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  1. Primary TKA Patients with Quantifiably Balanced Soft-Tissue Achieve Significant Clinical Gains Sooner than Unbalanced Patients

    PubMed Central

    Gustke, Kenneth A.; Golladay, Gregory J.; Roche, Martin W.; Elson, Leah C.; Anderson, Christopher R.

    2014-01-01

    Although total knee arthroplasty has a high success rate, poor outcomes and early revision are associated with ligament imbalance. This multicenter evaluation was performed in order to provide 1-year followup of a previously reported group of patients who had sensor-assisted TKA, comparing the clinical outcomes of quantitatively balanced versus unbalanced patients. At 1 year, the balanced cohort scored 179.3 and 10.4 in KSS and WOMAC, respectively; the unbalanced cohort scored 156.1 and 17.9 in KSS and WOMAC (P < 0.001; P = 0.085). The average activity level scores of quantitatively balanced patients were 68.6 (corresponding to tennis, light jogging, and heavy yard work), while the average activity level of unbalanced patients was 46.7 (corresponding to light housework, and limited walking distances) (P = 0.015). Out of all confounding variables, a balanced articulation was the most significant contributing factor to improved postoperative outcomes (P < 0.001). PMID:25210632

  2. Clinically significant responses achieved with romidepsin across disease compartments in patients with cutaneous T-cell lymphoma

    PubMed Central

    Kim, Ellen J.; Kim, Youn H.; Rook, Alain H.; Lerner, Adam; Duvic, Madeleine; Reddy, Sunil; Robak, Tadeusz; Becker, Jürgen C.; Samtsov, Alexey; McCulloch, William; Waksman, Joel; Whittaker, Sean

    2015-01-01

    Cutaneous T-cell lymphoma (CTCL) is a rare heterogeneous group of non-Hodgkin lymphomas that arises in the skin but can progress to systemic disease (lymph nodes, blood, viscera). Historically, in clinical trials of CTCL there has been little consistency in how responses were defined in each disease “compartment”; some studies only assessed responses in the skin. The histone deacetylase inhibitor romidepsin is approved by the US Food and Drug Administration for the treatment of CTCL in patients who have received at least one prior systemic therapy. Phase II studies that led to approval used rigorous composite end points that incorporated disease assessments in all compartments. The objective of this analysis was to thoroughly examine the activity of romidepsin within each disease compartment in patients with CTCL. Romidepsin was shown to have clinical activity across disease compartments and is suitable for use in patients with CTCL having skin involvement only, erythroderma, lymphadenopathy and/or blood involvement. PMID:25791237

  3. Achieving clinical integration.

    PubMed

    Redding, John

    2013-11-01

    To develop an effective and sustainable clinically integrated network (CIN) that positions a healthcare organization for value-based payment and other effects of healthcare reform, leaders of CIN initiatives should: Embrace progress rather than perfection; Constrain the development timeline by project managing in reverse; Ensure that physician leaders play an oversight role in the development process. PMID:24340650

  4. "Clinical" Significance: "Clinical" Significance and "Practical" Significance are NOT the Same Things

    ERIC Educational Resources Information Center

    Peterson, Lisa S.

    2008-01-01

    Clinical significance is an important concept in research, particularly in education and the social sciences. The present article first compares clinical significance to other measures of "significance" in statistics. The major methods used to determine clinical significance are explained and the strengths and weaknesses of clinical significance…

  5. Significant results: statistical or clinical?

    PubMed Central

    2016-01-01

    The null hypothesis significance test method is popular in biological and medical research. Many researchers have used this method for their research without exact knowledge, though it has both merits and shortcomings. Readers will know its shortcomings, as well as several complementary or alternative methods, as such the estimated effect size and the confidence interval. PMID:27066201

  6. Clinical significance of complement deficiencies.

    PubMed

    Pettigrew, H David; Teuber, Suzanne S; Gershwin, M Eric

    2009-09-01

    The complement system is composed of more than 30 serum and membrane-bound proteins, all of which are needed for normal function of complement in innate and adaptive immunity. Historically, deficiencies within the complement system have been suspected when young children have had recurrent and difficult-to-control infections. As our understanding of the complement system has increased, many other diseases have been attributed to deficiencies within the complement system. Generally, complement deficiencies within the classical pathway lead to increased susceptibility to encapsulated bacterial infections as well as a syndrome resembling systemic lupus erythematosus. Complement deficiencies within the mannose-binding lectin pathway generally lead to increased bacterial infections, and deficiencies within the alternative pathway usually lead to an increased frequency of Neisseria infections. However, factor H deficiency can lead to membranoproliferative glomerulonephritis and hemolytic uremic syndrome. Finally, deficiencies within the terminal complement pathway lead to an increased incidence of Neisseria infections. Two other notable complement-associated deficiencies are complement receptor 3 and 4 deficiency, which result from a deficiency of CD18, a disease known as leukocyte adhesion deficiency type 1, and CD59 deficiency, which causes paroxysmal nocturnal hemoglobinuria. Most inherited deficiencies of the complement system are autosomal recessive, but properidin deficiency is X-linked recessive, deficiency of C1 inhibitor is autosomal dominant, and mannose-binding lectin and factor I deficiencies are autosomal co-dominant. The diversity of clinical manifestations of complement deficiencies reflects the complexity of the complement system. PMID:19758139

  7. Clinical significance of adaptive thermogenesis.

    PubMed

    Major, G C; Doucet, E; Trayhurn, P; Astrup, A; Tremblay, A

    2007-02-01

    The epidemic of obesity is developing faster than the scientific understanding of an efficient way to overcome it, as reflected by the low success rate of short- and long-term weight loss interventions. From a clinical standpoint, this suggests that the body tends to defend a set point of possible genetic origin in the context of a weight-reducing program. As described in this paper, this limited therapeutic success may depend on adaptive thermogenesis, which represents in this case the decrease in energy expenditure (EE) beyond what could be predicted from the changes in fat mass or fat-free mass under conditions of standardized physical activity in response to a decrease in energy intake. This issue has been documented in recent studies that have shown in obese individuals adhering to a weight reduction program a greater than predicted decrease in EE, which in some cases was quantitatively sufficient to overcome the prescribed energy restriction, suggesting a role for adaptive thermogenesis in unsuccessful weight loss interventions and reduced body weight maintenance. As also discussed in this paper, this 'adaptive thermogenesis' can be influenced by environmental factors, which have not been frequently considered up to now. This is potentially the case for plasma organochlorine concentration and oxygen desaturation in obstructive sleep apnea syndrome. It is concluded that health professionals should be aware that in some vulnerable individuals, adaptive thermogenesis can be multi-causal, and has the capacity to compensate, at least partly, for the prescribed energy deficit, possibly going beyond any good compliance of some patients. PMID:17260010

  8. Clinical significance of monocyte heterogeneity.

    PubMed

    Stansfield, Brian K; Ingram, David A

    2015-01-01

    Monocytes are primitive hematopoietic cells that primarily arise from the bone marrow, circulate in the peripheral blood and give rise to differentiated macrophages. Over the past two decades, considerable attention to monocyte diversity and macrophage polarization has provided contextual clues into the role of myelomonocytic derivatives in human disease. Until recently, human monocytes were subdivided based on expression of the surface marker CD16. "Classical" monocytes express surface markers denoted as CD14(++)CD16(-) and account for greater than 70% of total monocyte count, while "non-classical" monocytes express the CD16 antigen with low CD14 expression (CD14(+)CD16(++)). However, recognition of an intermediate population identified as CD14(++)CD16(+) supports the new paradigm that monocytes are a true heterogeneous population and careful identification of specific subpopulations is necessary for understanding monocyte function in human disease. Comparative studies of monocytes in mice have yielded more dichotomous results based on expression of the Ly6C antigen. In this review, we will discuss the use of monocyte subpopulations as biomarkers of human disease and summarize correlative studies in mice that may yield significant insight into the contribution of each subset to disease pathogenesis. PMID:25852821

  9. Prediction of Achievement in Clinical Pharmacy Courses

    ERIC Educational Resources Information Center

    Simon, Lee S.

    1978-01-01

    A study sought to identify student characteristics which account for academic achievement in clinical pharmacy courses. Preclinical grade point average was the best predictor. Subscales of the California Personality Inventory and the Myers-Briggs Type Indicator, work experience, sex, and age were the other predictor variables. (SW)

  10. SOARing Into Strategic Planning: Engaging Nurses to Achieve Significant Outcomes.

    PubMed

    Wadsworth, Barbara; Felton, Fiona; Linus, Rita

    2016-01-01

    In 2013, a new system chief nursing officer engaged the nursing leaders and staff in an Appreciative Inquiry process utilizing strengths, opportunities, aspirations, and results (SOAR), and a Journey of Excellence to assess and understand the current environment. The ultimate goal was to engage all nurses in strategic planning and goal setting to connect their patient care to the system strategic initiatives. This work led to the creation of a nursing vision, a revised professional practice model and greater council alignment, resulting in significant positive change and ongoing advancement throughout the system. The shared decision-making structure was key to the process with a direct connection of each council's goals, leading to the successful achievement of 34 of the 36 goals in 2 years. This article outlines the process, tools, and staff engagement strategies used to achieve system-wide success. This methodology has improved the outcomes across the organization in both small and system-wide work groups. This work can easily be replicated and adapted to help disparate staffs brought together through mergers or acquisitions to become aligned as a new team. This process, model, and framework, provides structure and results in significant outcomes that recognizes and celebrates the work of individual entities while aligning future strategies and goals. PMID:27584888

  11. Clinical significance of human papillomavirus genotyping

    PubMed Central

    Choi, Youn Jin

    2016-01-01

    Cervical cancer is the fourth most common cancer in women worldwide, and the human papillomavirus (HPV) is the main causative agent for its development. HPV is a heterogeneous virus, and a persistent infection with a high-risk HPV contributes to the development of cancer. In recent decades, great advances have been made in understanding the molecular biology of HPV, and HPV’s significance in cervical cancer prevention and management has received increased attention. In this review, we discuss the role of HPV genotyping in cervical cancer by addressing: clinically important issues in HPV virology; the current application of HPV genotyping in clinical medicine; and potential future uses for HPV genotyping. PMID:26768784

  12. Are Carotid Stent Fractures Clinically Significant?

    SciTech Connect

    Garcia-Toca, Manuel; Rodriguez, Heron E.; Naughton, Peter A.; Keeling, Aiofee; Phade, Sachin V.; Morasch, Mark D.; Kibbe, Melina R.; Eskandari, Mark K.

