivity may contribute to disease progression. Ventilatory and gas exchange impairment, cardiac dysfunction, and skeletal muscle dysfunction are present to a variable degree in patients with mild COPD, and collectively may contribute to exercise intolerance. As such, there is increasing interest in evaluating exercise tolerance and physical activity in symptomatic patients with COPD who have mild airway obstruction, as defined by spirometry. Simple questionnaires, eg, the modified British Medical Research Council dyspnea scale and the COPD Assessment Test, or exercise tests, eg, the 6-minute or incremental and endurance exercise tests can be used to assess exercise performance and functional status. Pedometers and accelerometers are used to evaluate physical activity, and endurance tests (cycle or treadmill) using constant work rate protocols are used to assess the effects of interventions such as pulmonary rehabilitation. In addition, alternative outcome measurements, such as tests of small airway dysfunction and laboratory-based exercise tests, are used to measure the extent of physiological impairment in individuals with persistent dyspnea. This review describes the mechanisms of exercise limitation in patients with mild COPD and the interventions that can potentially improve exercise tolerance. Also discussed are the benefits of pulmonary rehabilitation and the potential role of pharmacologic treatment in symptomatic patients with mild COPD. PMID:24940054

  8. Activity restriction in mild COPD: a challenging clinical problem

    PubMed Central

    O’Donnell, Denis E; Gebke, Kevin B

    2014-01-01

    Dyspnea, exercise intolerance, and activity restriction are already apparent in mild chronic obstructive pulmonary disease (COPD). However, patients may not seek medical help until their symptoms become troublesome and persistent and significant respiratory impairment is already present; as a consequence, further sustained physical inactivity may contribute to disease progression. Ventilatory and gas exchange impairment, cardiac dysfunction, and skeletal muscle dysfunction are present to a variable degree in patients with mild COPD, and collectively may contribute to exercise intolerance. As such, there is increasing interest in evaluating exercise tolerance and physical activity in symptomatic patients with COPD who have mild airway obstruction, as defined by spirometry. Simple questionnaires, eg, the modified British Medical Research Council dyspnea scale and the COPD Assessment Test, or exercise tests, eg, the 6-minute or incremental and endurance exercise tests can be used to assess exercise performance and functional status. Pedometers and accelerometers are used to evaluate physical activity, and endurance tests (cycle or treadmill) using constant work rate protocols are used to assess the effects of interventions such as pulmonary rehabilitation. In addition, alternative outcome measurements, such as tests of small airway dysfunction and laboratory-based exercise tests, are used to measure the extent of physiological impairment in individuals with persistent dyspnea. This review describes the mechanisms of exercise limitation in patients with mild COPD and the interventions that can potentially improve exercise tolerance. Also discussed are the benefits of pulmonary rehabilitation and the potential role of pharmacologic treatment in symptomatic patients with mild COPD. PMID:24940054

  9. Evolution & Phylogenetic Analysis: Classroom Activities for Investigating Molecular & Morphological Concepts

    ERIC Educational Resources Information Center

    Franklin, Wilfred A.

    2010-01-01

    In a flexible multisession laboratory, students investigate concepts of phylogenetic analysis at both the molecular and the morphological level. Students finish by conducting their own analysis on a collection of skeletons representing the major phyla of vertebrates, a collection of primate skulls, or a collection of hominid skulls.

  10. Designing the Perfect Plant: Activities to Investigate Plant Ecology

    ERIC Educational Resources Information Center

    Lehnhoff, Erik; Woolbaugh, Walt; Rew, Lisa

    2008-01-01

    Plant ecology is an important subject that often receives little attention in middle school, as more time during science classes is devoted to plant biology. Therefore, the authors have developed a series of activities, including a card game--Designing the Perfect Plant--to introduce student's to plant ecology and the ecological trade offs…

  11. Development and Pilot Investigation of Behavioral Activation for Negative Symptoms

    ERIC Educational Resources Information Center

    Mairs, Hilary; Lovell, Karina; Campbell, Malcolm; Keeley, Philip

    2011-01-01

    Negative symptoms cause functional impairment and impede recovery from psychosis, not least, because of limited developments in empirically validated treatments. This article details a pilot evaluation of a behavioral activation (BA) treatment with eight people presenting with psychosis and marked negative symptoms. The rationale for this…

  12. Recess Physical Activity Packs in Elementary Schools: A Qualitative Investigation

    ERIC Educational Resources Information Center

    Elliott, Steven; Combs, Sue; Boyce, Robert

    2011-01-01

    To supplement the present weekly allotment of 30 minutes of physical education, a school district in southeastern North Carolina identified recess time as part of the state mandated (HSP-S-000) 150 minutes of physical activity (PA) per week and have purchased fitness equipment (recess packs) for the children to use. Twelve participants were…

  13. Our Economy: How It Works. Activities and Investigation. Teacher's Edition.

    ERIC Educational Resources Information Center

    Clawson, Elmer U.

    To help junior and senior high school students develop a better understanding of the United States' economy, this teacher's guide presents a series of learning activities centered around eight general themes. The topics (corresponding to the document's eight chapters) include both international and global economic issues as well as current…

  14. [Investigation of Aerosol Mixed State and CCN Activity in Nanjing].

    PubMed

    Zhu, Lin; Ma, Yan; Zheng, Jun; Li, Shi-zheng; Wang, Li-peng

    2016-04-15

    During 11-18 September 2014, the size-resolved aerosol Cloud Condensation Nuclei (CCN) activity and mixing state were measured using Cloud Condensation Nuclei Counter (CCNC), Aerosol Particle Mass (APM) and Scanning Mobility Particle Sizer (SMPS). The results showed that aerosols mainly existed as an internal mixture. For 76, 111, 138 and 181 nm particles, black carbon (BC) accounted for 5.4%, 10%, l0.7% and 6.7% of the particle mass, but as high as 51%, 57%, 70% and 59% of the particle number concentrations, respectively, suggesting that BC was a type of important condensation nuclei in the atmosphere and made significant contributions to particle numbers. The occasionally observed external mixtures were mainly present in 111 and 138 nm particles. The critical supersaturation was 0.25%, 0.13%, 0.06% and 0.015% for 76, 111, 138 and 181 nm particles, respectively. Precipitation and haze had significant effects on the particle CCN activity. The hygroscopicity parameter K was 0.37, 0.29 and 0.39 in rainy, clear and hazy days, respectively. Particle density and CCN activity were impacted by chemical compositions. Compared with clear days, higher contents of inorganic salts and lower contents of organics were found on hazy days, accompanied by lower particle density and higher CCN activity. PMID:27548938

  15. An expanding universe of noncoding RNAs between the poles of basic science and clinical investigations.

    PubMed

    Weil, Patrick P; Hensel, Kai O; Weber, David; Postberg, Jan

    2016-03-01

    The Keystone Symposium 'MicroRNAs and Noncoding RNAs in Cancer', Keystone, CO, USA, 7-12 June 2015 Since the discovery of RNAi, great efforts have been undertaken to unleash the potential biomedical applicability of small noncoding RNAs, mainly miRNAs, involving their use as biomarkers for personalized diagnostics or their usability as active agents or therapy targets. The research's focus on the noncoding RNA world is now slowly moving from a phase of basic discoveries into a new phase, where every single molecule out of many hundreds of cataloged noncoding RNAs becomes dissected in order to investigate these molecules' biomedical relevance. In addition, RNA classes neglected before, such as long noncoding RNAs or circular RNAs attract more attention. Numerous timely results and hypotheses were presented at the 2015 Keystone Symposium 'MicroRNAs and Noncoding RNAs in Cancer'. PMID:26418087

  16. Clinical significance of serum protease-activated receptor-1 levels in gastric cancer patients

    PubMed Central

    TAS, FARUK; KARABULUT, SENEM; TASTEKIN, DIDEM; DURANYILDIZ, DERYA

    2016-01-01

    Protease-activated receptor-1 (PAR-1) has a significant role in the pathogenesis of various malignancies and its expression mainly affects the survivals of cancer patients. The aim of the present study was to determine the clinical significance of the serum concentrations of PAR-1 in patients with gastric carcinoma. A total of 63 pathologically confirmed gastric cancer patients were enrolled in this study, with a median age of 62 years. Serum PAR-1 concentrations were determined by the enzyme-linked immunosorbent assay method and no significant difference in the baseline serum PAR-1 concentrations was found between patients and normal controls (P=0.5). The investigated clinical variables, including patient age, gender, localization of lesion, histology, grade of pathology, disease stage and serum tumor markers (lactate dehydrogenase, carcinoembryonic antigen and carbohydrate antigen 19-9) were not correlated with serum PAR-1 levels (P>0.05). Furthermore, no association was identified between the serum PAR-1 level and chemotherapy responsiveness (P=0.43). Serum PAR-1 level also had no prognostic role for survival (P=0.27). In conclusion, the serum PAR-1 concentration has no diagnostic, predictive and prognostic values in gastric cancer patients. PMID:27073639

  17. In vitro antibacterial activity of panduratin A against enterococci clinical isolates.

    PubMed

    Rukayadi, Yaya; Han, Sunghwa; Yong, Dongeun; Hwang, Jae-Kwan

    2010-01-01

    Panduratin A, a natural chalcone compound isolated from the rhizome of fingerroot (Boesenbergia rotunda (L.) MANSF. A). The antibacterial activity of panduratin A against clinical enterococci isolates was compared in terms of minimum inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) to those of commonly used antimicrobials, according to the CLSI guidelines. Time-kill curves were constructed to assess the concentration between MIC and bactericidal activity of panduratin A at concentrations ranging from 0x MIC to 4x MIC. The activity of panduratin A against biofilm-producing enterococcal strains was also evaluated. The growth of all clinical enterococci isolates (n=23) were inhibited by panduratin A at a concentration of 2 microg/ml. Panduratin A was able to kill all clinical enterococci isolates with a MBC of 8 microg/ml. The time-kill curves demonstrated that the bactericidal endpoint for clinical enterococci was reached after 30 min of incubation at a panduratin A concentration of 4x MIC. The growth of biofilm-producing enterococcal strains can be inhibited and eradicated by panduratin A at concentrations of activity of panduratin A against all clinical enterococci isolates was generally more potent than commonly used antimicrobials. Panduratin A has stronger activity against biofilm-producing enterococcal strains than daptomycin and linezolid. Panduratin A is an antimicrobial agent with high in vitro activity against clinical enterococci, including organisms resistant to other antimicrobials. PMID:20823562

  18. Antimicrobial activity and chemical investigation of Brazilian Drosera.

    PubMed

    Ferreira, Dalva Trevisan; Andrei, César Cornélio; Saridakis, Halha Ostrensky; Faria, Terezinha de Jesus; Vinhato, Elisângela; Carvalho, Kátia Eliane; Daniel, Juliana Feijó Souza; Machado, Sílvio Luiz; Saridakis, Dennis Panayotis; Braz-Filho, Raimundo

    2004-11-01

    The antimicrobial activity of three different extracts (hexanic, ethyl acetate, methanol) obtained from Brazilian Drosera species (D. communis, D. montana var. montana, D. brevifolia, D. villosa var. graomogolensis, D. villosa var. villosa, Drosera sp. 1, and Drosera sp. 2 ) were tested against Staphylococcus aureus (ATCC 25923), Enterococcus faecium (ATCC23212), Pseudomonas aeruginosa (ATCC27853), Escherichia coli (ATCC11229), Salmonella choleraesuis (ATCC10708), Klebsiella pneumoniae (ATCC13883), and Candida albicans (a human isolate). Better antimicrobial activity was observed with D. communis and D. montana var. montana ethyl acetate extracts. Phytochemical analyses from D. communis, D. montana var. montana and D. brevifolia yielded 5-hydroxy-2-methyl-1,4-naphthoquinone (plumbagin); long chain aliphatic hydrocarbons were isolated from D. communis and from D. villosa var. villosa, a mixture of long chain aliphatic alcohols and carboxylic acids, was isolated from D. communis and 3b-O-acetylaleuritolic acid from D. villosa var. villosa. PMID:15654434

  19. Investigation into biologically active constituents of Geum rivale L.

    PubMed

    Owczarek, Aleksandra; Gudej, Jan

    2013-01-01

    Aerial and underground parts of Geum rivale (Rosaceae) were investigated. Tiliroside, gallic acid, ellagic acid and a sterol fraction were isolated from aerial parts of the plant. The sterol fraction was analyzed using GC-MS. Eleven phenolic acids were identified in aerial parts of the plant, and eight in underground parts, by means of RP-HPLC analysis. The quantitative determination of phenolic acids, tannins and flavonoids was also carried out. PMID:23610965

  20. Comparative investigation of antimutagenic activity of sterically hindered phenols

    SciTech Connect

    Pashin, Yu.V.; Bakhitova, L.M.; Bentkhen, T.I.

    1985-07-01

    Mutagenic properties of primarily inactive carcinogenic polycyclic aromatic hydrocarbons (PAH) are manifested after metabolic oxidation by microsomal enzymes. It has been established that activation of carcinogens in biological systems is accompanied by intensification of free-radical processes, effective inhibition of which is achieved by sterically hindered phenols (SHP). The authors studied the effect of SHP on the mutagenic activity of benzo(a)pyrene (BP) using estimation of induced direct gene mutation at the locus for hypoxanthine-guanine-phosphoribosyl transferase (HGPRT) in somatic Chinese hamster cells of line V-79 cultured in vitro and with estimation of the induction of micronuclei in polychromatophilic erythrocytes of mouse bone marrow in vivo. The reference mutagen was BP from Fluka and the following SHP were used: dibunol, F-800, and F-804. Genetic activity of each substance tested and their combination was studied in an in vitro system under conditions of metabolic activation by mouse liver microsomes and in vivo according to induction of micronuclei in polychromatophilic bone marrow erythrocytes in (CBA x C57B1/6J)F/sub 1/ mice 60-80 days old, which reflects gross defects of chromosomes at the erythroblast stage. In order to establish optimal time for recording the frequency of induction of micronuclei, bone marrow samples were taken from the animals, 24, 48, 72, and 96 h after a single intraperitoneal injection of the agents. The BP was dissolved in sunflower oil and used in a concentration constituting 1/3 of the lowest lethal dose in mice. The SHP was then dissolved in water or dimethyl sulfoxide and administered in a ratio with BP of 1:1 or 1:0.5. The smears were then stained in methanol, washed with twice-distilled water, and stained in 7% Giemsa solution.

  1. Investigations on iodothyronine deiodinase activity in the maturing rat brain.

    PubMed

    Ködding, R; Fuhrmann, H; von zur Mühlen, A

    1986-04-01

    5-Monodeiodination of T4 and T3 and 5'-monodeiodination of T4 and rT3 were studied in brain homogenates of male Sprague-Dawley rats, aged 1-60 days. Portions of the homogenates were incubated with the substrates at 37 C for 30 min. The reaction products were estimated by specific RIAs. All of the four reactions were dependent upon time, temperature, pH, and upon the concentrations of substrate, thiol, and tissue protein. Maximal reactions were obtained between 40 and 160 mM dithioerythritol. T4 5'-deiodination proceeded optimally at pH 7.4 and 0.4 microM substrate, the other reactions at pH 8.5 and 10 microM substrate. The four reactions were inactivated by heat (56 C, 30 min) and inhibited by 10(-5) M iopanoic acid. Only rT3 5'-deiodination was inhibited by 3 X 10(-4) M propylthiouracil (greater than 95%). In cerebellum, basal ganglia, brainstem, and hypothalamus both T4 and T3 5-deiodinase activity were very high in perinatal rats [up to 5.56 pmol/(min X mg protein) in hypothalamus], and decreased rapidly with age. In cortex and olfactory bulb these enzyme activities were low after birth, followed by an increase during the growth spurt [up to 632 fmol/(min X mg protein) in olfactory bulb]. T4 and rT3 5'-deiodinase activity in all brain regions studied were at their lowest in perinatal rats. During and after the growth spurt an increase was observed [up to 457 fmol/(min X mg protein) in cerebellum]. The reciprocal course of 5- and 5'-deiodination between birth and growth spurt in most of the brain regions studied might lead to a reduced intracellular thyromimetic activity during the perinatal period. PMID:3948784

  2. Reply to B. Rimland's "Comments on 'Secretin and Autism: A Two-Part Clinical Investigation'".

    ERIC Educational Resources Information Center

    Chez, Michael G.; Buchanan, Cathleen P.

    2000-01-01

    The authors of a study (EC 625 006) of the clinical effects of the hormone secretin on autism respond to critical comments (EC 625 007) by defending their conclusion that secretin offers no observable clinical improvement in children with autism, their choice of methodology, and use of the Childhood Autism Rating Scales. (Contains references.) (DB)

  3. Simultaneous Bilateral Carotid Stenting for Symptomatic Bilateral High-Grade Carotid Stenosis: A Retrospective Clinical Investigation.

    PubMed

    Ye, Ziming; Liu, Ying; Deng, Xiao; Chen, Xiangren; Lin, Cuiting; Tang, Yanyan; Su, Ying; Fang, Lanji; Wu, Yuan; Qin, Chao

    2016-01-01

    BACKGROUND This retrospective clinical investigation aimed to evaluate the short-term effectiveness and safety of SBCAS for symptomatic bilateral high-grade CS. MATERIAL AND METHODS From 2009 to 2014, 145 patients were recruited. Among them, 70 underwent SBCAS, and other 75 patients underwent SAMM and served as controls. The immediate postprocedural complications and postprocedural neurological evaluation, as well as restenosis at 6-month and 1-year follow-ups in the SBCAS group are reported. Additionally, baseline risk factors for ischemic stroke, adverse effects of drugs, and outcomes at 30-day, 6-month, and 1-year follow-ups were compared between the 2 groups. RESULTS Our data did not reveal significant differences between the 2 groups in baseline risk factors for ischemic stroke. In the SBCAS group, both HPS (5.7%) and HD (40%) occurred, but they were not very severe, and no patients had postprocedural neurological deficit. Moreover, restenosis only occurred in 3 patients at 3 stent placement sites (4.3%) at 1-year follow-up. Adverse effects of drugs did not occur in SBCAS group, but adverse effects of Bayer aspirin and Lipitor occurred in 4 patients (5.4%) and 18 patients (24.3%), respectively, at 6-month follow-up in the control group. Furthermore, there were significant differences in outcomes between the 2 groups at 30-day, 6-month, and 1-year follow-ups, in that NIHSS, CS ratio, and incidence of endpoint events, as well as 1-year cumulative probability of endpoint events, were all lower in the SBCAS group than in the control group (p<0.05). CONCLUSIONS Compared to SAMM, we found that SBCAS was more effective and safer for symptomatic bilateral high-grade CS. PMID:27542158

  4. Simultaneous Bilateral Carotid Stenting for Symptomatic Bilateral High-Grade Carotid Stenosis: A Retrospective Clinical Investigation

    PubMed Central

    Ye, Ziming; Liu, Ying; Deng, Xiao; Chen, Xiangren; Lin, Cuiting; Tang, Yanyan; Su, Ying; Fang, Lanji; Wu, Yuan; Qin, Chao

    2016-01-01

    Background This retrospective clinical investigation aimed to evaluate the short-term effectiveness and safety of SBCAS for symptomatic bilateral high-grade CS. Material/Methods From 2009 to 2014, 145 patients were recruited. Among them, 70 underwent SBCAS, and other 75 patients underwent SAMM and served as controls. The immediate postprocedural complications and postprocedural neurological evaluation, as well as restenosis at 6-month and 1-year follow-ups in the SBCAS group are reported. Additionally, baseline risk factors for ischemic stroke, adverse effects of drugs, and outcomes at 30-day, 6-month, and 1-year follow-ups were compared between the 2 groups. Results Our data did not reveal significant differences between the 2 groups in baseline risk factors for ischemic stroke. In the SBCAS group, both HPS (5.7%) and HD (40%) occurred, but they were not very severe, and no patients had postprocedural neurological deficit. Moreover, restenosis only occurred in 3 patients at 3 stent placement sites (4.3%) at 1-year follow-up. Adverse effects of drugs did not occur in SBCAS group, but adverse effects of Bayer aspirin and Lipitor occurred in 4 patients (5.4%) and 18 patients (24.3%), respectively, at 6-month follow-up in the control group. Furthermore, there were significant differences in outcomes between the 2 groups at 30-day, 6-month, and 1-year follow-ups, in that NIHSS, CS ratio, and incidence of endpoint events, as well as 1-year cumulative probability of endpoint events, were all lower in the SBCAS group than in the control group (p<0.05). Conclusions Compared to SAMM, we found that SBCAS was more effective and safer for symptomatic bilateral high-grade CS. PMID:27542158

  5. Investigation of a clinical PET detector module design that employs large-area avalanche photodetectors

    NASA Astrophysics Data System (ADS)

    Peng, Hao; Olcott, Peter D.; Spanoudaki, Virginia; Levin, Craig S.

    2011-06-01

    We investigated the feasibility of designing an Anger-logic PET detector module using large-area high-gain avalanche photodiodes (APDs) for a brain-dedicated PET/MRI system. Using Monte Carlo simulations, we systematically optimized the detector design with regard to the scintillation crystal, optical diffuser, surface treatment, layout of large-area APDs, and signal-to-noise ratio (SNR, defined as the 511 keV photopeak position divided by the standard deviation of noise floor in an energy spectrum) of the APD devices. A detector prototype was built comprising an 8 × 8 array of 2.75 × 3.00 × 20.0 mm3 LYSO (lutetium-yttrium-oxyorthosilicate) crystals and a 22.0 × 24.0 × 9.0 mm3 optical diffuser. From the four designs of the optical diffuser tested, two designs employing a slotted diffuser are able to resolve all 64 crystals within the block with good uniformity and peak-to-valley ratio. Good agreement was found between the simulation and experimental results. For the detector employing a slotted optical diffuser, the energy resolution of the global energy spectrum after normalization is 13.4 ± 0.4%. The energy resolution of individual crystals varies between 11.3 ± 0.3% and 17.3 ± 0.4%. The time resolution varies between 4.85 ± 0.04 (center crystal), 5.17 ± 0.06 (edge crystal), and 5.18 ± 0.07 ns (corner crystal). The generalized framework proposed in this work helps to guide the design of detector modules for selected PET system configurations, including scaling the design down to a preclinical PET system, scaling up to a whole-body clinical scanner, as well as replacing APDs with other novel photodetectors that have higher gain or SNR such as silicon photomultipliers.

  6. Antibacterial Activity of Salvadora persica L. (Miswak) Extracts against Multidrug Resistant Bacterial Clinical Isolates

    PubMed Central

    Al-Ayed, Mohamed Saeed Zayed; Asaad, Ahmed Morad; Qureshi, Mohamed Ansar; Attia, Hany Goda; AlMarrani, Abduljabbar Hadi

    2016-01-01

    Much effort has focused on examining the inhibitory effect of Salvadora persica (miswak) on oral microorganisms, but information concerning its antibacterial activity against other human pathogens, particularly multidrug resistant (MDR) isolates, is scarce. Therefore, this study aimed to assess the in vitro antibacterial activities of Salvadora persica L. extracts against 10 MDR bacterial clinical isolates other than oral pathogens. The antibacterial activity of aqueous and methanol miswak extracts was assessed using the agar dilution and minimum inhibitory concentration (MIC) methods. Overall, the 400 mg/mL of miswak extract was the most effective on all strains. The methanol extract exhibited a stronger antibacterial activity against Gram-negative (3.3–13.6 mm) than Gram-positive (1.8–8.3 mm) bacteria. The lowest MIC value was seen for E. coli (0.39, 1.56 µg/mL), followed by Streptococcus pyogenes (1.56 µg/mL). The highest MIC value (6.25, 12.5 µg/mL) was recorded for methicillin-resistant Staphylococcus aureus (MRSA), Acinetobacter baumannii, and Stenotrophomonas maltophilia. This study demonstrates, for the first time, the moderate to strong antibacterial activity of miswak extracts against all tested MDR-pathogens. Methanol extract appears to be a potent antimicrobial agent that could be considered as complementary and alternative medicine against resistant pathogens. Further studies on a large number of MDR organisms are necessary to investigate and standardize the inhibitory effect of miswak extracts against these emerging pathogens. PMID:26904146

  7. Perspectives on Barriers and Facilitators to Minority Recruitment for Clinical Trials among Cancer Center Leaders, Investigators, Research Staff and Referring Clinicians

    PubMed Central

    Durant, Raegan W.; Wenzel, Jennifer A.; Scarinci, Isabel C.; Paterniti, Debora A.; Fouad, Mona N.; Hurd, Thelma C.; Martin, Michelle Y.

    2015-01-01

    Background The study of disparities in minority recruitment to cancer clinical trials has focused primarily on inquiries among minority populations. Yet, very little is known about the perceptions of individuals actively involved in minority recruitment to clinical trials within cancer centers. Therefore, we sought to assess the perspectives of cancer center clinical and research personnel on barriers and facilitators to minority recruitment. Methods We conducted 91 qualitative interviews at 5 U.S. cancer centers among 4 stakeholder groups: cancer center leaders, principal investigators, research staff, and referring clinicians. All interviews were recorded and transcribed. Qualitative analyses of response data was focused on identifying prominent themes related to barriers and facilitators to minority recruitment. Results The perspectives of the 4 stakeholder groups were largely overlapping with some variations based on their unique roles in minority recruitment. Four prominent themes were identified: 1) Racial and ethnic minorities are influenced by varying degrees of skepticism related to trial participation; 2) Potential minority participants often face multi-level barriers that preclude them from being offered an opportunity to participate in a clinical trial; 3) Facilitators at both the institutional- and participant-level potentially encourage minority recruitment; and 4) Variation between internal and external trial referral procedures may limit clinical trial opportunities for racial and ethnic minorities. Conclusions Multi-level approaches are needed to address barriers and optimize facilitators within cancer centers to enhance minority recruitment for cancer clinical trials. PMID:24643647

  8. [Is the structure of surgical clinics in Germany changing? A current investigation into the structure of surgical clinics in the Federal Republic of Germany].

    PubMed

    Lob, G; Lob, T; Bauer, H; Niethard, F; Polonius, J; Siebert, H

    2009-04-01

    Medical developments have led to extensive specialization in the field of surgery. This has already been reflected for many years in altered structure and organization forms of surgical clinics. Indispensable quality standards, statutory general conditions, increasing competition in service providers and health insurance with transparency of the service procedure all intensify this trend. The aim of this investigation was, therefore, to determine how far this differentiation of service supply in the field of surgery is also reflected in the area and in surgical departments and clinics of basic and routine supply. To achieve this, all available published information on the structure and organization of surgical clinics in the Federal Republic of Germany was classified according to current departmentalization into "undivided" or general/visceral surgery facilities compared to orthopedic/trauma surgery departments. PMID:19290506

  9. [Microcalorimetric investigation of two cephalosporins on colon bacteria activity].

    PubMed

    Xu, Fen; Song, Cheng-Gong; Wu, Rui-Hua; Yang, Li-Ni; Sun, Li-Xian; Zhao, Zong-Bao; Zhang, Zhi-Heng; Cao, Zhong; Zhang, Ling

    2009-10-01

    The effects of cephradinum and ceftazidime on the metabolism of Escherichia coli (E. coli) DH5alpha was determined by microcalorimetry. The microbial activity was recorded as power-time curves through an ampoule method with a TAM Air Isothermal Microcalorimeter at 37 degrees C. The parameters such as the growth rate constant (k), inhibitory ratio (I), the maximum power output (Pm) and the time (tm) corresponding to the maximum power output were calculated. The results show that the ceftazidime has a better inhibitory effect on E. coli DH5alpha than cephradinum. PMID:20055136

  10. Synthesis of marmycin A and investigation into its cellular activity

    NASA Astrophysics Data System (ADS)

    Cañeque, Tatiana; Gomes, Filipe; Mai, Trang Thi; Maestri, Giovanni; Malacria, Max; Rodriguez, Raphaël

    2015-09-01

    Anthracyclines such as doxorubicin are used extensively in the treatment of cancers. Anthraquinone-related angucyclines also exhibit antiproliferative properties and have been proposed to operate via similar mechanisms, including direct genome targeting. Here, we report the chemical synthesis of marmycin A and the study of its cellular activity. The aromatic core was constructed by means of a one-pot multistep reaction comprising a regioselective Diels-Alder cycloaddition, and the complex sugar backbone was introduced through a copper-catalysed Ullmann cross-coupling, followed by a challenging Friedel-Crafts cyclization. Remarkably, fluorescence microscopy revealed that marmycin A does not target the nucleus but instead accumulates in lysosomes, thereby promoting cell death independently of genome targeting. Furthermore, a synthetic dimer of marmycin A and the lysosome-targeting agent artesunate exhibited a synergistic activity against the invasive MDA-MB-231 cancer cell line. These findings shed light on the elusive pathways through which anthraquinone derivatives act in cells, pointing towards unanticipated biological and therapeutic applications.

  11. Green synthesis, spectroscopic investigation and photocatalytic activity of lead nanoparticles.

    PubMed

    Elango, Ganesh; Roopan, Selvaraj Mohana

    2015-03-15

    Most of researcher focused their research towards synthesize of nanoparticles by the method of applied chemical method which was one of the costliest method. We have focused cheapest and simplest method for the synthesizing of lead nanoparticles (Pb-NPs) using cocos nucifera L extract. The methanolic extract of cocos nucifera L was efficiently used as a reducing agent for synthesizing Pb-NPs. On treatment of lead acetate with cocos nucifera coir extracts, stable Pb-NPs were formed. The synthesized Pb-NPs were further confirmed by UV-visible spectroscopy, X-ray diffraction (XRD), Transmission electron microscope (TEM) and Energy Dispersive (EDAX) analysis. The secondary metabolites present in methanolic extract which can mainly act as a reducing and capping agents for the formation of Pb-NPs were identified by GC-MS. Anti-microbial activity for Pb-NPs against four pathogenic strain's such as Staphylococcus aureus, Escheria coli, Staphylococcus epidermis and Bacillus subtilis. Result states that Pb-NPs size was 47 nm and also shows good activity against S. aureus. Further we report on photocatalytic absorption of malachite green dye processed in short UV wavelength at 254 nm. UV spectral analysis showed peak absorbance at 613 nm with special reference to the excitation of surfaces plasmon vibration by Pb-NPs. PMID:25574657

  12. Green synthesis, spectroscopic investigation and photocatalytic activity of lead nanoparticles

    NASA Astrophysics Data System (ADS)

    Elango, Ganesh; Roopan, Selvaraj Mohana

    2015-03-01

    Most of researcher focused their research towards synthesize of nanoparticles by the method of applied chemical method which was one of the costliest method. We have focused cheapest and simplest method for the synthesizing of lead nanoparticles (Pb-NPs) using cocos nucifera L extract. The methanolic extract of cocos nucifera L was efficiently used as a reducing agent for synthesizing Pb-NPs. On treatment of lead acetate with cocos nucifera coir extracts, stable Pb-NPs were formed. The synthesized Pb-NPs were further confirmed by UV-visible spectroscopy, X-ray diffraction (XRD), Transmission electron microscope (TEM) and Energy Dispersive (EDAX) analysis. The secondary metabolites present in methanolic extract which can mainly act as a reducing and capping agents for the formation of Pb-NPs were identified by GC-MS. Anti-microbial activity for Pb-NPs against four pathogenic strain's such as Staphylococcus aureus, Escheria coli, Staphylococcus epidermis and Bacillus subtilis. Result states that Pb-NPs size was 47 nm and also shows good activity against S. aureus. Further we report on photocatalytic absorption of malachite green dye processed in short UV wavelength at 254 nm. UV spectral analysis showed peak absorbance at 613 nm with special reference to the excitation of surfaces plasmon vibration by Pb-NPs.

  13. Virtual Investigations of an Active Deep Sea Volcano

    NASA Astrophysics Data System (ADS)

    Sautter, L.; Taylor, M. M.; Fundis, A.; Kelley, D. S.; Elend, M.

    2013-12-01

    Axial Seamount, located on the Juan de Fuca spreading ridge 300 miles off the Oregon coast, is an active volcano whose summit caldera lies 1500 m beneath the sea surface. Ongoing construction of the Regional Scale Nodes (RSN) cabled observatory by the University of Washington (funded by the NSF Ocean Observatories Initiative) has allowed for exploration of recent lava flows and active hydrothermal vents using HD video mounted on the ROVs, ROPOS and JASON II. College level oceanography/marine geology online laboratory exercises referred to as Online Concept Modules (OCMs) have been created using video and video frame-captured mosaics to promote skill development for characterizing and quantifying deep sea environments. Students proceed at their own pace through a sequence of short movies with which they (a) gain background knowledge, (b) learn skills to identify and classify features or biota within a targeted environment, (c) practice these skills, and (d) use their knowledge and skills to make interpretations regarding the environment. Part (d) serves as the necessary assessment component of the laboratory exercise. Two Axial Seamount-focused OCMs will be presented: 1) Lava Flow Characterization: Identifying a Suitable Cable Route, and 2) Assessing Hydrothermal Vent Communities: Comparisons Among Multiple Sulfide Chimneys.

  14. Investigation of x ray variability in highly active cool stars

    NASA Technical Reports Server (NTRS)

    Stern, Robert A.

    1989-01-01

    Ginga x ray observations of highly active cool star coronae were obtained and analyzed in an effort to better understand the nature of their time variability. The possible types of variability studied included x ray occultations via eclipses in a binary system, rotational modulation of x ray emission, flares, and a search for microflaring. Observation of both sigma(sup 2) CrB and Algol were performed successfully by Ginga. The sigma(sup 2) CrB observations occurred on 27 to 30 June 1988, and the Algol observations on 12 to 14 January 1989. In the sigma(sup 2) CrB observation, simultaneous IUE and Very Large Array (VLA) observations were obtained during part of the Ginga observation. Flaring activity was detected on sigma(sup 2) CrB in the Ginga 1.7 to 11 KeV band and in the IUE microwave region. A large flare on Algol which lasted well over 12 hours was detected, began with a maximum temperature of 65 MK which gradually decayed to 36 MK, and evidence was shown of highly ionized Fe line emission.

  15. Investigating the clinical usefulness of the Social Responsiveness Scale (SRS) in a tertiary level, autism spectrum disorder specific assessment clinic.

    PubMed

    Aldridge, Fiona J; Gibbs, Vicki M; Schmidhofer, Katherine; Williams, Megan

    2012-02-01

    The Social Responsiveness Scale (SRS; Constantino and Gruber in Social Responsiveness Scale (SRS). Western Psychological Services, Los Angeles, 2005) is a commonly used screening tool for identifying children with possible autism spectrum disorder (ASD). This study investigated the relationship between SRS scores and eventual diagnostic outcome for children referred to a tertiary level, autism specific assessment service. Forty eight children (mean age = 8.10; 92% male) underwent a comprehensive ASD assessment. Parent and teacher SRS scores were subsequently compared with diagnostic outcome. Sensitivity was high (91% for parent report; 84% for teacher report), however specificity was much lower (8% for parent report; 41% for teacher report). Results demonstrate a need for caution when interpreting SRS results based on current cut-off scores, particularly in children with previously identified social developmental problems. PMID:21516433

  16. Clinical evaluation of spermatogenic activity of processed Shilajit in oligospermia.

    PubMed

    Biswas, T K; Pandit, S; Mondal, S; Biswas, S K; Jana, U; Ghosh, T; Tripathi, P C; Debnath, P K; Auddy, R G; Auddy, B

    2010-02-01

    The safety and spermatogenic activity of processed Shilajit (PS) were evaluated in oligospermic patients. Initially, 60 infertile male patients were assessed and those having total sperm counts below 20 million ml(-1) semen were considered oligospermic and enrolled in the study (n = 35). PS capsule (100 mg) was administered twice daily after major meals for 90 days. Total semenogram and serum testosterone, luteinising hormone and follicle-stimulating hormone were estimated before and at the end of the treatment. Malondialdehyde (MDA), a marker for oxidative stress, content of semen and biochemical parameters for safety were also evaluated. Twenty-eight patients who completed the treatment showed significant (P < 0.001) improvement in spermia (+37.6%), total sperm count (+61.4%), motility (12.4-17.4% after different time intervals), normal sperm count (+18.9%) with concomitant decrease in pus and epithelial cell count compared with baseline value. Significant decrease of semen MDA content (-18.7%) was observed. Moreover, serum testosterone (+23.5%; P < 0.001) and FSH (+9.4%; P < 0.05) levels significantly increased. HPLC chromatogram revealed inclusion of PS constituents in semen. Unaltered hepatic and renal profiles of patients indicated that PS was safe at the given dose. The present findings provide further evidence of the spermatogenic nature of Shilajit, as attributed in Ayurvedic medicine, particularly when administered as PS. PMID:20078516

  17. Investigations of biomechanical activity of macrophages during phagocytosis

    NASA Astrophysics Data System (ADS)

    Kovari, Daniel; Curtis, Jennifer

    2012-02-01

    Phagocytosis has traditionally been investigated in terms of the relevant biochemical signaling pathways that trigger the process and lead to the deformation of the cell as it engulfs a target. Physical changes in the cell include rearrangement and polymerization of actin in the phagocytic cup, large membrane deformations, increased membrane area via exocytosis, and closure of the phagocytic cup through membrane fusion. Hence, phagocytosis is a fine-tuned balance between biophysical cellular events and chemical signaling, which are responsible for driving these materials and mechanical changes. We present a series of assays designed to probe the physical/mechanical parameters that govern a cell during phagocytosis. Custom built micropipette manipulators are used to manipulate individual cells, facilitating high-resolution microscopy of individual phagocytic events. This work has been supported by NSF PoLS #0848797.

  18. Characteristics of admissions and variations in the use of basic investigations, treatments and outcomes in Kenyan hospitals within a new Clinical Information Network

    PubMed Central

    Ayieko, Philip; Ogero, Morris; Makone, Boniface; Julius, Thomas; Mbevi, George; Nyachiro, Wycliffe; Nyamai, Rachel; Were, Fred; Githanga, David; Irimu, Grace; English, Mike

    2016-01-01

    Background Lack of detailed information about hospital activities, processes and outcomes hampers planning, performance monitoring and improvement in low-income countries (LIC). Clinical networks offer one means to advance methods for data collection and use, informing wider health system development in time, but are rare in LIC. We report baseline data from a new Clinical Information Network (CIN) in Kenya seeking to promote data-informed improvement and learning. Methods Data from 13 hospitals engaged in the Kenyan CIN between April 2014 and March 2015 were captured from medical and laboratory records. We use these data to characterise clinical care and outcomes of hospital admission. Results Data were available for a total of 30 042 children aged between 2 months and 15 years. Malaria (in five hospitals), pneumonia and diarrhoea/dehydration (all hospitals) accounted for the majority of diagnoses and comorbidity was found in 17 710 (59%) patients. Overall, 1808 deaths (6%) occurred (range per hospital 2.5%–11.1%) with 1037 deaths (57.4%) occurring by day 2 of admission (range 41%–67.8%). While malaria investigations are commonly done, clinical health workers rarely investigate for other possible causes of fever, test for blood glucose in severe illness or ascertain HIV status of admissions. Adherence to clinical guideline-recommended treatment for malaria, pneumonia, meningitis and acute severe malnutrition varied widely across hospitals. Conclusion Developing clinical networks is feasible with appropriate support. Early data demonstrate that hospital mortality remains high in Kenya, that resources to investigate severe illness are limited, that care provided and outcomes vary widely and that adoption of effective interventions remains slow. Findings suggest considerable scope for improving care within and across sites. PMID:26662925

  19. Theory, Investigation and Stability of Cathode Electrocatalytic Activity

    SciTech Connect

    Ding, Dong; Liu, Mingfei; Lai, Samson; Blinn, Kevin; Liu, Meilin

    2012-09-30

    The main objective of this project is to systematically characterize the surface composition, morphology, and electro-catalytic properties of catalysts coated on LSCF, aiming to establish the scientific basis for rational design of high-performance cathodes by combining a porous backbone (such as LSCF) with a thin catalyst coating. The understanding gained will help us to optimize the composition and morphology of the catalyst layer and microstructure of the LSCF backbone for better performance. More specifically, the technical objectives include: (1) to characterize the surface composition, morphology, and electro-catalytic properties of catalysts coated on LSCF; (2) to characterize the microscopic details and stability of the LSCF-catalyst (e.g., LSM) interfaces; (3) to establish the scientific basis for rational design of high-performance cathodes by combining a porous backbone (such as LSCF) with a thin catalyst coating; and (4) to demonstrate that the performance and stability of porous LSCF cathodes can be enhanced by the application of a thin-film coating of LSM through a solution infiltration process in small homemade button cells and in commercially available cells of larger dimension. We have successfully developed dense, conformal LSM films with desired structure, composition, morphology, and thickness on the LSCF surfaces by two different infiltration processes: a non-aqueous and a water-based sol-gel process. It is demonstrated that the activity and stability of LSCF cathodes can be improved by the introduction of a thin-film LSM coating through an infiltration process. Surface and interface of the LSM-coated LSCF cathode were systematically characterized using advanced microscopy and spectroscopy techniques. TEM observation suggests that a layer of La and Sr oxide was formed on LSCF surfaces after annealing. With LSM infiltration, in contrast, we no longer observe such La/Sr oxide layer on the LSM-coated LSCF samples after annealing under similar

  20. Clinical relevance of autophagic therapy in cancer: Investigating the current trends, challenges, and future prospects.

    PubMed

    Mukhopadhyay, Subhadip; Sinha, Niharika; Das, Durgesh Nandini; Panda, Prashanta Kumar; Naik, Prajna Paramita; Bhutia, Sujit Kumar

    2016-08-01

    Oncophagy (cancer-related autophagy) has a complex dual character at different stages of tumor progression. It remains an important clinical problem to unravel the reasons that propel the shift in the role of oncophagy from tumor inhibition to a protective mechanism that shields full-blown malignancy. Most treatment strategies emphasize curbing protective oncophagy while triggering the oncophagy that is lethal to tumor cells. In this review, we focus on the trends in current therapeutics as well as various challenges in clinical trials to address the oncophagic dilemma and evaluate the potential of these developing therapies. A detailed analysis of the clinical and pre-clinical scenario of the anticancer medicines highlights the various inducers and inhibitors of autophagy. The ways in which tumor stage, the microenvironment and combination drug treatment continue to play an important tactical role are discussed. Moreover, autophagy targets also play a crucial role in developing the best possible solution to this oncophagy paradox. In this review, we provide a comprehensive update on the current clinical impact of autophagy-based cancer therapeutic drugs and try to lessen the gap between translational medicine and clinical science. PMID:26743568

  1. Molecular Epigenetics in the Management of Ovarian Cancer: Are We Investigating a Rational Clinical Promise?

    PubMed Central

    Nguyen, Ha T.; Tian, Geng; Murph, Mandi M.

    2014-01-01

    Epigenetics is essentially a phenotypical change in gene expression without any alteration of the DNA sequence; the emergence of epigenetics in cancer research and mainstream oncology is fueling new hope. However, it is not yet known whether this knowledge will translate to improved clinical management of ovarian cancer. In this malignancy, women are still undergoing chemotherapy similar to what was approved in 1978, which to this day represents one of the biggest breakthroughs for treating ovarian cancer. Although liquid tumors are benefiting from epigenetically related therapies, solid tumors like ovarian cancer are not (yet?). Herein, we will review the science of molecular epigenetics, especially DNA methylation, histone modifications and microRNA, but also include transcription factors since they, too, are important in ovarian cancer. Pre-clinical and clinical research on the role of epigenetic modifications is also summarized. Unfortunately, ovarian cancer remains an idiopathic disease, for the most part, and there are many areas of patient management, which could benefit from improved technology. This review will also highlight the evidence suggesting that epigenetics may have pre-clinical utility in pharmacology and clinical applications for prognosis and diagnosis. Finally, drugs currently in clinical trials (i.e., histone deacetylase inhibitors) are discussed along with the promise for epigenetics in the exploitation of chemoresistance. Whether epigenetics will ultimately be the answer to better management in ovarian cancer is currently unknown; but we hope so in the future. PMID:24782983

  2. Noninvasive control of dental caries in children with active initial lesions. A randomized clinical trial.

    PubMed

    Hausen, H; Seppa, L; Poutanen, R; Niinimaa, A; Lahti, S; Kärkkäinen, S; Pietilä, I

    2007-01-01

    The aim of this study was to investigate whether DMFS increment can be decreased among children with active initial caries by oral hygiene and dietary counseling and by using noninvasive preventive measures. Except for mentally disabled and handicapped children attending special schools, all 11- to 12-year-olds in Pori, Finland, with at least one active initial caries lesion were invited to participate in the study and were then randomized into two groups. Children in the experimental group (n = 250) were offered an individually designed patient-centered preventive program aimed at identifying and eliminating factors that had led to the presence of active caries. The program included counseling sessions with emphasis on enhancing use of the children's own resources in everyday life. Toothbrushes, fluoride toothpaste and fluoride and xylitol lozenges were distributed to the children. They also received applications of fluoride/chlorhexidine varnish. The children in the control group (n = 247) received basic prevention offered as standard in the public dental clinics in Pori. For both groups, the average follow-up period was 3.4 years. A community level program of oral health promotion was run in Pori throughout this period. Mean DMFS increments for the experimental and control groups were 2.56 (95% CI 2.07, 3.05) and 4.60 (3.99, 5.21), respectively (p < 0.0001): prevented fraction 44.3% (30.2%, 56.4%). The results show that by using a regimen that includes multiple measures for preventing dental decay, caries increment can be significantly reduced among caries-active children living in an area where the overall level of caries experience is low. PMID:17713339

  3. A Systemic Review on Aloe arborescens Pharmacological Profile: Biological Activities and Pilot Clinical Trials.

    PubMed

    Singab, Abdel-Naser B; El-Hefnawy, Hala M; Esmat, Ahmed; Gad, Haidy A; Nazeam, Jilan A

    2015-12-01

    Since ancient times, plants and herbal preparations have been used as medicine. Research carried out in the last few decades has verified several such claims. Aloe arborescens Miller, belonging to the Aloe genus (Family Asphodelaceae), is one of the main varieties of Aloe used worldwide. The popularity of the plant in traditional medicine for several ailments (antitumor, immunomodulatory, antiinflammatory, antiulcer, antimicrobial and antifungal activity) focused the investigator's interest on this plant. Most importantly, the reported studies have shown the plant effectiveness on various cancer types such as liver, colon, duodenal, skin, pancreatic, intestinal, lung and kidney types. These multiple biological actions make Aloe an important resource for developing new natural therapies. However, the biological activities of isolated compounds such as glycoprotein, polysaccharides, enzyme and phenolics were insufficient. Considering all these, this contribution provides a systematic review outlining the evidence on the biological efficacy of the plant including the pharmacology and the related mechanisms of action, with specific attention to the various safety precautions, and preclinical and clinical studies, indicating the future research prospects of this plant. PMID:26768148

  4. Comparison of the activities of the lantibiotics nisin and lacticin 3147 against clinically significant mycobacteria.

    PubMed

    Carroll, James; Draper, Lorraine A; O'Connor, Paula M; Coffey, Aidan; Hill, Colin; Ross, R Paul; Cotter, Paul D; O'Mahony, Jim

    2010-08-01

    The aim of this study was to use the microtitre alamarBlue assay to investigate and compare the antimycobacterial potential of the lantibiotics nisin and lacticin 3147 against a representative cohort of clinically significant mycobacteria, i.e. Mycobacterium tuberculosis H37Ra, Mycobacterium avium subsp. paratuberculosis (MAP) ATCC 19698 and Mycobacterium kansasii CIT11/06. Lacticin 3147 displayed potent activity against all strains of mycobacteria, with MIC(90) values (lowest concentration of lantibiotic that prevented growth of >90% of the bacterial population) of 60 mg/L and 15 mg/L for M. kansasii and MAP, respectively. Lacticin 3147 was particularly effective against M. tuberculosis H37Ra, with a MIC(90) value of 7.5mg/L. Nisin, although inhibitory, was generally less potent against all strains of mycobacteria, with MIC(90) values of 60 mg/L for M. kansasii and >60 mg/L for MAP and M. tuberculosis H37Ra. Thus, lacticin 3147 is a potent antimycobacterial peptide that shows superior activity compared with nisin at physiological pH. PMID:20547041

  5. Clinical effects of deep cervical flexor muscle activation in patients with chronic neck pain

    PubMed Central

    Kim, Jin Young; Kwag, Kwang Il

    2016-01-01

    [Purpose] The purpose of this study was to investigate clinical effects of deep cervical flexor (DCF) muscles exercise on pain, Neck Disability Index (NDI), and neck and shoulder postures in patients with chronic neck pain. [Subjects and Methods] Twenty-eight patients with chronic neck pain were randomly assigned into either the general strengthening exercise (GSE) group or the DCF activation group as control and experimental groups, respectively. All exercises were performed three times per week over 4 weeks. NDI and numeric rating scale (NRS) score for pain were determined and radiological assessment of neck-shoulder postures (head tilt angle [HTA], neck flexion angle [NFA], and forward shoulder angle [FSA]) was performed before (baseline), 4 weeks after, and 8 weeks after exercise in order to directly compare the exercise effects between the groups. [Results] In the DCF group, the NDI, NRS score, and neck-shoulder postures (analyzed by uisng HTA, NFA, and FSA) were significantly improved. [Conclusion] DCF activation exercise was effective to alleviate pain, recover functions, and correct forward head posture in the patients with neck pain. Hence, it might be recommended in the rehabilitation of patients with chronic neck pain. PMID:26957772

  6. Deciphering logopenic primary progressive aphasia: a clinical, imaging and biomarker investigation.

    PubMed

    Teichmann, Marc; Kas, Aurélie; Boutet, Claire; Ferrieux, Sophie; Nogues, Marie; Samri, Dalila; Rogan, Christina; Dormont, Didier; Dubois, Bruno; Migliaccio, Raffaella

    2013-11-01

    Within primary progressive aphasia the logopenic variant remains less understood than the two other main variants, namely semantic and non-fluent progressive aphasia. This may be because of the relatively small number of explored patients and because of the lack of investigations with a comprehensive three-level characterization of cognitive, brain localization and biological aspects. The aim of the present study was to decipher the logopenic variant through a multimodal approach with a large cohort of 19 patients (age 66.5 ± 8.7 years, symptom duration 3.2 ± 0.6 years) using detailed cognitive and linguistic assessments, magnetic resonance imaging and perfusion single-photon emission computed tomography as well as cerebrospinal fluid biomarkers screening for Alzheimer pathology. The linguistic assessment unveiled that language dysfunction is not limited to the typical feature of word finding and verbal working memory impairments but that it extends into the language system affecting to some degree syntactic production, phonological encoding and semantic representations. Perfusion tomography revealed damage of the temporal-parietal junction with a peak of significance in the superior temporal gyrus (Brodmann area 42), and of some less significant prefrontal areas (Brodmann areas 8, 9 and 46), whereas hippocampal cortices were unaffected. Magnetic resonance imaging, which was visually assessed in a larger group of 54 patients with logopenic, non-fluent, semantic variants as well as with posterior cortical atrophy, confirmed that the logopenic variant demonstrates predominant atrophy of left temporal-parietal junction, but that this atrophy pattern has a relatively poor sensitivity and specificity for clinical diagnosis. Finally, the biomarker study revealed that two-thirds of the logopenic patients demonstrated a profile indicative of Alzheimer pathology whereas one-third had a non-Alzheimer profile. Splitting the two groups showed that logopenic aphasia due to

  7. Subliminal affective priming in clinical depression and comorbid anxiety: a longitudinal investigation.

    PubMed

    Dannlowski, Udo; Kersting, Anette; Lalee-Mentzel, Judith; Donges, Uta-Susan; Arolt, Volker; Suslow, Thomas

    2006-06-30

    In the present study, the sequential affective priming paradigm developed by Fazio et al. [Fazio, R.H., Sanbonmatsu, D.M., Powell, M.C., Kardes, F.R., 1986. On the automatic activation of attitudes. Journal of Personality and Social Psychology 50, 229-238.] was applied for the first time to investigate automatic cognitive bias in depressed patients. Unipolar depressed patients (n=22) were tested on admission and after about 7 weeks of inpatient psychotherapy. Half of the patients (n=11) were suffering from a comorbid anxiety disorder. Twenty-two healthy subjects served as controls. Affectively polarized prime words were presented subliminally followed by positive or negative target words, which had to be evaluated. Subjects' affective state was assessed by self-report measures. In the course of psychotherapy, patients recovered significantly. Study groups exhibited qualitatively different affective priming effects: In non-comorbid depressed patients, no affective priming was found. Instead, a highly significant main effect of prime valence emerged, indicating a Stroop-like interference of negative prime words at time 1. This negative bias was associated with depression level at time 1 and could not be found after recovery. Affective priming was observed in controls and comorbid patients, but in opposite directions. Direction and strength of affective priming was directly associated with anxiety level at both times. The affective priming paradigm provides evidence for differential group effects regarding unconscious emotional information processing. PMID:16725208

  8. 21 CFR 50.53 - Clinical investigations involving greater than minimal risk and no prospect of direct benefit to...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... knowledge about the subjects' disorder or condition. 50.53 Section 50.53 Food and Drugs FOOD AND DRUG... knowledge about the subjects' disorder or condition. Any clinical investigation within the scope described... knowledge about the subjects' disorder or condition that is of vital importance for the understanding...

  9. 21 CFR 50.52 - Clinical investigations involving greater than minimal risk but presenting the prospect of direct...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 1 2011-04-01 2011-04-01 false Clinical investigations involving greater than minimal risk but presenting the prospect of direct benefit to individual subjects. 50.52 Section 50.52 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROTECTION OF HUMAN SUBJECTS Additional Safeguards...

  10. Experimenting Clinical Pathways in General Practice: a Focus Group Investigation with Italian General Practitioners

    PubMed Central

    Zannini, Lucia; Cattaneo, Cesarina; Peduzzi, Paolo; Lopiccoli, Silvia; Auxilia, Francesco

    2012-01-01

    Background Clinical governance is considered crucial in primary care. Since 2005, clinical pathways have been experimentally implemented at the Local Health Authority of Monza Brianza (ASLMB), Italy, to develop general practitioners’ (GPs) care of patients affected by some chronic diseases. The experimentation was aimed at introducing clinical governance in primary care, increasing GPs’ involvement in the care of their patients, and improving both patients’ and professionals’ satisfaction. In the period 2005-2006, 12% of the 763 employed GPs in the ASLMB were involved in the experiment, while this percentage increased to 15-20% in 2007-2008. Design and Methods Twenty-four GPs were purposively sampled, randomly divided into two groups and asked to participate in focus groups (FGs) held in 2008, aimed at evaluating their perception of the experiment. The FGs were audio-recorded, dialogues were typed out and undergone to a thematic analysis, according to the Interpretative Phenomenological Approach. Results Four major themes emerged: i) clinical pathways can result in GPs working in a more efficient and effective fashion; ii) they can assure higher levels of both patient and professional satisfaction, since they sustain a caring approach and strengthen the GPs’ role; iii) nevertheless, clinical pathways increase the bureaucratic workload and problems can arise in relationships among GPs and the LHA; iv) the implementation of clinical pathways can be improved, especially by reducing bureaucracy and by assuring their continuity. Conclusions Managerial aspects should be considered with care in order to experimentally introduce clinical pathways in general practice, and continuity of the experimentation should be guaranteed to improve GPs’ adherence and commitment. Acknowledgments the Authors thank Dr. AP. Cantù and Dr D. Cereda who participated in the two focus groups as observers. PMID:25181354

  11. Disaccharidase activities in camel small intestine: biochemical investigations of maltase-glucoamylase activity.

    PubMed

    Mohamed, Saleh A; Fahmy, Afaf S; Salah, Hala A

    2007-01-01

    Disaccharidases (maltase, cellobiase, lactase, and sucrase), alpha-amylase, and glucoamylase in the camel small intestine were investigated to integrate the enzymatic digestion profile in camel. High activities were detected for maltase and glucoamylase, followed by moderate levels of sucrase and alpha-amylase. Very low activity levels were detected for lactase and cellobiase. Camel intestinal maltase-glucoamylase (MG) was purified by DEAE-Sepharose and Sephacryl S-200 columns. The molecular weight of camel small intestinal MG4 and MG6 were estimated to be 140,000 and 180,000 using Sephacryl S-200. These values were confirmed by SDS-PAGE, where the two enzymes migrated as single subunits. This study encompassed characterization of MGs from camel intestine. The Km values of MG4 and MG6 were estimated to be 13.3 mM and 20 mM maltose, respectively. Substrate specificity for MG4 and MG6 indicated that the two enzymes are maltase-glucoamylases because they catalysed the hydrolysis of maltose and starch with alpha-1,4 and alpha-1,6 glycosidic bonds, but not sucrose with alpha-1,2 glycosidic bond which was hydrolyzed by sucrase-isomaltase. Camel intestinal MG4 and MG6 had the same optimum pH at 7.0 and temperature optimum at 50 degrees C and 40 degrees C, respectively. The two enzymes were stable up to 50 degrees C and 40 degrees C, followed by strong decrease in activity at 60 degrees C and 50 degrees C, respectively. The effect of divalent cations on the activity of camel intestinal MG4 and MG6 was studied. All the examined divalent cations Ca(2+), Mn(2+), Mg(2+), Co(2+) and Fe(3+) had slight effects on the two enzymes except Hg(2+) which had a strong inhibitory effect. The effect of different inhibitors on MG4 and MG6 indicated that the two enzymes had a cysteine residue. PMID:17098455

  12. Informed consent for clinical trials in acute coronary syndromes and stroke following the European Clinical Trials Directive: investigators' experiences and attitudes

    PubMed Central

    Iwanowski, Piotr; Budaj, Andrzej; Członkowska, Anna; Wąsek, Wojciech; Kozłowska-Boszko, Beata; Olędzka, Urszula; Masełbas, Wojciech

    2008-01-01

    Background During clinical trials in emergency medicine, providing appropriate oral and written information to a patient is usually a challenge. There is little published information regarding patients' opinions and competence to provide informed consent, nor on physicians' attitudes towards the process. We have investigated the problem of obtaining consent from patients in emergency-setting clinical trials (such as acute coronary syndromes (ACS) and stroke) from a physicians' perspective. Methods A standardised anonymous 14-item questionnaire was distributed to Polish cardiac and stroke centres. Results Two hundred and fourteen informative investigator responses were received. Of these investigators, 73.8% had experience with ACS and 25.2% had experience with acute stroke trials (and 1% with both fields). The complete model of informed consent (embracing all aspects required by Good Clinical Practice (GCP) and law) was used in 53.3% of cases in emergency settings, whereas the legal option of proxy consent was not used at all. While less than 15% of respondents considered written information to have been fully read by patients, 80.4% thought that the amount of information being given to emergency patients is too lengthy. Although there is no legal obligation, more than half of the investigators sought parallel consent (assent) from patients' relatives. Most investigators confirmed that they would adopt the model proposed by the GCP guidelines: abbreviated verbal and written consent in emergency conditions with obligatory "all-embracing" deferred consent to continue the trial once the patient is able to provide it. However, this model would not follow current Polish and European legislation. Conclusion An update of national and European regulations is required to enable implementation of the emergency trial consent model referred to in GCP guidelines. PMID:18644120

  13. Investigating common clinical presentations in first opinion small animal consultations using direct observation

    PubMed Central

    Robinson, N. J.; Dean, R. S.; Cobb, M.; Brennan, M. L.

    2015-01-01

    Understanding more about the clinical presentations encountered in veterinary practice is vital in directing research towards areas relevant to practitioners. The aim of this study was to describe all problems discussed during a convenience sample of consultations using a direct observation method. A data collection tool was used to gather data by direct observation during small animal consultations at eight sentinel practices. Data were recorded for all presenting and non-presenting specific health problems discussed. A total of 1901 patients were presented with 3206 specific health problems discussed. Clinical presentation varied widely between species and between presenting and non-presenting problems. Skin lump, vomiting and inappetence were the most common clinical signs reported by the owner while overweight/obese, dental tartar and skin lump were the most common clinical examination findings. Skin was the most frequently affected body system overall followed by non-specific problems then the gastrointestinal system. Consultations are complex, with a diverse range of different clinical presentations seen. Considering the presenting problem only may give an inaccurate view of the veterinary caseload, as some common problems are rarely the reason for presentation. Understanding the common diagnoses made is the next step and will help to further focus questions for future research. PMID:25564472

  14. Correlation of alkaline phosphatase activity to clinical parameters of inflammation in smokers suffering from chronic periodontitis

    PubMed Central

    Grover, Vishakha; Malhotra, Ranjan; Kapoor, Anoop; Bither, Rupika; Sachdeva, Sonia

    2016-01-01

    Context: Current clinical periodontal diagnostic techniques emphasize the assessment of clinical and radiographic signs of periodontal diseases which can provide a measure of history of disease. Hence, new methodologies for early identification and determination of periodontal disease activity need to be explored which will eventually result in expedited treatment. Aim: To evaluate the correlation of alkaline phosphatase (ALP) activity in gingival crevicular fluid (GCF) to clinical parameters of periodontal inflammation in smokers with chronic periodontitis. Materials and Methods: Study population included 15 smoker male patients in the age group of 35–55 years suffering from moderate generalized chronic periodontitis with history of smoking present. Following parameters were evaluated at baseline, 1 month and 3 months after scaling and root planing: plaque index, bleeding index, probing pocket depth (PD), relative attachment level (RAL), and GCF ALP activity. Statistical Analysis Used: Independent variables for measurements over time were analyzed by using Wilcoxon signed rank test. Results: A statistically significant reduction in all the clinical parameters and GCF ALP activity was observed from baseline to 1 month and 3 months. A correlation was observed between change in GCF ALP activity and PD reduction as well as gain in RAL at 3 months. Conclusion: The present study emphasizes that total ALP activity could be used as a marker for periodontal disease activity in smokers. Estimation of changes in the levels of this enzyme has a potential to aid in the detection of progression of periodontal disease and monitoring the response to periodontal therapy. PMID:27563197

  15. Iranian Clinical Nurses’ Activities for Self-Directed Learning: A Qualitative Study

    PubMed Central

    Ghiyasvandian, Shahrzad; Malekian, Morteza; Cheraghi, Mohammad Ali

    2016-01-01

    Background: Clinical nurses need lifelong learning skills for responding to the rapid changes of clinical settings. One of the best strategies for lifelong learning is self-directed learning. The aim of this study was to explore Iranian clinical nurses’ activities for self-directed learning. Methods: In this qualitative study, 23 semi-structured personal interviews were conducted with nineteen clinical nurses working in all four hospitals affiliated to Isfahan Social Security Organization, Isfahan, Iran. Study data were analyzed by using the content analysis approach. The study was conducted from June 2013 to October 2014. Findings: Study participants’ activities for self-directed learning fell into two main categories of striving for knowledge acquisition and striving for skill development. The main theme of the study was ‘Revising personal performance based on intellectual-experiential activities’. Conclusions: Study findings suggest that Iranian clinical nurses continually revise their personal performance by performing self-directed intellectual and experiential activities to acquire expertise. The process of acquiring expertise is a linear process which includes two key steps of knowledge acquisition and knowledge development. In order to acquire and advance their knowledge, nurses perform mental learning activities such as sensory perception, self-evaluation, and suspended judgment step-by-step. Moreover, they develop their skills through doing activities like apprenticeship, masterly performance, and self-regulation. The absolute prerequisite to expertise acquisition is that a nurse needs to follow these two steps in a sequential manner. PMID:26652072

  16. Musculoskeletal disorders of the neck and upper limb among sewing machine operators: a clinical investigation.

    PubMed

    Andersen, J H; Gaardboe, O

    1993-12-01

    One hundred and seven women participated in a clinical study of an age-stratified random sample of sewing machine operators compared to a group of auxiliary nurses and home helpers. Four groups, according to years of being a sewing machine operator, consisted of: (controls) 25; (0-7 years) 21; (8-15 years) 25; and (more than 15 years) 36. The numbers of the main clinical diagnoses in the four groups were: cervicobrachial fibromyalgia (myofascial pain syndrome) 2, 4, 11, 24; cervical syndrome 0, 1, 3, 10; and rotator cuff syndrome 1, 1, 6, 11. The observed exposure-response relationship between clinical outcomes and years as a sewing machine operator was maintained when adjusting for current exposure to musculoskeletal strain and other potential confounders. Muscle palpation proved to be a reproducible examination with kappa values around 0.70. PMID:8311099

  17. Activities of Tannins--From In Vitro Studies to Clinical Trials.

    PubMed

    Sieniawska, Elwira

    2015-11-01

    Tannins are considered as valuable plant secondary metabolites providing many benefits for human health. In this review information was gathered about bioactivity in vitro and in vivo, as well as about conducted clinical trials. The literature research was based on ScienceDirect, Scopus, and Cochrane databases and presents a wide range of tested activities of tannins. The described clinical trials verify laboratory tests and show the effective health benefits taken from supplementation with tannins. PMID:26749816

  18. Correlation between clinical and MRI disease activity scores in axial spondyloarthritis.

    PubMed

    MacKay, James W; Aboelmagd, Sharief; Gaffney, J Karl

    2015-09-01

    Magnetic resonance (MR) imaging-based disease activity scores (DAS) in axial spondyloarthritis (axSpA) are rarely employed in the normal clinical setting, whereas clinical DAS are used routinely to monitor disease activity and set thresholds for biologic treatment. The objectives of this study were to evaluate the correlation between MR and clinical DAS in a general axSpA outpatient population and to assess the difference in MR DAS in individuals with high and low clinical DAS. This was a prospective, cross-sectional observational study. Forty participants with axSpA who presented for MR of the whole spine and sacroiliac joints as part of ongoing management were included. Completion of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS) was performed at the time of MR examination. MR images were scored by two independent observers using the Spondyloarthritis Research Consortium of Canada (SPARCC) MR DAS. There were weak, non-significant correlations between total SPARCC score and BASDAI (r = 0.18, p = 0.26), ASDAS using erythrocyte sedimentation rate (ASDAS-ESR) (r = 0.31, p = 0.07) and ASDAS using C-reactive protein level (ASDAS-CRP) (r = 0.31, p = 0.05). There was no significant difference in the SPARCC score of participants with high and low clinical DAS. MR DAS may provide information about disease activity not provided by the current standard of clinical DAS and may be considered as a useful adjunct in clinical practice. PMID:25894437

  19. The role of ultrasound simulators in education: an investigation into sonography student experiences and clinical mentor perceptions.

    PubMed

    Gibbs, Vivien

    2015-11-01

    Simulation as an effective pedagogy is gaining momentum at all levels of health care education. Limited research has been undertaken on the role of simulated learning in health care and further evaluation is needed to explore the quality of learning opportunities offered, and their effectiveness in the preparation of students for clinical practice. This study was undertaken to explore ways of integrating simulation-based learning into sonography training to enhance clinical preparation. A qualitative study was undertaken, using interviews to investigate the experiences of a group of sonography students after interacting with an ultrasound simulator. The perceptions of their clinical mentors on the effectiveness of this equipment to support the education and development of sonographers were also explored. The findings confirm that ultrasound simulators provide learning opportunities in an unpressurised environment, which reduces stress for the student and potential harm to patients. Busy clinical departments acknowledge the advantages of opportunities for students to acquire basic psychomotor skills in a classroom setting, thereby avoiding the inevitable reduction in patient throughput which results from clinical training. The limitations of simulation equipment to support the development of the full range of clinical skills required by sonographers were highlighted and suggestions made for more effective integration of simulation into the teaching and learning process. Ultrasound simulators have a role in sonography education, but continued research needs to be undertaken in order to develop appropriate strategies to support students, educators and mentors to effectively integrate this methodology. PMID:27433260

  20. A phenomenological investigation of overvalued ideas and delusions in clinical and subclinical anorexia nervosa.

    PubMed

    Mountjoy, Rachel L; Farhall, John F; Rossell, Susan L

    2014-12-15

    Anorexia Nervosa (AN) is an eating disorder characterised by distorted cognitions about body weight and shape; but little is known about the phenomenological characteristics of these beliefs. In this study, multidimensional and insight-based measurements were used to compare beliefs about body weight and shape in AN to body image dissatisfaction in the general population, and delusional beliefs in schizophrenia. Twenty participants with clinical and sub-clinical AN, 27 participants with schizophrenia and schizoaffective disorder, and 23 healthy controls completed the Brown Assessment of Beliefs Scale and the Psychotic Symptom Rating Scale in relation to a dominant belief regarding body weight/shape (or body dissatisfaction in healthy controls) or a current delusion. All groups completed the Peters Delusions Inventory to assess the prevalence of a range of delusion-like beliefs. Participants with clinical and subclinical AN experienced significantly higher preoccupation and distress for their belief in comparison to both participants with schizophrenia/schizoaffective disorder rating a delusional belief and the healthy controls rating a belief of body dissatisfaction. Both clinical groups were comparable on ratings of belief conviction and disruption. The data raise questions regarding the current frameworks that are used to describe beliefs in AN. PMID:25138896

  1. It Takes a Village: Investigating the Critical Role Clinical Faculty Play in Mathematics Teacher Education

    ERIC Educational Resources Information Center

    Bahr, Damon L.

    2013-01-01

    The dispositions of preservice elementary education teachers toward reform-oriented mathematics education were surveyed before and after an extended pre-student teaching practicum. During the practicum, university and school-based personnel served as 'clinical faculty' as they supported the preservice teachers' practicum…

  2. An Empirical Investigation of Group Treatment for a Clinical Population of Adult Female Incest Survivors.

    ERIC Educational Resources Information Center

    Saxe, Brenda J.; Johnson, Susan M.

    1999-01-01

    Empirically assesses the effectiveness of a group treatment program on intrapersonal symptomatology and interpersonal difficulties in a clinical population of women with a history of incest. Results indicate that a time-limited group, which focuses on the original trauma, is effective in reducing intrapersonal symptomatology for women with a…

  3. Investigating the Effects of an Experimental Approach to Comprehension Instruction within a Literacy Clinic

    ERIC Educational Resources Information Center

    Ortlieb, Evan; McDowell, F. D.

    2015-01-01

    Reading comprehension levels of elementary students have not significantly improved in the 21st century and as a result, the need for systematic and intensive reading interventions is as high as ever. Literacy clinics are an ideal setting for struggling readers to experience success through the implementation of a cyclical approach to individual…

  4. Phase II clinical trials on Investigational drugs for the Treatment of Pancreatic Cancers

    PubMed Central

    Kim, Edward J.; Semrad, Thomas J.; Bold, Richard J.

    2015-01-01

    Introduction Despite some recent advances in treatment options, pancreatic cancer remains a devastating disease with poor outcomes. In a trend contrary to most malignancies, both incidence and mortality continue to rise due to pancreatic cancer. The majority of patients present with advanced disease and there are no treatment options for this stage that have demonstrated a median survival greater than 1 year. As the penultimate step prior to phase III studies involving hundreds of patients, phase II clinical trials provide an early opportunity to evaluate the efficacy of new treatments that are desperately needed for this disease. Areas Covered This review covers the results of published phase II clinical trials in advanced pancreatic adenocarcinoma published within the past 5 years. The treatment results are framed in the context of the current standards of care and the historic challenge of predicting phase III success from phase II trial results. Expert opinion Promising therapies remain elusive in pancreatic cancer based on recent phase II clinical trial results. Optimization and standardization of clinical trial design in the phase II setting, with consistent incorporation of biomarkers, is needed to more accurately identify promising therapies that warrant phase III evaluation. PMID:25809274

  5. 77 FR 34958 - Draft Guidance for Institutional Review Boards, Clinical Investigators, and Sponsors...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-12

    ....gov/ScienceResearch/SpecialTopics/RunningClinicalTrials/ProposedRegulationsandDraftGuidances/default... Drug Information, Center for Drug Evaluation and Research (CDER), Food and Drug Administration, 10903... and Research (CBER), Food and Drug Administration, 1401 Rockville Pike, Suite 200N, Rockville,...

  6. 77 FR 11555 - Guidance for Institutional Review Boards, Clinical Investigators, and Sponsors: Institutional...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-27

    .../ScienceResearch/SpecialTopics/RunningClinicalTrials/GuidancesInformationSheetsandNotices/ucm113709.htm... Research (CDER), Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, Rm. 2201, Silver Spring... Development (HFM-40), Center for Biologics Evaluation and Research (CBER), Food and Drug Administration,...

  7. In vitro antimicrobial activity of ten medicinal plants against clinical isolates of oral cancer cases

    PubMed Central

    2011-01-01

    Background Suppression of immune system in treated cancer patients may lead to secondary infections that obviate the need of antibiotics. In the present study, an attempt was made to understand the occurrence of secondary infections in immuno-suppressed patients along with herbal control of these infections with the following objectives to: (a) isolate the microbial species from the treated oral cancer patients along with the estimation of absolute neutrophile counts of patients (b) assess the in vitro antimicrobial activity medicinal plants against the above clinical isolates. Methods Blood and oral swab cultures were taken from 40 oral cancer patients undergoing treatment in the radiotherapy unit of Regional Cancer Institute, Pt. B.D.S. Health University, Rohtak, Haryana. Clinical isolates were identified by following general microbiological, staining and biochemical methods. The absolute neutrophile counts were done by following the standard methods. The medicinal plants selected for antimicrobial activity analysis were Asphodelus tenuifolius Cav., Asparagus racemosus Willd., Balanites aegyptiaca L., Cestrum diurnum L., Cordia dichotoma G. Forst, Eclipta alba L., Murraya koenigii (L.) Spreng. , Pedalium murex L., Ricinus communis L. and Trigonella foenum graecum L. The antimicrobial efficacy of medicinal plants was evaluated by modified Kirby-Bauer disc diffusion method. MIC and MFC were investigated by serial two fold microbroth dilution method. Results Prevalent bacterial pathogens isolated were Staphylococcus aureus (23.2%), Escherichia coli (15.62%), Staphylococcus epidermidis (12.5%), Pseudomonas aeruginosa (9.37%), Klebsiella pneumonia (7.81%), Proteus mirabilis (3.6%), Proteus vulgaris (4.2%) and the fungal pathogens were Candida albicans (14.6%), Aspergillus fumigatus (9.37%). Out of 40 cases, 35 (87.5%) were observed as neutropenic. Eight medicinal plants (A. tenuifolius, A. racemosus, B. aegyptiaca, E. alba, M. koenigii, P. murex R. communis and T

  8. Recent activities of EC4 in the harmonization of clinical chemistry in the European Union.

    PubMed

    Sanders, G T; Jansen, R T; Beastall, G; Gurr, E; Kenny, D; Kohse, K P; Zérah, S

    1999-04-01

    This article describes the recent activities of the European Communities Confederation of Clinical Chemistry (EC4). Main goal of EC4 is harmonization of clinical chemistry in the European Union and Europe. EC4's actions connected to that are training and registration of professionals, and accreditation of laboratories. The 35000 professionals practising clinical chemistry in the EU have different backgrounds (medical, pharmaceutical, science-oriented, veterinary, or microbiological). Thus, for the harmonization of training of clinical chemists, EC4 has published a European Syllabus for Postgraduate Training, and instituted a European Union Register for Clinical Chemists. The Syllabus is an indication of the level of requirements in postgraduate training. The EC4 initiative to implement the European Register for Clinical Chemists is based on the 8 years vocational training necessary to obtain sufficient knowledge in clinical chemistry according to the European Syllabus. A guide to the EC4 Register has been published; registration leads to the title European Clinical Chemist (EurClinChem). The accreditation of laboratories must be based on a total quality management system. EC4 has described guidelines (essential criteria) which it judges appropriate for establishing the quality of medical laboratory service; it does not wish to fulfil the role of an accrediting body. Moreover, a working group has been set up to seek to harmonize the work of national accrediting bodies. Therefore, it is logical that EC4 monitors the activities of the different standardizing bodies that might influence the practice of clinical chemistry in the EU. Finally, some aspects concerning the future strategy of EC4 are brought forward. PMID:10369121

  9. Health literacy screening of patients attending a student-led osteopathy clinic: A pilot investigation.

    PubMed

    Vaughan, Brett; Mulcahy, Jane; Fitzgerald, Kylie

    2016-08-01

    Adequate levels of health literacy (HL) are required for patients to access appropriate health services and develop an understanding of the options for managing their healthcare needs. There is limited literature on HL of patients seeking care for a musculoskeletal complaint. The present study sought to screen the HL of patients presenting to an Australian osteopathy student-led clinic using a single screening question 'Are you confident completing medical forms?'. Less than 10% of patients attending the clinic were considered to have below adequate levels of HL using this question, consistent with other work in Australian populations. Logistic regression analysis identified that the most significant demographic variables associated with lower HL were patients who did not speak English at home, those with lower education levels, and those who were less satisfied with their life. Evaluation of a patients' HL may assist practitioners to improve patient education and management strategies. PMID:27502799

  10. An Intelligent Computerized Stretch Reflex Measurement System For Clinical And Investigative Neurology

    NASA Astrophysics Data System (ADS)

    Flanagan, P. M.; Chutkow, J. G.; Riggs, M. T.; Cristiano, V. D.

    1987-05-01

    We describe the design of a reliable, user-friendly preprototype system for quantifying the tendon stretch reflexes in humans and large mammals. A hand-held, instrumented reflex gun, the impactor of which contains a single force sensor, interfaces with a computer. The resulting test system can deliver sequences of reproducible stimuli at graded intensities and adjustable durations to a muscle's tendon ("tendon taps"), measure the impacting force of each tap, and record the subsequent reflex muscle contraction from the same tendon -- all automatically. The parameters of the reflex muscle contraction include latency; mechanical threshold; and peak time, peak magnitude, and settling time. The results of clinical tests presented in this paper illustrate the system's potential usefulness in detecting neurologic dysfunction affecting the tendon stretch reflexes, in documenting the course of neurologic illnesses and their response to therapy, and in clinical and laboratory neurologic research.

  11. Methodology guideline for clinical studies investigating traditional Chinese medicine and integrative medicine: executive summary.