    2012-04-15

    Purpose: Late stent fatigue is a known complication after carotid artery stenting (CAS) for cervical carotid occlusive disease. The purpose of this study was to determine the prevalence and clinical significance of carotid stent fractures. Materials and Methods: A single-center retrospective review of 253 carotid bifurcation lesions treated with CAS and mechanical embolic protection from April 2001 to December 2009 was performed. Stent integrity was analyzed by two independent observers using multiplanar cervical plain radiographs with fractures classified into the following types: type I = single strut fracture; type II = multiple strut fractures; type III = transverse fracture; and type IV = transverse fracture with dislocation. Mean follow-up was 32 months. Results: Follow-up imaging was completed on 106 self-expanding nitinol stents (26 closed-cell and 80 open-cell stents). Eight fractures (7.5%) were detected (type I n = 1, type II n = 6, and type III n = 1). Seven fractures were found in open-cell stents (Precise n = 3, ViVEXX n = 2, and Acculink n = 2), and 1 fracture was found in a closed-cell stent (Xact n = 1) (p = 0.67). Only a previous history of external beam neck irradiation was associated with fractures (p = 0.048). No associated clinical sequelae were observed among the patients with fractures, and only 1 patient had an associated significant restenosis ({>=}80%) requiring reintervention. Conclusions: Late stent fatigue after CAS is an uncommon event and rarely clinically relevant. Although cell design does not appear to influence the occurrence of fractures, lesion characteristics may be associated risk factors.

  13. Clinically significant drug interactions with newer antidepressants.

    PubMed

    Spina, Edoardo; Trifirò, Gianluca; Caraci, Filippo

    2012-01-01

    After the introduction of selective serotonin reuptake inhibitors (SSRIs), other newer antidepressants with different mechanisms of action have been introduced in clinical practice. Because antidepressants are commonly prescribed in combination with other medications used to treat co-morbid psychiatric or somatic disorders, they are likely to be involved in clinically significant drug interactions. This review examines the drug interaction profiles of the following newer antidepressants: escitalopram, venlafaxine, desvenlafaxine, duloxetine, milnacipran, mirtazapine, reboxetine, bupropion, agomelatine and vilazodone. In general, by virtue of a more selective mechanism of action and receptor profile, newer antidepressants carry a relatively low risk for pharmacodynamic drug interactions, at least as compared with first-generation antidepressants, i.e. monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs). On the other hand, they are susceptible to pharmacokinetic drug interactions. All new antidepressants are extensively metabolized in the liver by cytochrome P450 (CYP) isoenzymes, and therefore may be the target of metabolically based drug interactions. Concomitant administration of inhibitors or inducers of the CYP isoenzymes involved in the biotransformation of specific antidepressants may cause changes in their plasma concentrations. However, due to their relatively wide margin of safety, the consequences of such kinetic modifications are usually not clinically relevant. Conversely, some newer antidepressants may cause pharmacokinetic interactions through their ability to inhibit specific CYPs. With regard to this, duloxetine and bupropion are moderate inhibitors of CYP2D6. Therefore, potentially harmful drug interactions may occur when they are coadministered with substrates of these isoforms, especially compounds with a narrow therapeutic index. The other new antidepressants are only weak inhibitors or are not inhibitors of CYP isoforms at

  14. The clinical significance of marginal fit.

    PubMed

    Larson, Thomas D

    2012-01-01

    Clinical evaluation of restoration acceptability includes marginal adaptation, restoration and preservation of anatomic form, color match, cavosurface discoloration, and presence of marginal caries. This paper will review what is known about marginal fit of all materials relative to their acceptable fit. Some explanation will be given of how material properties affect marginal fit, what the expected longevity of different materials is relative to marginal fit, and how marginal fit affects development of secondary or marginal caries. Marginal fit is assumed to affect restoration longevity by either encouraging or discouraging microleakage and development of secondary or marginal caries. Marginal fit and its effect on the health of the gingival tissues have been reviewed in an earlier paper on polishing and will not be reviewed here. Is there some correlation between marginal fit of the various materials used in restorative dentistry and this assumption? This paper will review the literature found on Medline and present the science behind the clinical significance of marginal fit utilizing in vitro studies where necessary and in vivo studies whenever possible. Numerous authors replicating these studies are used to improve reliability and replicability. PMID:22439529

  15. Clinical significance of MET in gastric cancer

    PubMed Central

    Inokuchi, Mikito; Otsuki, Sho; Fujimori, Yoshitaka; Sato, Yuya; Nakagawa, Masatoshi; Kojima, Kazuyuki

    2015-01-01

    Chemotherapy has become the global standard treatment for patients with metastatic or unresectable gastric cancer (GC), although outcomes remain unfavorable. Many molecular-targeted therapies inhibiting signaling pathways of various tyrosine kinase receptors have been developed, and monoclonal antibodies targeting human epidermal growth factor receptor 2 or vascular endothelial growth factor receptor 2 have become standard therapy for GC. Hepatocyte growth factor and its receptor, c-MET (MET), play key roles in tumor growth through activated signaling pathways from receptor in GC cells. Genomic amplification of MET leads to the aberrant activation found in GC tumors and is related to survival in patients with GC. This review discusses the clinical significance of MET in GC and examines MET as a potential therapeutic target in patients with GC. Preclinical studies in animal models have shown that MET antibodies or small-molecule MET inhibitors suppress tumor-cell proliferation and tumor progression in MET-amplified GC cells. These drugs are now being evaluated in clinical trials as treatments for metastatic or unresectable GC. PMID:26600931

  16. Subchorionic hemorrhage: sonographic diagnosis and clinical significance.

    PubMed

    Abu-Yousef, M M; Bleicher, J J; Williamson, R A; Weiner, C P

    1987-10-01

    Twenty-one pregnancies with sonographic evidence of subchorionic hemorrhage were evaluated clinically and sonographically. Clinical evaluation included maternal age, gravidity, parity, gestational age, presence of pain, presence and amount of bleeding, and pregnancy outcome. Sonographic evaluation included the relative and absolute size of the hematoma, its echogenicity and location in relation to the placenta, the presence of marginal placental abruption, and progress on follow-up examinations. The outcome of these pregnancies was unfavorable in 15 cases (71%) and correlated well with the relative and absolute size of the hematoma, severity of vaginal bleeding, change in hematoma size on follow-up examination, and presence of pain. There was no significant correlation between the outcome and the echogenicity of the hematoma, presence of placental margin elevation, gestational and maternal age, gravidity, or parity. All hematomas extended to the margin of the placenta. Subchorionic hemorrhage is a frequent cause of first and second trimester bleeding and has a grave prognosis. Familiarity with the varied sonographic appearances and meticulous sonographic examination with special attention to the placental margins can be helpful in the diagnosis. PMID:3307354

  17. The clinical significance of small subarachnoid hemorrhages.

    PubMed

    Albertine, Paul; Borofsky, Samuel; Brown, Derek; Patel, Smita; Lee, Woojin; Caputy, Anthony; Taheri, M Reza

    2016-06-01

    With advancing technology, the sensitivity of computed tomography (CT) for the detection of traumatic subarachnoid hemorrhage (tSAH) continues to improve. Increased resolution has allowed for the detection of hemorrhage that is limited to one or two images of the CT exam. At our institution, all patients with a SAH require intensive care unit (ICU) admission, regardless of size. It was our hypothesis that patients with small subarachnoid hemorrhage experience favorable outcomes, and may not require the intensive monitoring offered in the ICU. This retrospective study evaluated 62 patients between 2011 and 2014 who presented to our Level I trauma center emergency room for acute traumatic injuries, and found to have subarachnoid hemorrhages on CT examination. The grade of subarachnoid hemorrhage was determined using previously utilized scoring systems, such as the Fisher, Modified Fisher, and Claassen grading systems. Electronic medical records were used to evaluate for medical decline, neurological decline, neurosurgical intervention, and overall hospital course. Admitting co-morbidities were noted, as were the presence of patient intoxication and use of anticoagulants. Patient outcomes were based on discharge summaries upon which the neurological status of the patient was assessed. Each patient was given a score based on the Glasgow outcome scale. The clinical and imaging profile of 62 patients with traumatic SAH were studied. Of the 62 patients, 0 % underwent neurosurgical intervention, 6.5 % had calvarial fractures, 25.8 % had additional intracranial hemorrhages, 27.4 % of the patients had significant co-morbidities, and 1.6 % of the patients expired. Patients with low-grade tSAH spent less time in the ICU, demonstrated neurological and medical stability during hospitalization. None of the patients with low-grade SAH experienced seizure during their admission. In our study, patients with low-grade tSAH demonstrated favorable clinical outcomes. This suggests

  18. Emotional Intelligence Skills: Significant Factors in Freshmen Achievement and Retention.

    ERIC Educational Resources Information Center

    Nelson, Darwin B.; Nelson, Kaye W.

    This study investigated the role of emotional skills in the academic achievement and retention of university freshmen. The research group was a randomly selected sample of first semester freshmen students (N=165), and cumulative grade point average was used as the criterion for academic success. The study was designed to investigate: (a) the…

  19. Boise Inc. St. Helens Paper Mill Achieves Significant Fuel Savings

    SciTech Connect

    Not Available

    2008-05-01

    This case study describes how the Boise Inc. paper mill in St. Helens, Oregon, achieved annual savings of approximately 154,000 MMBtu and more than $1 million after receiving a DOE Save Energy Now energy assessment and implementing recommendations to improve the efficiency of its steam system.

  20. Boise Inc. St. Helens Paper Mill Achieves Significant Fuel Savings

    SciTech Connect

    2008-05-01

    This case study describes how the Boise Inc. paper mill in St. Helens, Oregon, achieved annual savings of approximately 154,000 MMBtu and more than $1 million. This was accomplished after receiving a DOE Save Energy Now energy assessment and implementing recommendations to improve the efficiency of its steam system.

  1. Significance of FISH in clinical cytogenetics

    SciTech Connect

    Gopal Rao, V.V.N.; Harris, S.; Roop, H.

    1994-09-01

    Ever since its discovery, FISH technology has become an invaluable adjunct to conventional cytogenetics. FISH has been instrumental in resolving previously unresolved cytogenetic dilemmas. FISH has been used to elucidate complex as well as subtle chromosomal translocations, in detection of microdeletions, to confirm duplications and inversions and to identify marker chromosomes. We report a few selected cases where FISH proved to be invaluable in not only confirming the anomaly, but also in arriving at an accurate diagnosis and appropriate counseling of the patients. These include 3 cases of prenatal and 3 cases of postnatal diagnosis. The results clearly demonstrate the significance of FISH in identifying and interpreting the difficult karyotype in clinical cytogenetics. In addition, FISH has been used to rule out microdeletions in Prader-Willi (16), Angelman (3), Miller-Dieker (7), DiGeorge (4) and Smith-Magenis (1) syndrome patients. Without FISH in the majority of these cases, it would not have been possible to accurately identify the karyotype and interpret the results. Hence, we recommend that FISH be used as a powerful adjunct to conventional cytogenetics in order to arrive at an accurate interpretation of the results but not to replace routine cytogenetic studies.