    PubMed

    Liu, Jian-Ping; Chen, Ke-Ji

    2015-10-01

    This guideline aims to provide a methodological guidance for clinical studies in TCM and integrative medicine in terms of study design, execution, and reporting. The commonly used methods including experimental and observational methods were introduced in this guideline such as randomized clinical trials, cohort study, case-control study, case series, and qualitative method which can be incorporated into above quantitative methods. The guideline can be used for the evaluation of therapeutic effect of TCM therapies or their combination with conventional therapy. TCM therapy refers to one of the followings or their combination: herbal medicine, acupuncture, moxibustion, cupping, Taichi/Qigong, and Guasha,Tuina (therapeutic massage). It is also suitable for research and development of ethnopharmaceuticals or folk medicine. PMID:26615617

  12. Investigation of the clinical features in filamentary keratitis in Hangzhou, east of China

    PubMed Central

    Chen, Siming; Ruan, Yimeng; Jin, Xiuming

    2016-01-01

    Abstract Filamentary keratitis (FK) is a chronic and recurrent disorder of the cornea. FK is reportedly associated with various kinds of ocular surface diseases or conditions. Until now, there have been lacks of studies based on quantitative sample analysis concerning FK incidence regularity and inducement characteristics at different ages. This was a retrospective study of 147 patients (162 eyes) with FK who had been continuously and completely recorded from August 2012 to August 2015 at the Second Affiliated Hospital of Zhejiang University in Hangzhou, east of China. Our results suggest that the causative factors of FK varied at different ages and the distribution of filaments on the corneal surface was also diverse with different inducements. By exploring the frequency and clinical features of FK, we believe that the findings from our research will be clinically significant and aid in the early prevention and treatment guidance of the disease. PMID:27583881

  13. Investigation of the clinical features in filamentary keratitis in Hangzhou, east of China.

    PubMed

    Chen, Siming; Ruan, Yimeng; Jin, Xiuming

    2016-08-01

    Filamentary keratitis (FK) is a chronic and recurrent disorder of the cornea. FK is reportedly associated with various kinds of ocular surface diseases or conditions. Until now, there have been lacks of studies based on quantitative sample analysis concerning FK incidence regularity and inducement characteristics at different ages. This was a retrospective study of 147 patients (162 eyes) with FK who had been continuously and completely recorded from August 2012 to August 2015 at the Second Affiliated Hospital of Zhejiang University in Hangzhou, east of China. Our results suggest that the causative factors of FK varied at different ages and the distribution of filaments on the corneal surface was also diverse with different inducements.By exploring the frequency and clinical features of FK, we believe that the findings from our research will be clinically significant and aid in the early prevention and treatment guidance of the disease. PMID:27583881

  14. Opinions and perceptions regarding the impact of new regulatory guidelines: A survey in Indian Clinical Trial Investigators

    PubMed Central

    Kadam, Rashmi; Borde, Sanghratna; Madas, Sapna; Nagarkar, Aarti; Salvi, Sundeep; Limaye, Sneha

    2016-01-01

    Background: Clinical research in India experienced dramatic changes with series of stringent guidelines introduced by regulatory authorities. These guidelines posed significant challenges for the clinical trial industry. Objective: To assess the perceptions and opinion of Indian Investigators about the new regulatory guidelines. Methods: We developed a survey questionnaire on recent regulatory guidelines which was hosted on a web portal. Seventy-three investigators from India participated in the survey. Results: Central registration of Ethics Committees (ECs) was agreed by 90.1% participants, 76.8% participants agreed to compensation of subjects for study related Serious Adverse Events (SAE's). The compulsion to include government sites in clinical trials was not agreed by 49.3% participants while 21.2% agreed to it. Restriction on a number of trials per investigator was agreed by 49.3% of participants while 40.9% disagreed. Participants (50.7%) disagreed to the introduction of audio-video (AV) recording of informed consent, 36.6% agreed and 12.7% were neutral. Discussion: Participants observed that post central registration; ECs have improved systems with adequate member composition, functional Standard Operating Procedures, and timely approvals. Participants agreed that compensation of study related SAE's would assure subject protection and safety. The introduction of AV consenting was strongly debated sighting sociocultural issues in the implementation of the same. Conclusion: Participants endorsed guidelines pertaining to the central registration of ECs, SAE related compensation. Restrictions on a number of trials per investigator and AV consenting were debated ardently. The response of the survey participants who are clinical trial investigators in India showed general acceptance, effectiveness and anticipated compliance to the new regulatory guidelines. PMID:27141474

  15. A psychometric investigation of "macroscopic" speech measures for clinical and psychological science.

    PubMed

    Cohen, Alex S; Renshaw, Tyler L; Mitchell, Kyle R; Kim, Yunjung

    2016-06-01

    The analysis of vocal expression is a critical endeavor for psychological and clinical sciences and is an increasingly popular application for computer-human interfaces. Despite this, and despite advances in the efficiency, affordability, and sophistication of vocal analytic technologies, there is considerable variability across studies regarding what aspects of vocal expression are studied. Vocal signals can be quantified in a myriad of ways, and their underlying structure, at least with respect to "macroscopic" measures from extended speech, is presently unclear. To address this issue, we evaluated the psychometric properties-notably, the structural and construct validity-of a systematically defined set of global vocal features. Our analytic strategy focused on (a) identifying redundant variables among this set, (b) employing principal components analysis (PCA) to identify nonoverlapping domains of vocal expression, (c) examining the degrees to which the vocal variables are modulated as a function of changes in speech task, and (d) evaluating the relationship between the vocal variables and cognitive (i.e., verbal fluency) and clinical (i.e., depression, anxiety, and hostility) variables. Spontaneous speech samples from 11 independent studies of young adults (>60 s in length), employing one of three different speaking tasks, were examined (N = 1,350). Confounding variables (i.e., sex, ethnicity) were statistically controlled for. The PCA identified six distinct domains of vocal expression. Collectively, vocal expression (defined in terms of these domains) was modulated as a function of speech task and was related to the cognitive and clinical variables. These findings provide empirically grounded implications for the study of vocal expression in psychological and clinical sciences. PMID:25862539

  16. Clinical and MRI investigation of temporomandibular joint in major depressed patients

    PubMed Central

    Lopes, SLPC; Costa, ALF; Cruz, AD; Li, LM; de Almeida, SM

    2012-01-01

    Objective The aim of the present study was to describe the clinical and MRI findings of the temporomandibular joint (TMJ) in patients with major depressive disorders (MDDs) of the non-psychotic type. Methods 40 patients (80 TMJs) who were diagnosed as having MDDs were selected for this study. The clinical examination of the TMJs was conducted according to the research diagnostic criteria and temporomandibular disorders (TMDs). The MRIs were obtained bilaterally in each patient with axial, parasagittal and paracoronal sections within a real-time dynamic sequence. Two trained oral radiologists assessed all images. For statistical analyses, Fisher's exact test and χ2 test were applied (α = 0.05). Results Migraine was reported in 52.5% of subjects. Considering disc position, statistically significant differences between opening patterns with and without alteration (p = 0.00) and between present and absent joint noises (p = 0.00) were found. Regarding muscular pain, patients with and without abnormalities in disc function and patients with and without abnormalities in disc position were not statistically significant (p = 0.42 and p = 0.40, respectively). Significant differences between mandibular pathway with and without abnormalities (p = 0.00) and between present and absent joint noises (p = 0.00) were observed. Conclusion Based on the preliminary results observed by clinical and MRI examination of the TMJ, no direct relationship could be determined between MDDs and TMDs. PMID:22517997

  17. Investigation of ultra low-dose scans in the context of quantum-counting clinical CT

    NASA Astrophysics Data System (ADS)

    Weidinger, T.; Buzug, T. M.; Flohr, T.; Fung, G. S. K.; Kappler, S.; Stierstorfer, K.; Tsui, B. M. W.

    2012-03-01

    In clinical computed tomography (CT), images from patient examinations taken with conventional scanners exhibit noise characteristics governed by electronics noise, when scanning strongly attenuating obese patients or with an ultra-low X-ray dose. Unlike CT systems based on energy integrating detectors, a system with a quantum counting detector does not suffer from this drawback. Instead, the noise from the electronics mainly affects the spectral resolution of these detectors. Therefore, it does not contribute to the image noise in spectrally non-resolved CT images. This promises improved image quality due to image noise reduction in scans obtained from clinical CT examinations with lowest X-ray tube currents or obese patients. To quantify the benefits of quantum counting detectors in clinical CT we have carried out an extensive simulation study of the complete scanning and reconstruction process for both kinds of detectors. The simulation chain encompasses modeling of the X-ray source, beam attenuation in the patient, and calculation of the detector response. Moreover, in each case the subsequent image preprocessing and reconstruction is modeled as well. The simulation-based, theoretical evaluation is validated by experiments with a novel prototype quantum counting system and a Siemens Definition Flash scanner with a conventional energy integrating CT detector. We demonstrate and quantify the improvement from image noise reduction achievable with quantum counting techniques in CT examinations with ultra-low X-ray dose and strong attenuation.

  18. Blood stream infections caused by Acinetobacter baumannii group in Japan - Epidemiological and clinical investigation.

    PubMed

    Fujikura, Yuji; Yuki, Atsushi; Hamamoto, Takaaki; Kawana, Akihiko; Ohkusu, Kiyofumi; Matsumoto, Tetsuya

    2016-06-01

    Acinetobacter calcoaceticus-Acinetobacter baumannii complex, especially A. baumannii, Acinetobacter pittii and Acinetobacter nosocomialis, constitutes an important group of nosocomial pathogens; however, epidemiological or clinical characteristics and prognosis is limited in Japan. From 2009 to 2013, 47 blood stream infection cases resulting from A. baumannii group were reviewed at the National Defense Medical College, an 800-bed tertiary hospital. To determine the genospecies, further comparative nucleotide sequence analyses of the RNA polymerase b-subunit (rpoB) gene were performed. Sequence analysis of rpoB gene showed that 25 (49.0%), 17 (33.3%) and 5 (9.8%) cases were caused by A. baumannii, A. pittii and A. nosocomialis, respectively. The 30-day and in-hospital mortality rates of A. baumannii were 8.5% and 25.5%, respectively, and there were no significant differences between Acinetobacter species. Clinical characteristics were statistically insignificant. Multidrug-resistant Acinetobacter species were detected in 3 cases (5.9%) with same pulsed-field gel electrophoresis (PFGE) pattern and A. baumannii was less susceptible to amikacin and levofloxacin. In this study, the mortality and clinical characteristics were similar among A. baumannii group isolate cases despite some showing drug resistance. However, identification of Acinetobacter species helps to initiate appropriate antibiotic therapy in earlier treatment phase, because A. baumannii shows some drug resistance. PMID:26993173

  19. 75 FR 31794 - Information Sheet Guidance for Sponsors, Clinical Investigators, and IRBs; Frequently Asked...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-04

    ... FR 5861), which describes FDA's intention to update the process for developing, issuing, and making... Guidances as needed. In the Federal Register of July 29, 2008 (73 FR 43940), FDA announced the availability... Investigators, and IRBs; Frequently Asked Questions--Statement of Investigator (Form FDA 1572);...

  20. 77 FR 69631 - Draft Guidance for IRBs, Clinical Investigators, and Sponsors: IRB Responsibilities for Reviewing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-20

    ... Persons with access to the Internet may obtain the document at http://www.fda.gov/ScienceResearch/Special... Sponsors: IRB Responsibilities for Reviewing the Qualifications of Investigators, Adequacy of Research... Responsibilities for Reviewing the Qualifications of Investigators, Adequacy of Research Sites, and...

  1. Activities of Clinafloxacin, Gatifloxacin, Gemifloxacin, and Trovafloxacin against Recent Clinical Isolates of Levofloxacin-Resistant Streptococcus pneumoniae

    PubMed Central

    Jorgensen, J. H.; Weigel, L. M.; Swenson, J. M.; Whitney, C. G.; Ferraro, M. J.; Tenover, F. C.

    2000-01-01

    The activities of two investigational fluoroquinolones and three fluoroquinolones that are currently marketed were determined for 182 clinical isolates of Streptococcus pneumoniae. The collection included 57 pneumococcal isolates resistant to levofloxacin (MIC ≥ 8 μg/ml) recovered from patients in North America and Europe. All isolates were tested with clinafloxacin, gatifloxacin, gemifloxacin, levofloxacin, and trovafloxacin by the National Committee for Clinical Laboratory Standards broth microdilution and disk diffusion susceptibility test methods. Gemifloxacin demonstrated the greatest activity on a per gram basis, followed by clinafloxacin, trovafloxacin, gatifloxacin, and levofloxacin. Scatterplots of the MICs and disk diffusion zone sizes revealed a well-defined separation of levofloxacin-resistant and -susceptible strains when the isolates were tested against clinafloxacin and gatifloxacin. DNA sequence analyses of the quinolone resistance-determining regions of gyrA, gyrB, parC, and parE from 21 of the levofloxacin-resistant strains identified eight different patterns of amino acid changes. Mutations among the four loci had the least effect on the MICs of gemifloxacin and clinafloxacin, while the MICs of gatifloxacin and trovafloxacin increased by up to six doubling dilutions. These data indicate that the newer fluoroquinolones have greater activities than levofloxacin against pneumococci with mutations in the DNA gyrase or topoisomerase IV genes. Depending upon pharmacokinetics and safety, the greater potency of these agents could provide improved clinical efficacy against levofloxacin-resistant pneumococcal strains. PMID:11036007

  2. Impact of the 2010 Consensus Recommendations of the Clinical Trial Design Task Force of the NCI Investigational Drug Steering Committee.

    PubMed

    Seymour, Lesley; Groshen, Susan; Rosner, Gary L; Sullivan, Daniel M; Spriggs, David R; Reeves, Steven; Gravell, Amy; Ivy, S Percy; Ratain, Mark J

    2015-11-15

    Oncology phase III trials have a high failure rate, leading to high development costs. The Clinical Trials Design Task Force of the Investigational Drug Steering Committee of the NCI Cancer Therapy and Evaluation Program developed Recommendations regarding the design of phase II trials. We report here on the results of a Concordance Group review charged with documenting whether concordance rates improved after the publication of the Recommendations. One hundred and fifty-five trials were reviewed. Letter of Intents (LOI) from the post-Recommendation period were more likely to be randomized (44% vs. 34%) and biomarker selected (19% vs. 10%). Single-arm studies using time-to-event endpoints (benchmarked against historical data) were similar, as was the type of tumor. There was a significant improvement in the rate of concordance, with 74% of LOIs scored as concordant compared with 58% before the Recommendations (P = 0.042). This included a marked decrease in the use of single-arm designs to evaluate the activity of drug combinations (19% vs. 5%, P = 0.009). There were areas for which clarification was warranted, including the need for protocols to include further development plans, the use of realistic benchmarks, the careful evaluation of historical controls, and the use of a standard treatment option as a control. Ongoing critical evaluation of current trial design methodology and the development of new Guidelines when appropriate will continue to improve drug development ensuring that safe and effective cancer therapeutics are made available to our patients as quickly and efficiently as possible. PMID:26567365

  3. Active video games to promote physical activity in children with cancer: a randomized clinical trial with follow-up

    PubMed Central

    2014-01-01

    Background Low levels of physical activity, musculoskeletal morbidity and weight gain are commonly reported problems in children with cancer. Intensive medical treatment and a decline in physical activity may also result in reduced motor performance. Therefore, simple and inexpensive ways to promote physical activity and exercise are becoming an increasingly important part of children’s cancer treatment. Methods The aim of this study is to evaluate the effect of active video games in promotion of physical activity in children with cancer. The research is conducted as a parallel randomized clinical trial with follow-up. Patients between 3 and 16 years old, diagnosed with cancer and treated with vincristine in two specialized medical centers are asked to participate. Based on statistical estimates, the target enrollment is 40 patients. The intervention includes playing elective active video games and, in addition, education and consultations for the family. The control group will receive a general recommendation for physical activity for 30 minutes per day. The main outcomes are the amount of physical activity and sedentary behavior. Other outcomes include motor performance, fatigue and metabolic risk factors. The outcomes are examined with questionnaires, diaries, physical examinations and blood tests at baseline and at 2, 6, 12 and 30 months after the baseline. Additionally, the children’s perceptions of the most enjoyable activation methods are explored through an interview at 2 months. Discussion This trial will help to answer the question of whether playing active video games is beneficial for children with cancer. It will also provide further reasoning for physical activity promotion and training of motor skills during treatment. Trial registration ClinicalTrials.gov identifier: NCT01748058 (October 15, 2012). PMID:24708773

  4. Changes in muscle activity determine progression of clinical symptoms in patients with chronic spine-related muscle pain. A complex clinical and neurophysiological approach

    PubMed Central

    Wytra̦żek, Marcin; Huber, Juliusz; Lisiński, Przemysław

    Summary Spine-related muscle pain can affect muscle strength and motor unit activity. This study was undertaken to investigate whether surface electromyographic (sEMG) recordings performed during relaxation and maximal contraction reveal differences in the activity of muscles with or without trigger points (TRPs). We also analyzed the possible coexistence of characteristic spontaneous activity in needle electromyographic (eEMG) recordings with the presence of TRPs. Thirty patients with non-specific cervical and back pain were evaluated using clinical, neuroimaging and electroneurographic examinations. Muscle pain was measured using a visual analog scale (VAS), and strength using Lovett’s scale; trigger points were detected by palpation. EMG was used to examine motor unit activity. Trigger points were found mainly in the trapezius muscles in thirteen patients. Their presence was accompanied by increased pain intensity, decreased muscle strength, increased resting sEMG amplitude, and decreased sEMG amplitude during muscle contraction. eEMG revealed characteristic asynchronous discharges in TRPs. The results of EMG examinations point to a complexity of muscle pain that depends on progression of the myofascial syndrome PMID:22152435

  5. CLINICAL SURFACES - Activity-Based Computing for Distributed Multi-Display Environments in Hospitals

    NASA Astrophysics Data System (ADS)

    Bardram, Jakob E.; Bunde-Pedersen, Jonathan; Doryab, Afsaneh; Sørensen, Steffen

    A multi-display environment (MDE) is made up of co-located and networked personal and public devices that form an integrated workspace enabling co-located group work. Traditionally, MDEs have, however, mainly been designed to support a single “smart room”, and have had little sense of the tasks and activities that the MDE is being used for. This paper presents a novel approach to support activity-based computing in distributed MDEs, where displays are physically distributed across a large building. CLINICAL SURFACES was designed for clinical work in hospitals, and enables context-sensitive retrieval and browsing of patient data on public displays. We present the design and implementation of CLINICAL SURFACES, and report from an evaluation of the system at a large hospital. The evaluation shows that using distributed public displays to support activity-based computing inside a hospital is very useful for clinical work, and that the apparent contradiction between maintaining privacy of medical data in a public display environment can be mitigated by the use of CLINICAL SURFACES.

  6. Scientific Rationale Supporting the Clinical Development Strategy for the Investigational Aurora A Kinase Inhibitor Alisertib in Cancer

    PubMed Central

    Niu, Huifeng; Manfredi, Mark; Ecsedy, Jeffrey A.

    2015-01-01

    Alisertib (MLN8237) is a selective small molecule inhibitor of Aurora A kinase that is being developed in multiple cancer indications as a single agent and in combination with other therapies. A significant amount of research has elucidated a role for Aurora A in orchestrating numerous activities of cells transiting through mitosis and has begun to shed light on potential non-mitotic roles for Aurora A as well. These biological insights laid the foundation for multiple clinical trials evaluating the antitumor activity of alisertib in both solid cancers and heme-lymphatic malignancies. Several key facets of Aurora A biology as well as empirical data collected in experimental systems and early clinical trials have directed the development of alisertib toward certain cancer types, including neuroblastoma, small cell lung cancer, neuroendocrine prostate cancer, atypical teratoid/rhabdoid tumors, and breast cancer among others. In addition, these scientific insights provided the rationale for combining alisertib with other therapies, including microtubule perturbing agents, such as taxanes, EGFR inhibitors, hormonal therapies, platinums, and HDAC inhibitors among others. Here, we link the key aspects of the current clinical development of alisertib to the originating scientific rationale and provide an overview of the alisertib clinical experience to date. PMID:26380220

  7. Drug interaction profile of the HIV integrase inhibitor cabotegravir: assessment from in vitro studies and a clinical investigation with midazolam.

    PubMed

    Reese, Melinda J; Bowers, Gary D; Humphreys, Joan E; Gould, Elizabeth P; Ford, Susan L; Webster, Lindsey O; Polli, Joseph W

    2016-01-01

    1. Cabotegravir (CAB; GSK1265744) is a potent HIV integrase inhibitor in clinical development as an oral lead-in tablet and long-acting injectable for the treatment and prevention of HIV infection. 2. This work investigated if CAB was a substrate for efflux transporters, the potential for CAB to interact with drug-metabolizing enzymes and transporters to cause clinical drug interactions, and the effect of CAB on the pharmacokinetics of midazolam, a CYP3A4 probe substrate, in humans. 3. CAB is a substrate for Pgp and BCRP; however, its high intrinsic membrane permeability limits the impact of these transporters on its intestinal absorption. 4. At clinically relevant concentrations, CAB did not inhibit or induce any of the CYP or UGT enzymes evaluated in vitro and had no effect on the clinical pharmacokinetics of midazolam. 5. CAB is an inhibitor of OAT1 (IC50 0.81 µM) and OAT3 (IC50 0.41 µM) but did not or only weakly inhibited Pgp, BCRP, MRP2, MRP4, MATE1, MATE2-K, OATP1B1, OATP1B3, OCT1, OCT2 or BSEP. 6. Based on regulatory guidelines and quantitative extrapolations, CAB has a low propensity to cause clinically significant drug interactions, except for coadministration with OAT1 or OAT3 substrates. PMID:26340566

  8. Clinical NECR in 18F-FDG PET scans: optimization of injected activity and variable acquisition time. Relationship with SNR

    NASA Astrophysics Data System (ADS)

    Carlier, T.; Ferrer, L.; Necib, H.; Bodet-Milin, C.; Rousseau, C.; Kraeber-Bodéré, F.

    2014-10-01

    The injected activity and the acquisition time per bed position for 18F-FDG PET scans are usually optimized by using metrics obtained from phantom experiments. However, optimal activity and time duration can significantly vary from a phantom set-up and from patient to patient. An approach using a patient-specific noise equivalent count rate (NECR) modelling has been previously proposed for optimizing clinical scanning protocols. We propose using the clinical NECR on a large population as a function of the body mass index (BMI) for deriving the optimal injected activity and acquisition duration per bed position. The relationship between the NEC and the signal-to-noise ratio (SNR) was assessed both in a phantom and in a clinical setting. 491 consecutive patients were retrospectively evaluated and divided into 4 BMI subgroups. Two criteria were used to optimize the injected activity and the time per bed position was adjusted using the NECR value while keeping the total acquisition time constant. Finally, the relationship between NEC and SNR was investigated using an anthropomorphic phantom and a population of 507 other patients. While the first dose regimen suggested a unique injected activity (665 MBq) regardless of the BMI, the second dose regimen proposed a variable activity and a total acquisition time according to the BMI. The NEC improvement was around 35% as compared with the local current injection rule. Variable time per bed position was derived according to BMI and anatomical region. NEC and number of true events were found to be highly correlated with SNR for the phantom set-up and partially confirmed in the patient study for the BMI subgroup under 28 kg m-2 suggesting that for the scanner, the nonlinear reconstruction algorithm used in this study and BMI < 28 kg m-2, NEC, or the number of true events linearly correlated with SNR2.

  9. The pathogenesis of rheumatoid arthritis and the development of therapeutic strategies for the clinical investigation of biologics.

    PubMed

    Panayi, G S

    1995-01-01

    This review discusses current concepts of the pathogenesis of rheumatoid arthritis. It is proposed that RA is a T cell mediated disease following which a large number of subsequent inflammatory events are unleashed. Many of the pathogenetic steps are targets for new therapies including biologics. Laboratory, clinical and radiological methods of assessing disease activity are sufficiently sensitive and reproducible to permit their use in multicentre studies capable of detecting a biologic with disease modifying activity. The clinical assessment of the efficacy and toxicity of biologics poses unique problems. These have been illustrated by the example of 3 monoclonal antibodies directed against ICAM-1, CD4 and TNF alpha. The main role of most biologics may be to pinpoint important therapeutic targets which can be attacked by more easily administered and less costly xenobiotic drugs. PMID:7785487

  10. ASSESSMENT OF UPPER EXTREMITY IMPAIRMENT, FUNCTION, AND ACTIVITY FOLLOWING STROKE: FOUNDATIONS FOR CLINICAL DECISION MAKING

    PubMed Central

    Lang, Catherine E.; Bland, Marghuretta D.; Bailey, Ryan R.; Schaefer, Sydney Y.; Birkenmeier, Rebecca L.

    2012-01-01

    The purpose of this review is to provide a comprehensive approach for assessing the upper extremity (UE) after stroke. First, common upper extremity impairments and how to assess them are briefly discussed. While multiple UE impairments are typically present after stroke, the severity of one impairment, paresis, is the primary determinant of UE functional loss. Second, UE function is operationally defined and a number of clinical measures are discussed. It is important to consider how impairment and loss of function affect UE activity outside of the clinical environment. Thus, this review also identifies accelerometry as an objective method for assessing UE activity in daily life. Finally, the role that each of these levels of assessment should play in clinical decision making is discussed in order to optimize the provision of stroke rehabilitation services. PMID:22975740

  11. Recruitment and enrollment of caregivers for a lifestyle physical activity clinical trial.

    PubMed

    Etkin, Caryn D; Farran, Carol J; Barnes, Lisa L; Shah, Raj C

    2012-02-01

    This article presents the efficacy of the recruitment framework used for a clinical trial with sedentary family caregivers of persons with Alzheimer's disease. An integrated social marketing approach with principles of community-based participatory research provided the theoretical framework for organizing recruitment activities. This multi-pronged approach meant that caregivers were identified from a range of geographic locations and numerous sources including a federally funded Alzheimer's disease center, health care providers, community based and senior organizations, and broad-based media. Study enrollment projections were exceeded by 11% and resulted in enrolling n = 211 caregivers into this clinical trial. We conclude that social marketing and community-based approaches provide a solid foundation for organizing recruitment activities for clinical trials with older adults. PMID:22083931

  12. Two preclinical tests to evaluate anticancer activity and to help validate drug candidates for clinical trials

    PubMed Central

    López-Lázaro, Miguel

    2015-01-01

    Current approaches to assessing preclinical anticancer activity do not reliably predict drug efficacy in cancer patients. Most of the compounds that show remarkable anticancer effects in preclinical models actually fail when tested in clinical trials. We blame these failures on the complexity of the disease and on the limitations of the preclinical tools we require for our research. This manuscript argues that this lack of clinical response may also be caused by poor in vitro and in vivo preclinical designs, in which cancer patients' needs are not fully considered. Then, it proposes two patient-oriented tests to assess in vitro and in vivo anticancer activity and to help validate drug candidates for clinical evaluation. PMID:25859551

  13. Efficient Delivery of Investigational Antibacterial Agents via Sustainable Clinical Trial Networks.

    PubMed

    McDonnell, Anthony; Rex, John H; Goossens, Herman; Bonten, Marc; Fowler, Vance G; Dane, Aaron

    2016-08-15

    The economics of antibiotics can be improved by infectious diseases-specific clinical trial networks. While developers would still need to implement an independent phase 1 program as well as studies focused on highly resistant pathogens, standardized procedures in a network focused on usual drug resistance phenotype isolates would permit sharing of controls and would predictably generate high-quality pivotal data for product registration while creating cost and time savings in the range of 30%-40%. This would reduce economic barriers to antibiotic development and contribute to public health. PMID:27481955

  14. Preliminary investigation of thiamine and alcohol intake in clinical and healthy samples.

    PubMed

    Stacey, Phillip S; Sullivan, Karen A

    2004-06-01

    Insufficient thiamine intake during heavy alcohol dependence has been well established as a precursor to alcohol-related brain damage, including Wernicke-Korsakoff syndrome. This study compared the alcohol and thiamine intakes of 35 alcohol-dependent patients upon admission for detoxification with 49 healthy young undergraduates. Subjects were interviewed using a retrospective diary that recorded alcohol and food and vitamin consumption for the previous seven days. As predicted, the clinical group consumed significantly less thiamine than the healthy group, and well below the minimum safe daily intakes. Findings have implications for the prevention of alcohol-related brain damage and public health policy. PMID:15217037

  15. Functional investigations on embryonic stem cells labeled with clinically translatable iron oxide nanoparticles

    NASA Astrophysics Data System (ADS)

    Liu, Jing; Wang, Liqin; Cao, Jianbo; Huang, Yue; Lin, Yu; Wu, Xiaoyun; Wang, Zhiyong; Zhang, Fan; Xu, Xiuqin; Liu, Gang

    2014-07-01

    Stem cell based therapies offer significant potential in the field of regenerative medicine. The development of superparamagnetic iron oxide (SPIO) nanoparticle labeling and magnetic resonance imaging (MRI) have been increasingly used to track the transplanted cells, enabling in vivo determination of cell fate. However, the impact of SPIO-labeling on the cell phenotype and differentiation capacity of embryonic stem cells (ESCs) remains unclear. In this study, we wrapped SPIO nanoparticles with stearic acid grafted PEI600, termed as Stearic-LWPEI-SPIO, to generate efficient and non-toxic ESC labeling tools. Our results showed that efficient labeling of ESCs at an optimized low dosage of Stearic-LWPEI-SPIO nanoparticles did not alter the differentiation and self-renewal properties of ESCs. The localization of the transplanted ESCs observed by MRI correlated well with histological studies. These findings demonstrate that Stearic-LWPEI-SPIO nanoparticles have potential to be clinically translatable MRI probes and may enable non-invasive in vivo tracking of ESCs in experimental and clinical settings during cell-based therapies.Stem cell based therapies offer significant potential in the field of regenerative medicine. The development of superparamagnetic iron oxide (SPIO) nanoparticle labeling and magnetic resonance imaging (MRI) have been increasingly used to track the transplanted cells, enabling in vivo determination of cell fate. However, the impact of SPIO-labeling on the cell phenotype and differentiation capacity of embryonic stem cells (ESCs) remains unclear. In this study, we wrapped SPIO nanoparticles with stearic acid grafted PEI600, termed as Stearic-LWPEI-SPIO, to generate efficient and non-toxic ESC labeling tools. Our results showed that efficient labeling of ESCs at an optimized low dosage of Stearic-LWPEI-SPIO nanoparticles did not alter the differentiation and self-renewal properties of ESCs. The localization of the transplanted ESCs observed by MRI

  16. Sentinel Lymph Node Biopsy in Pelvic Tumors: Clinical Indications and Protocols Under Investigation.

    PubMed

    Maccauro, Marco; Lorenzoni, Alice; Crippa, Flavio; Manca, Gianpiero; Chondrogiannis, Sotirios; Giammarile, Francesco; Colletti, Patrick M; Cook, Gary J; Rubello, Domenico

    2016-06-01

    Sentinel lymph node (SLN) sampling is an attractive alternative to complete lymphadenectomy. Based on the identification and sampling of the first LN draining a primary tumor, SLN biopsy is the most accurate and the only reliable method for microscopic nodal staging for solid tumors including breast cancer and melanoma. Lymph node status in pelvic tumors remains the most important prognostic factor for recurrence and survival and a major decision criterion for adjuvant therapy. We review the clinical indications, controversies, and perspective of SLN biopsy in male and female pelvic cancers. PMID:26914577

  17. Investigating the genetic background of bovine digital dermatitis using improved definitions of clinical status.

    PubMed

    Schöpke, K; Gomez, A; Dunbar, K A; Swalve, H H; Döpfer, D

    2015-11-01

    Bovine digital dermatitis (DD) is an increasing claw health problem in all cattle production systems worldwide. The objective of this study was to evaluate the use of an improved scoring of the clinical status for DD via M-scores accounting for the dynamics of the disease; that is, the transitions from one stage to another. The newly defined traits were then subjected to a genetic analysis to determine the genetic background for susceptibility to DD. Data consisted of 6,444 clinical observations from 729 Holstein heifers in a commercial dairy herd, collected applying the M-score system. The M-score system is a classification scheme for stages of DD that allows a macroscopic scoring based on clinical inspections of the bovine foot, thus it describes the stages of lesion development. The M-scores were used to define new DD trait definitions with different complexities. Linear mixed models and logistic models were used to identify fixed environmental effects and to estimate variance components. In total, 68% of all observations showed no DD status, whereas 11% were scored as infectious for and affected by DD, and 21% of all observations exhibited an affected but noninfectious status. For all traits, the probability of occurrence and clinical status were associated with age at observation and period of observation. Risk of becoming infected increased with age, and month of observation significantly affected all traits. Identification of the optimal month concerning DD herd status was consistent for all trait definitions; the last month of the trial was identified. In contrast, months exhibiting the highest least squares means of transformed scores differed depending on trait definition. In this respect, traits that can distinguish between healthy, infectious, and noninfectious stages of DD can account for the infectious potential of the herd and can serve as an alert tool. Estimates of heritabilities of traits studied ranged between 0.19 (±0.11) and 0.52 (±0

  18. Investigation of benefits and costs of an ophthalmic outreach clinic in general practice.

    PubMed Central

    Gillam, S J; Ball, M; Prasad, M; Dunne, H; Cohen, S; Vafidis, G

    1995-01-01

    BACKGROUND: With the advent of general practitioner fundholding, there has been growth in outreach clinics covering many specialties. The benefits and costs of this model of service provision are unclear. AIM: A pilot study aimed to evaluate an outreach model of ophthalmic care in terms of its impact on general practitioners, their use of secondary ophthalmology services, patients' views, and costs. METHOD: A prospective study, from April 1992 to March 1993, of the introduction of an ophthalmic outreach service in 17 general practices in London was undertaken. An ophthalmic outreach team, comprising an ophthalmic medical practitioner and an ophthalmic nurse, held clinics in the practices once a month. Referral rates to Edgware General Hospital ophthalmology outpatient department over one year from the study practices were compared with those from 17 control practices. General practitioners' assessments of the scheme and its impact on their knowledge and practice of ophthalmology were sought through a postal survey of all partners and interviews with one partner in each practice. Patient surveys were conducted using self-administered structured questionnaires. A costings exercise compared the outreach model with the conventional hospital ophthalmology outpatient clinic. RESULTS: Of 1309 patients seen by the outreach team in the study practices, 480 (37%) were referred to the ophthalmology outpatient department. The annual referral rate to this department from control practices was 9.5 per 10,000 registered patients compared with 3.8 per 10,000 registered patients from study practices. A total of 1187 patients were referred to the outpatient department from control practices. An increase in knowledge of ophthalmology was reported by 18 of 47 general practitioners (38%). Nineteen (40%) of 47 general practitioners took advantage of the opportunity for inservice training with the outreach team; they were more likely to change their routine practice for ophthalmic care

  19. Efficient Delivery of Investigational Antibacterial Agents via Sustainable Clinical Trial Networks

    PubMed Central

    McDonnell, Anthony; Rex, John H.; Goossens, Herman; Bonten, Marc; Fowler, Vance G.; Dane, Aaron

    2016-01-01

    The economics of antibiotics can be improved by infectious diseases–specific clinical trial networks. While developers would still need to implement an independent phase 1 program as well as studies focused on highly resistant pathogens, standardized procedures in a network focused on usual drug resistance phenotype isolates would permit sharing of controls and would predictably generate high-quality pivotal data for product registration while creating cost and time savings in the range of 30%–40%. This would reduce economic barriers to antibiotic development and contribute to public health. PMID:27481955

  20. Anti-angiogenic, vascular-disrupting and anti-metastatic activities of vinflunine, the latest vinca alkaloid in clinical development.

    PubMed

    Kruczynski, Anna; Poli, Maura; Dossi, Romina; Chazottes, Eric; Berrichon, Géraldine; Ricome, Christel; Giavazzi, Raffaella; Hill, Bridget T; Taraboletti, Giulia

    2006-11-01

    The aim of this study was to investigate the anti-angiogenic, vascular-disrupting and anti-metastatic properties of vinflunine, the latest vinca alkaloid in phase III clinical development. The effects of vinflunine on in vitro endothelial cell functions relevant to the performance of an already formed vasculature and to the angiogenic process were evaluated. The in vivo anti-angiogenic properties of vinflunine were also investigated, as were its activity against a model of experimental metastasis. In vitro vinflunine induced a rapid change in the morphology of endothelial cells and disrupted the network of capillary-like structures, indicating potential vascular-disrupting activity. Furthermore, vinflunine showed anti-angiogenic properties, since it inhibited endothelial cell migration and the capacity of these cells to organise into a network of capillary-like structures. All these effects were observed under conditions that only marginally affect endothelial cell proliferation. In vivo, vinflunine inhibited bFGF-induced angiogenesis in Matrigel implants at doses 40-20-fold lower than its maximal therapeutic dose (MTD). Treatment of mice with vinflunine reduced the number of liver metastases induced by intrasplenic injection of LS174T cells, with significant effects also observed at low doses; i.e. 16-fold lower than the MTD. This study demonstrates that vinflunine expresses both vascular-disrupting and anti-angiogenic activities and induced marked effects against experimental metastases, all properties that support its ongoing clinical development. PMID:16973349

  1. Decisions to Withhold Diagnostic Investigations in Nursing Home Patients with a Clinical Suspicion of Venous Thromboembolism

    PubMed Central

    Schouten, Henrike J.; Koek, Huiberdina L.; Kruisman-Ebbers, Marije; Geersing, Geert-Jan; Oudega, Ruud; Kars, Marijke C.; Moons, Karel G. M.; van Delden, Johannes J. M.

    2014-01-01

    Background This study aimed to gather insights in physicians' considerations for decisions to either refer for- or to withhold additional diagnostic investigations in nursing home patients with a suspicion of venous thromboembolism. Methods Our study was nested in an observational study on diagnostic strategies for suspected venous thromboembolism in nursing home patients. Patient characteristics, bleeding-complications and mortality were related to the decision to withhold investigations. For a better understanding of the physicians' decisions, 21 individual face-to-face in-depth interviews were performed and analysed using the grounded theory approach. Results Referal for additional diagnostic investigations was forgone in 126/322 (39.1%) patients with an indication for diagnostic work-up. ‘Blind’ anticoagulant treatment was initiated in 95 (75.4%) of these patients. The 3month mortality rates were higher for patients in whom investigations were withheld than in the referred patients, irrespective of anticoagulant treatment (odds ratio 2.45; 95% confidence interval 1.40 to 4.29) but when adjusted for the probability of being referred (i.e. the propensity score), there was no relation of non-diagnosis decisions to mortality (odds ratio 1.75; 0.98 to 3.11). In their decisions to forgo diagnostic investigations, physicians incorporated the estimated relative impact of the potential disease; the potential net-benefits of diagnostic investigations and whether performing investigations agreed with established management goals in advance care planning. Conclusion Referral for additional diagnostic investigations is withheld in almost 40% of Dutch nursing home patients with suspected venous thromboembolism and an indication for diagnostic work-up. We propose that, given the complexity of these decisions and the uncertainty regarding their indirect effects on patient outcome, more attention should be focused on the decision to either use or withhold additional

  2. Clinical Response, Outbreak Investigation, and Epidemiology of the Fungal Meningitis Epidemic in the United States: Systematic Review

    PubMed Central

    Abbas, Kaja M.; Dorratoltaj, Nargesalsadat; O'Dell, Margaret L.; Bordwine, Paige; Kerkering, Thomas M.; Redican, Kerry J.

    2016-01-01

    We conducted a systematic review of the 2012-2013 multistate fungal meningitis epidemic in the United States from the perspectives of clinical response, outbreak investigation, and epidemiology. Articles focused on clinical response, outbreak investigation, and epidemiology were included, whereas articles focused on compounding pharmacies, legislation and litigation, diagnostics, microbiology, and pathogenesis were excluded. We reviewed 19 articles by use of the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) framework. The source of the fungal meningitis outbreak was traced to the New England Compounding Center in Massachusetts, where injectable methylprednisolone acetate products were contaminated with the predominant pathogen, Exserohilum rostratum. As of October 23, 2013, the final case count stood at 751 patients and 64 deaths, and no additional cases are anticipated. The multisectoral public health response to the fungal meningitis epidemic from the hospitals, clinics, pharmacies, and the public health system at the local, state, and federal levels led to an efficient epidemiological investigation to trace the outbreak source and rapid implementation of multiple response plans. This systematic review reaffirms the effective execution of a multisectoral public health response and efficient delivery of the core functions of public health assessment, policy development, and service assurances to improve population health. PMID:26681583

  3. Risk Factors for Clinically Significant Intimate Partner Violence among Active-Duty Members

    ERIC Educational Resources Information Center

    Smith Slep, Amy M.; Foran, Heather M.; Heyman, Richard E.; Snarr, Jeffery D.

    2011-01-01

    Hypothesized risk factors for men's and women's clinically significant intimate partner violence (CS-IPV) from four ecological levels (i.e., individual, family, workplace, community) were tested in a representative sample of active-duty U.S. Air Force members (N = 42,744). When considered together, we expected only individual and family factors to…

  4. Reductions in disease activity in the AMPLE trial: clinical response by baseline disease duration

    PubMed Central

    Schiff, Michael; Weinblatt, Michael E; Valente, Robert; Citera, Gustavo; Maldonado, Michael; Massarotti, Elena; Yazici, Yusuf; Fleischmann, Roy

    2016-01-01

    Objectives To evaluate clinical response by baseline disease duration using 2-year data from the AMPLE trial. Methods Patients were randomised to subcutaneous abatacept 125 mg weekly or adalimumab 40 mg bi-weekly, with background methotrexate. As part of a post hoc analysis, the achievement of validated definitions of remission (Clinical Disease Activity Index (CDAI) ≤2.8, Simplified Disease Activity Index (SDAI) ≤3.3, Routine Assessment of Patient Index Data 3 (RAPID3) ≤3.0, Boolean score ≤1), low disease activity (CDAI <10, SDAI <11, RAPID3 ≤6.0), Health Assessment Questionnaire-Disability Index response and American College of Rheumatology responses were evaluated by baseline disease duration (≤6 vs >6 months). Disease Activity Score 28 (C-reactive protein) <2.6 or ≤3.2 and radiographic non-progression in patients achieving remission were also evaluated. Results A total of 646 patients were randomised and treated (abatacept, n=318; adalimumab, n=328). In both treatment groups, comparable responses were achieved in patients with early rheumatoid arthritis (≤6 months) and in those with later disease (>6 months) across multiple clinical measures. Conclusions Abatacept or adalimumab with background methotrexate were associated with similar onset and sustainability of response over 2 years. Patients treated early or later in the disease course achieved comparable clinical responses. Trial registration number NCT00929864, Post-results. PMID:27110385

  5. Clinical Study of Student Learning Using Mastery Style versus Immediate Feedback Online Activities

    ERIC Educational Resources Information Center

    Gladding, Gary; Gutmann, Brianne; Schroeder, Noah; Stelzer, Timothy

    2015-01-01

    This paper is part of a series of studies to improve the efficacy of online physics homework activities by integrating narrated animated solutions with mastery inspired exercises. In a clinical study using first- and second-year university students, the mastery group attempted question sets in four levels, with animated solutions between each…

  6. The continuing legacy of the Tuskegee Syphilis Study: considerations for clinical investigation.

    PubMed

    Corbie-Smith, G

    1999-01-01

    The Tuskegee Study, an observational study of over 400 sharecroppers with untreated syphilis, was conducted by the U.S. Public Health Service to document the course of the disease in blacks, and racial differences in the clinical manifestations of syphilis. The men were not told they had syphilis, not given counseling on avoiding spread of the disease, and not given treatment throughout the course of the study. The study became the longest (1932-1972) nontherapeutic experiment on humans in the history of medicine, and has come to represent not only the exploitation of blacks in medical history, but the potential for exploitation of any population that may be vulnerable because of race, ethnicity, gender, disability, age or social class. It is important for physicians who will be caring for an increasingly diverse nation to understand the lasting implications of this study for their patients, but the effects of the Tuskegee Syphilis Study are demonstrated most strikingly by unsuccessful attempts at improving representation of minority patients in clinical trials. PMID:9892266

  7. PET/SPECT molecular imaging in clinical neuroscience: recent advances in the investigation of CNS diseases

    PubMed Central

    Lu, Feng-Mei

    2015-01-01

    Molecular imaging is an attractive technology widely used in clinical practice that greatly enhances our understanding of the pathophysiology and treatment in central nervous system (CNS) diseases. It is a novel multidisciplinary technique that can be defined as real-time visualization, in vivo characterization and qualification of biological processes at the molecular and cellular level. It involves the imaging modalities and the corresponding imaging agents. Nowadays, molecular imaging in neuroscience has provided tremendous insights into disturbed human brain function. Among all of the molecular imaging modalities, positron emission tomography (PET) and single photon emission computed tomography (SPECT) have occupied a particular position that visualize and measure the physiological processes using high-affinity and high-specificity molecular radioactive tracers as imaging probes in intact living brain. In this review, we will put emphasis on the PET/SPECT applications in Alzheimer’s disease (AD) and Parkinson’s disease (PD) as major CNS disorders. We will first give an overview of the main classical molecular neuroimaging modalities. Then, the major clinical applications of PET and SPECT along with molecular probes in the fields of psychiatry and neurology will be discussed. PMID:26029646

  8. Terbinafine hydrochloride nanovesicular gel: In vitro characterization, ex vivo permeation and clinical investigation.

    PubMed

    AbdelSamie, Sara M; Kamel, Amany O; Sammour, Omaima A; Ibrahim, Shady M

    2016-06-10

    In this work, nanovesicular chitosan gels were prepared for dermal delivery of terbinafine hydrochloride (TBN HCl). Ethosomes and vesicles containing different types of penetration enhancers (PEs) viz. Terpenes (cineole and limonene), labrasol and transcutol were developed. The prepared vesicles were evaluated for physical characteristics as well as skin interaction. The selected vesicles were incorporated into chitosan gel. An in vivo animal study was done on rat induced superficial Candida infection model. Moreover, randomized double blind clinical study was done on patients to compare the effect of the selected nanovesicular gel against the market product. Results showed the formation of nearly spherical, mostly deformable vesicular systems with size range of 95.5-530nm, zeta potential range of -0.1 to 15mV and entrapment efficiency range of 20-96.7%. Penetration enhancer vesicles (PEVs) prepared with 4% limonene (ELI4) showed the highest percent of drug deposition in the skin (53%) and the highest local accumulation efficiency value (35.3). In vivo animal study showed that the lowest fungal burden produced with ELI4 chitosan gel. Clinical studies showed cure rate of 86% within 7days treatment in case of limonene nanovesicular gel compared to 20% for market product (Lamisil® cream). PMID:27072432

  9. Lithogenic activity and clinical relevance of lipids extracted from urines and stones of nephrolithiasis patients.

    PubMed

    Boonla, Chanchai; Youngjermchan, Phantip; Pumpaisanchai, Somkiat; Tungsanga, Kriang; Tosukhowong, Piyaratana

    2011-02-01

    We investigated contents and classes of urinary and stone matrix lipids, and evaluated their clinical relevance in nephrolithiasis patients. Lithogenic role of major lipid classes was explored. Urine (24 h) and stone samples were collected from 47 patients with nephrolithiasis. Control urines were obtained from 29 healthy subjects. Urinary 8-hydroxy-deoxyguanosine (8-OHdG), malondialdehyde (MDA), N-acetyl-β-glucosaminidase (NAG) activity and total proteins were measured. Total lipids were extracted from centrifuged urines (10,000 rpm, 30 min) and stones by chloroform/methanol method. Major classes of lipids were identified using multi-one-dimensional thin-layer chromatography (MOD-TLC). Influence of each lipid class purified from stone matrices on stone formation was evaluated using crystallization and crystal aggregation assays. Urinary NAG activity and 8-OHdG were significantly elevated in nephrolithiasis patients. Total lipids in centrifuged urines of the patients were not significantly different from that of controls. In nephrolithiasis, urinary excretion of total lipids was linearly correlated to urinary MDA, 8-OHdG, NAG activity and total proteins. Lipid contents in stone matrices varied among stone types. Uric acid stone contained lower amount of total lipids than calcium oxalate and magnesium ammonium phosphate stones. MOD-TLC lipid chromatograms of healthy urines, nephrolithiasis urines and stone matrices were obviously different. Triacylglyceride was abundant in urines, but scarcely found in stone matrices. Stone matrices were rich in glycolipids and high-polar lipids (phospholipids/gangliosides). Partially purified glycolipids significantly induced crystal aggregation while cholesterol was a significant inducer of both crystal formation and agglomeration. In conclusion, total lipids in centrifuged urines did not differ between nephrolithiasis and healthy subjects. Our finding suggests that the significant sources of lipids in patients' urine may be

  10. 77 FR 31022 - Agency Information Collection Activities; Proposed Collection; Comment Request; Investigational...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-24

    ... device or to the clinical protocol without FDA approval of an investigational device exemption (IDE) supplement. An IDE allows a device, which would otherwise be subject to provisions of the FD&C Act, such as... ethical standards, the discovery and development of useful devices intended for human use. The...

  11. Hypothalamic-Ptuitary-Adrenal (HPA) Axis Activity in Adults with Intellectual Disabilities: A Preliminary Investigation

    ERIC Educational Resources Information Center

    Presland, A. D.; Clare, I. C. H.; Broughton, S.; Luke, L.; Wheeler, E.; Fairchild, G.; Watson, P. C.; Chan, W. Y. S.; Kearns, A.; Ring, H. A.

    2013-01-01

    Background: Cortisol is a marker of physiological arousal, exhibiting a characteristic pattern of diurnal activity. The daily cortisol profile has been examined extensively and is atypical in a number of clinical disorders. However, there are very few studies focussing on the cortisol profile in adults with intellectual disabilities (ID). This…

  12. Comparison of Antifungal Activities and 16S Ribosomal DNA Sequences of Clinical and Environmental Isolates of Stenotrophomonas maltophilia

    PubMed Central

    Minkwitz, Arite; Berg, Gabriele

    2001-01-01

    In recent years, the gram-negative bacterium Stenotrophomonas maltophilia has become increasingly important in biotechnology and as a nosocomial pathogen, giving rise to a need for new information about its taxonomy and epidemiology. To determine intraspecies diversity and whether strains can be distinguished based on the sources of their isolation, 50 S. maltophilia isolates from clinical and environmental sources, including strains of biotechnological interest, were investigated. The isolates were characterized by in vitro antagonism against pathogenic fungi and the production of antifungal metabolites and enzymes. Phenotypically the strains showed variability that did not correlate significantly with their sources of isolation. Clinical strains displayed remarkable activity against the human pathogenic fungus Candida albicans. Antifungal activity against plant pathogens was more common and generally more severe from the environmental isolates, although not exclusive to them. All isolates, clinical and environmental, produced a range of antifungal metabolites including antibiotics, siderophores, and the enzymes proteases and chitinases. From 16S ribosomal DNA sequencing analysis, the isolates could be separated into three clusters, two of which consisted of isolates originating from the environment, especially rhizosphere isolates, and one of which consisted of clinical and aquatic strains. In contrast to the results of other recent investigations, these strains could be grouped based on their sources of isolation, with the exception of three rhizosphere isolates. Because there was evidence of nucleotide signature positions within the sequences that are suitable for distinguishing among the clusters, the clusters could be defined as different genomovars of S. maltophilia. Key sequences on the 16S ribosomal DNA could be used to develop a diagnostic method that differentiates these genomovars. PMID:11136762

  13. Functional investigations on human mesenchymal stem cells exposed to magnetic fields and labeled with clinically approved iron nanoparticles

    PubMed Central

    2010-01-01

    Background For clinical applications of mesenchymal stem cells (MSCs), labeling and tracking is crucial to evaluate cell distribution and homing. Magnetic resonance imaging (MRI) has been successfully established detecting MSCs labeled with superparamagnetic particles of iron oxide (SPIO). Despite initial reports that labeling of MSCs with SPIO is safe without affecting the MSC's biology, recent studies report on influences of SPIO-labeling on metabolism and function of MSCs. Exposition of cells and tissues to high magnetic fields is the functional principle of MRI. In this study we established innovative labeling protocols for human MSCs using clinically established SPIO in combination with magnetic fields and investigated on functional effects (migration assays, quantification of colony forming units, analyses of gene and protein expression and analyses on the proliferation capacity, the viability and the differentiation potential) of magnetic fields on unlabeled and labeled human MSCs. To evaluate the imaging properties, quantification of the total iron load per cell (TIL), electron microscopy, and MRI at 3.0 T were performed. Results Human MSCs labeled with SPIO permanently exposed to magnetic fields arranged and grew according to the magnetic flux lines. Exposure of MSCs to magnetic fields after labeling with SPIO significantly enhanced the TIL compared to SPIO labeled MSCs without exposure to magnetic fields resulting in optimized imaging properties (detection limit: 1,000 MSCs). Concerning the TIL and the imaging properties, immediate exposition to magnetic fields after labeling was superior to exposition after 24 h. On functional level, exposition to magnetic fields inhibited the ability of colony formation of labeled MSCs and led to an enhanced expression of lipoprotein lipase and peroxisome proliferator-activated receptor-γ in labeled MSCs under adipogenic differentiation, and to a reduced expression of alkaline phosphatase in unlabeled MSCs under

  14. Molecular Testing for Clinical Diagnosis and Epidemiological Investigations of Intestinal Parasitic Infections

    PubMed Central

    Stensvold, C. Rune

    2014-01-01

    SUMMARY Over the past few decades, nucleic acid-based methods have been developed for the diagnosis of intestinal parasitic infections. Advantages of nucleic acid-based methods are numerous; typically, these include increased sensitivity and specificity and simpler standardization of diagnostic procedures. DNA samples can also be stored and used for genetic characterization and molecular typing, providing a valuable tool for surveys and surveillance studies. A variety of technologies have been applied, and some specific and general pitfalls and limitations have been identified. This review provides an overview of the multitude of methods that have been reported for the detection of intestinal parasites and offers some guidance in applying these methods in the clinical laboratory and in epidemiological studies. PMID:24696439

  15. Unsuspected (clinically silent) multiple sclerosis. Quantitative investigations in one autoptic case.

    PubMed

    Heinsen, H; Lockemann, U; Püschel, K

    1995-01-01

    The incidental retrieval of a few, well-circumscribed, chronic multiple sclerosis plaques in a 49-year-old female who died from myocardial infarct is reported. In serial gallocyanin stained frontal sections of the brain one plaque in the left and four plaques in the right hemisphere were encountered. A total of 1.25 cm3 or 0.24% of the right hemispheric volume and a total of 0.93 cm3 or 0.2% of the left hemispheric volume was afflicted. The size as well as the topography of the plaques could explain the absence of clinical symptoms. Methodological issues concerning in vivo and post mortem diagnosis of multiple sclerosis and their impact on the epidemiology of this disease are discussed. PMID:7632604

  16. Clinical Investigations and Management of Refractive Changes in Pregnancy: A Case Report.

    PubMed

    Ekpenyong, Bernadine N; Aruotu, Nwakuso A; Uzodike, Ebele B; Njoku, Chimela G

    2015-12-01

    Pregnancy also presents with ocular changes, just as it affects other non-reproductive systems of the female. It has been reported to be associated with development of new health conditions or can exacerbate pre- existing health conditions. This paper reviews the management of Mrs AA, a 41 year old pregnant woman (primigravida) with refractive changes from myopia in the first trimester, to hyperopia in the second and third trimesters of her pregnancy. A comprehensive ocular examination was performed including fundus photograph and Optical Coherent Tomography. The results revealed signs of Central Serous Chorioretinopathy in both eyes which may have been due to various hormonal changes in pregnancy with resultant changes in refractive error. These ocular changes associated with pregnancy are, most often transient in nature, though occasionally permanent. This condition therefore requires clinical observation and monitoring until the resolution of the serous detachment is complete, and vision returned back to normal. Other ocular changes that are pregnancy related were reviewed. PMID:27337860

  17. Patients' willingness and ability to participate actively in the reduction of clinical errors: a systematic literature review.

    PubMed

    Doherty, Carole; Stavropoulou, Charitini

    2012-07-01

    This systematic review identifies the factors that both support and deter patients from being willing and able to participate actively in reducing clinical errors. Specifically, we add to our understanding of the safety culture in healthcare by engaging with the call for more focus on the relational and subjective factors which enable patients' participation (Iedema, Jorm, & Lum, 2009; Ovretveit, 2009). A systematic search of six databases, ten journals and seven healthcare organisations' web sites resulted in the identification of 2714 studies of which 68 were included in the review. These studies investigated initiatives involving patients in safety or studies of patients' perspectives of being actively involved in the safety of their care. The factors explored varied considerably depending on the scope, setting and context of the study. Using thematic analysis we synthesized the data to build an explanation of why, when and how patients are likely to engage actively in helping to reduce clinical errors. The findings show that the main factors for engaging patients in their own safety can be summarised in four categories: illness; individual cognitive characteristics; the clinician-patient relationship; and organisational factors. We conclude that illness and patients' perceptions of their role and status as subordinate to that of clinicians are the most important barriers to their involvement in error reduction. In sum, patients' fear of being labelled "difficult" and a consequent desire for clinicians' approbation may cause them to assume a passive role as a means of actively protecting their personal safety. PMID:22541799

  18. Activated protein C promotes neuroprotection: mechanisms and translation to the clinic.

    PubMed

    Griffin, John H; Fernández, José A; Lyden, Patrick D; Zlokovic, Berislav V

    2016-05-01

    Activated protein C (APC) is a plasma serine protease that is capable of antithrombotic, anti-inflammatory, anti-apoptotic, and cell-signaling activities. Animal injury studies show that recombinant APC and some of its mutants are remarkably therapeutic for a wide range of injuries. In particular, for neurologic injuries, APC reduces damage caused by ischemia/reperfusion in the brain, by acute brain trauma, and by chronic neurodegenerative conditions. For these neuroprotective effects, APC requires endothelial cell protein C receptor. APC activates cell signaling networks with alterations in gene expression profiles by activating protease activated receptors 1 and 3. To minimize APC-induced bleeding risk, APC variants were engineered to lack > 90% anticoagulant activity but retain normal cell signaling. The neuroprotective APC mutant, 3K3A-APC which has Lys191-193 mutated to Ala191-193, is very neuroprotective and it is currently in clinical trials for ischemic stroke. PMID:27207428

  19. An Investigation of the Use of E-Mail as a Supplemental Modality for Clinical Supervision

    ERIC Educational Resources Information Center

    Clingerman, Tamara L.; Bernard, Janine M.

    2004-01-01

    The authors investigated the use of student-initiated e-mail as a supplemental modality for supervision. Nineteen students e-mailed their instructors weekly during their 15-week practicum: these e-mails were analyzed across 3 time periods using the categories of the discrimination model (J. M. Bernard, 1979, 1997) and an adaptation of W. Lanning's…

  20. Assessing the Effectiveness of Parent-Child Interaction Therapy with Language Delayed Children: A Clinical Investigation

    ERIC Educational Resources Information Center

    Falkus, Gila; Tilley, Ciara; Thomas, Catherine; Hockey, Hannah; Kennedy, Anna; Arnold, Tina; Thorburn, Blair; Jones, Katie; Patel, Bhavika; Pimenta, Claire; Shah, Rena; Tweedie, Fiona; O'Brien, Felicity; Leahy, Ruth; Pring, Tim

    2016-01-01

    Parent-child interaction therapy (PCIT) is widely used by speech and language therapists to improve the interactions between children with delayed language development and their parents/carers. Despite favourable reports of the therapy from clinicians, little evidence of its effectiveness is available. We investigated the effects of PCIT as…

  1. [In vitro bactericidal activities of new oral penem, faropenem against the various clinical isolates].

    PubMed

    Matsuzaki, K; Nishiyama, T; Hasegawa, M; Kobayashi, I; Kaneko, A; Sasaki, J

    1999-05-01

    The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of faropenem (FRPM) more compared with those of various oral beta-lactams against 15 isolates each of 6 species of microorganism. FRPM possessed potent in vitro antibacterial activity against both aerobic and anaerobic Gram-positive bacteria tested. FRPM showed the same activity as new oral cephems such as cefdinir, cefditoren and cefcapene against all Gram-negative bacteria, but K. pneumoniae strains were less susceptible. The MBC of FRPM against S. pneumoniae and the other strains tested equal and were within 1 dilution the MIC of that, respectively. These results suggest that FRPM has excellent in vitro bactericidal activity against clinical isolates and is a clinically useful for the chemotherapy of bacterial infections. PMID:10480050

  2. Clinical utility of the liposteroid therapy: Potential effects on the macrophage activation.

    PubMed

    Wakiguchi, Hiroyuki; Ohga, Shouichi

    2016-01-01

      Liposteroid, a lipid emulsion containing dexamethasone, was developed in Japan. This drug is effective against rheumatoid arthritis, and has fewer side effects than dexamethasone. Moreover, at high dosage, liposteroid has been effectively used for the treatment of macrophage activation syndrome, because the lipid emulsions are easily taken up by phagocytes, and are retained in macrophages. Its anti-inflammatory effect was found to be 2-5 times higher than that of dexamethasone in arthritis and granuloma rat models. Japanese researchers have reported the clinical efficacy and utility of liposteroid in the treatment of diseases with macrophage activation. These include hemophagocytic lymphohistiocytosis, graft-versus-host disease, and pulmonary hemosiderosis. Here, we describe the clinical effects of liposteroid on macrophage activation syndrome and the hypothalamus-pituitary-adrenal axis in patients. PMID:27320934

  3. Cell-associated hemolysis activity in the clinical strain of Pseudomonas fluorescens MFN1032

    PubMed Central

    2010-01-01

    Background MFN1032 is a clinical Pseudomonas fluorescens strain able to grow at 37°C. MFN1032 cells induce necrosis and apoptosis in rat glial cells at this temperature. This strain displays secretion-mediated hemolytic activity involving phospholipase C and cyclolipopeptides. Under laboratory conditions, this activity is not expressed at 37°C. This activity is tightly regulated and is subject to phase variation. Results We found that MFN1032 displays a cell-associated hemolytic activity distinct from the secreted hemolytic activity. Cell-associated hemolysis was expressed at 37°C and was only detected in vitro in mid log growth phase in the presence of erythrocytes. We studied the regulation of this activity in the wild-type strain and in a mutant defective in the Gac two-component pathway. GacS/GacA is a negative regulator of this activity. In contrast to the Pseudomonas fluorescens strains PfO-1 and Pf5, whose genomes have been sequenced, the MFN1032 strain has the type III secretion-like genes hrcRST belonging to the hrpU operon. We showed that disruption of this operon abolished cell-associated hemolytic activity. This activity was not detected in P.fluorescens strains carrying similar hrc genes, as for the P. fluorescens psychrotrophic strain MF37. Conclusions To our knowledge this the first demonstration of cell-associated hemolytic activity of a clinical strain of Pseudomonas fluorescens. Moreover, this activity seems to be related to a functional hrpU operon and is independent of biosurfactant production. Precise link between a functional hrpU operon and cell-associated hemolytic activity remains to be elucidated. PMID:20416103

  4. Tobacco Assessment in Actively Accruing National Cancer Institute Cooperative Group Program Clinical Trials

    PubMed Central

    Peters, Erica N.; Torres, Essie; Toll, Benjamin A.; Cummings, K. Michael; Gritz, Ellen R.; Hyland, Andrew; Herbst, Roy S.; Marshall, James R.; Warren, Graham W.

    2012-01-01

    Purpose Substantial evidence suggests that tobacco use has adverse effects on cancer treatment outcomes; however, routine assessment of tobacco use has not been fully incorporated into standard clinical oncology practice. The purpose of this study was to evaluate tobacco use assessment in patients enrolled onto actively accruing cancer clinical trials. Methods Protocols and forms for 155 actively accruing trials in the National Cancer Institute's (NCI's) Clinical Trials Cooperative Group Program were evaluated for tobacco use assessment at enrollment and follow-up by using a structured coding instrument. Results Of the 155 clinical trials reviewed, 45 (29%) assessed any form of tobacco use at enrollment, but only 34 (21.9%) assessed current cigarette use. Only seven trials (4.5%) assessed any form of tobacco use during follow-up. Secondhand smoke exposure was captured in 2.6% of trials at enrollment and 0.6% during follow-up. None of the trials assessed nicotine dependence or interest in quitting at any point during enrollment or treatment. Tobacco status assessment was higher in lung/head and neck trials as well as phase III trials, but there was no difference according to year of starting accrual or cooperative group. Conclusion Most actively accruing cooperative group clinical trials do not assess tobacco use, and there is no observable trend in improvement over the past 8 years. Failure to incorporate standardized tobacco assessments into NCI-funded Cooperative Group Clinical Trials will limit the ability to provide evidence-based cessation support and will limit the ability to accurately understand the precise effect of tobacco use on cancer treatment outcomes. PMID:22689794

  5. Stock Market Returns and Clinical Trial Results of Investigational Compounds: An Event Study Analysis of Large Biopharmaceutical Companies

    PubMed Central

    Hwang, Thomas J.

    2013-01-01

    Background For biopharmaceutical companies, investments in research and development are risky, and the results from clinical trials are key inflection points in the process. Few studies have explored how and to what extent the public equity market values clinical trial results. Methods Our study dataset matched announcements of clinical trial results for investigational compounds from January 2011 to May 2013 with daily stock market returns of large United States-listed pharmaceutical and biotechnology companies. Event study methodology was used to examine the relationship between clinical research events and changes in stock returns. Results We identified public announcements for clinical trials of 24 investigational compounds, including 16 (67%) positive and 8 (33%) negative events. The majority of announcements were for Phase 3 clinical trials (N = 13, 54%), and for oncologic (N = 7, 29%) and neurologic (N = 6, 24%) indications. The median cumulative abnormal returns on the day of the announcement were 0.8% (95% confidence interval [CI]: –2.3, 13.4%; P = 0.02) for positive events and –2.0% (95% CI: –9.1, 0.7%; P = 0.04) for negative events, with statistically significant differences from zero. In the day immediately following the announcement, firms with positive events were associated with stock price corrections, with median cumulative abnormal returns falling to 0.4% (95% CI: –3.8, 12.3%; P = 0.33). For firms with negative announcements, the median cumulative abnormal returns were –1.7% (95% CI: –9.5, 1.0%; P = 0.03), and remained significantly negative over the two day event window. The magnitude of abnormal returns did not differ statistically by indication, by trial phase, or between biotechnology and pharmaceutical firms. Conclusions The release of clinical trial results is an economically significant event and has meaningful effects on market value for large biopharmaceutical companies. Stock return

  6. Clinical hypothermia temperatures increase complement activation and cell destruction via the classical pathway

    PubMed Central

    2014-01-01

    Background Therapeutic hypothermia is a treatment modality that is increasingly used to improve clinical neurological outcomes for ischemia-reperfusion injury-mediated diseases. Antibody-initiated classical complement pathway activation has been shown to contribute to ischemia-reperfusion injury in multiple disease processes. However, how therapeutic hypothermia affects complement activation is unknown. Our goal was to measure the independent effect of temperature on complement activation, and more specifically, examine the relationship between clinical hypothermia temperatures (31–33°C), and complement activation. Methods Antibody-sensitized erythrocytes were used to assay complement activation at temperatures ranging from 0-41°C. Individual complement pathway components were assayed by ELISA, Western blot, and quantitative dot blot. Peptide Inhibitor of complement C1 (PIC1) was used to specifically inhibit activation of C1. Results Antibody-initiated complement activation resulting in eukaryotic cell lysis was increased by 2-fold at 31°C compared with 37°C. Antibody-initiated complement activation in human serum increased as temperature decreased from 37°C until dramatically decreasing at 13°C. Quantitation of individual complement components showed significantly increased activation of C4, C3, and C5 at clinical hypothermia temperatures. In contrast, C1s activation by heat-aggregated IgG decreased at therapeutic hypothermia temperatures consistent with decreased enzymatic activity at lower temperatures. However, C1q binding to antibody-coated erythrocytes increased at lower temperatures, suggesting that increased classical complement pathway activation is mediated by increased C1 binding at therapeutic hypothermia temperatures. PIC1 inhibited hypothermia-enhanced complement-mediated cell lysis at 31°C by up to 60% (P = 0.001) in a dose dependent manner. Conclusions In summary, therapeutic hypothermia temperatures increased antibody

  7. Imipenem and meropenem: Comparison of in vitro activity, pharmacokinetics, clinical trials and adverse effects

    PubMed Central

    Zhanel, George G; Simor, Andrew E; Vercaigne, Lavern; Mandell, Lionell

    1998-01-01

    OBJECTIVE: To compare and contrast imipenem and meropenem in terms of in vitro activity, pharmacokinetics, clinical efficacy and adverse effects. DATA SELECTION: MEDLINE search from 1975 to 1997 and follow-up of references. DATA EXTRACTION: Clinical trials comparing imipenem with meropenem, or either imipenem or meropenem with standard therapy in the treatment of serious infections were selected. DATA SYNTHESIS: Imipenem, the first carbapenem, was first marketed in 1987; meropenem was introduced to the market in 1996. In general, imipenem is more active against Gram-positive cocci while meropenem is more active against Gram-negative bacilli. The agents display similar pharmacokinetics. Clinical studies in patients with serious infections (intra-abdominal infection, respiratory infection, septicemia, febrile neutropenia) report similar bacteriological and clinical cure rates with imipenem and meropenem. Meropenem is approved for the treatment of bacterial meningitis, whereas imipenem is not. Adverse effects are similar. CONCLUSIONS: Current literature supports the use of imipenem at a dose of 500 mg every 6 h and meropenem at 1 g every 8 h for the treatment of severe infections. For the treatment of serious infections, imipenem (500 mg every 6 h or 2 g/day [$98/day]) is more economical than meropenem (1 g every 8 h or 3 g/day [$142/day]) based on acquisition cost. PMID:22346545

  8. Helicobacter pylori neutrophil-activating protein: From molecular pathogenesis to clinical applications

    PubMed Central

    Fu, Hua-Wen

    2014-01-01

    Helicobacter pylori (H. pylori) neutrophil-activating protein (HP-NAP) was originally identified as a virulence factor of H. pylori for its ability to activate neutrophils to generate respiratory burst by releasing reactive oxygen species. Later on, HP-NAP was also found to be involved in the protection of H. pylori from DNA damage, supporting the survival of H. pylori under oxidative stress. This protein is highly conserved and expressed by virtually all clinical isolates of H. pylori. The majority of patients infected with H. pylori produced antibodies specific for HP-NAP, suggesting its important role in immunity. In addition to acting as a pathogenic factor by activating the innate immunity through a wide range of human leukocytes, including neutrophils, monocytes, and mast cells, HP-NAP also mediates adaptive immunity through the induction of T helper cell type I responses. The pro-inflammatory and immunomodulatory properties of HP-NAP not only make it play an important role in disease pathogenesis but also make it a potential candidate for clinical use. Even though there is no convincing evidence to link HP-NAP to a disease outcome, recent findings supporting the pathogenic role of HP-NAP will be reviewed. In addition, the potential clinical applications of HP-NAP in vaccine development, clinical diagnosis, and drug development will be discussed. PMID:24833859

  9. Olfactory Hallucinations without Clinical Motor Activity: A Comparison of Unirhinal with Birhinal Phantosmia

    PubMed Central

    Henkin, Robert I.; Potolicchio, Samuel J.; Levy, Lucien M.

    2013-01-01

    Olfactory hallucinations without subsequent myoclonic activity have not been well characterized or understood. Herein we describe, in a retrospective study, two major forms of olfactory hallucinations labeled phantosmias: one, unirhinal, the other, birhinal. To describe these disorders we performed several procedures to elucidate similarities and differences between these processes. From 1272, patients evaluated for taste and smell dysfunction at The Taste and Smell Clinic, Washington, DC with clinical history, neurological and otolaryngological examinations, evaluations of taste and smell function, EEG and neuroradiological studies 40 exhibited cyclic unirhinal phantosmia (CUP) usually without hyposmia whereas 88 exhibited non-cyclic birhinal phantosmia with associated symptomology (BPAS) with hyposmia. Patients with CUP developed phantosmia spontaneously or after laughing, coughing or shouting initially with spontaneous inhibition and subsequently with Valsalva maneuvers, sleep or nasal water inhalation; they had frequent EEG changes usually ipsilateral sharp waves. Patients with BPAS developed phantosmia secondary to several clinical events usually after hyposmia onset with few EEG changes; their phantosmia could not be initiated or inhibited by any physiological maneuver. CUP is uncommonly encountered and represents a newly defined clinical syndrome. BPAS is commonly encountered, has been observed previously but has not been clearly defined. Mechanisms responsible for phantosmia in each group were related to decreased gamma-aminobutyric acid (GABA) activity in specific brain regions. Treatment which activated brain GABA inhibited phantosmia in both groups. PMID:24961619

  10. Defective von willebrand factor activity detected by the filterometer in three clinical conditions.

    PubMed

    O'Brien, J R; Tsai, H M; Etherington, M D

    2000-11-01

    When exposed to high levels of shear in a filterometer, platelets bind to von Willebrand factor (vWF) via receptors Ib and IIb/IIIa, forming aggregates that block the filteromer. In this study we used the filterometer to explore the mechanisms by which abnormal vWF-platelet interaction might occur. In the first phase of the study, the global vWF-platelet interaction in native blood was investigated. In the second phase, to eliminate the difference that platelets might contribute, samples of platelet-poor plasma from test individuals were added to normal control blood and the mixtures were investigated by the filterometer. The filterometer results were adjusted for the antigen concentrations to obtain vWF potency ratios. Sodium dodecyl sulphate (SDS) agarose gel electrophoresis and SDS-Polyacylamide gel electrophoresis (PAGE) were used to analyze multimeric size and proteolytic profiles of vWF. Pregnancy was associated with high platelet retention, high vWF antigen concentration, normal multimeric size distribution, but decreased vWF potency ratios. The plasma samples of pregnancy contained one 183-kDa fragment not detected in normal plasma. These results suggested that in pregnancy, platelets were highly active. However, presumably due to abnormal proteolytic cleavage, vWF potency was decreased. This decrease in vWF potency might minimize the risk of thrombosis in association with highly active platelets. Renal transplant patients had normal platelet retention but high vWF levels. The plasma vWF contained normal multimers. A decrease in vWF potency, presumably caused by toxic inhibitors in the plasma, was detected. Aortic valve stenosis patients had decreased platelet retention, normal or slightly increased vWF antigen concentration and a decrease in large multimers. As a result, the vWF potency was markedly decreased. However, the results obtained with the filterometer became normal when the studies were repeated 3 months postpartum, when renal function had

  11. Inflammatory bowel disease in children--clinical, endoscopic, radiologic and histopathologic investigation.

    PubMed

    Seo, J K; Yeon, K M; Chi, J G

    1992-09-01

    This paper reviews our five years' clinical experience (1987 to 1991) of 22 patients with inflammatory bowel disease (IBD). There were 12 patients with Crohn's disease and 10 patients with ulcerative colitis. The mean age at diagnosis was 8.7 years (2 to 14 years). Clinical impressions before referral were chronic diarrhea in 11, irritable bowel syndrome in 5, colon polyp in 4, lymphoma in 3, intestinal tuberculosis in 2, amoebic colitis in 2, ulcerative colitis in 2 children and other diseases. The mean interval from the onset of symptoms to the diagnosis of IBD was 18 months. Diagnosis of Crohn's disease was delayed for more than 13 months in 8 (67%), whereas that of ulcerative colitis was delayed for more than 13 months in 4 (40%). Diarrhea (50%), abdominal pain (36%) and rectal bleeding (36%) were the three most frequent presenting complaints of IBD. Moderately severe abdominal pain was a more common chief complaint in Crohn's disease (58%) than in ulcerative colitis (10%). Hematochezia (90% vs 17%) and moderately severe diarrhea (90% vs 75%) were more common gastrointestinal manifestations in ulcerative colitis than in Crohn's disease. The associated extraintestinal manifestations were oral ulcer in 7, arthralgia in 11 and arthritis in 4, skin lesions in 2, eye lesions in 2 and growth failure in 9 patients. Of 12 children with Crohn's disease, granuloma was found in 5, aphthous ulcerations in 8, cobble stone appearance in 8, skip area or asymmetric lesions in 6, transmural involvement in 7, and perianal fistula in 3. Among 10 children with ulcerative Colitis, there were crypt abscess in 8, granularity or friability in 10 and rectosigmoid ulcerations with purulent exudate in 8 children. The main sites of involvement in children with Crohn's disease were both the small and large bowels in 7 (58%), small bowel only in 2 (16%), and colon only in 3 (25%). Terminal ileum involvement was seen in 75% of Crohn's disease cases. The main sites of involvement in children

  12. A rare case of amelanotic malignant melanoma in the oral region: Clinical investigation and immunohistochemical study

    PubMed Central

    OHNISHI, YUICHI; WATANABE, MASAHIRO; FUJII, TOMOKO; SUNADA, NORIKO; YOSHIMOTO, HITOSHI; KUBO, HIROHITO; WATO, MASAHIRO; KAKUDO, KENJI

    2015-01-01

    Amelanotic malignant melanoma (AMM) is rare in the oral region. The present study examined the clinical features of this tumor in an attempt to establish diagnostic criteria. The expression of three melanocytic differentiation markers, HMB-45, S-100 and Melan-A, was also measured in primary oral AMMs in order to determine whether the markers could be used to diagnose primary oral AMMs and to find out which marker was the most sensitive. It may be particularly difficult to correctly diagnose AMM that lacks a radial growth phase without immunohistochemical assistance. In the present study, mixtures of polygonal and spindle cells at different ratios were observed in the tumors with and without a radial growth phase. Immunohistochemistry was used to examine the HMB-45, S-100 and Melan-A expression in the formalin-fixed paraffin-embedded specimens of primary oral AMMs. Comparison of staining intensities (SIs) and labeling indices (LIs) of the markers was also performed. The immunostaining results revealed that the SI of Melan-A was significantly higher than that of S-100 (P=0.0011). HMB-45, S-100 and Melan-A also exhibited high positive rates and LIs in AMMs and, therefore, may be good markers for the immunohistochemical diagnosis of primary oral AMMs. Furthermore, Melan-A may be a more sensitive marker than S-100 and HMB-45, as it has a higher SI. PMID:26788204

  13. Clinicians' emotional responses and Psychodynamic Diagnostic Manual adult personality disorders: A clinically relevant empirical investigation.

    PubMed

    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. PMID:25868053

  14. The First Korean Case of HDR Syndrome Confirmed by Clinical and Molecular Investigation

    PubMed Central

    Kim, Gu-Hwan; Yoo, Han-Wook

    2015-01-01

    Hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome is a rare condition inherited as autosomal dominant trait and characterized by hypoparathyroidism, sensorineural deafness, and renal dysplasia. HDR syndrome is caused by haploinsufficiency of the GATA3 gene located on chromosome 10p15. Here, we report the case of a 32-day-old Korean male with HDR syndrome. He was presented due to repeated seizures over previous 3 days. The patient was born after 40 weeks of gestation with birth weight of 2930 g, and was the first-born baby of healthy Korean parents. Hypoparathyroidism was first noticed due to seizure. A multicystic left dysplastic kidney and vesicoureteral reflux were detected by ultrasound after birth. Auditory brainstem response (ABR) testing revealed that the patient had moderate sensorineural deafness, with hearing losses of 80 dB at the mid and higher frequencies for both ears. Echocardiography finding revealed secundum atrial septal deftect. Based on biochemical results and clinical findings, a presumptive diagnosis of HDR syndrome was made. GATA3 mutation analysis identified a heterozygous deletion, c.153del (p.Phe51Leufs*144) in exon 1 causing a frameshift mutation, which is a novel de novo mutation. Therefore, we suggest that HDR syndrome should be considered in the differential diagnosis in symptomatic or asymptomatic patients with hypoparathyroidism, and that renal ultrasound or ABR testing be performed to prevent a missed diagnosis. This is the first report on Korean patient with confirmed HDR syndrome with novel mutation. PMID:25510779

  15. The first Korean case of HDR syndrome confirmed by clinical and molecular investigation.

    PubMed

    Cheon, Chong Kun; Kim, Gu Hwan; Yoo, Han Wook

    2015-01-01

    Hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome is a rare condition inherited as autosomal dominant trait and characterized by hypoparathyroidism, sensorineural deafness, and renal dysplasia. HDR syndrome is caused by haploinsufficiency of the GATA3 gene located on chromosome 10p15. Here, we report the case of a 32-day-old Korean male with HDR syndrome. He was presented due to repeated seizures over previous 3 days. The patient was born after 40 weeks of gestation with birth weight of 2930 g, and was the first-born baby of healthy Korean parents. Hypoparathyroidism was first noticed due to seizure. A multicystic left dysplastic kidney and vesicoureteral reflux were detected by ultrasound after birth. Auditory brainstem response (ABR) testing revealed that the patient had moderate sensorineural deafness, with hearing losses of 80 dB at the mid and higher frequencies for both ears. Echocardiography finding revealed secundum atrial septal deftect. Based on biochemical results and clinical findings, a presumptive diagnosis of HDR syndrome was made. GATA3 mutation analysis identified a heterozygous deletion, c.153del (p.Phe51Leufs*144) in exon 1 causing a frameshift mutation, which is a novel de novo mutation. Therefore, we suggest that HDR syndrome should be considered in the differential diagnosis in symptomatic or asymptomatic patients with hypoparathyroidism, and that renal ultrasound or ABR testing be performed to prevent a missed diagnosis. This is the first report on Korean patient with confirmed HDR syndrome with novel mutation. PMID:25510779

  16. Performance and specificity rates in the Test of Memory Malingering: an investigation into pediatric clinical populations.