  2. Clinical significance of epithelial-mesenchymal transition

    PubMed Central

    2014-01-01

    The concept of epithelial-mesenchymal transition (EMT), a process where cells change their epithelial towards a mesenchymal phenotype, has gained overwhelming attention especially in the cancer research community. Thousands of scientific reports investigated changes in gene, mRNA and protein expression compatible with EMT and their possible correlation with tumor invasion, metastatic spread or patient prognosis; however, up to now, a proof of clinical significance of the concept is still missing. This review, with a main focus on the role of EMT in tumors, will summarize the basic molecular events underlying EMT including the signaling pathways capable of its induction as well as changes in EMT-associated protein expression and will very briefly touch the role of microRNAs in EMT. We then outline protein markers that are used most frequently for the assessment of EMT in research and diagnostic evaluation of tumor specimens and depict the link between EMT, a cancer stem cell (CSC) phenotype and resistance to conventional antineoplastic therapies. Furthermore, we evaluate a possible correlation between EMT marker expression and patient prognosis as well as current therapeutic concepts targeting the EMT process to slow down or prevent metastatic spread of malignant tumors. PMID:25050175

  3. Creating a Middle Grades Environment that Significantly Improves Student Achievement

    ERIC Educational Resources Information Center

    L'Esperance, Mark E.; Lenker, Ethan; Bullock, Ann; Lockamy, Becky; Mason, Cathy

    2013-01-01

    This article offers an overview of the framework that Sampson County Public Schools (North Carolina) used to critically reflect on the current state of their middle grades schools. The article also highlights the changes that resulted from the district-wide analysis and the ways in which these changes led to a significant increase in the academic…

  4. [The significance of biobanks for clinical development].

    PubMed

    Thomas, Marlene; Kiermaier, Astrid; Cannarile, Michael

    2016-03-01

    Access to samples in biobanks and collection of samples for evaluation of biomarkers in clinical trials are an essential basis for the identification and development of biomarkers. From the perspective of a research-based pharmaceutical company identification of biomarkers and the accompanying diagnostics are an essential prerequisite for the further evolution of personalised healthcare-and the key to more effective and efficient healthcare. Research-based pharmaceutical companies can basically use four types of biobanks: biobanks of university hospitals, commercial providers, collaborative groups and company-owned biobanks. Areas of application, arising from the use of biobanks in the context of clinical development, are collection of prevalence data, evaluation of biomarker stability in different disease stages, technical validation of assays, an optimized course of clinical studies by focusing on defined, biomarker-stratified groups of patients and pharmacogenetic research. Challenges are, in particular, the availability of clinically annotated samples and tissue matching blood samples, in addition to sample quality, number and amount. An acceptable legal and regulatory framework, as well as the positive perception of biomarker data by politicians and the public, are important prerequisites for translational research for identification of biomarkers in clinical studies. Also, the early establishment of research alliances between academia and the pharmaceutical industry are required to transfer research results in new strategies for prevention, diagnosis and treatment of patients. PMID:26847235

  5. Barnacle Geese Achieve Significant Energetic Savings by Changing Posture

    PubMed Central

    Tickle, Peter G.; Nudds, Robert L.; Codd, Jonathan R.

    2012-01-01

    Here we report the resting metabolic rate in barnacle geese (Branta leucopsis) and provide evidence for the significant energetic effect of posture. Under laboratory conditions flow-through respirometry together with synchronous recording of behaviour enabled a calculation of how metabolic rate varies with posture. Our principal finding is that standing bipedally incurs a 25% increase in metabolic rate compared to birds sitting on the ground. In addition to the expected decrease in energy consumption of hindlimb postural muscles when sitting, we hypothesise that a change in breathing mechanics represents one potential mechanism for at least part of the observed difference in energetic cost. Due to the significant effect of posture, future studies of resting metabolic rates need to take into account and/or report differences in posture. PMID:23071672

  6. Intracranial Artery Calcification and Its Clinical Significance

    PubMed Central

    Wu, Xiao Hong; Wang, Li Juan; Wong, Ka Sing

    2016-01-01

    Intracranial arterial calcification (IAC) is an easily identifiable entity on plain head computed tomography scans. Recent studies have found high prevalence rates for IAC worldwide, and this may be associated with ischemic stroke and cognitive decline. Aging, traditional cardiovascular risk factors, and chronic kidney disease have been found to be associated with IAC. The severity of IAC can be assessed using different visual grading scales or various quantitative methods (by measuring volume or intensity). An objective method for assessing IAC using consistent criteria is urgently required to facilitate comparisons between multiple studies involving diverse populations. There is accumulating evidence from clinical studies that IAC could be utilized as an indicator of intracranial atherosclerosis. However, the pathophysiology underlying the potential correlation between IAC and ischemic stroke—through direct arterial stenosis or plaque stability—remains to be determined. More well-designed clinical studies are needed to explore the predictive values of IAC in vascular events and the underlying pathophysiological mechanisms. PMID:27165425

  7. Drug chirality and its clinical significance.

    PubMed

    Hutt, A J; Tan, S C

    1996-01-01

    Approximately 1 in 4 therapeutic agents are marked as racemic mixtures, the individual enantiomers of which frequently differ in both their pharmacodynamic and pharmacokinetic profiles. The use of racemates has become the subject of considerable discussion in recent years, and an area of concern for both the pharmaceutical industry and regulatory authorities. The use of single enantiomers has a number of potential clinical advantages, including an improved therapeutic/pharmacological profile, a reduction in complex drug interactions, and simplified pharmacokinetics. In a number of instances stereochemical considerations have contributed to an understanding of the observed pharmacological effects of a drug administered as a racemate. However, relatively little is known of the influence of patient factors (e.g. disease state, age, gender and genetics) on drug enantiomer disposition and action in man. Examples may also be cited where the use of a single enantiomers, nonracemic mixtures and racemates of currently used agents may offer clinical advantages. The issues associated with drug chirality are complex and depend upon the relative merits of the individual agent. In the future it is likely that a number of existing racemates will be re-marketed as single enantiomer products with potentially improved clinical profiles and possible novel therapeutic indications. PMID:8922553

  8. Unexpected Findings in Magnetic Resonance Enterography and Their Clinical Significance

    PubMed Central

    Ravindran, Srivathsan; Hancox, Sarah Helen; Barlow, Neil; Dunk, Arthur; Howlett, David

    2016-01-01

    Aims. To identify the prevalence of colonic and extraenteric incidental findings in magnetic resonance enterography (MRE) and their clinical significance. Methods. We retrospectively analysed 470 MRE studies carried out between March 2012 and 2014. Incidental findings were defined as those not expected from or made apparent on the referral. MRE reports were reviewed for colonic and extraenteric findings, subcategorised into “clinically significant” and “insignificant.” Follow-up was identified from the electronic patient record. Results. The majority of MRE requests were made for inflammatory bowel disease (97%). In total, 114 incidental findings were noted in 94 (20%) scans performed. There were 29 “colonic” findings (25%) with 55% having a diagnosis of colitis. Out of 85 extraenteric findings, ovarian cysts (25%), renal cysts (10%), and abdominal lymphadenopathy (9%) were the commonest. Cumulatively, 59 cases were clinically significant (52%); of these, 30 findings were not previously diagnosed, amounting to 26% of all incidental findings. This led to intervention in seven patients. Conclusions. Incidental findings are common in MRE and there is a substantial proportion that is clinically significant and requires further investigation. There need to be stratification of risk and employment of local guidelines in order to achieve this. PMID:27446837

  9. Clinically significant factors in dowel design.

    PubMed

    Sorensen, J A; Martinoff, J T

    1984-07-01

    When a method of intracoronal reinforcement is selected, many factors must be weighed. The hazards include (1) the induced stresses and the risk of fracture during placement of the dowel, (2) the probability of root perforation during post space preparation, (3) the wedging action of tapered dowels, and (4) the incidence of fracture with self-threading pins in devitalized teeth. The amount of tooth structure that remains after endodontic therapy and post space preparation is paramount. Endodontic and restorative treatment must be aimed at preserving tooth structure to provide strength and resistance to fracture of the pulpless tooth. To fabricate a large-diameter dowel with a strength that greatly exceeds that of the endodontically treated root decreases the prognosis for clinical success. PMID:6379161

  10. Vasa Vasorum in Atherosclerosis and Clinical Significance

    PubMed Central

    Xu, Junyan; Lu, Xiaotong; Shi, Guo-Ping

    2015-01-01

    Atherosclerosis is a chronic inflammatory disease that leads to several acute cardiovascular complications with poor prognosis. For decades, the role of the adventitial vasa vasorum (VV) in the initiation and progression of atherosclerosis has received broad attention. The presence of VV neovascularization precedes the apparent symptoms of clinical atherosclerosis. VV also mediates inflammatory cell infiltration, intimal thickening, intraplaque hemorrhage, and subsequent atherothrombosis that results in stroke or myocardial infarction. Intraplaque neovessels originating from VV can be immature and hence susceptible to leakage, and are thus regarded as the leading cause of intraplaque hemorrhage. Evidence supports VV as a new surrogate target of atherosclerosis evaluation and treatment. This review provides an overview into the relationship between VV and atherosclerosis, including the anatomy and function of VV, the stimuli of VV neovascularization, and the available underlying mechanisms that lead to poor prognosis. We also summarize translational researches on VV imaging modalities and potential therapies that target VV neovascularization or its stimuli. PMID:26006236

  11. Macrolide antibacterials. Drug interactions of clinical significance.

    PubMed

    von Rosensteil, N A; Adam, D

    1995-08-01

    Macrolide antibiotics can interact adversely with commonly used drugs, usually by altering metabolism due to complex formation and inhibition of cytochrome P-450 IIIA4 (CYP3A4) in the liver and enterocytes. In addition, pharmacokinetic drug interactions with macrolides can result from their antibiotic effect on microorganisms of the enteric flora, and through enhanced gastric emptying due to a motilin-like effect. Macrolides may be classified into 3 different groups according to their affinity for CYP3A4, and thus their propensity to cause pharmacokinetic drug interactions. Troleandomycin, erythromycin and its prodrugs decrease drug metabolism and may produce drug interactions (group 1). Others, including clarithromycin, flurithromycin, midecamycin, midecamycin acetate (miocamycin; ponsinomycin), josamycin and roxithromycin (group 2) rarely cause interactions. Azithromycin, dirithromycin, rikamycin and spiramycin (group 3) do not inactivate CYP3A4 and do not engender these adverse effects. Drug interactions with carbamazepine, cyclosporin, terfenadine, astemizole and theophylline represent the most frequently encountered interactions with macrolide antibiotics. If the combination of a macrolide and one of these compounds cannot be avoided, serum concentrations of concurrently administered drugs should be monitored and patients observed for signs of toxicity. Rare interactions and those of dubious clinical importance are those with alfentanil and sufentanil, antacids and cimetidine, oral anticoagulants, bromocriptine, clozapine, oral contraceptive steroids, digoxin, disopyramide, ergot alkaloids, felodipine, glibenclamide (glyburide), levodopa/carbidopa, lovastatin, methylprednisolone, phenazone (antipyrine), phenytoin, rifabutin and rifampicin (rifampin), triazolam and midazolam, valproic acid (sodium valproate) and zidovudine. PMID:7576262

  12. [Microbiologic and clinical significance of cefotiam].