    PubMed

    Loughan, Ashlee R; Perna, Robert

    2014-01-01

    Symptom validity tests are becoming standard as an effort measure during pediatric neuropsychological assessment. An important component of symptom validity test use is understanding limitations of these measures and how select clinical groups may have difficulty with them. Research has begun to clarify the limits of the Test of Memory Malingering (TOMM) with diverse childhood diagnoses. This study compared TOMM scores of children (N = 86) classified with common childhood disorders. Findings suggest that a substantial proportion of children performed below the recommended cutoff score of 45 on Trial 2 and attained varied specificity rates. This included children with conduct disorders (85%), affective disorders (92%), traumatic brain injury (83%), attention-deficit hyperactivity disorder (93%), learning disabilities (100%), and pervasive developmental disorder (88%). The group with the most children scoring below the cutoff was children with intellectual disabilities (76%). This finding is consistent with some of the adult research suggesting that very limited cognitive ability may compromise TOMM performance. Caution may be necessary when drawing conclusions about test-taking effort based on the recommended TOMM cutoff scores when evaluating children with disabilities. PMID:24236938

  17. Pressure Drop in Tortuosity/Kinking of the Internal Carotid Artery: Simulation and Clinical Investigation

    PubMed Central

    Wang, Lijun; Zhao, Feng; Wang, Daming; Hu, Shen; Liu, Jiachun; Zhou, Zhilun; Lu, Jun; Qi, Peng; Song, Shiying

    2016-01-01

    Background. Whether carotid tortuosity/kinking of the internal carotid artery leads to cerebral ischemia remains unclear. There is very little research about the hemodynamic variation induced by carotid tortuosity/kinking in the literature. The objective of this study was to research the blood pressure changes induced by carotid tortuosity/kinking. Methods. We first created a geometric model of carotid tortuosity/kinking. Based on hemodynamic boundary conditions, the hemodynamics of carotid tortuosity and kinking were studied via a finite element simulation. Then, an in vitro system was built to validate the numerical simulation results. The mean arterial pressure changes before and after carotid kinking were measured using pressure sensors in 12 patients with carotid kinking. Results. Numerical simulation revealed that the pressure drops increased with increases in the kinking angles. Clinical tests and in vitro experiments confirmed the numerical simulation results. Conclusions. Carotid kinking leads to blood pressure reduction. In certain conditions, kinking may affect the cerebral blood supply and be associated with cerebral ischemia. PMID:27195283

  18. Investigation of vibration-induced artifact in clinical diffusion-weighted imaging of pediatric subjects.

    PubMed

    Berl, Madison M; Walker, Lindsay; Modi, Pooja; Irfanoglu, M Okan; Sarlls, Joelle E; Nayak, Amritha; Pierpaoli, Carlo

    2015-12-01

    It has been reported that mechanical vibrations of the magnetic resonance imaging scanner could produce spurious signal dropouts in diffusion-weighted images resulting in artifactual anisotropy in certain regions of the brain with red appearance in the Directionally Encoded Color maps. We performed a review of the frequency of this artifact across pediatric studies, noting differences by scanner manufacturer, acquisition protocol, as well as weight and position of the subject. We also evaluated the ability of automated and quantitative methods to detect this artifact. We found that the artifact may be present in over 50% of data in certain protocols and is not limited to one scanner manufacturer. While a specific scanner had the highest incidence, low body weight and positioning were also associated with appearance of the artifact for both scanner types evaluated, making children potentially more susceptible than adults. Visual inspection remains the best method for artifact identification. Software for automated detection showed very low sensitivity (10%). The artifact may present inconsistently in longitudinal studies. We discuss a published case report that has been widely cited and used as evidence to set policy about diagnostic criteria for determining vegetative state. That report attributed longitudinal changes in anisotropy to white matter plasticity without considering the possibility that the changes were caused by this artifact. Our study underscores the need to check for the presence of this artifact in clinical studies, analyzes circumstances for when it may be more likely to occur, and suggests simple strategies to identify and potentially avoid its effects. PMID:26350492

  19. Clinical Assessment and Management of Spondyloarthritides in the Middle East: A Multinational Investigation.

    PubMed

    Hammoudeh, Mohammed; Al Rayes, Hanan; Alawadhi, Adel; Gado, Kamel; Shirazy, Khalid; Deodhar, Atul

    2015-01-01

    Data on spondyloarthritis (SpA) from the Middle East are sparse and the management of these diseases in this area of the world faces a number of challenges, including the relevant resources to enable early diagnosis and referral and sufficient funds to aid the most appropriate treatment strategy. The objective was to report on the characteristics, disease burden, and treatment of SpA in the Middle East region and to highlight where management strategies could be improved, with the overall aim of achieving better patient outcomes. This multicenter, observational, cross-sectional study collected demographic, clinical, laboratory, and treatment data on 169 consecutive SpA patients at four centers (Egypt, Kuwait, Qatar, and Saudi Arabia). The data collected presents the average time from symptom onset to diagnosis along with the presence of comorbidities in the region and comparisons between treatment with NSAIDs and biologics. In the absence of regional registries of SpA patients, the data presented here provide a rare snapshot of the characteristics, disease burden, and treatment of these patients, highlighting the management challenges in the region. PMID:26793241

  20. Clinical Assessment and Management of Spondyloarthritides in the Middle East: A Multinational Investigation

    PubMed Central

    Hammoudeh, Mohammed; Al Rayes, Hanan; Gado, Kamel; Shirazy, Khalid; Deodhar, Atul

    2015-01-01

    Data on spondyloarthritis (SpA) from the Middle East are sparse and the management of these diseases in this area of the world faces a number of challenges, including the relevant resources to enable early diagnosis and referral and sufficient funds to aid the most appropriate treatment strategy. The objective was to report on the characteristics, disease burden, and treatment of SpA in the Middle East region and to highlight where management strategies could be improved, with the overall aim of achieving better patient outcomes. This multicenter, observational, cross-sectional study collected demographic, clinical, laboratory, and treatment data on 169 consecutive SpA patients at four centers (Egypt, Kuwait, Qatar, and Saudi Arabia). The data collected presents the average time from symptom onset to diagnosis along with the presence of comorbidities in the region and comparisons between treatment with NSAIDs and biologics. In the absence of regional registries of SpA patients, the data presented here provide a rare snapshot of the characteristics, disease burden, and treatment of these patients, highlighting the management challenges in the region. PMID:26793241

  1. A Mixed-methods Investigation of Sensory Response Patterns in Barth Syndrome: A Clinical Phenotype?

    PubMed Central

    Reynolds, Stacey; Kreider, Consuelo; Bendixen, Roxanna

    2012-01-01

    Barth syndrome is a genetic disorder that affects approximately 1/500,000 boys each year. While treatment of medical complications associated with Barth is of primary importance, there is a concomitant need to look at behavioral and clinical features of the disorder. The purpose of this study was to examine the prevalence of atypical sensory processing in 21 boys with Barth syndrome and to explore if phenotypic patterns of sensory responsiveness may be useful in early diagnosis. Using a mixed methods approach, we found that sensory issues related to feeding and eating were ubiquitous in our sample, with some behaviors such as strong gag reflex identifiable early in development. Specifically, boys with Barth had a strong preference for salty, cheesy, and spicy foods while having an overall restricted repertoire of foods they would eat (e.g. picky eaters). In boys with Barth as they age, auditory sensitivity and auditory filtering issues also emerged as potential sensory-related behaviors affecting academic performance and participation. Overall, this study suggests that early identification of sensory patterns in Barth may assist in differential diagnosis and create opportunities for early interventions that may minimize the impact of these behaviors on function and participation. PMID:22711649

  2. Structural Investigation of Alkali Activated Clay Minerals for Application in Water Treatment Systems

    NASA Astrophysics Data System (ADS)

    Bumanis, G.; Bajare, D.; Dembovska, L.

    2015-11-01

    Alkali activation technology can be applied for a wide range of alumo-silicates to produce innovative materials with various areas of application. Most researches focuse on the application of alumo-silicate materials in building industry as cement binder replacement to produce mortar and concrete [1]. However, alkali activation technology offers high potential also in biotechnologies [2]. In the processes where certain pH level, especially alkaline environment, must be ensured, alkali activated materials can be applied. One of such fields is water treatment systems where high level pH (up to pH 10.5) ensures efficient removal of water pollutants such as manganese [3]. Previous investigations had shown that alkali activation technology can be applied to calcined clay powder and aluminium scrap recycling waste as a foam forming agent to create porous alkali activated materials. This investigation focuses on the structural investigation of calcined kaolin and illite clay alkali activation processes. Chemical and mineralogical composition of both clays were determined and structural investigation of alkali activated materials was made by using XRD, DTA, FTIR analysis; the microstructure of hardened specimens was observed by SEM. Physical properties of the obtained material were determined. Investigation indicates the essential role of chemical composition of the clay used in the alkali activation process, and potential use of the obtained material in water treatment systems.

  3. Matrix metalloproteinase levels and gelatinolytic activity in clinically healthy and inflamed human dental pulps.

    PubMed

    Gusman, Heloisa; Santana, Ronaldo B; Zehnder, Matthias

    2002-10-01

    The role of matrix metalloproteinases (MMPs) in the breakdown of pulp tissue of teeth with severe caries has not yet been directly elucidated. This study was to determine the levels of selected MMPs and the overall gelatinolytic activity in clinically healthy and inflamed human dental pulps of 29 healthy subjects, aged 10-19 yr. Seventeen pulps were collected from subjects diagnosed with symptomatic pulpitis, and 18 control pulps were obtained from 12 subjects following premolar extraction for orthodontic reasons. The levels of MMP-1, MMP-2, MMP-3 and MMP-9 were determined with enzyme-linked immunosorbent assay. Densitometric analysis of gelatin zymograms was used to assay gelatinolytic activity in pulp supernatants. The MMP-1 levels were below the detection limit for both groups. Levels of MMP-2 and MMP-3 were significantly lower in symptomatic vs. clinically healthy pulps. In contrast, levels of MMP-9 in inflamed pulps were significantly higher than those recorded in clinically normal pulps. The overall gelatinolytic activity was elevated in inflamed pulps compared with healthy counterparts. Further, the gelatinolytic activity was positively correlated with MMP-9 levels. The data obtained suggest a key role of MMP-9 in the breakdown of inflamed human dental pulp tissue. PMID:12664465

  4. Determination of Carboxypeptidase Activity in Clinical Pathogens by Gas Chromatography–Mass Spectrometry

    PubMed Central

    Lough, Fraser; Perry, John D.; Stanforth, Stephen P.; Dean, John R.

    2016-01-01

    ABSTRACT A novel method for the determination of benzoic acid has been employed to identify carboxypeptidase activities in clinically relevant pathogens. Benzoic acid was determined after chemical derivatization by gas chromatography–mass spectrometry (GC–MS). N-Benzoyl amino acid substrates were evaluated for the detection of carboxypeptidase activities in a number of clinical pathogens. Upon enzymatic hydrolysis of these substrates, benzoic acid was produced which was detected by extraction from the liquid culture supernatant, derivatization as the trimethylsilyl ester, with subsequent analysis by GC–MS. Enzymatic hydrolysis of N-benzoyl glycine was observed for S. agalactiae, M. morganii, and A. baumannii. In addition, P. fluorescens was found to hydrolyze N-benzoyl-L-glutamic acid. Although the method provides an alternative approach for determining carboxypeptidase activity, ultimately it would not be a suitable method in a clinical setting. However, the method is well-suited for identifying carboxypeptidase activities that have not been previously described or to corroborate a carboxypeptidase assay with the ninhydrin reagent. PMID:27226648

  5. 76 FR 4914 - Agency Information Collection Activities: Proposed Collection; Comment Request; Investigational...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-27

    ... drug should be authorized; (3) ensure production of reliable data on the metabolism and pharmacological... HUMAN SERVICES Food and Drug Administration Agency Information Collection Activities: Proposed Collection; Comment Request; Investigational New Drug Regulations AGENCY: Food and Drug Administration,...

  6. Enhancement of antibiotic activity by efflux inhibitors against multidrug resistant Mycobacterium tuberculosis clinical isolates from Brazil

    PubMed Central

    Coelho, Tatiane; Machado, Diana; Couto, Isabel; Maschmann, Raquel; Ramos, Daniela; von Groll, Andrea; Rossetti, Maria L.; Silva, Pedro A.; Viveiros, Miguel

    2015-01-01

    Drug resistant tuberculosis continues to increase and new approaches for its treatment are necessary. The identification of M. tuberculosis clinical isolates presenting efflux as part of their resistant phenotype has a major impact in tuberculosis treatment. In this work, we used a checkerboard procedure combined with the tetrazolium microplate-based assay (TEMA) to study single combinations between antituberculosis drugs and efflux inhibitors (EIs) against multidrug resistant M. tuberculosis clinical isolates using the fully susceptible strain H37Rv as reference. Efflux activity was studied on a real-time basis by a fluorometric method that uses ethidium bromide as efflux substrate. Quantification of efflux pump genes mRNA transcriptional levels were performed by RT-qPCR. The fractional inhibitory concentrations (FIC) indicated synergistic activity for the interactions between isoniazid, rifampicin, amikacin, ofloxacin, and ethidium bromide plus the EIs verapamil, thioridazine and chlorpromazine. The FICs ranged from 0.25, indicating a four-fold reduction on the MICs, to 0.015, 64-fold reduction. The detection of active efflux by real-time fluorometry showed that all strains presented intrinsic efflux activity that contributes to the overall resistance which can be inhibited in the presence of the EIs. The quantification of the mRNA levels of the most important efflux pump genes on these strains shows that they are intrinsically predisposed to expel toxic compounds as the exposure to subinhibitory concentrations of antibiotics were not necessary to increase the pump mRNA levels when compared with the non-exposed counterpart. The results obtained in this study confirm that the intrinsic efflux activity contributes to the overall resistance in multidrug resistant clinical isolates of M. tuberculosis and that the inhibition of efflux pumps by the EIs can enhance the clinical effect of antibiotics that are their substrates. PMID:25972842

  7. [On the antipyretic effect of paracetamol. Clinical investigation with two different forms of application (author's transl)].

    PubMed

    Götte, R; Liedtke, R

    1978-01-01

    144 children, aged between 15 days and 12 years, suffering from febrile condition of various etiology, were treated with differentiated single doses of paracetamol (N-acetyl-p-aminophenol) in form of syrup, suppositories and a combination of syrup with the antihistamine doxylaminsuccinate. During investigation periods of four hours, applying reduced doses, the syrup application showed the same antipyretic effects as those obtained with paracetamol suppositories. When administering the combination with doxylaminsuccinate, the antipyretic effect was reduced and the psychomotoric superactivity did not improve. A control of the actual rectal dosage scheme for repetitive applications is recommended and the combination of paracetamol with sedatives is to be discussed. PMID:304522

  8. Medication Use in Early-HD Participants in Track-HD: an Investigation of its Effects on Clinical Performance.

    PubMed

    Keogh, Ruth; Frost, Chris; Owen, Gail; Daniel, Rhian M; Langbehn, Doug R; Leavitt, Blair; Durr, Alexandra; Roos, Raymund A C; Landwehrmeyer, G Bernhard; Reilmann, Ralf; Borowsky, Beth; Stout, Julie; Craufurd, David; Tabrizi, Sarah J

    2016-01-01

     Insufficient evidence exists to guide the long-term pharmacological management of Huntington's disease (HD) although most current interventions rely on symptomatic management. The effect of many frontline treatments on potential endpoints for HD clinical trials remains unknown. Our objective was to investigate how therapies widely used to manage HD affect the symptom for which they are prescribed and other endpoints using data from TRACK-HD. We used longitudinal models to estimate effects of medication use on performance on tests of motor, cognitive and neuropsychiatric function using data from 123 TRACK-HD stage 1/2 participants across four study visits. Adjustment for confounding by prior medication use, prior clinical performance, concomitant use of other medications, and baseline variables (sex, disease group, age, CAG, study site, education) enabled a closer-to-causal interpretation of the associations. Adjusting for baseline variables only, medication use was typically associated with worse clinical performance, reflecting greater medication use in more advanced patients. After additional adjustment for longitudinal confounders such "inverse" associations were generally eliminated and in the expected directions: participants taking neuroleptics tended to have better motor performance, improved affect and poorer cognitive performance, and those taking SSRI/SNRIs had less apathy, less affect and better total behaviour scores. However, we uncovered few statistically significant associations. Limitations include sample size and unmeasured confounding. In conclusion, adjustment for confounding by prior measurements largely eliminated associations between medication use and poorer clinical performance from simple analyses. However, there was little convincing evidence of causal effects of medication on clinical performance and larger cohorts or trials are needed. PMID:26819833

  9. Medication Use in Early-HD Participants in Track-HD: an Investigation of its Effects on Clinical Performance

    PubMed Central

    Keogh, Ruth; Frost, Chris; Owen, Gail; Daniel, Rhian M.; Langbehn, Doug R.; Leavitt, Blair; Durr, Alexandra; Roos, Raymund A.C.; Landwehrmeyer, G. Bernhard; Reilmann, Ralf; Borowsky, Beth; Stout, Julie; Craufurd, David; Tabrizi, Sarah J.

    2016-01-01

     Insufficient evidence exists to guide the long-term pharmacological management of Huntington’s disease (HD) although most current interventions rely on symptomatic management. The effect of many frontline treatments on potential endpoints for HD clinical trials remains unknown. Our objective was to investigate how therapies widely used to manage HD affect the symptom for which they are prescribed and other endpoints using data from TRACK-HD. We used longitudinal models to estimate effects of medication use on performance on tests of motor, cognitive and neuropsychiatric function using data from 123 TRACK-HD stage 1/2 participants across four study visits. Adjustment for confounding by prior medication use, prior clinical performance, concomitant use of other medications, and baseline variables (sex, disease group, age, CAG, study site, education) enabled a closer-to-causal interpretation of the associations. Adjusting for baseline variables only, medication use was typically associated with worse clinical performance, reflecting greater medication use in more advanced patients. After additional adjustment for longitudinal confounders such “inverse” associations were generally eliminated and in the expected directions: participants taking neuroleptics tended to have better motor performance, improved affect and poorer cognitive performance, and those taking SSRI/SNRIs had less apathy, less affect and better total behaviour scores. However, we uncovered few statistically significant associations. Limitations include sample size and unmeasured confounding. In conclusion, adjustment for confounding by prior measurements largely eliminated associations between medication use and poorer clinical performance from simple analyses. However, there was little convincing evidence of causal effects of medication on clinical performance and larger cohorts or trials are needed. PMID:26819833

  10. Clinical Relevance of VPAC1 Receptor Expression in Early Arthritis: Association with IL-6 and Disease Activity

    PubMed Central

    Seoane, Iria V.; Ortiz, Ana M.; Piris, Lorena; Lamana, Amalia; Juarranz, Yasmina; García-Vicuña, Rosario; González-Álvaro, Isidoro; Gomariz, Rosa P.; Martínez, Carmen

    2016-01-01

    Background The vasoactive intestinal peptide (VIP) receptors VPAC1 and VPAC2 mediate anti-inflammatory and immunoregulatory responses in rheumatoid arthritis (RA). Data on the expression of these receptors could complement clinical assessment in the management of RA. Our goal was to investigate the correlation between expression of both receptors and the 28-Joint Disease Activity Score (DAS28) in peripheral blood mononuclear cells (PBMCs) from patients with early arthritis (EA). We also measured expression of IL-6 to evaluate the association between VIP receptors and systemic inflammation. Methods We analyzed 250 blood samples collected at any of the 5 scheduled follow-up visits from 125 patients enrolled in the Princesa Early Arthritis Register Longitudinal study. Samples from 22 healthy donors were also analyzed. Sociodemographic, clinical, and therapeutic data were systematically recorded. mRNA expression levels were determined using real-time PCR. Then, longitudinal multivariate analyses were performed. Results PBMCs from EA patients showed significantly higher expression of VPAC2 receptors at baseline compared to healthy donors (p<0.001). With time, however, VPAC2 expression tended to be significantly lower while VPAC1 receptor expression increased in correlation with a reduction in DAS28 index. Our results reveal that more severe inflammation, based on high levels of IL-6, is associated with lower expression of VPAC1 (p<0.001) and conversely with increased expression of VPAC2 (p<0.001). A major finding of this study is that expression of VPAC1 is lower in patients with increased disease activity (p = 0.001), thus making it possible to differentiate between patients with various degrees of clinical disease activity. Conclusion Patients with more severe inflammation and higher disease activity show lower levels of VPAC1 expression, which is associated with patient-reported impairment. Therefore, VPAC1 is a biological marker in EA. PMID:26881970

  11. Pathology Imaging Informatics for Clinical Practice and Investigative and Translational Research

    PubMed Central

    Sadimin, Evita T.; Foran, David J

    2012-01-01

    Pathologists routinely interpret gross and microscopic specimens to render diagnoses and to engage in a broad spectrum of investigative research. Multiple studies have demonstrated that imaging technologies have progressed to a level at which properly digitized specimens provide sufficient quality comparable to the traditional glass slides examinations. Continued advancements in this area will have a profound impact on the manner in which pathology is conducted from this point on. Several leading institutions have already undertaken ambitious projects directed toward digitally imaging, archiving, and sharing pathology specimens. As a result of these advances, the use of informatics in diagnostic and investigative pathology applications is expanding rapidly. In addition, the advent of novel technologies such as multispectral imaging makes it possible to visualize and analyze imaged specimens using multiple wavelengths simultaneously. As these powerful technologies become increasingly accepted and adopted, the opportunities for gaining new insight into the underlying mechanisms of diseases as well as the potential for discriminating among subtypes of pathologies are growing accordingly. PMID:22855694

  12. Paraoxonase-1 Enzyme Activity Assay for Clinical Samples: Validation and Correlation Studies

    PubMed Central

    Garelnabi, Mahdi; Younis, Abdelmoneim

    2015-01-01

    Background Paraoxonase-1 (PON1) enzyme is reported in various types of tissues and linked to numerous pathophysiological disorders. It is a potential biomarker in many pathological conditions such as cardiovascular diseases. Material/Methods We conducted several small-scale studies to evaluate PON1 performance as affected by sample types, storage, and interferences. We also carried out short-term studies to compare the performance of the widely used PON1 assay to the similar commercially available PON1 kit assay method; sample size for the method comparison was N=40, and the number varied for other validation experiments. Results Our studies using various types of anticoagulants show that samples collected in tubes with NaF, citrate, EDTA, clot activator, and sodium heparin have increased PON1 levels that are 49%, 24.5%, 19.8%, 11.4%, and 8%, respectively, higher compared to serum samples collected in plain tubes. However, samples collected in lithium heparin tubes demonstrated 10.4% lower PON1 levels compared to serum collected in plain tubes. Biological interference such as hemolysis has little effect on PON1 levels; however, samples spiked with lipids have shown 13% lower PON 1 levels. Our studies comparing the PON1 method commonly available for PON1 assay and a similar non-ELISA commercially available PON1 kit method showed a weak Spearman correlation coefficient of R2=0.40 for the range of 104.9–245.6 U/L. Conclusions The current study provides new validation data on enzyme PON1 performance. While no appreciable change was seen with storage, samples type affects the enzyme performance. Our results should encourage additional clinical studies to investigate other aspects of factors known to affect PON1 enzyme function and performance. PMID:25814092

  13. Investigation of membrane active properties and antiradical activity of gossypol and its derivatives

    Technology Transfer Automated Retrieval System (TEKTRAN)

    New asymmetrical derivatives of gossypol were synthesized. The antioxidant activity of gossypol and these derivatives was studied. The interaction of these compounds with modeled lipid membranes was also studied. It was found that the antioxidant effects and ability to interact with membranes was...

  14. Antibacterial activity of three newly-synthesized chalcones & synergism with antibiotics against clinical isolates of methicillin-resistant Staphylococcus aureus

    PubMed Central

    Božić, Dragana D.; Milenković, Marina; Ivković, Branka; Cirković, Ivana

    2014-01-01

    Background & objectives: Multidrug-resistance of methicillin-resistant Staphylococcus aureus (MRSA) is a serious therapeutical problem. Chalcones belong to a group of naturally occurring flavonoids, usually found in various plant species, and have potent antibacterial, antiviral and antifungal activities. The goal of this study was to evaluate the antibacterial effect of three newly-synthesized chalcones against clinical isolates of MRSA, and their synergism with β-lactam and non- β-lactam antibiotics. Methods: Antimicrobial activity of the three newly-synthesized chalcones was tested against 19 clinical isolates of MRSA and a laboratory control strain of MRSA (ATCC 43300). The synergism with β-lactams: cefotaxime (CFX), ceftriaxone (CTX), and non-β-lactam antibiotics: ciprofloxacin (CIP), gentamicin (GEN) and trimethoprim/sulphamethoxazole (TMP-SMX) was investigated by checkerboard method. Results: All evaluated compounds showed significant anti-MRSA activity with MIC values from 25-200 μg/ml. Observed synergism with antibiotics demonstrated that chalcones significantly enhanced the efficacy of CIP, GEN and TMP-SMX. Interpretation & conclusions: Our study demonstrated that three newly-synthesized chalcones exhibited significant anti-MRSA effect and synergism with non-β-lactam antibiotics. The most effective compound was 1,3-Bis-(2-hydroxy-phenyl)-propenone. Our results provide useful information for future research of possible application of chalcones in combination with conventional anti-MRSA therapy as promising new antimicrobial agents. PMID:25222788

  15. The methylfolate axis in neural tube defects: in vitro characterisation and clinical investigation.

    PubMed

    Lucock, M D; Wild, J; Schorah, C J; Levene, M I; Hartley, R

    1994-08-01

    We have investigated various micronutrients important to folate metabolism in women with two previous neural tube defect (NTD)-affected pregnancies. Results suggest the disposition of plasma 5-methyltetrahydrofolate (5CH3-H4PteGlu) with respect to dietary intake may differ from that of the control population. It appears that to achieve a given plasma level of 5CH3-H4PteGlu, the population with a history of NTD pregnancies needs to take in more dietary folate than controls. We discuss this in the context of a potential lesion at or upstream from 5,10-methylenetetrahydrofolate reductase (MTHFR). This metabolic axis, which is responsible for the multienzymic conversion of PteGlu to 5CH3-H4PteGlu, has been investigated in a rat model using liver homogenate. The anticonvulsant drug (ACD) carbamazepine was found to inhibit the reaction in terms of a reduced Vmax and increased Km. Inhibition approaching maximal was found to occur at therapeutic levels of ACD. Various potential inhibitory sites along the methylfolate axis are considered and possible relationships to congenital malformations discussed. We describe folate and one carbon metabolism in relation to potential NTD lesion sites, not only in the light of present findings, but with respect to the published findings of other workers. Based on our hypothesis that an NTD lesion exists upstream from MTHFR, we expound how pteroylmonoglutamate supplementation may protect against NTD (i) by reducing endotoxic homocysteine and (ii) through inhibiting MTHFR (as do dihydrofolates) and thus diverting one carbon units into DNA thymine. PMID:7993656

  16. New Brunswick nurses' views on nursing research, and factors influencing their research activities in clinical practice.

    PubMed

    Robichaud-Ekstrand, Sylvie

    2016-06-01

    New Brunswick became the first province in Canada to require a baccalaureate degree in nursing as the entry to practice, yet nursing research in hospital settings remains quite low. This study examined clinical nurses' views on nursing research, and identified some contributing factors to the research-practice gap. This descriptive, cross-sectional multicenter study involved 1081 nurses working in the Francophone Regional Health Authority in New Brunswick, Canada. Nurses were eager to identify nursing-care problems to improve patient care (92.9%), and to be involved in collecting data for nursing research studies (95.2%). However, without research supervision, few had engaged in basic research activities, such as formulating or refining research questions (24.5%), presenting at research conferences (6.9%), or changing their practice based on research findings (27.2%). Younger, more educated nurses, nurse managers, and educators participated more readily in research. Sharing research and clinical expertise, as well as infrastructures between academic and clinical institutions is the key to enduring successful patient-centered nursing research in clinical settings. Concrete actions are proposed to build clinical nursing research. PMID:26822438

  17. Active surveillance for prostate cancer: a narrative review of clinical guidelines.

    PubMed

    Bruinsma, Sophie M; Bangma, Chris H; Carroll, Peter R; Leapman, Michael S; Rannikko, Antti; Petrides, Neophytos; Weerakoon, Mahesha; Bokhorst, Leonard P; Roobol, Monique J

    2016-03-01

    In the past decade active surveillance (AS) of men with localized prostate cancer has become an increasingly popular management option, and a range of clinical guidelines have been published on this topic. Existing guidelines regarding AS for prostate cancer vary widely, but predominantly state that the most suitable patients for AS are those with pretreatment clinical stage T1c or T2 tumours, serum PSA levels <10 ng/ml, biopsy Gleason scores of 6 or less, a maximum of one or two tumour-positive biopsy core samples and/or a maximum of 50% of cancer per core sample. Following initiation of an AS programme, most guidelines recommend serial serum PSA measurements, digital rectal examinations and surveillance biopsies to check for and identify pathological indications of tumour progression. Definitions of disease reclassification and progression differ among guidelines and multiple criteria for initiation of definitive treatment are proposed. The variety of descriptions of criteria for clinically insignificant prostate cancer indicates a lack of consensus on optimal AS and intervention thresholds. A single set of guidelines are needed in order to reduce variations in clinical practice and to optimize clinical decision-making. To enable truly evidence-based guidelines, further research that combines existing evidence, while also gathering information from more long-term studies is needed. PMID:26813955

  18. Activity of Natural Polyether Ionophores: Monensin and Salinomycin against Clinical Staphylococcus epidermidis Strains.

    PubMed

    Stefańska, Joann; Stępień, Karolina; Huczyński, Adam; Tyski, Stefan

    2015-01-01

    Staphylococcus epidermidis, a coagulase-negative Staphylococcus, is the most important pathogen responsible for chronic nosocomial infections. These bacteria produce extracellular slime and form biofilms on various biotic and abiotic surfaces. Bacterial biofilms are very resistant to standard antimicrobial therapy and difficult to eradicate, so it is important to search for new more effective anti-biofilm agents, for example in the group of natural substances. The aim of the study was to examine the activity of two ionophores-salinomycin and monensin against clinical S. epidermidis strains, using MIC/MBC method and biofilm formation inhibition assay. Bacterial strains were tested also for slime production using Congo Red Agar. Both tested ionophore antibiotics showed the highest activity against planktonic bacteria of clinical as well as standard S. epidermidis strains and effectively inhibited the formation of bacterial biofilm. PMID:26638535

  19. Clinical development of reovirus for cancer therapy: An oncolytic virus with immune-mediated antitumor activity

    PubMed Central

    Gong, Jun; Sachdev, Esha; Mita, Alain C; Mita, Monica M

    2016-01-01

    Reovirus is a double-stranded RNA virus with demonstrated oncolysis or preferential replication in cancer cells. The oncolytic properties of reovirus appear to be dependent, in part, on activated Ras signaling. In addition, Ras-transformation promotes reovirus oncolysis by affecting several steps of the viral life cycle. Reovirus-mediated immune responses can present barriers to tumor targeting, serve protective functions against reovirus systemic toxicity, and contribute to therapeutic efficacy through antitumor immune-mediated effects via innate and adaptive responses. Preclinical studies have demonstrated the broad anticancer activity of wild-type, unmodified type 3 Dearing strain reovirus (Reolysin®) across a spectrum of malignancies. The development of reovirus as an anticancer agent and available clinical data reported from 22 clinical trials will be reviewed. PMID:27019795

  20. Clinical development of reovirus for cancer therapy: An oncolytic virus with immune-mediated antitumor activity.

    PubMed

    Gong, Jun; Sachdev, Esha; Mita, Alain C; Mita, Monica M

    2016-03-26

    Reovirus is a double-stranded RNA virus with demonstrated oncolysis or preferential replication in cancer cells. The oncolytic properties of reovirus appear to be dependent, in part, on activated Ras signaling. In addition, Ras-transformation promotes reovirus oncolysis by affecting several steps of the viral life cycle. Reovirus-mediated immune responses can present barriers to tumor targeting, serve protective functions against reovirus systemic toxicity, and contribute to therapeutic efficacy through antitumor immune-mediated effects via innate and adaptive responses. Preclinical studies have demonstrated the broad anticancer activity of wild-type, unmodified type 3 Dearing strain reovirus (Reolysin(®)) across a spectrum of malignancies. The development of reovirus as an anticancer agent and available clinical data reported from 22 clinical trials will be reviewed. PMID:27019795

  1. Super Saver Investigators: An Elementary, Interdisciplinary, Environmental Studies Activity Guidebook about Solid Waste and Natural Resources.

    ERIC Educational Resources Information Center

    Landis, David; And Others

    This is an elementary, interdisciplinary, environmental studies activity guidebook about solid waste and natural resources. "Super Saver Investigators" what solid waste is, where it is generated, how we manage it and could manage it better, and the consequence of mismanagement. It contains many hands-on, skill enhancing activities for elementary…

  2. BENCH-SCALE INVESTIGATION OF MECHANISMS OF ELEMENTAL MERCURY CAPTURE BY ACTIVATED CARBON

    EPA Science Inventory

    The paper gives results of an investigation of the sorption and desorption of gaseous elemental mercury by activated carbon sorbents. wo sorbents were chosen for the study, one (PC-100) thermally activated and the other (HGR) chemically impregnated with sulfur. he sorbents had si...

  3. Teachers' Beliefs Related to Activity Play in the Preschool Setting: A Phenomenological Investigation

    ERIC Educational Resources Information Center

    Pisha, Lorelei Emma

    2012-01-01

    The purpose of the present study was to investigate how early childhood teachers working in Head Start programs made meaning of preschool-age children's physical activity play by exploring their personal childhood and professional experiences with physical activity play. The study was conducted to contribute research-based recommendations for…

  4. Understanding support mediated activity by investigating highly active, thermally stable, silica supported gold catalysts

    SciTech Connect

    Veith, Gabriel M; Lupini, Andrew R; Rashkeev, Sergey; Pennycook, Stephen J; Schwartz, Viviane; Mullins, David R; Dudney, Nancy J

    2009-01-01

    2.5 nm gold nanoparticles were grown on a fumed silica support using the physical vapor deposition technique magnetron sputtering. Combining electron microscopy, extended X-ray absorption fine structure (EXAFS) spectroscopy, and catalytic studies revealed that the silica supported gold catalysts are thermally stable when annealed in an oxygen containing environment up to at least 500oC. This surprising stability is attributed to the absence of residual halide impurities and a strong bond between gold and defects at the silica surface (2.7 - 3.8 eV), as estimated from density functional theory (DFT) calculations. The Au/SiO2 catalysts are slightly less active for CO oxidation than the prototypical Au/TiO2 catalysts, however they can be regenerated far more easily, fully recovering the activity of a freshly prepared catalyst after deactivation.

  5. [Activity and Future Perspective of Local Independent Clinical Trial Group (OGSG)].

    PubMed

    Tsujinaka, Toshimasa

    2016-04-01

    Osaka Gastrointestinal Cancer Chemotherapy Study Group (OGSG) was established in 2000 and has been conducting investigator initiated multi-institutional collaboration trials regarding the treatment of gastrointestinal cancer, especially using chemotherapeutic agents. Although organization of OGSG has been renovated to perform post-marketing clinical trials with high quality, OGSG is now facing severe financial crisis because of shortage of donation from pharmaceutical companies. Here, present problems and future perspectives are discussed. PMID:27220796

  6. Silibinin Improves the Effects of Methotrexate in Patients with Active Rheumatoid Arthritis: Pilot Clinical Study

    PubMed Central

    Hussain, Saad Abdulrahman; Mortada, Ahmed Hashem; Jasim, Nazar Abdulateef; Gorial, Faiq Isho

    2016-01-01

    Objectives Our study sought to evaluate the effects of silibinin in patients with active rheumatoid arthritis (RA) treated with methotrexate (MTX). Methods We conducted a randomized multi-center, double-blind, placebo-controlled clinical trial over a 16-week treatment period at the Al-Sader and Baghdad Teaching Hospitals in Najaf and Baghdad, respectively. A total of 60 patients (30 of each sex) with active RA, already maintained on 12 mg MTX weekly for at least three consecutive months, were included in the study. Patients were randomly allocated to receive either 120 mg silibinin twice daily or a placebo, combined with their regular MTX regimen. The patients were evaluated by measuring disease activity score using the 28-joint Disease Activity Score, Simple Disease Activity Index, and Health Assessment Questionnaire–Disability Index scores at the start and end of the study. Blood samples were evaluated for the erythrocyte sedimentation rate (ESR), hemoglobin (Hb), high-sensitivity C-reactive protein (hs-CRP), creatine kinase (CK), anti-cyclic citrullinated peptide (CCP), and the serum cytokine levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-8, IL-10, and IL-2. Results Silibinin significantly decreases the already elevated clinical scores compared to placebo treatment. ESR, IL-8, IL-6, TNF-α, anti-CCP, hs-CRP levels were significantly reduced. Additionally, the use of silibinin significantly increases Hb, IL-10, and IL-2 levels. Conclusion Silibinin may improve the effects of MTX on certain biochemical and clinical markers of patients with active RA. PMID:27403238

  7. DNA-PK mediates AKT activation and apoptosis inhibition in clinically acquired platinum resistance.

    PubMed

    Stronach, Euan A; Chen, Michelle; Maginn, Elaina N; Agarwal, Roshan; Mills, Gordon B; Wasan, Harpreet; Gabra, Hani

    2011-11-01

    Clinical resistance to chemotherapy is a frequent event in cancer treatment and is closely linked to poor outcome. High-grade serous (HGS) ovarian cancer is characterized by p53 mutation and high levels of genomic instability. Treatment includes platinum-based chemotherapy and initial response rates are high; however, resistance is frequently acquired, at which point treatment options are largely palliative. Recent data indicate that platinum-resistant clones exist within the sensitive primary tumor at presentation, implying resistant cell selection after treatment with platinum chemotherapy. The AKT pathway is central to cell survival and has been implicated in platinum resistance. Here, we show that platinum exposure induces an AKT-dependent, prosurvival, DNA damage response in clinically platinum-resistant but not platinum-sensitive cells. AKT relocates to the nucleus of resistant cells where it is phosphorylated specifically on S473 by DNA-dependent protein kinase (DNA-PK), and this activation inhibits cisplatin-mediated apoptosis. Inhibition of DNA-PK or AKT, but not mTORC2, restores platinum sensitivity in a panel of clinically resistant HGS ovarian cancer cell lines: we also demonstrate these effects in other tumor types. Resensitization is associated with prevention of AKT-mediated BAD phosphorylation. Strikingly, in patient-matched sensitive cells, we do not see enhanced apoptosis on combining cisplatin with AKT or DNA-PK inhibition. Insulin-mediated activation of AKT is unaffected by DNA-PK inhibitor treatment, suggesting that this effect is restricted to DNA damage-mediated activation of AKT and that, clinically, DNA-PK inhibition might prevent platinum-induced AKT activation without interfering with normal glucose homeostasis, an unwanted toxicity of direct AKT inhibitors. PMID:22131882

  8. DNA-PK Mediates AKT Activation and Apoptosis Inhibition in Clinically Acquired Platinum Resistance12

    PubMed Central

    Stronach, Euan A; Chen, Michelle; Maginn, Elaina N; Agarwal, Roshan; Mills, Gordon B; Wasan, Harpreet; Gabra, Hani

    2011-01-01

    Clinical resistance to chemotherapy is a frequent event in cancer treatment and is closely linked to poor outcome. High-grade serous (HGS) ovarian cancer is characterized by p53 mutation and high levels of genomic instability. Treatment includes platinum-based chemotherapy and initial response rates are high; however, resistance is frequently acquired, at which point treatment options are largely palliative. Recent data indicate that platinum-resistant clones exist within the sensitive primary tumor at presentation, implying resistant cell selection after treatment with platinum chemotherapy. The AKT pathway is central to cell survival and has been implicated in platinum resistance. Here, we show that platinum exposure induces an AKT-dependent, prosurvival, DNA damage response in clinically platinum-resistant but not platinum-sensitive cells. AKT relocates to the nucleus of resistant cells where it is phosphorylated specifically on S473 by DNA-dependent protein kinase (DNA-PK), and this activation inhibits cisplatin-mediated apoptosis. Inhibition of DNA-PK or AKT, but not mTORC2, restores platinum sensitivity in a panel of clinically resistant HGS ovarian cancer cell lines: we also demonstrate these effects in other tumor types. Resensitization is associated with prevention of AKT-mediated BAD phosphorylation. Strikingly, in patient-matched sensitive cells, we do not see enhanced apoptosis on combining cisplatin with AKT or DNA-PK inhibition. Insulin-mediated activation of AKT is unaffected by DNA-PK inhibitor treatment, suggesting that this effect is restricted to DNA damage-mediated activation of AKT and that, clinically, DNA-PK inhibition might prevent platinum-induced AKT activation without interfering with normal glucose homeostasis, an unwanted toxicity of direct AKT inhibitors. PMID:22131882

  9. Validation of clinical activity tracking system in Intensive Care Unit to assess nurse workload distribution.

    PubMed

    Peng Guo; Yeong Shiong Chiew; Shaw, Geoff; Chase, Geoff

    2015-08-01

    Therapeutic Intervention Score System (TISS-28) and the Nursing Activities Score (NAS) are common used to evaluate nursing workload in the Intensive Care Unit (ICU). However, they require experienced researchers to perform, are subject to user bias and experience, and are labor intensive, which all exclude regular use. A Clinical Activities Tracking System (CATS) was developed to evaluate bedside nursing activities automatically. This paper presents the validation of this system in quantifying bedside nursing activities. A total of 30 hours (1 hour/day) of nursing activities were manually recorded by trained researcher. The manually recorded total time spent on bedside nursing activities (Atime) was compared with time recorded using CATS (Ctime). A high correlation was found between Atime and Ctime with R = 0.882, and thus the actual time spent in nursing activity can be estimated using a first order polynomial function. In this study, it was found that the median Atime between 7 am-10 pm is 1.4-1.5 times higher than nursing activities at 10 pm-7 am. Results showed that CATS was able to provide unique and high information on patient bedside nursing activities. PMID:26736298

  10. Preoperative bevacizumab combined with letrozole and chemotherapy in locally advanced ER- and/or PgR-positive breast cancer: clinical and biological activity

    PubMed Central

    Torrisi, R; Bagnardi, V; Cardillo, A; Bertolini, F; Scarano, E; Orlando, L; Mancuso, P; Luini, A; Calleri, A; Viale, G; Goldhirsch, A; Colleoni, M

    2008-01-01

    The antiangiogenic agent bevacizumab showed synergistic effects when combined with chemotherapy in advanced breast cancer. We presently investigated the activity of bevacizumab in combination with chemotherapy, including capecitabine and vinorelbine, and endocrine therapy, including letrozole (+triptorelin in premenopausal women), as primary therapy for patients with ER and/or PgR ⩾10% T2–T4a-c, N0–N2, M0 breast cancer. Biological end point included the proliferative activity (Ki67), whereas clinical end points were clinical response rate, pathological complete response (pCR) and tolerability. Circulating endothelial cells (CECs) and their progenitors, as surrogate markers of antiangiogenic activity, were measured at baseline and at surgery.Thirty-six women are evaluable. A clinical response rate of 86% (95% CI, 70–95) and no pCR were observed; Ki67 was significantly decreased by 71% (interquartile range, −82%, −62%). Toxicity was manageable: two grade 3 hypertension, four grade 3 deep venous thrombosis and no grade >2 proteinuria were observed. Treatment significantly decreased the percentage of viable CECs and prevented the chemotherapy-induced mobilisation of circulating progenitors. Basal circulating progenitors were positively associated with clinical response. In conclusion, bevacizumab is feasible and active in association with primary chemoendocrine therapy for ER-positive tumours in terms of proliferation inhibition, clinical response and antiangiogenic activity. PMID:18941458

  11. Does size matter? An investigation into the Rey Complex Figure in a pediatric clinical sample.

    PubMed

    Loughan, Ashlee R; Perna, Robert B; Galbreath, Jennifer D

    2014-01-01

    The Rey Complex Figure Test (RCF) copy requires visuoconstructional skills and significant attentional, organizational, and problem-solving skills. Most scoring schemes codify a subset of the details involved in figure construction. Research is unclear regarding the meaning of figure size. The research hypothesis of our inquiry is that size of the RCF copy will have neuropsychological significance. Data from 95 children (43 girls, 52 boys; ages 6-18 years) with behavioral and academic issues revealed that larger figure drawings were associated with higher RCF total scores and significantly higher scores across many neuropsychological tests including the Wechsler Individual Achievement Test-Second Edition (WIAT-II) Word Reading (F = 5.448, p = .022), WIAT-II Math Reasoning (F = 6.365, p = .013), Children's Memory Scale Visual Delay (F = 4.015, p = .048), Trail-Making Test-Part A (F = 5.448, p = .022), and RCF Recognition (F = 4.862, p = .030). Results indicated that wider figures were associated with higher cognitive functioning, which may be part of an adaptive strategy in helping facilitate accurate and relative proportions of the complex details presented in the RCF. Overall, this study initiates the investigation of the RCF size and the relationship between size and a child's neuropsychological profile. PMID:24236943

  12. Clinical efficiency investigation of laparoscopic uterine artery occlusion combined with myomectomy for uterine fibroids.

    PubMed

    Yin, Xiang-Hua; Gao, Ling-Ling; Gu, Yang; Song, Jing-Zhe; Gao, Jing; Ji, Xiao-Ping

    2014-01-01

    To investigate the effectiveness of laparoscopic uterine artery occlusion combined with myomectomy for uterine fibroids. From August 2008 to August 2009, forty-eight women with uterine fibroids desiring to preserve their uteri underwent laparoscopic myomectomy. Among them, 18 women received laparoscopic uterine artery occlusion before uterine myomectomy while the others received laparoscopic myomectomy only. All of the 48 cases with uterine fibroids underwent laparoscopic myomectomy successfully, and no patient developed Intraoperative or postoperative complications. The average operation time was (105.6±27.6) min, and the average surgical blood loss was (87.52±18.35) ml. Blocking uterine artery before laparoscopic myomectomy is valuable and feasible for the management of women with symptomatic fibroids. Adopting this method can obtain pleasing therapeutic effect. The method can reduce blood loss thus make the surgical field clean and clear, and it can reduce the operating time and recurrence rate. It can also reduce electro-coagulation on the surgical surface and therefore cause less tissue necrosis and lower incidence of complications. PMID:24995096

  13. Clinical efficiency investigation of laparoscopic uterine artery occlusion combined with myomectomy for uterine fibroids

    PubMed Central

    Yin, Xiang-Hua; Gao, Ling-Ling; Gu, Yang; Song, Jing-Zhe; Gao, Jing; Ji, Xiao-Ping

    2014-01-01

    To investigate the effectiveness of laparoscopic uterine artery occlusion combined with myomectomy for uterine fibroids. From August 2008 to August 2009, forty-eight women with uterine fibroids desiring to preserve their uteri underwent laparoscopic myomectomy. Among them, 18 women received laparoscopic uterine artery occlusion before uterine myomectomy while the others received laparoscopic myomectomy only. All of the 48 cases with uterine fibroids underwent laparoscopic myomectomy successfully, and no patient developed Intraoperative or postoperative complications. The average operation time was (105.6±27.6) min, and the average surgical blood loss was (87.52±18.35) ml. Blocking uterine artery before laparoscopic myomectomy is valuable and feasible for the management of women with symptomatic fibroids. Adopting this method can obtain pleasing therapeutic effect. The method can reduce blood loss thus make the surgical field clean and clear, and it can reduce the operating time and recurrence rate. It can also reduce electro-coagulation on the surgical surface and therefore cause less tissue necrosis and lower incidence of complications. PMID:24995096

  14. Investigation of the use of thermography for research and clinical applications in pregnant women

    NASA Astrophysics Data System (ADS)

    Topalidou, Anastasia; Downe, Soo

    2016-03-01

    Background: The possibility of using thermal imaging, as a non-invasive method, in medicine may provide potential ability of advanced imaging. Objective: The conduction of a preliminary study in healthy non-pregnant females in order to investigate the imaging ability of thermography and its implementation; and to determine hot and cold areas in order to create a "map" of temperature distribution of the abdomen and the torso. Methods: Participants were 18-45 years old non-pregnant women (n = 10), who were measured at 4 different distances. Two thermal imaging cameras and their corresponding software were used to measure abdomen, low back, left and right side of the torso. Results: There were no statistically significant differences in the mean values of the exported temperatures according the distance and the angle between the camera and the subject. The inferior part of the rectus abdominis muscle recorded the coldest zone and the umbilicus appeared as the most prominent hot spot. Conclusions: Thermography shows to be a potential non-invasive technique offering new options in the evaluation of pregnant and laboring women.

  15. A New Multicolor Bioluminescence Imaging Platform to Investigate NF-κB Activity and Apoptosis in Human Breast Cancer Cells

    PubMed Central

    Mezzanotte, Laura; An, Na; Mol, Isabel M.; Löwik, Clemens W. G. M.; Kaijzel, Eric L.

    2014-01-01

    Background Evaluation of novel drugs for clinical development depends on screening technologies and informative preclinical models. Here we developed a multicolor bioluminescent imaging platform to simultaneously investigate transcription factor NF-κB signaling and apoptosis. Methods The human breast cancer cell line (MDA-MB-231) was genetically modified to express green, red and blue light emitting luciferases to monitor cell number and viability, NF-κB promoter activity and to perform specific cell sorting and detection, respectively. The pro-luciferin substrate Z-DEVD-animoluciferin was employed to determine apoptotic caspase 3/7 activity. We used the cell line for the in vitro evaluation of natural compounds and in vivo optical imaging of tumor necrosis factor TNFα-induced NF-κB activation. Results Celastrol, resveratrol, sulphoraphane and curcumin inhibited the NF-κB promoter activity significantly and in a dose dependent manner. All compounds except resveratrol induced caspase 3/7 dependent apoptosis. Multicolor bioluminescence in vivo imaging allowed the investigation of tumor growth and NF-κB induction in a mouse model of breast cancer. Conclusion Our new method provides an imaging platform for the identification, validation, screening and optimization of compounds acting on NF-κB signaling and apoptosis both in vitro and in vivo. PMID:24465597

  16. [Main progress on studies of pharmacological activities and clinical applications of Guizhi Fuling capsule].

    PubMed

    Su, Zhen-zhen; Li, Na; Cao, Liang; Wang, Tuan-jie; Zhang, Chen-feng; Ding, Gang; Wang, Zhen-zhong; Xiao, Wei

    2015-03-01

    Guizhi Fuling capsule is a traditional Chinese medicine composed of five kinds of medicinal plants, Cinnamomi Ramulus, Poria, Moutan Cortex, Persicae Semen, and Paeoniae Radix Alba. Pharmacology studies have shown that Guizhi Fuling capsule has many activities: anti-inflammatory, analgesic, anti-tumor, regulating smooth muscle, endocrine regulation and enhancing immunity. It achieved obvious effects in the treatment of uterine fibroids, pelvic inflammatory disease, dysmenorrheal, endometriosis, ovarian cysts, breast hyperplasia and other gynecological diseases. This paper reviewed the main progress on studies of pharmacological activities and clinical applications of Guizhi Fuling capsule in recent years. PMID:26226732

  17. Developing clinical competency in crisis event management: an integrated simulation problem-based learning activity.

    PubMed

    Liaw, S Y; Chen, F G; Klainin, P; Brammer, J; O'Brien, A; Samarasekera, D D

    2010-08-01

    This study aimed to evaluate the integration of a simulation based learning activity on nursing students' clinical crisis management performance in a problem-based learning (PBL) curriculum. It was hypothesized that the clinical performance of first year nursing students who participated in a simulated learning activity during the PBL session would be superior to those who completed the conventional problem-based session. The students were allocated into either simulation with problem-based discussion (SPBD) or problem-based discussion (PBD) for scenarios on respiratory and cardiac distress. Following completion of each scenario, students from both groups were invited to sit an optional individual test involving a systematic assessment and immediate management of a simulated patient facing a crisis event. A total of thirty students participated in the first post test related to a respiratory scenario and thirty-three participated in the second post test related to a cardiac scenario. Their clinical performances were scored using a checklist. Mean test scores for students completing the SPBD were significantly higher than those who completing the PBD for both the first post test (SPBD 20.08, PBD 18.19) and second post test (SPBD 27.56, PBD 23.07). Incorporation of simulation learning activities into problem-based discussion appeared to be an effective educational strategy for teaching nursing students to assess and manage crisis events. PMID:19916052

  18. Mass spectrometric detection of ricin and its activity in food and clinical samples.

    PubMed

    Kalb, Suzanne R; Barr, John R

    2009-03-15

    Ricin is a potent toxin capable of inhibiting protein synthesis and causing death or respiratory failure. Because of its high availability and lethality, ricin is considered a likely agent for bioterrorism. Rapidly determining contamination of food product with ricin and human exposure to ricin is therefore an important public health goal. In this work, we report the development of a method that detects ricin and its activity in food or clinical samples. This method involves immunocapture of the toxin, an examination of the activity of the ricin protein upon a DNA substrate that mimics the toxin's natural RNA target, and analysis of tryptic fragments of the toxin itself. It is the combination of these three techniques, all performed on the same sample, which allows for a sensitive and selective analysis of ricin isolated from a food or clinical sample. This measurement includes a measure of the toxin's activity. The utility of this method was demonstrated on ricin spiked into food and clinical samples consisting of milk, apple juice, serum, and saliva. PMID:19228034

  19. How do interprofessional student teams interact in a primary care clinic? A qualitative analysis using activity theory.

    PubMed

    Kent, Fiona; Francis-Cracknell, Alison; McDonald, Rachael; Newton, Jennifer M; Keating, Jennifer L; Dodic, Miodrag

    2016-10-01

    Practice based interprofessional education opportunities are proposed as a mechanism for health professionals to learn teamwork skills and gain an understanding of the roles of others. Primary care is an area of practice that offers a promising option for interprofessional student learning. In this study, we investigated what and how students from differing professions learn together. Our findings inform the design of future interprofessional education initiatives. Using activity theory, we conducted an ethnographic investigation of interprofessional education in primary care. During a 5 months period, we observed 14 clinic sessions involving mixed discipline student teams who interviewed people with chronic disease. Teams were comprised of senior medicine, nursing, occupational therapy, pharmacy and physiotherapy entry level students. Semi-structured interviews were also conducted with seven clinical educators. Data were analysed to ascertain the objectives, tools, rules and division of labour. Two integrated activity systems were identified: (1) student teams gathering information to determine patients' health care needs and (2) patients either as health consumers or student educators. Unwritten rules regarding 'shared contribution', 'patient as key information source' and 'time constraints' were identified. Both the significance of software literacy on team leadership, and a pre-determined structure of enquiry, highlighted the importance of careful consideration of the tools used in interprofessional education, and the way they can influence practice. The systems of practice identified provide evidence of differing priorities and values, and multiple perspectives of how to manage health. The work reinforced the value of the patients' voice in clinical and education processes. PMID:26781698

  20. fMRI investigation of response inhibition, emotion, impulsivity, and clinical high-risk behavior in adolescents

    PubMed Central

    Brown, Matthew R. G.; Benoit, James R. A.; Juhás, Michal; Dametto, Ericson; Tse, Tiffanie T.; MacKay, Marnie; Sen, Bhaskar; Carroll, Alan M.; Hodlevskyy, Oleksandr; Silverstone, Peter H.; Dolcos, Florin; Dursun, Serdar M.; Greenshaw, Andrew J.

    2015-01-01

    High-risk behavior in adolescents is associated with injury, mental health problems, and poor outcomes in later life. Improved understanding of the neurobiology of high-risk behavior and impulsivity shows promise for informing clinical treatment and prevention as well as policy to better address high-risk behavior. We recruited 21 adolescents (age 14–17) with a wide range of high-risk behavior tendencies, including medically high-risk participants recruited from psychiatric clinics. Risk tendencies were assessed using the Adolescent Risk Behavior Screen (ARBS). ARBS risk scores correlated highly (0.78) with impulsivity scores from the Barratt Impulsivity scale (BIS). Participants underwent 4.7 Tesla functional magnetic resonance imaging (fMRI) while performing an emotional Go/NoGo task. This task presented an aversive or neutral distractor image simultaneously with each Go or NoGo stimulus. Risk behavior and impulsivity tendencies exhibited similar but not identical associations with fMRI activation patterns in prefrontal brain regions. We interpret these results as reflecting differences in response inhibition, emotional stimulus processing, and emotion regulation in relation to participant risk behavior tendencies and impulsivity levels. The results are consistent with high impulsivity playing an important role in determining high risk tendencies in this sample containing clinically high-risk adolescents. PMID:26483645

  1. Antibiofilm Activity of the Brown Alga Halidrys siliquosa against Clinically Relevant Human Pathogens

    PubMed Central

    Busetti, Alessandro; Thompson, Thomas P.; Tegazzini, Diana; Megaw, Julianne; Maggs, Christine A.; Gilmore, Brendan F.

    2015-01-01

    The marine brown alga Halidrys siliquosa is known to produce compounds with antifouling activity against several marine bacteria. The aim of this study was to evaluate the antimicrobial and antibiofilm activity of organic extracts obtained from the marine brown alga H. siliquosa against a focused panel of clinically relevant human pathogens commonly associated with biofilm-related infections. The partially fractionated methanolic extract obtained from H. siliquosa collected along the shores of Co. Donegal; Ireland; displayed antimicrobial activity against bacteria of the genus Staphylococcus; Streptococcus; Enterococcus; Pseudomonas; Stenotrophomonas; and Chromobacterium with MIC and MBC values ranging from 0.0391 to 5 mg/mL. Biofilms of S. aureus MRSA were found to be susceptible to the algal methanolic extract with MBEC values ranging from 1.25 mg/mL to 5 mg/mL respectively. Confocal laser scanning microscopy using LIVE/DEAD staining confirmed the antimicrobial nature of the antibiofilm activity observed using the MBEC assay. A bioassay-guided fractionation method was developed yielding 10 active fractions from which to perform purification and structural elucidation of clinically-relevant antibiofilm compounds. PMID:26058011

  2. Antibiofilm Activity of the Brown Alga Halidrys siliquosa against Clinically Relevant Human Pathogens.

    PubMed

    Busetti, Alessandro; Thompson, Thomas P; Tegazzini, Diana; Megaw, Julianne; Maggs, Christine A; Gilmore, Brendan F

    2015-06-01

    The marine brown alga Halidrys siliquosa is known to produce compounds with antifouling activity against several marine bacteria. The aim of this study was to evaluate the antimicrobial and antibiofilm activity of organic extracts obtained from the marine brown alga H. siliquosa against a focused panel of clinically relevant human pathogens commonly associated with biofilm-related infections. The partially fractionated methanolic extract obtained from H. siliquosa collected along the shores of Co. Donegal; Ireland; displayed antimicrobial activity against bacteria of the genus Staphylococcus; Streptococcus; Enterococcus; Pseudomonas; Stenotrophomonas; and Chromobacterium with MIC and MBC values ranging from 0.0391 to 5 mg/mL. Biofilms of S. aureus MRSA were found to be susceptible to the algal methanolic extract with MBEC values ranging from 1.25 mg/mL to 5 mg/mL respectively. Confocal laser scanning microscopy using LIVE/DEAD staining confirmed the antimicrobial nature of the antibiofilm activity observed using the MBEC assay. A bioassay-guided fractionation method was developed yielding 10 active fractions from which to perform purification and structural elucidation of clinically-relevant antibiofilm compounds. PMID:26058011

  3. Evaluation of Potential Clinical Surrogate Markers of a Trauma Induced Alteration of Clotting Factor Activities

    PubMed Central

    Payas, Arzu; Schoeneberg, Carsten; Wegner, Alexander; Kauther, Max Daniel; Lendemans, Sven

    2016-01-01

    Objective. The aim of this study was to identify routinely available clinical surrogate markers for potential clotting factor alterations following multiple trauma. Methods. In 68 patients admitted directly from the scene of the accident, all soluble clotting factors were analyzed and clinical data was collected prospectively. Ten healthy subjects served as control group. Results. Patients showed reduced activities of clotting factors II, V, VII, and X and calcium levels (all P < 0.0001 to 0.01). Levels of hemoglobin and base deficit correlated moderately to highly with the activities of a number of clotting factors. Nonsurvivors and patients who needed preclinical intubation or hemostatic therapy showed significantly reduced factor activities at admission. In contrast, factor VIII activity was markedly elevated after injury in general (P < 0.0001), but reduced in nonsurvivors (P < 0.05). Conclusions. Multiple trauma causes an early reduction of the activities of nearly all soluble clotting factors in general. Initial hemoglobin and, with certain qualifications, base deficit levels demonstrated a potential value in detecting those underlying clotting factor deficiencies. Nevertheless, their role as triggers of a hemostatic therapy as well as the observed response of factor VIII to multiple trauma and also its potential prognostic value needs further evaluation. PMID:27433474

  4. Vitamin D Receptor Activators and Clinical Outcomes in Chronic Kidney Disease

    PubMed Central

    Gravellone, Luciana; Rizzo, Maria Antonietta; Martina, Valentina; Mezzina, Nicoletta; Regalia, Anna; Gallieni, Maurizio

    2011-01-01

    Vitamin D deficiency appears to be an underestimated risk factor for cardiovascular disease in patients with chronic kidney disease. Evidence from both basic science and clinical studies supports the possible protective role of vitamin D beyond its effect on mineral metabolism. Toxicity of pharmacologic doses of active vitamin D metabolites, in particular calcitriol, is mainly due to the possibility of positive calcium and phosphorus balance. Therefore, vitamin D analogs have been developed, which suppress PTH secretion and synthesis with reduced calcemic and phosphatemic effects. Observational studies suggest that in hemodialysis patients the use of a vitamin D receptor (VDR) activator, such as calcitriol, doxercalciferol, paricalcitol, or alfacalcidol, is associated with a reduced mortality when compared with nonusers of any VDR activator. In this article the existing literature on the topic is reviewed, although a more robust answer to the question of whether or not VDR activators have beneficial effects in hemodialysis patients will hopefully come from a randomized controlled trial. PMID:21647319

  5. [Formation and treatment of pathologic scars--clinical and micromorphologic investigations (author's transl)].

    PubMed

    Kerl, H; Auböck, L; Bayer, U

    1981-03-01

    The results of treatment with Calmurid and Calmurid-HC in patients with hypertrophic scars and keloids of various causes are reported. Histochemical and ultrastructural investigations were performed in individual cases before and after treatment. The following results were found: 1. In the context of keloid prophylaxis and scar care, application of Calmurid and Calmurid-HC has proved very effective. The results of treating hypertrophic scars with urea preparations are also to be evaluated optimistically. 2. The local treatment with Calmurid or Calmurid-HC generally does not have a substantial influence on cosmetically disturbing keloids. However, the skin becomes smoother, more elastic and more resistant under Calmurid or Calmurid-HC therapy; a reduction in the size of the keloid mass is observed only in individual cases. 3. In short, the results are consistent with those which can be obtained with other external preparations which are specially recommended for treatment of scars and keloids. Success of treatment is especially dependent on the age of the lesion. 4. Disturbances in glycosaminoglycan (GAG) and collagen metabolism as well as enzyme defects are the most significant factors in the pathogenesis of pathological scars. The histochemical and electron microscopic studies reveal (of course with the necessary caution in the interpretation) that Calmurid and Calmurid-HC show an effect on distribution of GAG and on the enzyme pattern of the fibroblasts. The preparations may possibly affect the disturbed processes of collagen and GAG synthesis. The reduction of the mast cells in keloids and hypertrophic scars under Calmurid treatment is noteworthy. PMID:7234039

  6. Application of PCR to a clinical and environmental investigation of a case of equine botulism.

    PubMed

    Szabo, E A; Pemberton, J M; Gibson, A M; Thomas, R J; Pascoe, R R; Desmarchelier, P M

    1994-08-01

    PCR for the detection of botulinum neurotoxin gene types A to E was used in the investigation of a case of equine botulism. Samples from a foal diagnosed with toxicoinfectious botulism in 1985 were reanalyzed by PCR and the mouse bioassay in conjunction with an environmental survey. Neurotoxin B was detected by mouse bioassay in culture enrichments of serum, spleen, feces, and intestinal contents. PCR results compared well with mouse bioassay results, detecting type B neurotoxin genes in these samples and also in a liver sample. Other neurotoxin types were not detected by either test. Clostridium botulinum type B was shown to be prevalent in soils collected from the area in which the foal was raised. Four methods were used to test for the presence of botulinum neurotoxin-producing organisms in 66 soil samples taken within a 5-km radius: PCR and agarose gel electrophoresis (types A to E), PCR and an enzyme-linked assay (type B), hybridization of crude alkaline cell lysates with a type B-specific probe, and the mouse bioassay (all types). Fewer soil samples were positive for C. botulinum type B by the mouse bioassay (15%) than by any of the DNA-based detection systems. Hybridization of a type B-specific probe to DNA dot blots (26% of the samples were positive) and PCR-enzyme-linked assay (77% of the samples were positive) were used for the rapid analysis of large numbers of samples, with sensitivity limits of 3 x 10(6) and 3,000 cells, respectively. Conventional detection of PCR products by gel electrophoresis was the most sensitive method (300-cell limit), and in the present environmental survey, neurotoxin B genes only were detected in 94% of the samples. PMID:7989554

  7. Effect of low-level laser therapy after rapid maxillary expansion: a clinical investigation.

    PubMed

    Garcia, Valentin Javier; Arnabat, J; Comesaña, Rafael; Kasem, Khaled; Ustrell, Josep Maria; Pasetto, Stefano; Segura, Oscar Pozuelo; ManzanaresCéspedes, Maria Cristina; Carvalho-Lobato, Patricia

    2016-08-01

    To evaluate the effectiveness low-level laser therapy (LLLT) on the repair of the mid palatal suture, after rapid maxillary expansion (RME). A single-operator, randomized single-blind placebo-controlled study was performed at the Orthodontic Department at the Dental Hospital of Bellvitge. Barcelona University, Hospitalet de Llobregat, Spain. Thirty-nine children (range 6-12 years old), completed RME and were randomized to receive active LLLT (n = 20) or placebo (n = 19). The laser parameters and dose were 660 nm, 100 mW, CW, InGaAlP laser, illuminated area 0.26 cm(2), 332 mW/cm(2), 60 s to four points along midpalatal suture, and 30 s to a point each side of the suture. A total of seven applications were made on days 1, 7, 14, 28, 42, 56, and 70 of the retention phase RME. A cone beam computed tomography (CBCT) scan was carried out on the day of the first laser treatment, and at day 75, a second CBCT scan was performed. Two radiologists synchronized the slices of two scans to be assessed. P = 0.05 was considered to be statistically significant. At day 75 of the suture, the irradiated patients presented a greater percentage of approximate zones in the anterior (p = 0.008) and posterior (p = 0.001) superior suture-and less approximation in the posterior superior suture (p = 0.040)-than the placebo group. LLLT appears to stimulate the repair process during retention phase after RME. PMID:27236292

  8. [In-vitro activity of panipenem against clinical isolates in 2006].

    PubMed

    Yoshida, Sanae; Koga, Tetsufumi; Kakuta, Masayo; Kobayashi, Intetsu; Matsuzaki, Kaoru; Urabe, Eriko; Omika, Kaoru; Hasegawa, Miyuki; Sato, Yumie

    2008-02-01

    The antimicrobial activity of various antibiotics against clinical bacterial isolates recovered from patients with infectious diseases at the medical facilities in the Kanto region between March and September 2006 was evaluated. A total of 1030 clinical isolates were available for susceptibility tests: 420 aerobic Gram-positive organisms, 520 aerobic Gram-negative organisms, 30 anaerobic Gram-positive organisms and 60 anaerobic Gram-negative pathogens. Antimicrobial susceptibility data for Streptococcus pneumoniae and Haemophilus influenzae isolates from pediatric and adult patients were analyzed separately. Panipenem (PAPM), imipenem (IPM), meropenem (MEPM), biapenem (BIPM), doripenem (DRPM), cefozopran (CZOP), cefepime (CFPM), and sulbactam/cefoperazone (SBT/CPZ) were used as test antibiotics. PAPM, IPM and DRPM exhibited excellent in vitro antibacterial activities against methicillin-susceptible Staphylococcus, with all isolates exhibiting a MIC of < or =0.06 microg/mL. Against Streptococcus including penicillin-resistant S. pneumoniae, PAPM demonstrated the strongest antibacterial activity among the carbapenems with a MIC range of < or =0.06 to 0.12 microg/mL. Against Enterobacteriaceae, MEPM showed the strongest antibacterial activity, and PAPM had comparable activity to IPM. Against the extended-spectrum beta-lactamase producing Escherichia coli, Klebsiella species and Proteus species, the MICs for the cephems were high, however, those for the carbepenems were low. Against H. influenzae, PAPM had comparable activity to IPM. With respect to anaerobes, each of the carbapenems tested demonstrated almost the same strong antibacterial activity. In conclusion, 13 years has passed since PAPM was launched in 1993, PAPM still maintains potent antibacterial activity and is considered an effective antimicrobial agent for various types of infectious diseases. PMID:18536215

  9. Qualitative investigation of patients’ experience of a glaucoma virtual clinic in a specialist ophthalmic hospital in London, UK

    PubMed Central

    Kotecha, Aachal; Bonstein, Karen; Cable, Richard; Cammack, Jocelyn; Clipston, Jane; Foster, Paul

    2015-01-01

    Objectives To explore how patients felt about delivery of care in a novel technician-delivered virtual clinic compared with delivery of care in a doctor-delivered model. Design A qualitative investigation using one-to-one interviews before and after patients’ appointments at either the standard outpatient glaucoma clinic or the new technician-delivered virtual glaucoma clinic (Glaucoma Screening and Stable Monitoring Service, GSMS). Setting A glaucoma clinic based in a tertiary ophthalmic specialist hospital in London. Participants 43 patients (38 Caucasian, 5 African/Afro-Caribbean) were interviewed prior to their glaucoma appointment; 38 patients were interviewed between 4 and 6 weeks after their appointment. Consecutive patients were identified from patient reception lists and telephoned prior to their appointment inviting them to participate. Results Trust in the patient–provider relationship emerged as a key theme in patients’ acceptance of not being seen in a traditional doctor-delivered service. Patients who were well informed regarding their glaucoma status and low risk of progression to sight loss were more accepting of the GSMS. Patients valued the reassurance received through effective communication with their healthcare practitioner at the time of their appointment. Conclusions This study suggests that patients are accepting of moving to a model of service delivery whereby the doctor is removed from the consultation as long as they are informed about the status of their condition and reassured by the interaction with staff they meet. This study highlights the importance of patient engagement when introducing new models of service delivery. PMID:26671959

  10. Clinical Research and the Training of Host Country Investigators: Essential Health Priorities for Disease-Endemic Regions

    PubMed Central

    Koita, Ousmane A.; Murphy, Robert L.; Fongoro, Saharé; Diallo, Boubakar; Doumbia, Seydou O.; Traoré, Moussa; Krogstad, Donald J.

    2016-01-01

    The health-care needs and resources of disease-endemic regions such as west Africa have been a major focus during the recent Ebola outbreak. On the basis of that experience, we call attention to two priorities that have unfortunately been ignored thus far: 1) the development of clinical research facilities and 2) the training of host country investigators to ensure that the facilities and expertise necessary to evaluate candidate interventions are available on-site in endemic regions when and where they are needed. In their absence, as illustrated by the recent uncertainty about the use of antivirals and other interventions for Ebola virus disease, the only treatment available may be supportive care, case fatality rates may be unacceptably high and there may be long delays between the time potential interventions become available and it becomes clear whether those interventions are safe or effective. On the basis of our experience in Mali, we urge that the development of clinical research facilities and the training of host country investigators be prioritized in disease-endemic regions such as west Africa. PMID:26598570

  11. Relationship between Histological and Clinical Course of Psoriasis: A Pilot Investigation by Reflectance Confocal Microscopy during Goeckerman Treatment.

    PubMed

    Archid, Rami; Duerr, Hans Peter; Patzelt, Alexa; Philipp, Sandra; Röwert-Huber, Hans-Joachim; Ulrich, Martina; Meinke, Martina Claudia; Knorr, Fanny; Lademann, Jürgen

    2016-01-01

    Alterations of the skin microvasculature are known to play an important role in the development and maintenance of psoriatic skin lesions. In this study, we investigated lesional skin in 11 psoriatic patients during a modified Goeckerman treatment using reflectance confocal microscopy (RCM) to study the relationship between clinical clearance and histological normalization of psoriatic skin and the significance of histological abnormalities on the course of disease. The treatment regimen resulted in a significant reduction of the Psoriasis Area and Severity Index (PASI) as well as capillary and papillary diameters (p < 0.0001). The capillary and papillary diameters were still enlarged when compared to those in normal skin (p < 0.001). Capillary and papillary diameters correlated with each other prior to and after treatment (correlation coefficient = 0.63 and 0.64, p = 0.01 and 0.002, respectively) but not with the PASI. Capillary and papillary diameters after treatment and percentage reduction of the PASI during treatment seemed to be better predictors for the clinical course of relapse than the PASI after treatment. These findings make the subclinical changes of psoriatic skin vessels and dermal papillae a legitimate target for treatment. Further investigations of a large group of patients are needed to evaluate the potential of RCM findings as successor of the PASI in the monitoring of psoriasis. PMID:26841099

  12. The 'idioglossia' cases of the 1890s and the clinical investigation and treatment of developmental language impairment.

    PubMed

    Lorch, Marjorie; Hellal, Paula

    2012-09-01

    The early history of developmental language impairment in late 19th century Britain is considered through the critical examination of three papers appearing in 1891 by Hadden, Golding-Bird and Hale White, and Taylor. They represent innovative investigations of child language disorders whose themes and concerns are resonant today. The term 'idioglossia' was coined to identify this new impairment and reflected the belief by some that these children spoke an invented language. Rather than viewing these children as having some constitutional deficiency, these 19th century physicians were novel in insisting that children with language impairments merited extensive clinical investigation and treatment. Their case descriptions and the subsequent debates regarding classification and prognosis are reviewed. Further consideration is given to how these cases led to questioning the relation between language and speech and other aspects of child development and disorder. Reflection on the early sources of clinical categories provides a new perspective on our current formulations for variation in developmental language trajectories. PMID:21907977

  13. Pott’s disease in Moroccan children: Clinical features and investigation of the IL-12/IFN-γ pathway

    PubMed Central

    el Azbaoui, Safa; Mrani, Nidal Alaoui; Sabri, Ayoub; Jouhadi, Zineb; Ailal, Fatima; Bousfiha, Ahmed Aziz; Najib, Jilali; Hafidi, Naima El; Deswarte, Caroline; Schurr, Erwin; Bustamante, Jacinta; Boisson-Dupuis, Stéphanie; Casanova, Jean-Laurent; Abel, Laurent; Baghdadi, Jamila EL

    2016-01-01

    Setting Tuberculosis spondylodiscitis (TS) or Pott’s disease is an extra-pulmonary form of TB that is rare and difficult to diagnose in children. Some cases of severe TB in children were recently explained by inborn errors of immunity affecting the IL-12/IFN-γ axis. Objective To analyze the clinical data for Moroccan children with TS, and to perform immunological and genetic explorations of the IL-12/IFN-γ axis. Design We studied nine children with TS diagnosed between 2012 and 2014. We investigated the IL-12/IFN-γ circuit by both whole-blood assays and sequencing of the coding regions of 14 core genes of this pathway. Results TS diagnosis was based on a combination of clinical, biological, histological, and radiological data. QuantiFERON TB Gold in Tube results were positive in 75% of patients. Whole-blood assays showed normal IL-12 and IFN-γ production in all but one patient, who displayed impaired decreased response to IL-12. No candidate disease-causing mutations were detected in the exonic regions of the 14 genes. Conclusions The diagnosis of TS in children remains challenging, and is based largely on imaging. Further investigations of TS in children are required to determine the role of genetic defects in pathways that may or may not be related to the IL-12/IFN-γ axis. PMID:26614186

  14. Clinical Research and the Training of Host Country Investigators: Essential Health Priorities for Disease-Endemic Regions.

    PubMed

    Koita, Ousmane A; Murphy, Robert L; Fongoro, Saharé; Diallo, Boubakar; Doumbia, Seydou O; Traoré, Moussa; Krogstad, Donald J

    2016-02-01

    The health-care needs and resources of disease-endemic regions such as west Africa have been a major focus during the recent Ebola outbreak. On the basis of that experience, we call attention to two priorities that have unfortunately been ignored thus far: 1) the development of clinical research facilities and 2) the training of host country investigators to ensure that the facilities and expertise necessary to evaluate candidate interventions are available on-site in endemic regions when and where they are needed. In their absence, as illustrated by the recent uncertainty about the use of antivirals and other interventions for Ebola virus disease, the only treatment available may be supportive care, case fatality rates may be unacceptably high and there may be long delays between the time potential interventions become available and it becomes clear whether those interventions are safe or effective. On the basis of our experience in Mali, we urge that the development of clinical research facilities and the training of host country investigators be prioritized in disease-endemic regions such as west Africa. PMID:26598570

  15. Feasibility and Validity of the Pediatric Ulcerative Colitis Activity Index in Routine Clinical Practice

    PubMed Central

    Dotson, Jennifer L.; Crandall, Wallace V.; Zhang, Peixin; Forrest, Christopher B; Bailey, L. Charles; Colletti, Richard B.; Kappelman, Michael D.

    2014-01-01

    Objectives The Pediatric Ulcerative Colitis Activity Index (PUCAI) is a non-invasive disease activity index developed as a clinical trial endpoint. More recently, practice guidelines have recommended the use of PUCAI in routine clinical care. We therefore sought to evaluate the feasibility, validity and responsiveness of PUCAI in a large, diverse collection of pediatric gastroenterology practices. Methods We extracted data from the two most recent encounters for patients with ulcerative colitis in the ImproveCareNow registry. Feasibility was determined by the percent of patients for whom all PUCAI components were recorded, validity by correlation of PUCAI scores across Physician Global Assessment (PGA) categories, and responsiveness to change by the correlation between the change in PUCAI and PGA scores between visits. Results 2503 patients were included (49.5% male, age 15.2±4.1 years, disease duration 3.7±3.2 years). All items in the PUCAI were completed for 96% of visits. PUCAI demonstrated excellent discriminatory ability between remission, mild and moderate disease; discrimination between moderate and severe disease was less robust. There was good correlation with PGA [r=0.76 (p<0.001), weighted kappa k=0.73 (p<0.001)]. The PUCAI change scores correlated well with PGA change scores (p<0.001). Test-retest reliability of the PUCAI was good (intra-class correlation coefficient=0.72 [95% CI 0.70–0.75], p<0.001). Guyatt’s responsiveness statistic was 1.18 and the correlation of ΔPUCAI with ΔPGA was 0.69 (p<0.001). Conclusions The PUCAI is feasible to use in routine clinical settings. Evidence of its validity and responsiveness support its use as a clinical tool for monitoring disease activity for patients with ulcerative colitis. PMID:25221935

  16. Distinct properties of telmisartan on agonistic activities for peroxisome proliferator-activated receptor γ among clinically used angiotensin II receptor blockers: drug-target interaction analyses.

    PubMed

    Kakuta, Hirotoshi; Kurosaki, Eiji; Niimi, Tatsuya; Gato, Katsuhiko; Kawasaki, Yuko; Suwa, Akira; Honbou, Kazuya; Yamaguchi, Tomohiko; Okumura, Hiroyuki; Sanagi, Masanao; Tomura, Yuichi; Orita, Masaya; Yonemoto, Takako; Masuzaki, Hiroaki

    2014-04-01

    A proportion of angiotensin II type 1 receptor blockers (ARBs) improves glucose dyshomeostasis and insulin resistance in a clinical setting. Of these ARBs, telmisartan has the unique property of being a partial agonist for peroxisome proliferator-activated receptor γ (PPARγ). However, the detailed mechanism of how telmisartan acts on PPARγ and exerts its insulin-sensitizing effect is poorly understood. In this context, we investigated the agonistic activity of a variety of clinically available ARBs on PPARγ using isothermal titration calorimetry (ITC) and surface plasmon resonance (SPR) system. Based on physicochemical data, we then reevaluated the metabolically beneficial effects of telmisartan in cultured murine adipocytes. ITC and SPR assays demonstrated that telmisartan exhibited the highest affinity of the ARBs tested. Distribution coefficient and parallel artificial membrane permeability assays were used to assess lipophilicity and cell permeability, for which telmisartan exhibited the highest levels of both. We next examined the effect of each ARB on insulin-mediated glucose metabolism in 3T3-L1 preadipocytes. To investigate the impact on adipogenesis, 3T3-L1 preadipocytes were differentiated with each ARB in addition to standard inducers of differentiation for adipogenesis. Telmisartan dose-dependently facilitated adipogenesis and markedly augmented the mRNA expression of adipocyte fatty acid-binding protein (aP2), accompanied by an increase in the uptake of 2-deoxyglucose and protein expression of glucose transporter 4 (GLUT4). In contrast, other ARBs showed only marginal effects in these experiments. In accordance with its highest affinity of binding for PPARγ as well as the highest cell permeability, telmisartan superbly activates PPARγ among the ARBs tested, thereby providing a fresh avenue for treating hypertensive patients with metabolic derangement. PMID:24424487

  17. Antibacterial Activity of Rhodomyrtus tomentosa (Aiton) Hassk. Leaf Extract against Clinical Isolates of Streptococcus pyogenes

    PubMed Central

    Limsuwan, Surasak; Kayser, Oliver; Voravuthikunchai, Supayang Piyawan

    2012-01-01

    Ethanol extract of Rhodomyrtus tomentosa (Aiton) Hassk. leaf was evaluated for antibacterial activity against 47 clinical isolates of Streptococcus pyogenes. The extract exhibited good anti-S. pyogenes activity against all the tested isolates with similar minimum inhibitory concentration (MIC, 3.91–62.5 μg mL−1) and minimum bactericidal concentration (MBC, 3.91–62.5 μg mL−1) ranges. No surviving cells were detected at 16 h after treatment with 8 × MIC of the extract. The extract-treated cells demonstrated no lysis and cytoplasmic leakage through the bacterial membrane. Electron micrographs further revealed that the extract did not cause any dramatic changes on the treated cells. Rhodomyrtone, an isolated compound, exhibited good anti-S. pyogenes activity (14 isolates), expressed very low MIC (0.39–1.56 μg mL−1) and MBC (0.39-1.56 μg mL−1) values. Rhodomyrtus tomentosa leaf extract and rhodomyrtone displayed promising antibacterial activity against clinical isolates of S. pyogenes. PMID:22973404

  18. In vitro antimicrobial activity of gatifloxacin compared with other quinolones against clinical isolates from cancer patients.

    PubMed

    Rolston, Kenneth V I; Vaziri, Irfan; Frisbee-Hume, Susan; Streeter, Harriet; LeBlanc, Barbara

    2004-11-01

    Owing to the predominance of gram-positive pathogens in neutropenic cancer patients, newer generation quinolones with an expanded gram-positive spectrum and enhanced potency, may have a role to play for prophylaxis and/or empiric therapy in such patients. The in vitro activity of gatifloxacin was compared with that of ciprofloxacin, levofloxacin and trovafloxacin against 848 recent clinical isolates from cancer patients. Against gram-positive organisms, gatifloxacin was the most active agent tested inhibiting all Aerococcus, Listeria monocytogens, Micrococcus, Stomatococcus mucilaginous, Bacillus, and Rhodococcus equi strains at < or =2 mg/l, its designated susceptibility breakpoint. It was also very active against methicillin-susceptible staphylococci and Streptococcus spp. (including penicillin nonsusceptible Streptococcus pneumoniae and viridans streptococci). It had moderate activity against methicillin-resistant staphylococci and Enterococcus faecalis, inhibiting 68-80% of these strains at < or =2 mg/l. Gatifloxacin also had good activity against the Enterobacteriaceae (although ciprofloxacin was more potent) inhibiting >95% of isolates at < or =1 mg/l. Nonfermentative gram-negative organisms were less susceptible to all 4 agents. Gatifloxacin was very active against Acinetobacter lwoffi (MIC100 0.12 mg/l) and had moderate activity against Acinetobacter baumanii, Chryseobacterium spp., Stenotrophomonas maltophilia, Pseudomonas aeruginosa and other Pseudomonas species. Alcaligenes xylosoxidans strains were relatively resistant to all 4 agents. PMID:15523180

  19. [Informed consent for clinical investigation in the critically ill patient. An introduction to the regulation 536/2014/EC on clinical investigation of medicinal products for human use, repealing Directive 2001/20/EC].