    PubMed

    Tauchnitz, C; Ezold, R; Bauer, I; Berger, H D; Buhl, C; Goedecke, A; Morawietz, I

    1985-03-01

    Modern cephalosporins are of considerable importance for the therapy of severe infections by multiresistant organisms. According to in-vitro-findings on ampicillin-resistant E. coli as well as Klebsiella spp., Proteus spp., and serratia spp., altogether 159 strains, instead of cefotaxime nearly always also cefotiam can be used. The two remedies are clearly superior to cephalothin. cefotiam is ineffective to Pseudomonas aeruginosa. But in this case also cefotaxime is clearly inferior to azlocillin. In 6 of 7 casuistic instances the clinical effectiveness of cefotiam could be confirmed with good tolerability. The contemporary establishment of staph. aureus in mixed infections of serratiastaphylococci proved as as particular advantage. A primary therapeutic failure referred to a necrotizing pancreatitis, when no causative organism was proved, in which case also cefotaxime remained without any effect. Despite the improved individual medical possibilities the control of the infectious hospitalism by critical administration of antibiotics and improved hospital hygiene, particularly strict non-infection, must remain the pre-eminent task. PMID:3857792

  13. Lupus thrombocytopenia: clinical implications and prognostic significance

    PubMed Central

    Ziakas, P; Giannouli, S; Zintzaras, E; Tzioufas, A; Voulgarelis, M

    2005-01-01

    Methods: 632 patients were reviewed retrospectively. Fifty patients with thrombocytopenia were included as cases and matched with 100 control patients. Clinical manifestations at first thrombocytopenic episode were recorded. Classification criteria at diagnosis, basic immunological profiles, disease activity (ECLAM), and end organ damage (SLICC) were recorded. Results: 29/50 (58%) had thrombocytopenia at diagnosis of lupus. Haemorrhagic manifestations were associated with the degree of thrombocytopenia (p<0.001). Anticardiolipin antibodies were not related to the degree of thrombocytopenia or the severity of haemorrhagic manifestations. Megakaryocytes were normal or increased in 26/28 (93%) bone marrow specimens, indicating peripheral platelet destruction. Patients with high disease activity were more thrombocytopenic than controls (OR = 2.61, 95% CI 1.13 to 5.96, p = 0.009). Patients with low C3 or CH50 were more likely to be thrombocytopenic (OR = 2.36, 95% CI 1.05 to 5.26, p = 0.029). Median SLICC for lupus patients with thrombocytopenia was 2 (range 0–11) compared with 1 (range 0–12) for controls (p<0.001). No deaths occurred during thrombocytopenic episodes. Conclusions: Thrombocytopenia is not directly associated with end organ damage and mortality, but defines a subgroup of patients with higher morbidity and is thus a major complication of systemic lupus erythematosus, affecting overall prognosis. PMID:16100344

  14. Clinical significance of severe isolated diaphragm weakness.

    PubMed

    Laroche, C M; Carroll, N; Moxham, J; Green, M

    1988-10-01

    We studied six patients with isolated bilateral paralysis or severe weakness of the diaphragm, present for 2 to 60 months (mean = 25), to document the clinical and respiratory sequelae of the condition. Severe diaphragm dysfunction was confirmed by the demonstration of the very low maximal transdiaphragmatic pressure (Pdi) generated by either a sniff (13 +/- 6 cm H2O, normal 148 +/- 24) or a static inspiration (11 +/- 8, normal 108 +/- 30) and during bilateral phrenic nerve stimulation (0.8 +/- 2.0, normal 22 +/- 4). Resting arterial blood gases were normal (SaO2 = 95 to 97%) and no oxygen desaturation occurred during maximal exercise on a treadmill. Maximum voluntary ventilation was low and related to PImax (r = 0.89). Overnight sleep monitoring showed that time spent in rapid eye movement sleep was normal (mean 55 +/- 36 min, range 26 to 117 min). Mean maximum increment in transcutaneous CO2 was within normal limits (6 +/- 2 mm Hg, range 3 to 9 mm Hg). Three patients had occasional brief episodes of oxygen desaturation (mean maximal decrease 13 +/- 10%, range 2 to 27%); however, only two of these spent a measurable proportion of total sleep time (TST) with an SaO2 of less than 80% (1% and 3% TST, respectively). No patient has developed any symptoms of nocturnal hypoventilation or chronic respiratory failure during periods of observation of up to five yr. We conclude that bilateral paralysis or very severe weakness of the diaphragm does not of itself lead to respiratory failure unless weakness of other respiratory muscles is present. PMID:3202460

  15. Different clinical electrodes achieve similar electrical nerve conduction block

    NASA Astrophysics Data System (ADS)

    Boger, Adam; Bhadra, Narendra; Gustafson, Kenneth J.

    2013-10-01

    Objective. We aim to evaluate the suitability of four electrodes previously used in clinical experiments for peripheral nerve electrical block applications. Approach. We evaluated peripheral nerve electrical block using three such clinical nerve cuff electrodes (the Huntington helix, the Case self-sizing Spiral and the flat interface nerve electrode) and one clinical intramuscular electrode (the Memberg electrode) in five cats. Amplitude thresholds for the block using 12 or 25 kHz voltage-controlled stimulation, onset response, and stimulation thresholds before and after block testing were determined. Main results. Complete nerve block was achieved reliably and the onset response to blocking stimulation was similar for all electrodes. Amplitude thresholds for the block were lowest for the Case Spiral electrode (4 ± 1 Vpp) and lower for the nerve cuff electrodes (7 ± 3 Vpp) than for the intramuscular electrode (26 ± 10 Vpp). A minor elevation in stimulation threshold and reduction in stimulus-evoked urethral pressure was observed during testing, but the effect was temporary and did not vary between electrodes. Significance. Multiple clinical electrodes appear suitable for neuroprostheses using peripheral nerve electrical block. The freedom to choose electrodes based on secondary criteria such as ease of implantation or cost should ease translation of electrical nerve block to clinical practice.

  16. Identification of Synergistic, Clinically Achievable, Combination Therapies for Osteosarcoma

    PubMed Central

    Yu, Diana; Kahen, Elliot; Cubitt, Christopher L.; McGuire, Jeremy; Kreahling, Jenny; Lee, Jae; Altiok, Soner; Lynch, Conor C.; Sullivan, Daniel M.; Reed, Damon R.

    2015-01-01

    Systemic therapy has improved osteosarcoma event-free and overall survival, but 30–50% of patients originally diagnosed will have progressive or recurrent disease, which is difficult to cure. Osteosarcoma has a complex karyotype, with loss of p53 in the vast majority of cases and an absence of recurrent, targetable pathways. In this study, we explored 54 agents that are clinically approved for other oncologic indications, agents in active clinical development, and others with promising preclinical data in osteosarcoma at clinically achievable concentrations in 5 osteosarcoma cell lines. We found significant single-agent activity of multiple agents and tested 10 drugs in all permutations of two-drug combinations to define synergistic combinations by Chou and Talalay analysis. We then evaluated order of addition to choose the combinations that may be best to translate to the clinic. We conclude that the repurposing of chemotherapeutics in osteosarcoma by using an in vitro system may define novel drug combinations with significant in vivo activity. In particular, combinations of proteasome inhibitors with histone deacetylase inhibitors and ixabepilone and MK1775 demonstrated excellent activity in our assays. PMID:26601688

  17. Outcomes of pharmacological management of nocturia with non-antidiuretic agents: does statistically significant equal clinically significant?

    PubMed

    Smith, Ariana L; Wein, Alan J

    2011-05-01

    To evaluate the statistical and clinical efficacy of the pharmacological treatments of nocturia using non-antidiuretic agents. A literature review of treatments of nocturia specifically addressing the impact of alpha blockers, 5-alpha reductase inhibitors (5ARI) and antimuscarinics on reduction in nocturnal voids. Despite commonly reported statistically significant results, nocturia has shown a poor clinical response to traditional therapies for benign prostatic hyperplasia including alpha blockers and 5ARI. Similarly, nocturia has shown a poor clinical response to traditional therapies for overactive bladder including antimuscarinics. Statistical success has been achieved in some groups with a variety of alpha blockers and antimuscarinic agents, but the clinical significance of these changes is doubtful. It is likely that other types of therapy will need to be employed in order to achieve a clinically significant reduction in nocturia. PMID:21518417

  18. Variability in Clinical Integration Achieved by Athletic Training Students across Different Clinical Sport Assignments

    ERIC Educational Resources Information Center

    Dodge, Thomas M.; Mazerolle, Stephanie M.; Bowman, Thomas G.

    2015-01-01

    Context: Clinical integration impacts athletic training students' (ATSs) motivation and persistence. Research has yet to elucidate the manner in which different clinical placements can influence clinical integration. Objective: To examine differences in the levels of clinical integration achieved by ATSs across various clinical sport assignments.…

  19. Assessing clinical significance of treatment outcomes using the DASS-21.

    PubMed

    Ronk, Fiona R; Korman, James R; Hooke, Geoffrey R; Page, Andrew C

    2013-12-01

    Standard clinical significance classifications are based on movement between the "dysfunctional" and "functional" distributions; however, this dichotomy ignores heterogeneity within the "dysfunctional" population. Based on the methodology described by Tingey, Lambert, Burlingame, and Hansen (1996), the present study sought to present a 3-distribution clinical significance model for the 21-item version of the Depression Anxiety Stress Scales (DASS-21; P. F. Lovibond & Lovibond, 1995) using data from a normative sample (n = 2,914), an outpatient sample (n = 1,000), and an inpatient sample (n = 3,964). DASS-21 scores were collected at pre- and post-treatment for both clinical samples, and patients were classified into 1 of 5 categories based on whether they had made a reliable change and whether they had moved into a different functional range. Evidence supported the validity of the 3-distribution model for the DASS-21, since inpatients who were classified as making a clinically significant change showed lower symptom severity, higher perceived quality of life, and higher clinician-rated functioning than those who did not make a clinically significant change. Importantly, results suggest that the new category of recovering is an intermediate point between recovered and making no clinically significant change. Inpatients and outpatients have different treatment goals and therefore use of the concept of clinical significance needs to acknowledge differences in what constitutes a meaningful change. PMID:23730826

  20. Clinical and biological significance of aneuploidy in human tumours.

    PubMed Central

    Friedlander, M L; Hedley, D W; Taylor, I W

    1984-01-01

    Aneuploidy is a well recognised feature of human tumours, but the investigation of its biological and clinical significance has been hampered by technological constraints. Quantitative DNA analysis reflects the total chromosomal content of tumour cells and can now be determined rapidly and reliably using flow cytometry; this has resulted in renewed interest in its potential clinical applications. This article reviews the accumulating evidence that tumour ploidy reflects the biological behaviour of a large number of tumour types and that diploid tumours in particular have a relatively good prognosis. The measurement of tumour ploidy is likely to become a valuable adjunct to the clinical and histopathological assessment of cancers. PMID:6381555

  1. Reversible mechanisms of enzyme inhibition and resulting clinical significance.

    PubMed

    Ring, Barbara; Wrighton, Steven A; Mohutsky, Michael

    2014-01-01

    Inhibition of a drug-metabolizing enzyme by the reversible interaction of a drug with the enzyme, thus decreasing the metabolism of another drug, is a major cause of clinically significant drug-drug interactions. This chapter defines the four reversible mechanisms of inhibition exhibited by drugs: competitive, noncompetitive, uncompetitive, and mixed competitive/noncompetitive. An in vitro procedure to determine the potential of a drug to be a reversible inhibitor is also provided. Finally, a number of examples of clinically significant drug-drug interactions resulting from reversible inhibition are described. PMID:24523108