    PubMed

    Savonitto, Stefano; Coppola, Teresa; Braglia, Paola; Ciccone, Alfonso

    2016-05-01

    The principle of patient information, awareness and documented consent for the participation in clinical trials is a cornerstone in the modern ethics of clinical research. However, this procedure is seldom applicable in the critically ill patient who becomes suddenly incapable of fully evaluating the risk vs benefit of the alternative therapeutic options. This issue becomes particularly problematic in those conditions where the benefit of any intervention is highly time-dependent, such as acute myocardial infarction, stroke, cardiac arrest, polytrauma and other similar conditions. The new directive 536/2014/EC defines the concept that in these cases the expert clinician and the Ethics Committees, based upon a rigorous study protocol, are in better conditions, as compared to patients' proxies and any legal representative, to take an appropriate decision. This decision should be later confirmed (deferred consent) by the patient, in case he returns competent, or by his proxies or legal tutor, in order to use experimental data. The new directive ends a long period of disparity among the Member States, some of which had taken unilateral decisions allowing the participation of incapable patients, whereas others, among which Italy, had a more conservative approach. Unfortunately, owing to technical and bureaucratic issues, the new regulation is unlikely to become active before the beginning of 2018. PMID:27310904

  20. Nanoformulation improves activity of the (pre)clinical anticancer ruthenium complex KP1019.

    PubMed

    Heffeter, P; Riabtseva, A; Senkiv, Y; Kowol, C R; Körner, W; Jungwith, U; Mitina, N; Keppler, B K; Konstantinova, T; Yanchuk, I; Stoika, R; Zaichenko, A; Berger, W

    2014-05-01

    Ruthenium anticancer drugs belong to the most promising non-platinum anticancer metal compounds in clinical evaluation. However, although the clinical results are promising regarding both activity and very low adverse effects, the clinical application is currently hampered by the limited solubility and stability of the drug in aqueous solution. Here, we present a new nanoparticle formulation based on polymer-based micelles loaded with the anticancer lead ruthenium compound KP1019. Nanoprepared KP1019 was characterised by enhanced stability in aqueous solutions. Moreover, the nanoparticle formulation facilitated cellular accumulation of KP1019 (determined by ICP-MS measurements) resulting in significantly lowered IC50 values. With regard to the mode of action, increased cell cycle arrest in G2/M phase (PI-staining), DNA damage (Comet assay) as well as enhanced levels of apoptotic cell death (caspase 7 and PARP cleavage) were found in HCT116 cells treated with the new nanoformulation of KP1019. Summarizing, we present for the first time evidence that nanoformulation is a feasible strategy for improving the stability as well as activity of experimental anticancer ruthenium compounds. PMID:24734541

  1. Investigating primary marine aerosol properties: CCN activity of sea salt and mixed particles

    NASA Astrophysics Data System (ADS)

    King, S. M.; Butcher, A. C.; Rosenoern, T.; Coz, E.; Lieke, K. I.; de Leeuw, G.; Nilsson, E. D.; Bilde, M.

    2012-04-01

    Sea salt particles ejected as a result of bubbles bursting from artificial seawater in a closed stainless steel tank were sampled for size distribution, morphology, and cloud condensation nucleus (CCN) activity. The two-component artificial seawater consisted of salt, either NaCl or sea salt, and one organic compound in deionized water. Several organic molecules representative of oceanic organic matter were investigated. Bubbles were generated either by aeration through a porous diffuser or by water jet impingement on the surface of the artificial seawater. The effect of bubble lifetime, which was controlled by varying the depth of the diffuser in the water column, on particle size and CCN activity was investigated and was found to be insignificant for the organic compounds studied. The CCN activities of particles produced from diffuser-generated bubbles were generally governed by the high hygroscopicity of salt, such that activation was indistinguishable from that of salt, except in the case of very low mass ratio of salt to organic matter in the seawater solution. There was, however, a considerable decrease in CCN activity for particles produced from jet impingement on seawater that had a salinity of 10‰ and contained 0.45 mM of sodium laurate, an organic surfactant. The production of a thick foam layer from impingement may explain the difference in activation and supports hypotheses that particle production from the two methods of generating bubbles is not similar. Accurate conclusions from observed CCN activities of particles from artificial seawater containing organic matter require knowledge of the CCN activity of the inorganic component, especially as a small amount of the inorganic can heavily influence activation. Therefore, the CCN activity of both artificial sea salt and NaCl were measured and compared. Part of the discrepancy observed between the CCN activities of the two salts may be due to morphological differences, which were investigated using

  2. [In vitro antibacterial activities of cefteram and other beta-lactam agents against recent clinical isolates].

    PubMed

    Yamaguchi, K; Ohno, A; Takahashi, S; Hayashi, M; Yamanaka, K; Hirakata, Y; Mitsuyama, J

    1998-01-01

    In vitro antibacterial activity of the third-generation oral cephem cefteram (CFTM)--ten years after its first use in the clinical setting--against recent clinical isolates was evaluated and compared with those of other oral cephems. A total of 851 clinical isolates belonging to 13 species used in this study were collected from five medical institutions across Japan during 1996. CFTM showed excellent antibacterial activity against methicillin-susceptible S. aureus and S. pyogenes, equivalent to those of other third-generation oral cephems, except cefixime. Of the S. pneumoniae strains, a high proportion, 34.1%, were penicillin-resistant strains (PRSP), with MIC values of 2.0 micrograms/ml or above, but the MIC50 of CFTM against PRSP was 1.0 microgram/ml. CFTM and the other third-generation oral cephems showed potent antibacterial activity against E. coli, K. pneumoniae, and P. mirabilis. A few strains of E. coli, however, were highly resistant to third-generation oral cephems; that might include extended-spectrum beta-lactamase producing strains. MIC values against P. vulgaris varied significantly, depending on whether they were determined by the broth micro-dilution method or the agar dilution method; growth was observed at high concentrations in the broth micro-dilution method, in which the skip phenomenon was demonstrated, but not in the agar dilution method. The reason for this discrepancy is unknown. Most strains of S. marcescens, C. freundii, and E. cloacae demonstrated resistance to CFTM and the other third-generation oral cephems. CFTM and the other third-generation oral cephems showed excellent antibacterial activities against M. (B.) catarrhalis, N. gonorrhoeae, and H. influenzae, including ampicillin-resistant strains. PMID:9557273

  3. Vortioxetine, a novel antidepressant with multimodal activity: review of preclinical and clinical data.

    PubMed

    Sanchez, Connie; Asin, Karen E; Artigas, Francesc

    2015-01-01

    Vortioxetine, a novel antidepressant for the treatment of major depressive disorder (MDD), is a 5-HT3, 5-HT7 and 5-HT1D receptor antagonist, 5-HT1B receptor partial agonist, 5-HT1A receptor agonist and serotonin (5-HT) transporter (SERT) inhibitor. Here we review its preclinical and clinical properties and discuss translational aspects. Vortioxetine increases serotonergic, noradrenergic, dopaminergic, cholinergic, histaminergic and glutamatergic neurotransmission in brain structures associated with MDD. These multiple effects likely derive from its interaction with 5-HT-receptor-mediated negative feedback mechanisms controlling neuronal activity. In particular, 5-HT3 receptors may play a prominent role, since their blockade i) increases pyramidal neuron activity by removing 5-HT3 receptor-mediated excitation of GABA interneurons, and ii) augments SSRI effects on extracellular 5-HT. However, modulation of the other 5-HT receptor subtypes also likely contributes to vortioxetine's pharmacological effects. Preclinical animal models reveal differences from SSRIs and SNRIs, including antidepressant-like activity, increased synaptic plasticity and improved cognitive function. Vortioxetine had clinical efficacy in patients with MDD: 11 placebo-controlled studies (including one in elderly) with efficacy in 8 (7 positive, 1 supportive), 1 positive active comparator study plus a positive relapse prevention study. In two positive studies, vortioxetine was superior to placebo in pre-defined cognitive outcome measures. The clinically effective dose range (5-20mg/day) spans ~50 to >80% SERT occupancy. SERT and 5-HT3 receptors are primarily occupied at 5mg, while at 20mg, all targets are likely occupied at functionally relevant levels. The side-effect profile is similar to that of SSRIs, with gastrointestinal symptoms being most common, and a low incidence of sexual dysfunction and sleep disruption possibly ascribed to vortioxetine's receptor modulation. PMID:25016186

  4. Clinical and Genetic Investigation of a Multi-generational Chinese Family Afflicted with Von Hippel-Lindau Disease

    PubMed Central

    Zhang, Jingyao; Ma, Jie; Du, Xiaoyun; Wu, Dapeng; Ai, Hong; Bai, Jigang; Dong, Shunbin; Yang, Qinling; Qu, Kai; Lyu, Yi; Valenzuela, Robert K; Liu, Chang

    2015-01-01

    Background: Von Hippel-Lindau (VHL) disease is a hereditary tumor disorder caused by mutations or deletions of the VHL gene. Few studies have documented the clinical phenotype and genetic basis of the occurrence of VHL disease in China. This study armed to present clinical and genetic analyses of VHL within a five-generation VHL family from Northwestern China, and summarize the VHL mutations and clinical characteristics of Chinese families with VHL according to previous studies. Methods: An epidemiological investigation of family members was done to collect the general information. A retrospective study of clinical VHL cases was launched to collect the relative clinical data. Genetic linkage and haplotype analysis were used to make sure the linkage of VHL to disease in this family. The VHL gene screening was performed by directly analyzing DNA sequence output. At last, we summarized the VHL gene mutation in China by the literature review. Results: A five-generation North-western Chinese family afflicted with VHL disease was traced in this research. The family consisted of 38 living family members, of whom nine were affected. The individuals afflicted with VHL exhibited multi-organ tumors that included pheochromocytomas (8), central nervous system hemangioblastomas (3), pancreatic endocrine tumors (2), pancreatic cysts (3), renal cysts (4), and paragangliomas (2). A linkage analysis resulted in a high maximal LOD score of 8.26 (theta = 0.0) for the marker D3S1263, which is in the same chromosome region as VHL. Sequence analysis resulted in the identification of a functional C>T transition mutation (c. 499 C>T, p.R167W) located in exon 3 of the 167th codon of VHL. All affected individuals shared this mutation, whereas the unaffected family members and an additional 100 unrelated healthy individuals did not. To date, 49 mutations have been associated with this disease in Chinese populations. The most frequent VHL mutations in China are p.S65 W, p.N78 S, p.R161Q and p

  5. Ethanolic extracts of Tinospora cordifolia and Alstonia scholaris show antimicrobial activity towards clinical isolates of methicillin-resistant and carbapenemase-producing bacteria.

    PubMed

    Bonvicini, Francesca; Mandrone, Manuela; Antognoni, Fabiana; Poli, Ferruccio; Gentilomi, Giovanna Angela

    2014-01-01

    The aim of this study was to determine the in vitro antimicrobial activity of crude extracts of three plants from Ayurveda tradition (Tinospora cordifolia, Alstonia scholaris, Crataeva nurvala) against reference microbial strains and clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) and carbapenemase-producing Klebsiella pneumoniae. IC50 values were obtained by micro-dilution methods meeting the requirements of the NCCLS standard. The cytotoxicity of the extracts was also investigated on a mammalian cell line. Extracts displayed a variable degree of antimicrobial activity and did not interfere with mammalian cell proliferation. T. cordifolia and A. scholaris exhibited a higher inhibitory activity against clinical isolates of MRSA and carbapenemase-producing K. pneumoniae compared with reference strains, while C. nurvala exhibited a different behaviour. An antifungal activity towards Candida albicans was observed for A. scholaris extract. Results indicate that constituents from T. cordifolia and A. scholaris may be a potential source of new therapeutic strategies for infectious diseases. PMID:24749692

  6. In vitro activity of tigecycline and 10 other antimicrobials against clinical isolates of the genus Corynebacterium.

    PubMed

    Fernandez-Roblas, R; Adames, H; Martín-de-Hijas, N Z; Almeida, D García; Gadea, I; Esteban, J

    2009-05-01

    We studied the in vitro activity of tigecycline and 10 other commonly used antibiotics against 135 clinical isolates of non-diphtheria Corynebacterium spp. using the Etest system. Tigecycline minimum inhibitory concentrations for 50% and 90% of the organisms (MIC(50) and MIC(90) values, respectively, in mg/L) were: Corynebacterium urealyticum, 0.094 and 0.125; Corynebacterium amycolatum, 0.125 and 2; Corynebacterium jeikeium, 0.094 and 0.75; Corynebacterium coyleae, 0.064 and 0.064; Corynebacterium striatum, 0.064 and 1; Corynebacterium aurimucosum, 0.094 and 0.125; and Corynebacterium afermentans, 0.064 and 0.094. The activities of all other antimicrobials were variable, with good activity of glycopeptides, linezolid, quinupristin/dalfopristin and daptomycin and with resistance to macrolides in a high number of isolates. Tigecycline is a good alternative for the therapy of infections caused by non-diphtheria corynebacteria. PMID:19153032

  7. Investigations into the in vitro antimicrobial activity and mode of action of the phenazine antibiotic D-alanylgriseoluteic acid.

    PubMed

    Giddens, Stephen R; Bean, David C

    2007-01-01

    D-Alanylgriseoluteic acid (AGA) is a potent antimicrobial phenazine compound produced by Pantoea agglomerans (Erwinia herbicola) Eh1087. Susceptibility tests against a range of microbes indicated that AGA had a broad spectrum of antimicrobial activity and was particularly active against Gram-positive pathogens. Comparison of the in vitro efficacy of AGA with eight other antibiotics against 119 clinical isolates of Streptococcus pneumoniae demonstrated that all were inhibited by low concentrations of AGA (minimal inhibitory concentration range Investigations into the mode of action of AGA revealed that it induced the SOS response in Escherichia coli and slightly increased the frequency of GC-AT transition mutations. In cell-free assays, both AGA and griseoluteic acid reduced cytochrome c in the presence of a redox recycler (ferredoxin-NADP(+) reductase), but AGA was six to seven times more readily reduced than griseoluteic acid in the absence of the reductase. The potency and broad spectrum of AGA activity suggest that AGA may warrant further investigation. PMID:17189100

  8. [Clinical relevance of antidepressant-induced activation syndrome: from a perspective of bipolar spectrum disorder].

    PubMed

    Tanaka, Teruaki; Inoue, Takeshi; Suzuki, Katsuji; Kitaichi, Yuji; Masui, Takuya; Denda, Kenzo; Koyama, Tsukasa

    2007-01-01

    Recent concerns have been raised regarding whether antidepressants, especially selective serotonin reuptake inhibitors (SSRIs) might increase suicidal tendencies and intense debate-rages over the pros and cons of their use. Although systematic reviews and population-based studies have been conducted, a consensus on this association remains to be established. Subsequently, the concept of so-called 'activation syndrome' associated with antidepressants has been accepted without its adequate verification. In the present report, we present our experience of seven cases considered of having 'activation syndrome' brought on by antidepressants, and examine its clinical relevance to bipolar spectrum disorder (Ghaemi, et al., 2001) both symptomatologically and diagnostically. Five patients, diagnosed as having major depressive disorder according to the diagnostic manual (DSM-IV), met the criteria of bipolar spectrum disorder and suffered from activation syndrome following the administration of SSRIs, mainly paroxetine. Similarly, hypomania developed in all five cases with depression; the diagnostic criteria of a hypomanic episode were not met. In the remaining two patients, who were both diagnosed with bipolar disorder, one showed irritability and insomnia through imipramine use, and the another developed a hypomanic and/or a mixed state after the co-administration of fluvoxamine and trazodone. From the results of our examination, 'bipolarity', which is the pivotal factor of bipolar spectrum, might exist behind the phenomenon recognized as activation syndrome, and be revealed by antidepressant treatment, just like manic switching. Moreover, the various problems encountered in the current practice of treating mood disorders, including unipolar-bipolar dichotomy, manic switching by antidepressants, and narrow criteria for a mixed episode, were pointed out a new through this concept of activation syndrome. Actually, the understanding of activation syndrome clinically leads to

  9. [Activity of ISO/TC212, clinical laboratory testing and in vitro diagnostic test systems].

    PubMed

    Kawai, T

    1998-10-01

    ISO is the International Organization for Standardization, which is a worldwide federation of national standards bodies from 130 countries, one from each country. ISO is a non-governmental organization established in 1947. ISO/TC212, Clinical laboratory testing and in vitro diagnostic test systems was newly established in 1995, consisting of 86 P-members and 12 O-members. ISO/TC212 secretariat is the American National Standards Institute, and NCCLS carries out its secretarial activity. On behalf of the Japanese Industrial Standards Committee (JISC), the Japanese Committee for Clinical Laboratory Standards (JCCLS) serves as the secretariat for the ISO/TC212 National Technical Advisory Group. Three working groups are in the process of preparing the Draft International Standards (DIS) among 9 work items. The next plenary session of ISO/TC212 will be held on May 19-21, 1999 in Tokyo, Japan. PMID:9816905

  10. Exercise and Physical Activity in Mental Disorders: Clinical and Experimental Evidence

    PubMed Central

    Zschucke, Elisabeth; Gaudlitz, Katharina

    2013-01-01

    Several epidemiological studies have shown that exercise (EX) and physical activity (PA) can prevent or delay the onset of different mental disorders, and have therapeutic benefits when used as sole or adjunct treatment in mental disorders. This review summarizes studies that used EX interventions in patients with anxiety, affective, eating, and substance use disorders, as well as schizophrenia and dementia/mild cognitive impairment. Despite several decades of clinical evidence with EX interventions, controlled studies are sparse in most disorder groups. Preliminary evidence suggests that PA/EX can induce improvements in physical, subjective and disorder-specific clinical outcomes. Potential mechanisms of action are discussed, as well as implications for psychiatric research and practice. PMID:23412549

  11. Preliminary investigation of a sealed, remotely activated silver-zinc battery

    NASA Technical Reports Server (NTRS)

    Wheat, C. G.

    1977-01-01

    Methods necessary to provide a remotely activated, silver zinc battery capable of an extended activated stand while in a sealed condition were investigated. These requirements were to be accomplished in a battery package demonstrating an energy density of at least 35 watt hours per pound. Several methods of gas suppression were considered in view of the primary nature of this unit and utilized the electroplated dendritic zinc electrode. Amalgamation of the electrode provided the greatest suppression of gas at the zinc electrode. The approach to extending the activated stand capability of the remotely activated battery was through evaluation of three basic methods of remote, multi-cell activation; 1) the electrolyte manifold, 2) the gas manifold and 3) the individual cell. All three methods of activation can be incorporated into units which will meet the minimum energy density requirement.

  12. Childhood-onset systemic lupus erythematosus in Singapore: clinical phenotypes, disease activity, damage, and autoantibody profiles.

    PubMed

    Tan, J H T; Hoh, S F; Win, M T M; Chan, Y H; Das, L; Arkachaisri, T

    2015-08-01

    Childhood-onset systemic lupus erythematosus (cSLE) is a multisystem autoimmune disease characterized by immune dysregulation affecting patients less than 18 years old. One-fifth of SLE cases are diagnosed during childhood. cSLE presents differently from adults and has a more severe and aggressive course. We describe the clinical and antibody profiles in our cSLE Singapore cohort. All cSLE patients who satisfied the 1997 American College of Rheumatology diagnostic criteria were captured in our lupus registry from January 2009 to January 2014. Data including demographic, cumulative clinical, serologic data, and damage indices were collected. Adjusted mean SLEDAI-2K (AMS) was used to summarize disease activity over multiple visits. Cluster analysis using non-hierarchical K-means procedure was performed on eight selected antibodies. The 64 patients (female:male ratio 5:1; Chinese 45.3%, Malay 28.1%, Indian 9.4%, and other races 17.2%) had a mean onset age of 11.5 years (range 2.1-16.7) and mean age at diagnosis was 11.9 years (range 2.6-18.0). Our study demonstrated differences in clinical manifestations for which hematologic involvement was the most common manifestation with less renal disease and uncommon neurologic manifestation as compared to other cSLE cohorts reported in our region. Antibody clusters were identified in our cohort but their clinical association/discrimination and outcome prediction required further validation study. Outcomes of our cohort in regard to disease activity after therapy and organ damages were comparable if not better to other cSLE cohorts elsewhere. Steroid-related damage, including symptomatic multifocal avascular necrosis and cataract, were not uncommon locally. Infection remains the major cause of death for the continent. Nevertheless, the five year survival rate of our cohort (98.4%) was high. PMID:25926055

  13. The association of body mass index with disease activity and clinical response to combination therapy in patients with rheumatoid arthritis

    PubMed Central

    Mirpourian, Maryam; Salesi, Mansour; Abdolahi, Hadi; Farajzadegan, Ziba; Karimzadeh, Hadi

    2014-01-01

    Background: The role of obesity in clinical curse of rheumatoid arthritis (RA) is not clear. We investigated the association of obesity and adiposity with disease activity and clinical response to combination therapy in RA patients. Materials and Methods: Active RA patients with the disease activity score using 28 joint counts (DAS28) > 2.6 were studied. Height, weight, and waist and hip circumferences were measured and body mass index (BMI) and waist to hip ratio were calculated. Patients were treated with methotrexate (7.5 to 10 mg/week) plus hydroxychloroquine (200 to 400 mg/day) and prednisolone (2.5 to 10 mg/day) and were followed by DAS28 for up to 24 weeks. Results: One hundred and six patients were studied; age = 48.5 ± 13.8 years, 87.7% female, disease duration = 4.4 years [SE = 0.48]. DAS28 was decreased from 4.5 ± 1.6 to 2.9 ± 1.4 (P < 0.001) after 24 weeks of treatment. Only in patients with disease duration of ≤2 years, BMI (r = –0.415, P = 0.005) and waist circumference (r = –0.296, P = 0.05) were correlated with baseline DAS28. Although BMI (r = –0.337, P = 0.025) and waist circumference (r = –0.315, P = 0.038) were correlated with change in DAS28 after therapy, these correlations were disappeared after controlling for baseline DAS28. Conclusion: Obesity and adiposity are associated with less severe disease activity in early stage of RA, but are not associated with response to combination therapy with methotrexate plus hydroxychloroquine in RA patients. PMID:25197291

  14. In Vitro Activity of Isavuconazole and Comparators against Clinical Isolates of the Mucorales Order

    PubMed Central

    Jensen, Rasmus Hare; Meletiadis, Joseph

    2015-01-01

    The in vitro activity of isavuconazole against Mucorales isolates measured by EUCAST E.Def 9.2 and CLSI M38-A2 methodologies was investigated in comparison with those of amphotericin B, posaconazole, and voriconazole. Seventy-two isolates were included: 12 of Lichtheimia corymbifera, 5 of Lichtheimia ramosa, 5 of group I and 9 of group II of Mucor circinelloides, 9 of Rhizomucor pusillus, 26 of Rhizopus microsporus, and 6 of Rhizopus oryzae. Species identification was confirmed by internal transcribed spacer (ITS) sequencing. EUCAST MICs were read on day 1 (EUCAST-d1) and day 2 (EUCAST-d2), and CLSI MICs were read on day 2 (CLSI-d2). Isavuconazole MIC50s (range) (mg/liter) by EUCAST-d1, CLSI-d2, and EUCAST-d2 were 1 (0.125 to 16), 1 (0.125 to 2), and 4 (0.5 to >16), respectively, across all isolates. The similar values for comparator drugs were as follows: posaconazole, 0.25 (≤0.03 to >16), 0.25 (0.06 to >16), and 1 (0.06 to >16); amphotericin, 0.06 (≤0.03 to 0.5), 0.06 (≤0.03 to 0.25), and 0.125 (≤0.03 to 1); voriconazole, 16 (2 to >16), 8 (1 to >16), and >16 (8 to >16), respectively. Isavuconazole activity varied by species: Lichtheimia corymbifera, 1 (0.5 to 2), 1 (1 to 2), and 2 (1 to 4); Lichtheimia ramosa, 0.25 (0.125 to 0.5), 1 (0.5 to 2), and 2 (0.5 to 4); Rhizomucor pusillus, 0.5 (0.5 to 1), 1 (0.125 to 1), and 2 (1 to 2); Rhizopus microsporus, 1 (0.5 to 4), 0.5 (0.125 to 1), and 4 (1 to 8); and Rhizopus oryzae, 1 (0.5 to 4), 1 (0.125 to 2), and 4 (0.5 to 8), respectively, were more susceptible than Mucor circinelloides: group I, 8 (4 to 8), 4 (2 to 4), and 16 (2 to 16), respectively, and group II, 8 (1 to 16), 8 (1 to 8), and 16 (4 to >16), respectively. This was also observed for posaconazole. The essential agreement was best between EUCAST-d1 and CLSI-d2 (75% to 83%). Isavuconazole displayed in vitro activity against Mucorales isolates with the exception of Mucor circinelloides. The MICs were in general 1 to 3 steps higher than those for

  15. In Vitro Activity of Isavuconazole and Comparators against Clinical Isolates of the Mucorales Order.

    PubMed

    Arendrup, Maiken Cavling; Jensen, Rasmus Hare; Meletiadis, Joseph

    2015-12-01

    The in vitro activity of isavuconazole against Mucorales isolates measured by EUCAST E.Def 9.2 and CLSI M38-A2 methodologies was investigated in comparison with those of amphotericin B, posaconazole, and voriconazole. Seventy-two isolates were included: 12 of Lichtheimia corymbifera, 5 of Lichtheimia ramosa, 5 of group I and 9 of group II of Mucor circinelloides, 9 of Rhizomucor pusillus, 26 of Rhizopus microsporus, and 6 of Rhizopus oryzae. Species identification was confirmed by internal transcribed spacer (ITS) sequencing. EUCAST MICs were read on day 1 (EUCAST-d1) and day 2 (EUCAST-d2), and CLSI MICs were read on day 2 (CLSI-d2). Isavuconazole MIC50s (range) (mg/liter) by EUCAST-d1, CLSI-d2, and EUCAST-d2 were 1 (0.125 to 16), 1 (0.125 to 2), and 4 (0.5 to >16), respectively, across all isolates. The similar values for comparator drugs were as follows: posaconazole, 0.25 (≤ 0.03 to >16), 0.25 (0.06 to >16), and 1 (0.06 to >16); amphotericin, 0.06 (≤ 0.03 to 0.5), 0.06 (≤ 0.03 to 0.25), and 0.125 (≤ 0.03 to 1); voriconazole, 16 (2 to >16), 8 (1 to >16), and >16 (8 to >16), respectively. Isavuconazole activity varied by species: Lichtheimia corymbifera, 1 (0.5 to 2), 1 (1 to 2), and 2 (1 to 4); Lichtheimia ramosa, 0.25 (0.125 to 0.5), 1 (0.5 to 2), and 2 (0.5 to 4); Rhizomucor pusillus, 0.5 (0.5 to 1), 1 (0.125 to 1), and 2 (1 to 2); Rhizopus microsporus, 1 (0.5 to 4), 0.5 (0.125 to 1), and 4 (1 to 8); and Rhizopus oryzae, 1 (0.5 to 4), 1 (0.125 to 2), and 4 (0.5 to 8), respectively, were more susceptible than Mucor circinelloides: group I, 8 (4 to 8), 4 (2 to 4), and 16 (2 to 16), respectively, and group II, 8 (1 to 16), 8 (1 to 8), and 16 (4 to >16), respectively. This was also observed for posaconazole. The essential agreement was best between EUCAST-d1 and CLSI-d2 (75% to 83%). Isavuconazole displayed in vitro activity against Mucorales isolates with the exception of Mucor circinelloides. The MICs were in general 1 to 3 steps higher than those for

  16. BE-ACTIV for Depression in Nursing Homes: Primary Outcomes of a Randomized Clinical Trial

    PubMed Central

    Van Haitsma, Kimberly; Schoenbachler, Ben; Looney, Stephen W.

    2015-01-01

    Objectives. To report the primary outcomes of a cluster randomized clinical trial of Behavioral Activities Intervention (BE-ACTIV), a behavioral intervention for depression in nursing homes. Method. Twenty-three nursing homes randomized to BE-ACTIV or treatment as usual (TAU); 82 depressed long-term care residents recruited from these nursing homes. BE-ACTIV participants received 10 weeks of individual therapy after a 2-week baseline. TAU participants received weekly research visits. Follow-up assessments occurred at 3- and 6-month posttreatment. Results. BE-ACTIV group participants showed better diagnostic recovery at posttreatment in intent-to-treat analyses adjusted for clustering. They were more likely to be remitted than TAU participants at posttreatment and at 3-month posttreatment but not at 6 months. Self-reported depressive symptoms and functioning improved in both groups, but there were no significant treatment by time interactions in these variables. Discussion. BE-ACTIV was superior to TAU in moving residents to full remission from depression. The treatment was well received by nursing home staff and accepted by residents. A large proportion of participants remained symptomatic at posttreatment, despite taking one or more antidepressants. The results illustrate the potential power of an attentional intervention to improve self-reported mood and functioning, but also the difficulties related to both studying and implementing effective treatments in nursing homes. PMID:24691156

  17. Clinical and Patient-reported Outcomes of a Zirconia Oral Implant: Three-year Results of a Prospective Cohort Investigation.

    PubMed

    Spies, B C; Balmer, M; Patzelt, S B M; Vach, K; Kohal, R J

    2015-10-01

    The objective of this study was to determine the clinical, radiographic, and patient-reported outcomes of a 1-piece alumina-toughened zirconia implant restored with single crowns (SCs) or 3-unit fixed dental prostheses (FDPs) after 3 y of observation. Forty patients received 53 implants, placed in a 1-stage operation with immediate temporization. Finally, 50 implants were restored with 24 SCs and 13 FDPs. To evaluate peri-implant bone loss, standardized radiographs were taken at implant insertion, at final restoration delivery, and after 1 and 3 y. Additionally, several soft tissue parameters and patient-reported outcome measures were evaluated. Linear mixed models with random intercept for each patient and patients as clusters were used to compare subgroups. Three patients did not receive a SC due to early implant loss, and 1 patient died. As a result, 36 patients with 49 implants were followed-up for 3 y, giving a cumulative survival rate of 94.2%. The average marginal bone loss amounted to 0.79 mm (SCs, 0.47 mm; FDPs, 1.07 mm; P < 0.001). After the delivery of the final prosthetic restoration, further bone loss was not statistically significant (0.09 mm; P = 0.700). Probing depth, clinical attachment level, and modified bleeding index increased significantly at the implant sites, whereas gingival recession decreased significantly. Compared with the pretreatment questionnaires, the patient-reported outcome measures showed a permanently improved perception of function, aesthetics, sense, speech and self-esteem. The survival rate of the investigated ceramic implant system seems to be comparable to reported survival rates of titanium implants when immediately restored. The recorded parameters suggest its potential for clinical utilization. PMID:26232388

  18. Novel generation of agents with proven clinical activity in multiple myeloma.

    PubMed

    Mateos, María-Victoria; Ocio, Enrique M; San Miguel, Jesús F

    2013-10-01

    The activity observed with proteasome inhibitors and immunomodulatory drugs (IMIDs) in multiple myeloma (MM) has prompted the development of second- and third-generation agents with similar, but not exactly the same, mechanisms of action as their predecessors. This review summarizes the mechanism of action and the available data on the clinical activity of novel proteasome inhibitors (carfilzomib, oprozomib, ixazomib, and marizomib) and novel IMIDs (pomalidomide), stressing the similarities and differences with bortezomib, and with thalidomide and lenalidomide, respectively. In summary, these novel agents have shown clinical activity as single agents and in combination with dexamethasone, with similar or even higher efficacy than their parental drugs; moreover, they may even overcome resistance, indicating that there are some differences in their mechanisms of action and resistance. These data indicate that both the inhibition of the proteasome and the modulation of the immune system are good strategies to target MM tumor cells and this, along with the absence of complete cross-resistance observed among these drugs, open new avenues to optimize their use through the most appropriate sequencing and combinations. PMID:24135407

  19. [Investigation of the presence of panton-valentin leucocidin (PVL) in Staphylococcus aureus strains isolated from clinical samples].

    PubMed

    Ozkul, Hilal; Oktem, I M Ali; Gülay, Zeynep

    2007-07-01

    Panton-Valentin leucocidin (PVL) is a cytotoxin which causes tissue necrosis by degradating leucocytes and other cell types. PVL has recently become very up to date as it has been shown to be the major virulance factor of community acquired methicillin resistant Staphylococcus aureus strains. In this study, the presence of PVL was investigated in methicillin sensitive and resistant S. aureus (MSSA and MRSA, respectively) strains which were isolated from clinical samples between January 2005-May 2006 at Dokuz Eylul University Hospital, Izmir. Fifty five MRSA and 79 MSSA strains which were isolated from blood, wound and respiratory tract samples were randomly included to the study. The presence of PVL was evaluated by multiplex polymerase chain reaction (PCR) which detects pvl and S. aureus-specific nuc genes. As a result, PVL positivities were detected in two (5%) of 40 MSSA and four (10.3%) of 39 MSSA strains isolated in the years 2005 and 2006, respectively. None of the MRSA isolates had pvl gene. Although this cytotoxin was rarely detected among MSSA isolates, it was interesting to note that the prevalence of PVL was twice more in the year 2006 compared to 2005. It was also worth to notify that four of six (66.7%) PVL positive strains had been isolated from the patients of general surgery inpatient or outpatient clinics. PMID:17933245

  20. Students' clinical learning in an emerging dental school: an investigation in international collaboration between Michigan and Ghana.

    PubMed

    Peters, Mathilde C; Adu-Ababio, Francis; Jarrett-Ananaba, Nejay P; Johnson, Lynn A

    2013-12-01

    The dearth of dental faculty members is a widely known problem that is exacerbated in countries that are attempting to begin dental education programs. This collaboration between Kwame Nkrumah University of Science and Technology and the University of Michigan investigated if dental students who have just started their clinical dental education can learn the knowledge and skills required for identifying and restoring cavitated caries lesions through compact course delivery. There were three instructional blocks: 1) didactic seminar; 2) seminar, simulated hands-on skills instruction, and clinical observation/assisting with treatment of schoolchildren; and 3) seminar, simulated skills training, and application to schoolchildren. Each dental student completed a questionnaire measuring knowledge and perceptions of knowledge, experience, and confidence at five points in time. The dental students' knowledge increased significantly as well as their perceived knowledge, experience, and confidence (p<0.0001). In general, the students showed proficiency in delivering simple treatments. The project showed that an integrated compact course delivery model may assist emerging dental schools to cope with the challenging shortage of resident faculty members. PMID:24319137

  1. Clinical Metabolomics: The New Metabolic Window for Inborn Errors of Metabolism Investigations in the Post-Genomic Era

    PubMed Central

    Tebani, Abdellah; Abily-Donval, Lenaig; Afonso, Carlos; Marret, Stéphane; Bekri, Soumeya

    2016-01-01

    Inborn errors of metabolism (IEM) represent a group of about 500 rare genetic diseases with an overall estimated incidence of 1/2500. The diversity of metabolic pathways involved explains the difficulties in establishing their diagnosis. However, early diagnosis is usually mandatory for successful treatment. Given the considerable clinical overlap between some inborn errors, biochemical and molecular tests are crucial in making a diagnosis. Conventional biological diagnosis procedures are based on a time-consuming series of sequential and segmented biochemical tests. The rise of “omic” technologies offers holistic views of the basic molecules that build a biological system at different levels. Metabolomics is the most recent “omic” technology based on biochemical characterization of metabolites and their changes related to genetic and environmental factors. This review addresses the principles underlying metabolomics technologies that allow them to comprehensively assess an individual biochemical profile and their reported applications for IEM investigations in the precision medicine era. PMID:27447622

  2. Diagnostic Accuracy of Behavioral, Activity, Ferritin, and Clinical Indicators of Restless Legs Syndrome

    PubMed Central

    Richards, Kathy C.; Bost, James E.; Rogers, Valerie E.; Hutchison, Lisa C.; Beck, Cornelia K.; Bliwise, Donald L.; Kovach, Christine R.; Cuellar, Norma; Allen, Richard P.

    2015-01-01

    Study Objectives: Lack of a valid diagnostic measure of restless legs syndrome (RLS) for persons with dementia, who do not have the cognitive ability to report complex symptoms, impedes RLS treatment and research in this population. The aim of this study was to determine the sensitivity and specificity of a combination of indicators for identifying RLS that could eventually be used to diagnose RLS in persons with dementia. Design: 3-day, prospective instrument validation. Setting: Sleep laboratory. Participants: Cognitively intact, 107 with RLS, 105 without RLS. Interventions: N/A. Measurements: Serial 20-min observations with a new measure, the Behavioral Indicators Test–Restless Legs (BIT-RL); leg movements with 3 nights of the Periodic Activity Monitor–Restless Legs (PAM-RL); ferritin; sleep history; clinical data; polysomnography; Hopkins Telephone Diagnostic Interview of RLS Symptoms. Results: The best-fitting diagnostic model for identifying RLS included previous history of iron deficiency (odds ratio [OR] 7.30), leg discomfort (OR 6.47), daytime fatigue (OR 6.15), difficulty falling asleep (OR 3.25), RLS family history (OR 2.60), BIT-RL (OR 1.49), and absence of diabetes (OR 0.27), with sensitivity 78%, specificity 79%, and 77% correctly classified. This model retained its predictive accuracy even with co-morbid sleep apnea. Conclusions: When compared to those without restless legs syndrome (RLS), persons with RLS have observable behaviors, such as rubbing the legs, that differentiate them, but the behaviors have no circadian and activity-related variability. The final model of clinical and sleep historical data and observation for RLS behaviors using the Behavioral Indicators Test–Restless Legs had good diagnostic accuracy. Citation: Richards KC, Bost JE, Rogers VE, Hutchison LC, Beck CK, Bliwise DL, Kovach CR, Cuellar N, Allen RP. Diagnostic accuracy of behavioral, activity, ferritin, and clinical indicators of restless legs syndrome. SLEEP 2015

  3. Leisure time physical activity, smoking and risk of recent symptomatic urolithiasis: Survey of stone clinic patients

    PubMed Central

    Soueidan, Michael; Bartlett, Susan J.; Noureldin, Yasser A.; Andersen, Ross E.; Andonian, Sero

    2015-01-01

    Introduction: We explore relationships between selected lifestyle factors and recent (≤6 months) symptomatic urolithiasis (RSU). Methods: Surveys querying socio-demographic, medical history, physical activity, diet and smoking were administered to a convenience sample of stone clinic patients at a tertiary care hospital. Leisure time physical activity (LTPA) was assessed with the International Physical Activity Questionnaire (long form). Multivariate logistic regression was used to identify associations between risk factors and RSU. Results: Of the 163 participants, most were male (64%) and white (78%), with a mean (standard deviation) age of 56.3 (14.2) years. The mean body mass index (BMI) was 27.3 (5.4) kg/m2 and 57 (35%) patients reported RSU. No significant (p < 0.05) differences were observed between participants with and without RSU in age, sex, ethnicity, BMI, or diet. Of the cohort, 52 (35%) participants met physical activity guidelines for walking (29%), moderate (27%) or vigorous activity (29%). LTPA did not differ significantly by RSU status. Compared to those without RSU, participants with RSU had higher rates of smoking (7% vs. 21%, p = 0.02 and had 8.5 (95% confidence interval 2.2–32.2) times the odds of being current smokers after controlling for sex, diet, and LTPA. Conclusions: Physical inactivity and smoking are common among stone clinic patients, though LPTA was not associated with RSU. Study limitations include its small sample size, selection bias, and reliance on self-reported RSU (recall bias). In addition, participants may have already been following dietary recommendations to prevent urolithiasis recurrence. Nonetheless, current smoking was a potent predictor of RSU. When desired, smokers should be referred for smoking cessation. PMID:26316909

  4. Clinical relevance of and risk factors for HSV-related tracheobronchitis or pneumonia: results of an outbreak investigation

    PubMed Central

    Engelmann, Ilka; Gottlieb, Jens; Meier, Astrid; Sohr, Dorit; Ruhparwar, Arjang; Henke-Gendo, Cornelia; Gastmeier, Petra; Welte, Tobias; Schulz, Thomas Friedrich; Mattner, Frauke

    2007-01-01

    Introduction Herpes simplex virus (HSV) type 1 was identified in respiratory specimens from a cluster of eight patients on a surgical intensive care unit within 8 weeks. Six of these patients suffered from HSV-related tracheobronchitis and one from HSV-related pneumonia only. Our outbreak investigation aimed to determine the clinical relevance of and risk factors associated with HSV-related tracheobronchitis or pneumonia in critically ill patients, and to investigate whether the cluster was caused by nosocomial transmission. Methods A retrospective cohort study was performed to identify risk factors for the outcomes of HSV-related tracheobronchitis or pneumonia and death using univariable analysis as well as logistic regression analysis. Viruses were typed by molecular analysis of a fragment of the HSV type 1 glycoprotein G. Results The cohort of patients covering the outbreak period comprised 53 patients, including six patients with HSV-related tracheobronchitis and one patient with pneumonia only. HSV-related tracheobronchitis or pneumonia was associated with increased mortality (100% in patients with versus 17.8% in patients without HSV-related tracheobronchitis or pneumonia; P < 0.0001). The interaction of longer duration of ventilation and tracheotomy was associated with HSV-related tracheobronchitis or pneumonia in multivariable analysis. Identical HSV type 1 glycoprotein G sequences were found in three patients and in two patients. The group of three identical viral sequences belonged to a widely circulating strain. The two identical viral sequences were recovered from bronchoalveolar lavages of one patient with HSV-related tracheobronchitis and of one patient without clinical symptoms. These viral sequences showed unique polymorphisms, indicating probable nosocomial transmission. Conclusion HSV-related tracheobronchitis or pneumonia is associated with increased mortality in critically ill patients. Care should be taken to avoid nosocomial transmission and

  5. Investigating a Novel Activation-Repolarisation Time Metric to Predict Localised Vulnerability to Reentry Using Computational Modelling

    PubMed Central

    Hill, Yolanda R.; Child, Nick; Hanson, Ben; Wallman, Mikael; Coronel, Ruben; Plank, Gernot; Rinaldi, Christopher A.; Gill, Jaswinder; Smith, Nicolas P.; Taggart, Peter; Bishop, Martin J.