  2. Improving International Research with Clinical Specimens: 5 Achievable Objectives

    PubMed Central

    LaBaer, Joshua

    2012-01-01

    Our increased interest in translational research has created a large demand for blood, tissue and other clinical samples, which find use in a broad variety of research including genomics, proteomics, and metabolomics. Hundreds of millions of dollars have been invested internationally on the collection, storage and distribution of samples. Nevertheless, many researchers complain in frustration about their inability to obtain relevant and/or useful samples for their research. Lack of access to samples, poor condition of samples, and unavailability of appropriate control samples have slowed our progress in the study of diseases and biomarkers. In this editorial, I focus on five major challenges that thwart clinical sample use for translational research and propose near term objectives to address them. They include: (1) defining our biobanking needs; (2) increasing the use of and access to standard operating procedures; (3) mapping inter-observer differences for use in normalizing diagnoses; (4) identifying natural internal protein controls; and (5) redefining the clinical sample paradigm by building partnerships with the public. In each case, I believe that we have the tools at hand required to achieve the objective within 5 years. Potential paths to achieve these objectives are explored. However we solve these problems, the future of proteomics depends on access to high quality clinical samples, collected under standardized conditions, accurately annotated and shared under conditions that promote the research we need to do. PMID:22998582

  3. Achieving clinical equality in an influenza pandemic: patent realities.

    PubMed

    Kane, Eileen M

    2009-01-01

    A twenty-first century novel influenza A (H1N1) pandemic is currently unfolding, and the eventual scope of this public health crisis is not clear. In addition, ongoing surveillance of the avian influenza A (H5N1) virus reveals outbreaks of human-to-human transmission of the virus, with significant mortality. Effective pandemic management depends on pharmaceutical intervention with two different clinical objectives: the generation of an immune response to specific viral strains (vaccination) and the reduction of viral replication in an infected individual (antiviral administration). The ability to offer pharmaceutical interventions for a public health crisis depends on three factors: development, capacity, and access. Pharmaceutical measures must be developed, capacity must be established, and access must be ensured. The article discusses the three nodes of patenting that influence the availability of pharmaceutical countermeasures in an influenza pandemic. Identification of the causative influenza virus is the first step in pandemic management and precedes vaccine design, and the virus and its RNA sequence are both knowledge assets and inputs for vaccine design. Vaccine development, therefore, will be influenced by any patents on the genetic sequences or proteins of the pandemic virus, as well as on novel methods for vaccine production, the actual vaccine or adjuvant technology, all of which are relevant to the assembly of a working vaccine on short notice. Pharmaceutical treatment of influenza infection during a pandemic could also rely on use of patented antiviral drugs, whose efficacy may be revealed as the pandemic unfolds. Unlike vaccines, these are not generally developed de novo for a pandemic, but their availability could be dependent on the exercise of patent rights by market incumbents. Patent rights could control capacity, which may determine access. Pandemic planning must consider how patenting can influence development, capacity and access to

  4. Assessing Clinical Significance: Does it Matter which Method we Use?

    ERIC Educational Resources Information Center

    Atkins, David C.; Bedics, Jamie D.; Mcglinchey, Joseph B.; Beauchaine, Theodore P.

    2005-01-01

    Measures of clinical significance are frequently used to evaluate client change during therapy. Several alternatives to the original method devised by N. S. Jacobson, W. C. Follette, & D. Revenstorf (1984) have been proposed, each purporting to increase accuracy. However, researchers have had little systematic guidance in choosing among…

  5. Clinical Significance of Mycobacterium kansasii Isolates from Respiratory Specimens

    PubMed Central

    Jeon, Kyeongman; Kim, Su-Young; Chung, Myung Jin; Huh, Hee Jae; Ki, Chang-Seok; Lee, Nam Yong; Shin, Sung Jae; Koh, Won-Jung

    2015-01-01

    The clinical significance of Mycobacterium kansasii respiratory isolates is uncertain. The aims of this study were to determine the clinical relevance of M. kansasii isolates and to identify the clinical features and outcomes of M. kansasii lung disease. We reviewed the medical records of 104 patients from whom at least one respiratory M. kansasii isolate was obtained from January 2003 to July 2014 at Samsung Medical Center, South Korea. Of these 104 patients, 54 (52%) met the diagnostic criteria for nontuberculous mycobacterial lung disease; among them, 41 (76%) patients received antibiotic treatment for a median time of 15.0 months (interquartile range [IQR], 7.0–18.0 months). The remaining 13 (24%) without overt disease progression were observed for a median period of 24.0 months (IQR, 5.0–34.5 months). Patients with M. kansasii lung disease exhibited various radiographic findings of lung disease, including the fibrocavitary form (n = 24, 44%), the nodular bronchiectatic form (n = 17, 32%), and an unclassifiable form (n = 13, 24%). The fibrocavitary form was more common in patients who received treatment (n = 23, 56%), while the nodular bronchiectatic form was more common in patients with M. kansasii lung disease who did not receive treatment (n = 9, 70%). None of the patients with a single sputum isolate (n = 18) developed M. kansasii disease over a median follow-up period of 12.0 months (IQR, 4.0–26.5 months). In total, 52% of all patients with M. kansasii respiratory isolates exhibited clinically significant disease. Moreover, patients with M. kansasii lung disease displayed diverse radiographic findings in addition to the fibrocavitary form. The nodular bronchiectatic form was more common in patients with M. kansasii lung disease with an indolent clinical course. Thus, since the clinical significance of a single M. kansasii respiratory isolate is not definite, strict adherence to recommended diagnostic criteria is advised. PMID:26431540

  6. Bilateral Chondroepitrochlearis Muscle: Case Report, Phylogenetic Analysis, and Clinical Significance.

    PubMed

    Palagama, Sujeewa P W; Tedman, Raymond A; Barton, Matthew J; Forwood, Mark R

    2016-01-01

    Anomalous muscular variants of pectoralis major have been reported on several occasions in the medical literature. Among them, chondroepitrochlearis is one of the rarest. Therefore, this study aims to provide a comprehensive description of its anatomy and subsequent clinical significance, along with its phylogenetic importance in pectoral muscle evolution with regard to primate posture. The authors suggest a more appropriate name to better reflect its proximal attachment to the costochondral junction and distal attachment to the epicondyle of humerus, as "chondroepicondylaris"; in addition, we suggest a new theory of phylogenetic significance to explain the twisting of pectoralis major tendon in primates that may have occurred with their adoption to bipedalism and arboreal lifestyle. Finally, the clinical significance of this aberrant muscle is elaborated as a cause of potential neurovascular entrapment and as a possible hurdle during axillary surgeries (i.e., mastectomy). PMID:27242928

  7. Bilateral Chondroepitrochlearis Muscle: Case Report, Phylogenetic Analysis, and Clinical Significance

    PubMed Central

    Palagama, Sujeewa P. W.; Tedman, Raymond A.; Barton, Matthew J.; Forwood, Mark R.

    2016-01-01

    Anomalous muscular variants of pectoralis major have been reported on several occasions in the medical literature. Among them, chondroepitrochlearis is one of the rarest. Therefore, this study aims to provide a comprehensive description of its anatomy and subsequent clinical significance, along with its phylogenetic importance in pectoral muscle evolution with regard to primate posture. The authors suggest a more appropriate name to better reflect its proximal attachment to the costochondral junction and distal attachment to the epicondyle of humerus, as “chondroepicondylaris”; in addition, we suggest a new theory of phylogenetic significance to explain the twisting of pectoralis major tendon in primates that may have occurred with their adoption to bipedalism and arboreal lifestyle. Finally, the clinical significance of this aberrant muscle is elaborated as a cause of potential neurovascular entrapment and as a possible hurdle during axillary surgeries (i.e., mastectomy). PMID:27242928

  8. Meconium in perinatal imaging: associations and clinical significance.

    PubMed

    Jerdee, Theodore; Newman, Beverley; Rubesova, Erika

    2015-04-01

    An abnormal location, distribution, volume, or appearance of meconium is associated with a spectrum of bowel abnormalities, including atresia, obstruction, perforation, fistula, aganglionosis, immaturity, and absorptive dysfunction. This review discusses the fetal and perinatal imaging of these entities, their differential diagnoses, clinical significance, and appropriate imaging workup. Understanding the spectrum of normal and abnormal, specific and nonspecific appearances of meconium and its associated abnormalities on imaging will provide a practical, useful framework for performing and interpreting imaging studies and guiding clinical management. PMID:26001945

  9. Emerging Bacterial Infection: Identification and Clinical Significance of Kocuria Species

    PubMed Central

    Palange, Padmavali; Vaish, Ritu; Bhatti, Adnan Bashir; Kale, Vinod; Kandi, Maheshwar Reddy; Bhoomagiri, Mohan Rao

    2016-01-01

    Recently there have been reports of gram-positive cocci which are morphologically similar to both Staphylococci and the Micrococci. These bacteria have been identified as Kocuria species with the help of automated identification system and other molecular methods including 16S rRNA (ribosomal ribonucleic acid) evaluation. Kocuria belongs to the family Micrococcaceae which also includes Staphylococcus species and Micrococcus species. Isolation and clinical significance of these bacteria from human specimens warrant great caution as it does not necessarily confirm infection due to their ubiquitous presence, and as a normal flora of skin and mucous membranes in human and animals. Most clinical microbiology laboratories ignore such bacteria as laboratory and specimen contaminants. With increasing reports of infections associated with these bacteria, it is now important for clinical microbiologists to identify and enumerate the virulence and antibiotic susceptibility patterns of such bacteria and assist clinicians in improving the patient care and management. We review the occurrence and clinical significance of Kocuria species.