    2016-01-01

    Exit sites associated with scar-related reentrant arrhythmias represent important targets for catheter ablation therapy. However, their accurate location in a safe and robust manner remains a significant clinical challenge. We recently proposed a novel quantitative metric (termed the Reentry Vulnerability Index, RVI) to determine the difference between activation and repolarisation intervals measured from pairs of spatial locations during premature stimulation to accurately locate the critical site of reentry formation. In the clinic, the method showed potential to identify regions of low RVI corresponding to areas vulnerable to reentry, subsequently identified as ventricular tachycardia (VT) circuit exit sites. Here, we perform an in silico investigation of the RVI metric in order to aid the acquisition and interpretation of RVI maps and optimise its future usage within the clinic. Within idealised 2D sheet models we show that the RVI produces lower values under correspondingly more arrhythmogenic conditions, with even low resolution (8 mm electrode separation) recordings still able to locate vulnerable regions. When applied to models of infarct scars, the surface RVI maps successfully identified exit sites of the reentrant circuit, even in scenarios where the scar was wholly intramural. Within highly complex infarct scar anatomies with multiple reentrant pathways, the identified exit sites were dependent upon the specific pacing location used to compute the endocardial RVI maps. However, simulated ablation of these sites successfully prevented the reentry re-initiation. We conclude that endocardial surface RVI maps are able to successfully locate regions vulnerable to reentry corresponding to critical exit sites during sustained scar-related VT. The method is robust against highly complex and intramural scar anatomies and low resolution clinical data acquisition. Optimal location of all relevant sites requires RVI maps to be computed from multiple pacing

  6. Investigating a Novel Activation-Repolarisation Time Metric to Predict Localised Vulnerability to Reentry Using Computational Modelling.

    PubMed

    Hill, Yolanda R; Child, Nick; Hanson, Ben; Wallman, Mikael; Coronel, Ruben; Plank, Gernot; Rinaldi, Christopher A; Gill, Jaswinder; Smith, Nicolas P; Taggart, Peter; Bishop, Martin J

    2016-01-01

    Exit sites associated with scar-related reentrant arrhythmias represent important targets for catheter ablation therapy. However, their accurate location in a safe and robust manner remains a significant clinical challenge. We recently proposed a novel quantitative metric (termed the Reentry Vulnerability Index, RVI) to determine the difference between activation and repolarisation intervals measured from pairs of spatial locations during premature stimulation to accurately locate the critical site of reentry formation. In the clinic, the method showed potential to identify regions of low RVI corresponding to areas vulnerable to reentry, subsequently identified as ventricular tachycardia (VT) circuit exit sites. Here, we perform an in silico investigation of the RVI metric in order to aid the acquisition and interpretation of RVI maps and optimise its future usage within the clinic. Within idealised 2D sheet models we show that the RVI produces lower values under correspondingly more arrhythmogenic conditions, with even low resolution (8 mm electrode separation) recordings still able to locate vulnerable regions. When applied to models of infarct scars, the surface RVI maps successfully identified exit sites of the reentrant circuit, even in scenarios where the scar was wholly intramural. Within highly complex infarct scar anatomies with multiple reentrant pathways, the identified exit sites were dependent upon the specific pacing location used to compute the endocardial RVI maps. However, simulated ablation of these sites successfully prevented the reentry re-initiation. We conclude that endocardial surface RVI maps are able to successfully locate regions vulnerable to reentry corresponding to critical exit sites during sustained scar-related VT. The method is robust against highly complex and intramural scar anatomies and low resolution clinical data acquisition. Optimal location of all relevant sites requires RVI maps to be computed from multiple pacing

  7. Consideration of cysteine protease activity for serological M-typing of clinical Streptococcus pyogenes isolates.

    PubMed

    Morita, Masatomo; Ikebe, Tadayoshi; Watanabe, Haruo

    2004-01-01

    Clinical isolates of Streptococcus pyogenes were classified by serological typing of their surface M protein. Non-M typeable strains with the emm1 gene were characterized as the degradation of M protein caused by overproduction of the extracellular cysteine protease, SpeB. These events are dependent on the growth phase. M protein produced prior to expression of SpeB is degraded in the stationary phase when the active form of SpeB is detected. The proteolytic degradation of M protein should be considered for precise M typing analysis. PMID:15502412

  8. Investigation of plant latices of Asteraceae and Campanulaceae regarding proteolytic activity.

    PubMed

    Sytwala, Sonja; Domsalla, André; Melzig, Matthias F

    2015-12-01

    Occurrence of plant latices is widespread, there are more than 40 families of plants characterized to establish lactiferous structures. The appearance of hydrolytic active proteins, incorporated in latices is already characterized, and hydrolytic active proteins are considerable, and for several plant families, the occurrence of hydrolytic active proteins is already specified e.g. Apocynaceae Juss., Caricaceae Dumort, Euphorbiaceae Juss., Moraceae Gaudich and Papaveraceae Juss. In our investigation, focused on latex bearing plants of order Asterales, Asteraceae and Campanulaceae in particular. The present outcomes represent a comprehensive study, relating to the occurrence of proteolytic active enzymes of order Asterales for the first time. 131 different species of Asteraceae and Campanulaceae were tested, and the appearance of plant latex proteases were determined in different quantities. Proteolytic activity was investigated by inhibitory studies and determination of residual activity in the following, enable us to characterize the proteases. Most of the considered species exhibit a serine protease activity and a multiplicity of species exhibited two or more subclasses of proteases. PMID:26458257

  9. Antibacterial activity of fresh pomegranate juice against clinical strains of Staphylococcus epidermidis

    PubMed Central

    Betanzos-Cabrera, Gabriel; Montes-Rubio, Perla Y.; Fabela-Illescas, Héctor E.; Belefant-Miller, Helen; Cancino-Diaz, Juan C.

    2015-01-01

    Background Polyphenols have received a great deal of attention due to their biological functions. Pomegranate (Punica granatum L.) is a polyphenol-rich fruit. In the past decade, studies testing the antimicrobial activity of pomegranates almost exclusively used solvent extracts instead of fresh pomegranate juice (FPJ). The use of FPJ instead of solvent extracts would reduce toxicity issues while increasing patient acceptance. We established a model to test FPJ as a natural antimicrobial agent. Objective To evaluate the antimicrobial activity of FPJ on clinical isolates of multidrug-resistant Staphylococcus epidermidis strains. Design Sixty strains of S. epidermidis isolated from ocular infections were grown in the presence of FPJ, and minimum inhibitory concentration (MIC) was determined by broth and agar dilution methods. Results FPJ at 20% had a MIC equal to 100% (MIC100%) on all 60 strains tested. This inhibition of FPJ was confirmed by the growth kinetics of a multidrug-resistant strain exposed to different concentrations of FPJ. Additionally, the antimicrobial activity of FPJ was compared against commercial beverages containing pomegranate: Ocean Spray® had a MIC100% at 20%, followed by Del Valle® with a MIC15% at 20% concentration only. The beverages Jumex® and Sonrisa® did not have any antimicrobial activity. FPJ had the highest polyphenol content and antioxidant capacity. Conclusions Overall, FPJ had antimicrobial activity, which might be attributed to its high polyphenol content and antioxidant capacity. PMID:25999265

  10. Increased in vitro activity of ceftriaxone by addition of tazobactam against clinical isolates of anaerobes.

    PubMed

    Aldridge, K E; Morice, N; Schiro, D D

    1994-08-01

    A total of 461 clinical strains of anaerobes were tested using a broth microdilution test to determine the activity of the combination of ceftriaxone and tazobactam and other antimicrobials against these isolates. Ceftriaxone was combined with tazobactam in ratios of 1:1, 2:1, 4:1, and 8:1 and twofold dilutions of ceftriaxone in constant concentrations to tazobactam of 2, 4, 8, 16, and 32 micrograms/ml. Against beta-lactamase-producing strains of the Bacteroides fragilis group, B. capillosus, and Prevotella species all combinations of ceftriaxone and tazobactam showed enhanced in vitro activity and were eight- to 2048-fold more active than ceftriaxone alone. By comparison ceftriaxone and tazobactam showed superior or equal activity to ampicillin and sulbactam, piperacillin and tazobactam, amoxicillin and clavulanate, ticarcillin and clavulanate, and metronidazole against these same strains. Against beta-lactamase nonproducing strains of Porphyromonas, Fusobacterium, Clostridium, Eubacterium, Peptostreptococcus, and Veillonella parvula the addition of tazobactam produced no appreciable enhanced ceftriaxone activity. Fixed concentrations of tazobactam at 2 and 4 micrograms/ml appear to be most suitable for susceptibility testing and are within the pharmacologic profile of this inhibitor. Pharmacologic and toxicity studies will be needed to define the role of ceftriaxone and tazobactam in infectious diseases. PMID:7851086

  11. Intracellular activity of clinical concentrations of phenothiazines including thioridiazine against phagocytosed Staphylococcus aureus.

    PubMed

    Ordway, Diane; Viveiros, Miguel; Leandro, Clara; Arroz, Maria Jorge; Amaral, Leonard

    2002-07-01

    The effect of thioridazine (TZ) was studied on the killing activity of human peripheral blood monocyte derived macrophages (HPBMDM) and of human macrophage cell line THP-1 at extracellular concentrations below those achievable clinically. These macrophages have nominal killing activity against bacteria and therefore, would not influence any activity that the compounds may have against intracellular localised Staphylococcus aureus. The results indicated that whereas TZ has an in vitro minimum inhibitory concentration (MIC) against the strains of S. aureus of 18, 0.1 mg/l of TZ in the medium completely inhibits the growth of S. aureus that has been phagocytosed by macrophages. The latter concentration was non-toxic to macrophages, did not cause cellular expression of activation marker CD69 nor induction of CD3+ T cell production of IFN-gamma, but blocked cellular proliferation and down-regulated the production of T cell-derived cytokines (IFN-gamma, IL-5). These results suggest that TZ induces intracellular bactericidal activities independent of the capacity to generate Type 1 responses against S. aureus. PMID:12127709

  12. Clinical Interest of Ambulatory Assessment of Physical Activity and Walking Capacity in Peripheral Artery Disease.

    PubMed

    de Müllenheim, P-Y; Chaudru, S; Mahé, G; Prioux, J; Le Faucheur, A

    2016-07-01

    The purpose of the present review was to provide, for the first time, a comprehensive analysis and synthesis of the available studies that highlighted the clinical interest of the ambulatory assessment of either physical activity (PA) or walking capacity in patients with lower extremity peripheral artery disease (PAD). We identified 96 related articles published up to March 2015 through a computer-assisted search of the MEDLINE, EMBASE, and Web of Science databases. Ambulatory-measured PA or related energy expenditure (EE) in PAD patients was performed in 87 of the 96 included studies. The main clinical interests of these measurements were (a) the assessment of PA/EE pattern; (b) the characterization of walking pattern; and (c) the control of training load during home-based walking programs. Ambulatory-measured walking capacity was performed in the remaining studies, using either Global Positioning System receivers or the Peripheral Arterial Disease Holter Control device. Highlighted clinical interests were (a) the assessment of community-based walking capacity; (b) the use of new outcomes to characterize walking capacity, besides the conventional absolute claudication distance; and (c) the association with the patient's self-perception of walking capacity. This review also provides for the clinicians step-by-step recommendations to specifically assess PA or walking capacity in PAD patients. PMID:26173488

  13. Locating Active Plate Boundaries by Earthquake Data. Crustal Evaluation Education Project. Teacher's Guide [and] Student Investigation.

    ERIC Educational Resources Information Center

    Stoever, Edward C., Jr.

    Crustal Evolution Education Project (CEEP) modules were designed to: (1) provide students with the methods and results of continuing investigations into the composition, history, and processes of the earth's crust and the application of this knowledge to man's activities and (2) to be used by teachers with little or no previous background in the…

  14. An Investigation into Social Learning Activities by Practitioners in Open Educational Practices

    ERIC Educational Resources Information Center

    Schreurs, Bieke; Van den Beemt, Antoine; Prinsen, Fleur; Witthaus, Gabi; Conole, Gráinne; De Laat, Maarten

    2014-01-01

    By investigating how educational practitioners participate in activities around open educational practices (OEP), this paper aims at contributing to an understanding of open practices and how these practitioners learn to use OEP. Our research is guided by the following hypothesis: Different social configurations support a variety of social…

  15. Investigating Acceptance toward Mobile Learning to Assist Individual Knowledge Management: Based on Activity Theory Approach

    ERIC Educational Resources Information Center

    Liaw, Shu-Sheng; Hatala, Marek; Huang, Hsiu-Mei

    2010-01-01

    Mobile devices could facilitate human interaction and access to knowledge resources anytime and anywhere. With respect to wide application possibilities of mobile learning, investigating learners' acceptance towards it is an essential issue. Based on activity theory approach, this research explores positive factors for the acceptance of m-learning…

  16. Problematic Internet Use among Turkish University Students: A Multidimensional Investigation Based on Demographics and Internet Activities

    ERIC Educational Resources Information Center

    Tekinarslan, Erkan; Gurer, Melih Derya

    2011-01-01

    This study investigated the Turkish undergraduate university students' problematic Internet use (PIU) levels on different dimensions based on demographics (e.g., gender, Internet use by time of day), and Internet activities (e.g., chat, entertainment, social networking, information searching, etc.). Moreover, the study explored some predictors of…

  17. Investigating Pre-Service Early Childhood Teachers' Attitudes towards the Computer Based Education in Science Activities

    ERIC Educational Resources Information Center

    Yilmaz, Nursel; Alici, Sule

    2011-01-01

    The purpose of this study was to investigate pre-service early childhood teachers' attitudes towards using Computer Based Education (CBE) while implementing science activities. More specifically, the present study examined the effect of different variables such as gender, year in program, experience in preschool, owing a computer, and the…

  18. Investigation of the Relations between Religious Activities and Subjective Well-Being of High School Students

    ERIC Educational Resources Information Center

    Eryilmaz, Ali

    2015-01-01

    This study aims to investigate the relation between participation in religious activities and the subjective wellbeing of high school students. The study group involves 196 participants, 99 female and 97 male; all of the participants were adolescents attending high school in Eskisehir, Turkey, their ages varying from 14 to 16. The measurement…

  19. Investigating Learner Attitudes toward E-Books as Learning Tools: Based on the Activity Theory Approach

    ERIC Educational Resources Information Center

    Liaw, Shu-Sheng; Huang, Hsiu-Mei

    2016-01-01

    This paper investigates the use of e-books as learning tools in terms of learner satisfaction, usefulness, behavioral intention, and learning effectiveness. Based on the activity theory approach, this research develops a research model to understand learner attitudes toward e-books in two physical sizes: 10? and 7?. Results suggest that screen…

  20. Authentic Experience within Investigative Activities: The Role of Reflection in the Learning Environment.

    ERIC Educational Resources Information Center

    Petrosino, Anthony J., Jr.

    This document examines how a unit on model rockets, designed to be a "hands-on" activity within the "Mission to Mars" curriculum that was implemented in the Nashville (Tennessee) area middle schools, has been used to investigate children's understanding of experimentation. A literature review explores some of the traditional constraints placed on…

  1. Going Underground: A Field Investigation and Lab Activity on Karst Topography and Water Systems

    ERIC Educational Resources Information Center

    O'Dell, Gary; Gonzalez-Espada, Wilson

    2011-01-01

    Students learn science best with activities that mirror the way scientists work. This article describes how geologists investigate groundwater flow systems in areas of karst topography--geologic formations shaped by dissolving bedrock--and provides a way for students to replicate this research. Students also use electric current to model water…

  2. Young Children's Literacy in the Activity Space of the Library: A Geosemiotic Investigation

    ERIC Educational Resources Information Center

    Nichols, Sue

    2011-01-01

    An ecological approach, emphasizing the importance of understanding multiple contexts for learning, underpins this study of libraries as activity spaces for young children's literacy participation. Five libraries serving a diversity of communities were the subject of ethnographic investigation incorporating participant observation, visual…

  3. Investigation of the free radical scavenging activity of Ginkgo biloba L. leaves.

    PubMed

    Ellnain-Wojtaszek, M; Kruczyński, Z; Kasprzak, J

    2003-02-01

    The free radical scavenging activity of methanolic, ethanolic and aqueous extracts from Ginkgo biloba leaves, has been determined by EPR (electron paramagnetic resonance) using the DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging method. The investigation has also included selected constituents of G. biloba leaves, protocatechuic and p-coumaric acids, quercetin, rutin, isoginkgetin and (+)-catechin. PMID:12628386

  4. Clinical study of student learning using mastery style versus immediate feedback online activities

    NASA Astrophysics Data System (ADS)

    Gladding, Gary; Gutmann, Brianne; Schroeder, Noah; Stelzer, Timothy

    2015-06-01

    This paper is part of a series of studies to improve the efficacy of online physics homework activities by integrating narrated animated solutions with mastery inspired exercises. In a clinical study using first- and second-year university students, the mastery group attempted question sets in four levels, with animated solutions between each attempt, until mastery was achieved on each level. This combined elements of formative assessment, the worked example effect, and mastery learning. The homework group attempted questions with immediate feedback and unlimited tries. The two groups took a similar amount of time to complete the activity. The mastery group significantly outperformed the homework group on a free response post-test that required students to show their work in solving near and far transfer problems.

  5. [Clinical trial of the new percutaneously active antirheumatic etofenamate. Summarising report (author's transl)].

    PubMed

    Heindl, I; Lorenz, D; Sieberns, S; Blumberger, W

    1977-01-01

    2-(2-Hydroxyethoxy)ethyl-N-(a,a,a-trifluoro-m-tolyl)anthranilate (etofenamate, Rheumon Gel), a percutaneously active antirheumatic containing etofenamate as active principle has been subjected to clinical studies in both hospitalized and out-patients in various types of rheumatic disease. These trials included double-blind studies against placebo gel, controlled comparative studies against two topical commercial products (ointmentI: combination of 2-hydroxyethyl salicylate and p-menthan-3-ol; ointment II: 3,5-dioxo-1,2-diphenyl-4-n-butylpyrazolidine) and open trials for efficacy and tolerance. Of the 760 patients taking part in the trials, 556 were treated with Rheumon Gel. PMID:144509

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

    PubMed

    Segarra, Ignacio; Gomez, Manuel

    2014-12-01

    We developed a pharmacology practicum assignment to introduce students to the research ethics and steps involved in a clinical trial. The assignment included literature review, critical analysis of bioethical situations, writing a study protocol and presenting it before a simulated ethics committee, a practice interview with a faculty member to obtain informed consent, and a student reflective assessment and self-evaluation. Students were assessed at various steps in the practicum; the learning efficiency of the activity was evaluated using an independent survey as well as students' reflective feedback. Most of the domains of Bloom's and Fink's taxonomies of learning were itemized and covered in the practicum. Students highly valued the translatability of theoretical concepts into practice as well as the approach to mimic professional practice. This activity was within a pharmacy program, but may be easily transferable to other medical or health sciences courses. PMID:25747690

  7. Identification of Anti-Persister Activity against Uropathogenic Escherichia coli from a Clinical Drug Library.

    PubMed

    Niu, Hongxia; Cui, Peng; Shi, Wanliang; Zhang, Shuo; Feng, Jie; Wang, Yong; Sullivan, David; Zhang, Wenhong; Zhu, Bingdong; Zhang, Ying

    2015-01-01

    Uropathogenic E. coli is a major cause of urinary tract infections (UTIs), but current antibiotics do not always effectively clear the persistent infection. To identify drugs that eliminate uropathogenic E. coli persisters, we screened a clinical drug library consisting of 1524 compounds using high throughput drug exposure assay in 96-well plates. Bacterial survival was assessed by growth on LB plates. We identified 14 drug candidates (tosufloxacin, colistin, sparfloxacin, moxifloxacin and gatifloxacin, enrofloxacin and sarafloxacin, octodrine, clofoctol, dibekacin, cephalosporin C, pazufloxacin, streptomycin and neomycin), which had high anti-persister activity. Among them, tosufloxacin and colistin had the highest anti-persister activity and could completely eradicate E. coli persisters in 3 days in vitro while the current UTI antibiotics failed to do so. Our findings may have implications for the development of a more effective treatment for UTIs. PMID:27025620

  8. In vitro activity of cefditoren versus other antibiotics against S. pneumoniae clinical strains isolated in Italy.

    PubMed

    Tempera, G; Furneri, P M; Ferranti, C; Genovese, C; Ripa, S; Ungheri, S; Nicoletti, G

    2010-01-01

    Over the last twenty years there has been an alarming increase in isolation of Streptococcus pneumoniae strains with a reduced susceptibility not only to penicillin, but also to other betalactams and macrolides. This phenomenon justifies the great interest in new antibiotics. Cefditoren, a new aminothiazolyl oral cephalosporin, recently commercialized in Italy, is characterized by an extended activity against penicillin-resistant S. pneumoniae. The aim of this study is to evaluate the incidence of the resistance/susceptibility to various antibiotics in 1000 strains of S. pneumoniae (678 SPSS, 219 SPPI and 103 SPPR), clinically isolated during 2009. The data obtained by our in vitro study show that cefditoren is the most active agent against S. pneumoniae. In fact, the MIC90 values of 0.5 micrograms/ml obtained could be particularly significant in therms of therapeutic predictivity. PMID:20943054

  9. Seeing the Moon: A Series of Inquiry Activities Using Light to Investigate the Moon

    NASA Astrophysics Data System (ADS)

    Shupla, Christine; Runyon, C.; Shipp, S.; Tremain, A. H.

    2007-12-01

    Seeing the Moon: Using Light to Investigate the Moon is a series of educational activity modules created for the Moon Mineralogy Mapper instrument aboard the Chandrayaan-1. In these modules, classroom students investigate light and the geologic history of the Moon. Through the hands-on inquiry based activities, 5th to 8th grade students experiment with light and color, collect and analyze authentic data from rock samples using an ALTA reflectance spectrometer, map the rock types of the Moon, and develop theories of the Moon's history. This poster will describe the activities and share the location of the modules. This poster will also share information on the availability of loaner kits which including rock samples and sets of the ALTA reflectance spectrometer.

  10. IMPROVING PHYSICAL ACTIVITY IN ARTHRITIS CLINICAL TRIAL (IMPAACT): STUDY DESIGN, RATIONALE, RECRUITMENT, AND BASELINE DATA

    PubMed Central

    Chang, Rowland W.; Semanik, Pamela A.; Lee, Jungwha; Feinglass, Joseph; Ehrlich-Jones, Linda; Dunlop, Dorothy D.

    2014-01-01

    Over 21 million Americans report an arthritis-attributable activity limitation. Knee osteoarthritis (OA) and rheumatoid arthritis (RA) are two of the most common/disabling forms of arthritis. Various forms of physical activity (PA) can improve a variety of health outcomes and reduce health care costs, but the proportion of the US population engaging in the recommended amount of PA is low and even lower among those with arthritis. The Improving Motivation for Physical Activity in Arthritis Clinical Trial (IMPAACT) is a randomized clinical trial that studied the effects of a lifestyle PA promotion intervention on pain and physical function outcomes. The IMPAACT intervention was based on a chronic care/disease management model in which allied health professionals promote patient self-management activities outside of traditional physician office encounters. The program was a motivational interviewing-based, individualized counseling and referral intervention, directed by a comprehensive assessment of individual patient barriers and strengths related to PA performance. The specific aims of IMPAACT were to test the efficacy of the IMPAACT intervention for persons with arthritis (N=185 persons with RA and 155 persons with knee OA) in improving arthritis-specific and generic self-reported pain and physical function outcomes, observed measures of function, and objectively measured and self-reported PA levels. Details of the stratified-randomized study design, subject recruitment, and data collection are described. The results from IMPAACT will generate empiric evidence pertaining to increasing PA levels in persons with arthritis and result in widely applicable strategies for health behavior change. PMID:25183043

  11. Clinical Outcomes of Anatomical Total Shoulder Arthroplasty in a Young, Active Population.

    PubMed

    Kusnezov, Nicholas; Dunn, John C; Parada, Stephen A; Kilcoyne, Kelly; Waterman, Brian R

    2016-01-01

    Glenohumeral arthritis in young, active patients poses many treatment challenges, and significant concerns about component loosening and failure limit the available surgical options. We conducted a study of the clinical outcomes of total shoulder arthroplasty (TSA) for glenohumeral arthritis in a young, high-demand population. We searched the Military Health System Management Analysis and Reporting Tool database to retrospectively review the cases of all US military service members who had undergone anatomical TSA (Current Procedural Terminology code 23472) between 2007 and 2014. Demographic information, occupational parameters, and clinical outcomes were extracted from electronic medical records. Twenty-four service members (26 shoulders) met the inclusion criteria. The cohort was predominantly male (n = 25). Mean age was 45.8 years (range, 35-54 years). The most common etiology of glenohumeral arthritis was post-instability arthropathy (50.0%). At mean follow-up of 41 months, 9 patients had a total of 12 complications (46.2%), including 6 component failures caused by neurologic injury (2 cases), adhesive capsulitis (2), and venous thrombosis (2). The reoperation rate for all component failures was 23.1% (6 cases, 5 patients). Ten patients (41.7%) remained on active duty at 2 years, and 5 (20.8%) were subsequently deployed. Ultimately, 9 patients (37.5%) underwent medical discharge for persistent shoulder disability. TSA in young, active patients provides reliable improvements in range of motion and pain. However, roughly one-third of patients in this study were unable to continue high-demand activities by 2 years after surgery. The short-term complication profile (46.2%) and reoperation rate for component failure (23.1%) should be emphasized during preoperative counseling. PMID:27552465

  12. In vitro activities of amphotericin B deoxycholate and liposomal amphotericin B against 604 clinical yeast isolates

    PubMed Central

    Lovero, Grazia; Coretti, Caterina; De Giglio, Osvalda; Martinelli, Domenico; Bedini, Andrea; Delia, Mario; Rosato, Antonio; Codeluppi, Mauro; Caggiano, Giuseppina

    2014-01-01

    We determined the in vitro antifungal activity of liposomal amphotericin B (L-AmB) against 604 clinical yeast isolates. Amphotericin B deoxycholate (D-AmB) was tested in parallel against all the isolates. Susceptibility testing was performed according to the Clinical and Laboratory Standards Institute (CLSI) M27-A3 method. Overall, L-AmB was highly active against the isolates (mean MIC, 0.42 µg ml−1; MIC90, 1 µg ml−1; 97.2 % of MICs were ≤1 µg ml−1) and comparable to D-AmB (mean MIC, 0.48 µg ml−1; MIC90, 1 µg ml−1; 97.3 % of MICs were ≤1 µg ml−1). The in vitro activity of D-AmB and L-AmB was correlated (R2 = 0.61; exp(b), 2.3; 95 % CI, 2.19–2.44, P<0.001). Candida albicans (mean MICs of D-AmB and L-AmB, 0.39 µg ml−1 and 0.31 µg ml−1, respectively) and Candida parapsilosis (mean MICs of D-AmB and L-AmB, 0.38 µg ml−1 and 0.35 µg ml−1, respectively) were the species most susceptible to the agents tested, while Candida krusei (currently named Issatchenkia orientalis) (mean MICs of D-AmB and L-AmB, 1.27 µg ml−1 and 1.13 µg ml−1, respectively) was the least susceptible. The excellent in vitro activity of L-AmB may have important implications for empirical treatment approaches and support its role in treatment of a wide range of invasive infections due to yeasts. PMID:25210203

  13. A Systematic Investigation on Barriers and Critical Success Factors for Clinical Information Systems in Integrated Care Settings

    PubMed Central

    Schweitzer, M.

    2015-01-01

    Summary Objectives Clinical Information Systems (CIS) have ever since the introduction of information technology in healthcare played an important role to support healthcare professionals and the process of treatment. With the rise of the concept of integrated care organizational borders, the sole focus on data aggregation or healthcare professionals as users disappear more and more. The manuscript discusses the concept of CISs and investigates critical success factors for CISs in the context of integrated care and in the course of time. Methods In order to identify critical success factors and barriers for CISs a systematic literature review was conducted based on the results from PubMed and Cochrane, using MaxQDA. Search results were thereby limited to reviews or meta-analysis. Results We have found 1919 references of which 40 met the inclusion criteria. The analysis of the manuscripts resulted in a comprehensive list of success factors and barriers related to CISs in integrated care settings. Most barriers were user-related whereas for the success factors an even distribution of organizational, technical and user-related factors was observed. The vast majority of publications was focused on healthcare professionals. Conclusion It is important to incorporate experiences made/collected over time, as the problems encountered seem to remain almost unvaried. In order to support further systematic investigations on the topic it is necessary to rethink existing concepts and definitions to realign them with the ideas of integrated care. PMID:26293853

  14. Functional Popliteal Artery Entrapment Syndrome: Poorly Understood and Frequently Missed? A Review of Clinical Features, Appropriate Investigations, and Treatment Options

    PubMed Central

    Hislop, Matthew; Kennedy, Dominic; Cramp, Brendan; Dhupelia, Sanjay

    2014-01-01

    Functional popliteal artery entrapment syndrome (PAES) is an important and possibly underrecognized cause of exertional leg pain (ELP). As it is poorly understood, it is at risk of misdiagnosis and mismanagement. The features indicative of PAES are outlined, as it can share features with other causes of ELP. Investigating functional PAES is also fraught with potential problems and if it is performed incorrectly, it can result in false negative and false positive findings. A review of the current vascular investigations is provided, highlighting some of the limitations standard tests have in determining functional PAES. Once a clinical suspicion for PAES is satisfied, it is necessary to further distinguish the subcategories of anatomical and functional entrapment and the group of asymptomatic occluders. When definitive entrapment is confirmed, it is important to identify the level of entrapment so that precise intervention can be performed. Treatment strategies for functional PAES are discussed, including the possibility of a new, less invasive intervention of guided Botulinum toxin injection at the level of entrapment as an alternative to vascular surgery. PMID:26464888

  15. Real-Time Patient Survey Data During Routine Clinical Activities for Rapid-Cycle Quality Improvement

    PubMed Central

    Jones, Robert E

    2015-01-01

    Background Surveying patients is increasingly important for evaluating and improving health care delivery, but practical survey strategies during routine care activities have not been available. Objective We examined the feasibility of conducting routine patient surveys in a primary care clinic using commercially available technology (Web-based survey creation, deployment on tablet computers, cloud-based management of survey data) to expedite and enhance several steps in data collection and management for rapid quality improvement cycles. Methods We used a Web-based data management tool (survey creation, deployment on tablet computers, real-time data accumulation and display of survey results) to conduct four patient surveys during routine clinic sessions over a one-month period. Each survey consisted of three questions and focused on a specific patient care domain (dental care, waiting room experience, care access/continuity, Internet connectivity). Results Of the 727 available patients during clinic survey days, 316 patients (43.4%) attempted the survey, and 293 (40.3%) completed the survey. For the four 3-question surveys, the average time per survey was overall 40.4 seconds, with a range of 5.4 to 20.3 seconds for individual questions. Yes/No questions took less time than multiple choice questions (average 9.6 seconds versus 14.0). Average response time showed no clear pattern by order of questions or by proctor strategy, but monotonically increased with number of words in the question (<20 words, 21-30 words, >30 words)—8.0, 11.8, 16.8, seconds, respectively. Conclusions This technology-enabled data management system helped capture patient opinions, accelerate turnaround of survey data, with minimal impact on a busy primary care clinic. This new model of patient survey data management is feasible and sustainable in a busy office setting, supports and engages clinicians in the quality improvement process, and harmonizes with the vision of a learning health

  16. Inhibition of Human Aldehyde Oxidase Activity by Diet-Derived Constituents: Structural Influence, Enzyme-Ligand Interactions, and Clinical Relevance

    PubMed Central

    Barr, John T.; Jones, Jeffrey P.; Oberlies, Nicholas H.

    2015-01-01

    The mechanistic understanding of interactions between diet-derived substances and conventional medications in humans is nascent. Most investigations have examined cytochrome P450–mediated interactions. Interactions mediated by other phase I enzymes are understudied. Aldehyde oxidase (AO) is a phase I hydroxylase that is gaining recognition in drug design and development programs. Taken together, a panel of structurally diverse phytoconstituents (n = 24) was screened for inhibitors of the AO-mediated oxidation of the probe substrate O6-benzylguanine. Based on the estimated IC50 (<100 μM), 17 constituents were advanced for Ki determination. Three constituents were described best by a competitive inhibition model, whereas 14 constituents were described best by a mixed-mode model. The latter model consists of two Ki terms, Kis and Kii, which ranged from 0.26–73 and 0.80–120 μM, respectively. Molecular modeling was used to glean mechanistic insight into AO inhibition. Docking studies indicated that the tested constituents bound within the AO active site and elucidated key enzyme-inhibitor interactions. Quantitative structure-activity relationship modeling identified three structural descriptors that correlated with inhibition potency (r2 = 0.85), providing a framework for developing in silico models to predict the AO inhibitory activity of a xenobiotic based solely on chemical structure. Finally, a simple static model was used to assess potential clinically relevant AO-mediated dietary substance–drug interactions. Epicatechin gallate and epigallocatechin gallate, prominent constituents in green tea, were predicted to have moderate to high risk. Further characterization of this uncharted type of interaction is warranted, including dynamic modeling and, potentially, clinical evaluation. PMID:25326286

  17. Inhibition of human aldehyde oxidase activity by diet-derived constituents: structural influence, enzyme-ligand interactions, and clinical relevance.

    PubMed

    Barr, John T; Jones, Jeffrey P; Oberlies, Nicholas H; Paine, Mary F

    2015-01-01

    The mechanistic understanding of interactions between diet-derived substances and conventional medications in humans is nascent. Most investigations have examined cytochrome P450-mediated interactions. Interactions mediated by other phase I enzymes are understudied. Aldehyde oxidase (AO) is a phase I hydroxylase that is gaining recognition in drug design and development programs. Taken together, a panel of structurally diverse phytoconstituents (n = 24) was screened for inhibitors of the AO-mediated oxidation of the probe substrate O(6)-benzylguanine. Based on the estimated IC50 (<100 μM), 17 constituents were advanced for Ki determination. Three constituents were described best by a competitive inhibition model, whereas 14 constituents were described best by a mixed-mode model. The latter model consists of two Ki terms, Kis and Kii, which ranged from 0.26-73 and 0.80-120 μM, respectively. Molecular modeling was used to glean mechanistic insight into AO inhibition. Docking studies indicated that the tested constituents bound within the AO active site and elucidated key enzyme-inhibitor interactions. Quantitative structure-activity relationship modeling identified three structural descriptors that correlated with inhibition potency (r(2) = 0.85), providing a framework for developing in silico models to predict the AO inhibitory activity of a xenobiotic based solely on chemical structure. Finally, a simple static model was used to assess potential clinically relevant AO-mediated dietary substance-drug interactions. Epicatechin gallate and epigallocatechin gallate, prominent constituents in green tea, were predicted to have moderate to high risk. Further characterization of this uncharted type of interaction is warranted, including dynamic modeling and, potentially, clinical evaluation. PMID:25326286

  18. An Investigation of a Cluster of Parapoxvirus Cases in Missouri, Feb–May 2006: Epidemiologic, Clinical and Molecular Aspects

    PubMed Central

    Lederman, Edith R.; Tao, Min; Reynolds, Mary G.; Li, Yu; Zhao, Hui; Smith, Scott K.; Sitler, Lisa; Haberling, Dana L.; Davidson, Whitni; Hutson, Christina; Emerson, Ginny; Schnurr, David; Regnery, Russell; Zhu, Bao-Ping; Pue, Howard; Damon, Inger K.

    2013-01-01

    Simple Summary In the spring of 2006, four human cases of parapoxvirus infections in Missouri residents were reported to the Centers for Disease Control and Prevention (CDC). We conducted surveys of herders and veterinarians, performed animal and environmental sampling and obtained sera from potential case-patients. We determined that, in general, infected persons may seek advice from veterinarians rather than physicians, thereby giving physicians less clinical experience. The initial perception of increased incidence in Missouri was likely due to reporting bias due to misdiagnosis and increased awareness due to recent publications. Basic personal protective measures are not being routinely utilized. Asymptomatic parapoxvirus infections in livestock may be common and warrants further investigation. Abstract In the spring of 2006, four human cases of parapoxvirus infections in Missouri residents were reported to the Centers for Disease Control and Prevention (CDC), two of which were initially diagnosed as cutaneous anthrax. This investigation was conducted to determine the level of recognition of zoonotic parapoxvirus infections and prevention measures, the degree to which veterinarians may be consulted on human infections and what forces were behind this perceived increase in reported infections. Interviews were conducted and clinical and environmental sampling was performed. Swab and scab specimens were analyzed by real-time polymerase chain reaction (PCR), whereas serum specimens were evaluated for parapoxvirus antibodies. Three case patients were found to have fed ill juvenile animals without using gloves. Forty-six percent of veterinarians reported having been consulted regarding suspected human orf infections. Orf virus DNA was detected from five of 25 asymptomatic sheep. Analysis of extracellular envelope gene sequences indicated that sheep and goat isolates clustered in a species-preferential fashion. Parapoxvirus infections are common in Missouri ruminants

  19. Investigation of the chemical composition-antibacterial activity relationship of essential oils by chemometric methods.

    PubMed

    Miladinović, Dragoljub L; Ilić, Budimir S; Mihajilov-Krstev, Tatjana M; Nikolić, Nikola D; Miladinović, Ljiljana C; Cvetković, Olga G

    2012-05-01

    The antibacterial effects of Thymus vulgaris (Lamiaceae), Lavandula angustifolia (Lamiaceae), and Calamintha nepeta (Lamiaceae) Savi subsp. nepeta var. subisodonda (Borb.) Hayek essential oils on five different bacteria were estimated. Laboratory control strain and clinical isolates from different pathogenic media were researched by broth microdilution method, with an emphasis on a chemical composition-antibacterial activity relationship. The main constituents of thyme oil were thymol (59.95%) and p-cymene (18.34%). Linalool acetate (38.23%) and β-linalool (35.01%) were main compounds in lavender oil. C. nepeta essential oil was characterized by a high percentage of piperitone oxide (59.07%) and limonene (9.05%). Essential oils have been found to have antimicrobial activity against all tested microorganisms. Classification and comparison of essential oils on the basis of their chemical composition and antibacterial activity were made by utilization of appropriate chemometric methods. The chemical principal component analysis (PCA) and hierachical cluster analysis (HCA) separated essential oils into two groups and two sub-groups. Thyme essential oil forms separate chemical HCA group and exhibits highest antibacterial activity, similar to tetracycline. Essential oils of lavender and C. nepeta in the same chemical HCA group were classified in different groups, within antibacterial PCA and HCA analyses. Lavender oil exhibits higher antibacterial ability in comparison with C. nepeta essential oil, probably based on the concept of synergistic activity of essential oil components. PMID:22389175

  20. Retargeting cytokine-induced killer cell activity by CD16 engagement with clinical-grade antibodies

    PubMed Central

    Cappuzzello, Elisa; Tosi, Anna; Zanovello, Paola; Sommaggio, Roberta; Rosato, Antonio

    2016-01-01

    ABSTRACT Cytokine-induced Killer (CIK) cells are a heterogeneous population of ex vivo expanded T lymphocytes capable of MHC-unrestricted antitumor activity, which share phenotypic and functional features with both NK and T cells. Preclinical data and initial clinical studies demonstrated their high tolerability in vivo, supporting CIK cells as a promising cell population for adoptive cell immunotherapy. In this study, we report for the first time that CIK cells display a donor-dependent expression of CD16, which can be engaged by trastuzumab or cetuximab to exert a potent antibody-dependent cell-mediated cytotoxicity (ADCC) against ovarian and breast cancer cell lines, leading to an increased lytic activity in vitro, and an enhanced therapeutic efficacy in vivo. Thus, an efficient tumor antigen-specific retargeting can be achieved by a combination therapy with clinical-grade monoclonal antibodies already widely used in cancer therapy, and CIK cell populations that are easily expandable in very large numbers, inexpensive, safe and do not require genetic manipulations. Overall, these data provide a new therapeutic strategy for the treatment of Her2 and EGFR expressing tumors by adoptive cell therapy, which could find wide implementation and application, and could also be expanded to the use of additional therapeutic antibodies.