  10. Clinical Significance of Endothelial Dysfunction in Essential Hypertension.

    PubMed

    Gkaliagkousi, Eugenia; Gavriilaki, Eleni; Triantafyllou, Areti; Douma, Stella

    2015-11-01

    The endothelium is recognized as a major determinant of vascular physiology and pathophysiology. Over the last few decades, a plethora of studies have implicated endothelial dysfunction in the progression of atherosclerosis and the subclinical target organ damage observed in essential hypertension. However, the clinical significance of diagnosing endothelial dysfunction in patients with essential hypertension remains under investigation. Although a number of vascular and non-vascular markers of endothelial dysfunction have been proposed, there is an ongoing quest for a marker in the clinical setting that is optimal, inexpensive, and reproducible. In addition, endothelial dysfunction emerges as a promising therapeutic target of agents that are readily available in clinical practice. In this context, a better understanding of its role in essential hypertension becomes of great importance. Here, we aim to investigate the clinical significance of endothelial dysfunction in essential hypertension by accumulating novel data on (a) early diagnosis using robust markers with prognostic value in cardiovascular risk prediction, (b) the association of endothelial dysfunction with subclinical vascular organ damage, and (c) potential therapeutic targets. PMID:26371063

  11. Prevalence and clinical significance of rare antinuclear antibody patterns.

    PubMed

    Vermeersch, Pieter; Bossuyt, Xavier

    2013-08-01

    While some of the more frequent antinuclear (auto)antibodies (ANA) patterns such as homogenous nuclear staining have been extensively studied, the prevalence and clinical significance of rare antinuclear antibody patterns are not well understood. For the purpose of this review, we defined rare patterns as patterns occurring in less than 1% of patients that test positive on indirect immunofluorescence. The prevalence of different ANA patterns was determined in 68,128 consecutive patients who attended the outpatient clinic or were hospitalized at the University Hospitals Leuven over a 14-year period (1998-2011). To avoid bias, we only included the first sample for each patient and patients who tested positive in the period 1980-1997 were excluded. There were 9268 patients who tested positive for ANA. With the exception of the clinical association of anti-multiple nuclear dots (at higher titers) and anti-nuclear envelope autoantibodies with autoimmune liver disease, there was no good clinical association of rare ANA patterns with the diagnosis of auto-immune disorders. The most important non-autoimmune cause of rare ANA patterns was carcinoma, particularly in patients with rare cell-cycle related ANAs. PMID:23583982

  12. Clinical significance in COPD patients followed in a real practice

    PubMed Central

    2013-01-01

    Background Chronic obstructive pulmonary disease (COPD) is an important public health issue in many countries which is estimated to become the fifth cause of disability and the third cause of mortality in the world within 2020. The objective of this study was to identify the clinical characteristics in the real clinical practice of a sample of patients with COPD followed in a pulmonology clinic. Methods The initial sample contained 207 subjects with respiratory claims that searched for specialized treatment and initiated regular monitoring between 2004 and 2009 in a private clinic localized in Cascavel, in the state of Parana, Brazil. Demographic data (weight, height, body mass index - BMI), history of comorbidities, use of respiratory and non respiratory drugs were also registered. Results The main cause related to the development of COPD was current or prior smoking (92.0%); the most frequently reported symptom was dyspnea (95.0%), followed by cough (86.1%), wheezing (69.4%) and sputum production (40.0%). During the follow up, 51 patients developed the need for oxygen therapy (28.3%). In 96 patients, there were periods of acute exacerbation, resulting in 37 hospitalizations. In addition to COPD, a significant number of comorbidities were identified, being cardiovascular disease and neurological disorders the most prevalent ones. Conclusions Based on the data collected, we could outline the profile of patients with COPD, showing characteristics of an elderly population, with multiple comorbidities, suggesting a health related quality of life lower than expected. PMID:23806051

  13. Clinical significance of lymph node micrometastasis in gastric cancer.

    PubMed

    Arigami, Takaaki; Uenosono, Yoshikazu; Yanagita, Shigehiro; Nakajo, Akihiro; Ishigami, Sumiya; Okumura, Hiroshi; Kijima, Yuko; Ueno, Shinichi; Natsugoe, Shoji

    2013-02-01

    Recently, the existence of lymph node micrometastasis (LNM), including isolated tumor cells, has been focused on during the development of molecular diagnostic tools for lymph node metastasis in various malignant neoplasms. In particular, immunohistochemistry and reverse transcription-polymerase chain reaction have been reported to be available for the detection of LNM in gastric cancer. However, at present, the clinical significance of LNM remains unclear in patients with gastric cancer. Therefore, we cannot strategically make light of this issue in clinical management. Currently, minimally invasive treatments, such as endoscopic submucosal dissection and laparoscopic surgery with personalized lymphadenectomy, are widely performed in consideration of postsurgical quality of life (QOL). However, it is important to maintain the balance between QOL and curability when selecting surgical treatments for patients with gastric cancer. If minimally invasive surgery based on LNM status was established for patients with early gastric cancer, it could be performed safely. We reviewed the clinical significance of LNM as an important strategic target in patients with gastric cancer. PMID:22546997

  14. Clinical significance of TIPE expression in gastric carcinoma

    PubMed Central

    Hu, Ruyi; Qiu, Xingfeng; Hong, Shifu; Meng, Luxi; Hong, Xinya; Qiu, Jinhua; Yang, Jingjing; Zhuang, Guohong; Liu, Zhongchen

    2016-01-01

    Background TNFAIP8, also known as TIPE, is a suppressor of apoptosis. High expression of both TIPE mRNA and protein has been detected in various cancer cell lines and clinical specimens compared to healthy tissues. Many reports have shown that there is a strong correlation between TIPE overexpression and cancer progression and poor prognosis in human solid cancers. Methods To illustrate the functional and clinical significance of TIPE in gastric cancer, we used reverse transcription polymerase chain reaction, quantitative real-time polymerase chain reaction, and immunohistochemistry to measure TIPE expression in clinical gastric specimens. Then, TIPE expression was knocked down by using shRNA and anti-DR5ScFv, to examine different expressions of TIPE in BGC823 cell lines, while cell proliferation and apoptosis were induced. Results We found that there was a strong correlation between TIPE expression and TNM stage (P=0.044), tumor depth (P=0.016), lymph node metastasis (P=0.026), and distant metastasis (P=0.045). No significant correlation was found between TIPE expression with the patients’ age (P=0.062) or sex (P=0.459). Anti-DR5ScFv induced TIPE depletion both in vitro and in vivo and resulted in apoptosis and suppression of proliferation. Conclusion Our results suggested that TIPE expression was associated with gastric cancer progression, and most importantly, suppressing TIPE expression might be an effective therapeutic strategy. PMID:27524904

  15. Lack of clinically significant drug interactions between nevirapine and buprenorphine.

    PubMed

    McCance-Katz, Elinore F; Moody, David E; Morse, Gene D; Ma, Qing; Rainey, Petrie M

    2010-01-01

    This study was conducted to determine whether drug interactions of clinical importance occur between buprenorphine, an opioid partial agonist medication used in treatment of opioid dependence, and the nonnucleoside reverse transcriptase inhibitor (NNRTI) nevirapine. Opioid-dependent, buprenorphine/naloxone-maintained, HIV-negative volunteers (n = 7) participated in 24-hour sessions to determine the pharmacokinetics of buprenorphine alone and of buprenorphine and nevirapine following administration of 200 mg nevirapine daily for 15 days. Opiate withdrawal symptoms, cognitive effects, and adverse events were determined prior to and following nevirapine administration. Modest decreases were observed for AUC for buprenorphine and its metabolites. There was a trend for more rapid clearance of both buprenorphine (p = .08) and buprenorphine-3-glucuronide (p = .08). While no single effect reached statistical significance, the joint probability that the consistent declines in all measures of exposure were due to chance was extremely low, indicating that nevirapine significantly reduces overall exposure to buprenorphine and buprenorphine metabolites. Clinically significant consequences of the interaction were not observed. Buprenorphine did not alter nevirapine pharmacokinetics. Dose adjustments of either buprenorphine or nevirapine are not likely to be necessary when these drugs are coadministered for the treatment of opiate dependence and HIV disease. PMID:20132119

  16. Clinical significance of pharmacokinetic interactions between antiepileptic and psychotropic drugs.

    PubMed

    Spina, Edoardo; Perucca, Emilio

    2002-01-01

    As antiepileptic drugs (AEDs) and psychotropic agents are increasingly used in combination, the possibility of pharmacokinetic interactions between these compounds is relatively common. Most pharmacokinetic interactions between AEDs and psychoactive drugs occur at a metabolic level, and usually involve changes in the activity of the cytochrome P450 mixed-function oxidases (CYP) involved in their biotransformation. As a consequence of CYP inhibition or induction, plasma concentrations of a given drug may reach toxic or subtherapeutic levels, and dosage adjustments may be required to avoid adverse effects or clinical failure. Enzyme-inducing AEDs, such as carbamazepine (CBZ), phenytoin (PHT), and barbiturates, stimulate the oxidative biotransformation of many concurrently prescribed psychotropics. In particular, these AEDs may decrease the plasma concentrations of tricyclic antidepressants, many antipsychotics, including traditional compounds, i.e., haloperidol and chlorpromazine, and newer agents, i.e., clozapine, risperidone, olanzapine, quetiapine, and ziprasidone, and some benzodiazepines. Conversely, new AEDs appear to have a lower potential for interactions with all psychotropic drugs. While antipsychotics and anxiolytics do not significantly influence the pharmacokinetics of most AEDs, some newer antidepressants, such as viloxazine, fluoxetine, and fluvoxamine, may lead to higher serum levels of some AEDs, namely CBZ and PHT, through inhibition of CYP enzymes. No significant pharmacokinetic interactions have been documented between AEDs and lithium. Information about CYP enzymes responsible for the biotransformation of individual agents and about the effects of these compounds on the activity of specific CYP enzymes may help in predicting and avoiding clinically significant interactions. Apart from careful clinical observation, serum level monitoring of AEDs and psychotropic drugs can be useful in determining the need for dosage adjustments, especially if

  17. The Prostate Health Index Selectively Identifies Clinically Significant Prostate Cancer

    PubMed Central

    Loeb, Stacy; Sanda, Martin G.; Broyles, Dennis L.; Shin, Sanghyuk S.; Bangma, Chris H.; Wei, John T.; Partin, Alan W.; Klee, George G.; Slawin, Kevin M.; Marks, Leonard S.; van Schaik, Ron H. N.; Chan, Daniel W.; Sokoll, Lori J.; Cruz, Amabelle B.; Mizrahi, Isaac A.; Catalona, William J.

    2015-01-01

    Purpose The Prostate Health Index (phi) is a new test combining total, free and [-2]proPSA into a single score. It was recently approved by the FDA and is now commercially available in the U.S., Europe and Australia. We investigate whether phi improves specificity for detecting clinically significant prostate cancer and can help reduce prostate cancer over diagnosis. Materials and Methods From a multicenter prospective trial we identified 658 men age 50 years or older with prostate specific antigen 4 to 10 ng/ml and normal digital rectal examination who underwent prostate biopsy. In this population we compared the performance of prostate specific antigen, % free prostate specific antigen, [-2]proPSA and phi to predict biopsy results and, specifically, the presence of clinically significant prostate cancer using multiple criteria. Results The Prostate Health Index was significantly higher in men with Gleason 7 or greater and “Epstein significant” cancer. On receiver operating characteristic analysis phi had the highest AUC for overall cancer (AUCs phi 0.708, percent free prostate specific antigen 0.648, [-2]proPSA 0.550 and prostate specific antigen 0.516), Gleason 7 or greater (AUCs phi 0.707, percent free prostate specific antigen 0.661, [-2]proPSA 0.558, prostate specific antigen 0.551) and significant cancer (AUCs phi 0.698, percent free prostate specific antigen 0.654, [-2]proPSA 0.550, prostate specific antigen 0.549). At the 90% sensitivity cut point for phi (a score less than 28.6) 30.1% of patients could have been spared an unnecessary biopsy for benign disease or insignificant prostate cancer compared to 21.7% using percent free prostate specific antigen. Conclusions The new phi test outperforms its individual components of total, free and [-2]proPSA for the identification of clinically significant prostate cancer. Phi may be useful as part of a multivariable approach to reduce prostate biopsies and over diagnosis. PMID:25463993

  18. Clinical significance and prevalence of Blastocystis hominis in Van, Turkey

    PubMed Central

    Beyhan, Yunus E.; Yilmaz, Hasan; Cengiz, Zeynep T.; Ekici, Abdurrahman

    2015-01-01

    Objectives: To determine the associated clinical symptoms and prevalence of Blastocystis hominis (B. hominis). Methods: Stool samples of 50,185 patients (26,784 males and 23,401 females) who were received at the Parasitology Laboratory of Yuzuncu Yil University Faculty of Medicine, Van, Turkey in the last 5 years were inspected microscopically using saline and iodine-stained wet-mount preparations. Age, gender, and symptoms of patients were recorded and their significance was evaluated. Results: The prevalence of B. hominis in the total sample was 0.54% (275/50185). Out of 275 infected patients, 143 (52%) were males, and 132 (48%) were female (χ2=0.884; p=0.348). The distribution of B. hominis infection was high in 7-13 aged children (34.9%) (χ2=306.8; p=0.001). Blastocystis was higher among symptomatic patients (70.2%) compared with asymptomatic patients (29.8%) (χ2=107.13; p=0.001). The most frequent clinical symptoms associated with the disease were abdominal pain (27.3%) and diarrhea (19.6%) followed by anorexia, fever, saliva, anal itching, and nausea. Conclusion: Blastocystis hominis is considered a causative agent of human disease in patients with recurrent symptoms. Due to the significant risk for zoonotic transmission, molecular techniques must be used to determine the route and source of infection. PMID:26318472

  19. Macroscopic serosal classification of colorectal cancer and its clinical significance

    PubMed Central

    Wang, Yong-Peng; Guo, Peng-Tao; Zhu, Zhi; Zhang, Hao; Xu, Yan; Ma, Si-Ping; Wang, Zhen-Ning; Xu, Hui-Mian

    2015-01-01

    Background: Macroscopic serosal classification of gastric cancer has been reported in previous studies, but rarely reported about it of colorectal cancer. The purpose of this study was to propose a macroscopic serosal classification of colorectal cancer and to investigate clinical significance of this classification. Materials and methods: Morphologic features of colorectal cancer were analyzed according to the macroscopic serosal appearance and clinicopathologic characteristics of these patients were retrospectively reviewed. Microscopic serosal structure was compared between different types under light microscope and transmission electron microscope. Results: Macroscopic serosal classification was divided into normal type, reactive type, nodular type and colloid type according to the macroscopic serosal appearance and microscopic structure. There were significant differences in tumor size, tumor gross type, histological type, histological grade, tumor necrosis, pT stage, number of nodes metastasis, lymph node metastasis ratio, pN stage, M stage and peritoneal metastasis between patients with different serosal types. Univariate analysis of prognosis revealed macroscopic serosal classification as one of factors significantly correlated with patient survival. However, multivariate analysis only revealed TNM stage significantly correlated with patient survival, while macroscopic serosal classification did not, maybe due to insufficient samples. Conclusions: Macroscopic serosal classification of colorectal cancer is preliminarily defined and divided into four types. Different macroscopic serosal types indicate different clinicopathologic features and correlate with prognosis of patients with colorectal cancer, but still cannot be proven as an independent factor. PMID:26884925

  20. Expression and clinical significance of Nectin-4 in hepatocellular carcinoma

    PubMed Central

    Ma, Jie; Sheng, ZhiYong; Lv, Yang; Liu, WenBin; Yao, QiYang; Pan, TingTing; Xu, ZhiJun; Zhang, ChuanHai; Xu, GeLiang

    2016-01-01

    Objective Nectin-4 is a member of the Nectin family of four Ca+-independent immunoglobulin-like cell adhesion molecules and implicated in cell adhesion, movement, proliferation, differentiation, polarization, and survival. The aberrant expression of Nectin-4 has been found in a variety of tumors; however, its expression in hepatocellular carcinoma (HCC) is still poorly understood. This study was to investigate the expression of Nectin-4 and its clinical significance in the patients with HCC. Methods The expression of Nectin-4 was assessed at mRNA and protein levels by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting assays in 20 HCC specimens and adjacent non-tumor live tissues. Furthermore, the clinical significance of Nectin-4 in 87 cases of HCC was confirmed by immunohistochemistry. Results The mRNA and protein levels of Nectin-4 were higher in HCC tumor tissues than in the matched non-tumor tissues. Nectin-4 was located in the cytoplasm of tumor cells and over-expressed in 67.82% (59/87) HCC tissues by immunohistochemical staining. Positive Nectin-4 expression was significantly correlated with tumor size (P=0.029), status of metastasis (P=0.023), vascular invasion (P=0.018) and tumor-node-metastasis stage (P=0.003). In addition, Kaplan–Meier survival analysis indicated that positive Nectin-4 expression was associated with worse recurrence-free survival (RFS) and overall survival (OS) (P=0.006 and P=0.005, respectively). In multivariate analysis, Nectin-4 was an independent prognostic factor for RFS and OS in the patients with HCC. Conclusion Nectin-4 is upregulated in HCC and may be a novel prognostic biomarker for the patients after surgical resection. PMID:26793002

  1. Clinical significance of computed tomography assessment for third molar surgery.

    PubMed

    Nakamori, Kenji; Tomihara, Kei; Noguchi, Makoto

    2014-07-28

    Surgical extraction of the third molar is the most commonly performed surgical procedure in the clinical practice of oral surgery. Third molar surgery is warranted when there is inadequate space for eruption, malpositioning, or risk for cyst or odontogenic tumor formation. Preoperative assessment should include a detailed morphologic analysis of the third molar and its relationship to adjacent structures and surrounding tissues. Due to developments in medical engineering technology, computed tomography (CT) now plays a critical role in providing the clear images required for adequate assessment prior to third molar surgery. Removal of the maxillary third molar is associated with a risk for maxillary sinus perforation, whereas removal of the mandibular third molar can put patients at risk for a neurosensory deficit from damage to the lingual nerve or inferior alveolar nerve. Multiple factors, including demographic, anatomic, and treatment-related factors, influence the incidence of nerve injury during or following removal of the third molar. CT assessment of the third molar prior to surgery can identify some of these risk factors, such as the absence of cortication between the mandibular third molar and the inferior alveolar canal, prior to surgery to reduce the risk for nerve damage. This topic highlight presents an overview of the clinical significance of CT assessment in third molar surgery. PMID:25071882

  2. Clinical significance of computed tomography assessment for third molar surgery

    PubMed Central

    Nakamori, Kenji; Tomihara, Kei; Noguchi, Makoto

    2014-01-01

    Surgical extraction of the third molar is the most commonly performed surgical procedure in the clinical practice of oral surgery. Third molar surgery is warranted when there is inadequate space for eruption, malpositioning, or risk for cyst or odontogenic tumor formation. Preoperative assessment should include a detailed morphologic analysis of the third molar and its relationship to adjacent structures and surrounding tissues. Due to developments in medical engineering technology, computed tomography (CT) now plays a critical role in providing the clear images required for adequate assessment prior to third molar surgery. Removal of the maxillary third molar is associated with a risk for maxillary sinus perforation, whereas removal of the mandibular third molar can put patients at risk for a neurosensory deficit from damage to the lingual nerve or inferior alveolar nerve. Multiple factors, including demographic, anatomic, and treatment-related factors, influence the incidence of nerve injury during or following removal of the third molar. CT assessment of the third molar prior to surgery can identify some of these risk factors, such as the absence of cortication between the mandibular third molar and the inferior alveolar canal, prior to surgery to reduce the risk for nerve damage. This topic highlight presents an overview of the clinical significance of CT assessment in third molar surgery. PMID:25071882

  3. Clinical significance of Aeromonas species isolated from patients with diarrhea.

    PubMed Central

    Moyer, N P

    1987-01-01

    A total of 248 strains of Aeromonas spp. were isolated from 3,334 human fecal specimens submitted to a state public health laboratory over a 2-year period to be cultured for enteric pathogens. Cary-Blair transport medium, blood ampicillin agar, and alkaline peptone water enrichment provided optimal recovery of Aeromonas spp. A questionnaire requesting clinical and epidemiological information was sent to physicians, who submitted stool samples for testing, with each laboratory report for 107 consecutive stool isolates of Aeromonas spp. The 56 questionnaires which were completed and returned were analyzed to determine the seasonal distribution of illness and the age and sex distribution of patients; characteristic symptoms; and predisposing factors for gastrointestinal disease caused by Aeromonas spp. It was concluded that some A. hydrophila, A. sobria, and A. caviae strains are capable of causing diarrhea and that antibiotic therapy and the drinking of untreated water are significant risk factors for susceptible hosts. PMID:3693537

  4. Imaging assessment and clinical significance of pneumatosis in adult patients.

    PubMed

    Lassandro, Francesco; Valente, Tullio; Rea, Gaetano; Lassandro, Giulia; Golia, Erica; Brunese, Luca; Laghi, Andrea

    2015-01-01

    Gas detection in the bowel wall and in portomesenteric venous vessels in adults has long been related to intestinal infarction and poor outcome; many case reports have shown that pneumatosis may be associated with a large variety of pathological situations, ranging from absolutely benign and asymptomatic forms to abdominal catastrophes. Several studies have been conducted on this topic with different conclusions, probably due to differences in population so that the clinical value of these signs is still questioned. Intestinal pneumatosis, especially if presenting with a band-like pattern and if associated with portomesenteric vein gas, when observed in an acute abdominal setting should raise the suspicion of mesenteric infarct and prompt a careful search for other signs of intestinal involvement, so as not to miss cases of life-threatening intestinal infarct or allow them to further evolve into extensive necrosis with worse prognosis. In this review we illustrate the most relevant aspects of these debated but significant radiological signs. PMID:25297049

  5. Clinical significance of serum claudin-1 levels in melanoma patients.

    PubMed

    Tas, Faruk; Bilgin, Elif; Erturk, Kayhan; Duranyildiz, Derya

    2016-08-01

    Claudins are the most important structural and functional components of tight-junction integral membrane proteins. They play roles in major cellular functions including growth and adhesion and are responsible for regulating the paracellular transport of molecules. The objective of this study was to determine the clinical significance of the serum levels of claudin-1, an oldest and important member of the claudin family, in melanoma patients. A total of 98 patients with a pathologically confirmed melanoma were enrolled into this study. Serum claudin-1 concentrations were determined by the solid-phase sandwich enzyme-linked immunosorbent assay method. Age-matched and sex-matched 43 healthy controls were included in the analysis. The median age at diagnosis was 51 years, ranging from 16 to 85 years. The majority of the patients were male (61%) and had axial localized (54%) and metastatic disease (61%). Moreover, most of the patients with metastatic disease had M1c (73%). The baseline serum claudin-1 levels of the melanoma patients were significantly lower than those of control subjects (median values 9.17 vs. 13.82 ng/ml, respectively, P<0.001). However, known clinical variables including age of the patient, sex, site of lesion, histology, lymph node involvement, stage of disease, serum lactate dehydrogenase levels, and response to chemotherapy were not found to be correlated with serum claudin-1 concentrations (P>0.05). Similarly, serum claudin-1 concentration was found to have no prognostic role in survival (P=0.524). In conclusion, serum levels of claudin-1 may have a diagnostic value in melanoma patients. However, its predictive and prognostic value has not been determined. PMID:26886788

  6. Expression and clinical significance of aquaglyceroporins in human hepatocellular carcinoma.

    PubMed

    Chen, Xiao-Feng; Li, Chuan-Fei; Lü, Lin; Mei, Zhe-Chuan

    2016-06-01

    Aquaglyceroporins (AQPs) are a subset of the aquaporin family, and are permeable to water and glycerol. The aim of the present study was to determine the expression and clinical significance of three AQPs, AQP3, 7 and 9 in hepatocellular carcinoma (HCC). Fresh HCC and adjacent non‑tumorous liver tissues were collected from 68 patients diagnosed with HCC. The expression levels of AQP3, 7 and 9 were detected by reverse transcription‑quantitative polymerase chain reaction, western blotting and immunohistochemical analysis. The association between the expression of AQPs and clinicopathological parameters of HCC were investigated. Compared with non‑tumorous liver tissue, HCC tissues exhibited a significant (P<0.05) increase in the expression of AQP3 and a concomitant reduction in the expression levels of AQP7 and AQP9, at both the mRNA and protein levels. Immunohistochemistry revealed that AQP9 was dominantly localized on the plasma membrane of hepatocytes, while AQP3 and AQP7 exhibited a predominantly cytoplasmic and nuclear distribution. High expression of AQP3 was significantly (P<0.05) associated with low expression levels of AQP7 and AQP9. High expression of AQP3 was correlated with tumor grade (P=0.017), tumor stage (P=0.010) and lymphatic metastasis (P=0.031). Low expression of AQP7 was correlated with tumor grade (P=0.043). AQP3 was upregulated, and AQP7 and AQP9 were downregulated in HCC. A high expression of AQP3 and low expression of AQP7 was significantly associated with the aggressive features of HCC. PMID:27121567

  7. Clinical significance of giant negative T waves in hypertrophic cardiomyopathy

    SciTech Connect

    Alfonso, F.; Nihoyannopoulos, P.; Stewart, J.; Dickie, S.; Lemery, R.; McKenna, W.J. )

    1990-04-01

    To assess the clinical significance of giant negative T waves in patients with hypertrophic cardiomyopathy from Western nations, clinical, echocardiographic, radionuclide and 48 h electrocardiographic (ECG) monitoring findings were compared in 27 patients with and 56 patients without giant negative T waves. Patients with giant negative T waves were older at diagnosis (43 +/- 15 versus 32 +/- 14 years, p less than 0.005), had greater ECG voltage (SV1 + RV5 = 57 +/- 20 versus 37 +/- 18 mm, p less than 0.001) and had a more vertical frontal plane axis (38.4 +/- 34 versus 13.4 +/- 45 degrees, p less than 0.05). Left ventricular wall thickness on two-dimensional echocardiography was similar at the mitral valve level (mean 16.5 +/- 4 versus 16.6 +/- 3 cm), but was greater at the papillary muscle level (mean 20.7 +/- 5 versus 17.6 +/- 3 mm, p less than 0.01) and apex (mean 23.3 +/- 5 versus 17.3 +/- 3 mm, p less than 0.001) in patients with giant negative T waves. Fewer patients with giant negative T waves had asymmetric septal hypertrophy (12 (44%) of 27 versus 36 (64%) of 56, p = 0.08) or systolic anterior motion of the mitral valve (4 (14%) of 27 versus 25 (45%) of 56, p less than 0.01), whereas left ventricular end-diastolic (44.1 +/- 6 versus 39.6 +/- 5 mm, p = 0.01) and end-systolic dimensions (27.8 +/- 4 versus 24 +/- 6 mm, p less than 0.05) were greater in this group. Nonsustained ventricular tachycardia was seen on ECG monitoring in 21% of patients in both groups.

  8. The clinical significance of patients’ sex in chronic lymphocytic leukemia

    PubMed Central

    Catovsky, Daniel; Wade, Rachel; Else, Monica

    2014-01-01

    We examined the prognostic influence of gender in chronic lymphocytic leukemia. Data from four randomized trials (involving 1821 patients) and three registration studies of stage-A disease (involving 1299 patients) were analyzed. Overall survival at 10 years was better for women than men in all trials (27% versus 15%; P=0.0001) and in the registration series (55% versus 43%; P<0.0001). More women than men in the trials were Binet stage A-progressive (26% versus 15%), but gender was an independent predictor of survival in multivariate analysis of clinical variables (P<0.0001). Women responded better to treatment (overall response 83%) than men (71%; P<0.0001), within each stage and age group, although fewer women than men received the full treatment dose (79% versus 85%; P=0.01). Women were more likely than men to experience toxicity (85% versus 78%, P=0.01), particularly gastro-intestinal toxicity (57% versus 42%, P<0.0001). Laboratory markers in the LRF CLL4 trial showed a significantly lower incidence in women than men of unmutated IGHV genes, raised beta-2 microglobulin, CD38 and Zap-70 positivity and TP53 deletions/mutations and/or 11q deletions. We also highlight the higher male:female ratios in randomized trials versus studies of early chronic lymphocytic leukemia and monoclonal B-cell lymphocytosis. Chronic lymphocytic leukemia in women runs a more benign clinical course than in men. Gender was also an independent predictor of response, suggesting that pharmacokinetic differences between the sexes and a possible effect of estrogens may contribute to the better outcome. Understanding the reasons for the different outcome by gender may improve patients’ management. (LRF CLL4 controlled-trials.com identifier: ISRCTN58585610). PMID:24658818

  9. Clinical significance of circulating plasma DNA in gastric cancer.

    PubMed

    Fang, Wen-Liang; Lan, Yuan-Tzu; Huang, Kuo-Hung; Liu, Chien-An; Hung, Yi-Ping; Lin, Chien-Hsing; Jhang, Fang-Yu; Chang, Shih-Ching; Chen, Ming-Huang; Chao, Yee; Lin, Wen-Chang; Lo, Su-Shun; Fen-Yau Li, Anna; Wu, Chew-Wun; Chiou, Shih-Hwa; Shyr, Yi-Ming

    2016-06-15

    With the progression of molecular techniques, the detection of circulating plasma DNA (cpDNA) is clinically feasible. However, the role of the cpDNA levels in gastric cancer is not well understood. This study assessed the mutational profile in primary tumors and clarified the clinical utility of quantitative and qualitative cpDNA alterations in 277 patients with advanced gastric cancer. The concentrations of cpDNA were measured by TaqMan qPCR, and 68 mutations in 8 genes were studied for cpDNA mutations. The median cpDNA concentrations in patients with stages I, II, and III gastric cancer were 3979, 3390 and 4278 copies/mL, respectively, and increased to 11,380 copies/mL in patients with Stage IV gastric cancer (p < 0.001). Among the 35 patients harboring cpDNA mutations, Stage IV patients (100%) were more likely to display high cpDNA levels than were Stage I (33.3%), II (75%) and III patients (66.7%) (p = 0.037). Patients displaying high cpDNA levels were more likely to experience peritoneal recurrence and exhibited significantly lower 5-year overall survival rates (39.2% vs. 45.8%, p = 0.039) than did patients displaying low cpDNA levels. Only for late stage (Stages III or IV) gastric cancer, patients harboring cpDNA mutations were more likely to experience vascular invasion (20% vs. 2.4%, p = 0.036) and exhibited a lower 5-year overall survival rate than did those lacking cpDNA mutations (5.6% vs. 31.5%, p = 0.028). High cpDNA levels are associated with peritoneal recurrence and poor prognosis in patients with advanced gastric cancer; harboring cpDNA mutations is associated with poor prognosis among patients with late stage gastric cancer. PMID:26815009

  10. Clinical significance of metallothioneins in cell therapy and nanomedicine

    PubMed Central

    Sharma, Sushil; Rais, Afsha; Sandhu, Ranbir; Nel, Wynand; Ebadi, Manuchair

    2013-01-01

    Mammalian metallothioneins (MTs) are low molecular weight (6–7 kDa) cysteine-rich proteins that are specifically induced by metal nanoparticles (NPs). MT induction in cell therapy may provide better protection by serving as antioxidant, anti-inflammatory, antiapoptotic agents, and by augmenting zinc-mediated transcriptional regulation of genes involved in cell proliferation and differentiation. Liposome-encapsulated MT-1 promoter has been used extensively to induce growth hormone or other genes in culture and gene-manipulated animals. MTs are induced as a defensive mechanism in chronic inflammatory conditions including neurodegenerative diseases, cardiovascular diseases, cancer, and infections, hence can serve as early and sensitive biomarkers of environmental safety and effectiveness of newly developed NPs for clinical applications. Microarray analysis has indicated that MTs are significantly induced in drug resistant cancers and during radiation treatment. Nutritional stress and environmental toxins (eg, kainic acid and domoic acid) induce MTs and aggregation of multilamellar electron-dense membrane stacks (Charnoly body) due to mitochondrial degeneration. MTs enhance mitochondrial bioenergetics of reduced nicotinamide adenine dinucleotide–ubiquinone oxidoreductase (complex-1), a rate-limiting enzyme complex involved in the oxidative phosphorylation. Monoamine oxidase-B inhibitors (eg, selegiline) inhibit α-synuclein nitration, implicated in Lewy body formation, and inhibit 1-methyl 4-phenylpyridinium and 3-morpholinosydnonimine-induced apoptosis in cultured human dopaminergic neurons and mesencephalic fetal stem cells. MTs as free radical scavengers inhibit Charnoly body formation and neurodegenerative α-synucleinopathies, hence Charnoly body formation and α-synuclein index may be used as early and sensitive biomarkers to assess NP effectiveness and toxicity to discover better drug delivery and surgical interventions. Furthermore, pharmacological

  11. Update on clinical significance of coagulase-negative staphylococci.

    PubMed Central

    Kloos, W E; Bannerman, T L

    1994-01-01

    The clinical significance of coagulase-negative Staphylococcus species (CNS) continues to increase as strategies in medical practice lead to more invasive procedures. Hospitalized patients that are immunocompromised and/or suffering from chronic diseases are the most vulnerable to infection. Since CNS are widespread on the human body and are capable of producing very large populations, distinguishing the etiologic agent(s) from contaminating flora is a serious challenge. For this reason, culture identification should proceed to the species and strain levels. A much stronger case can be made for the identification of a CNS etiologic agent if the same strain is repeatedly isolated from a series of specimens as opposed to the isolation of different strains of one or more species. Strain identity initially can be based on colony morphology, and then one or more molecular approaches can be used to gain information on the genotype. Many of the CNS species are commonly resistant to antibiotics that are being indicated for staphylococcal infections, with the exception of vancomycin. The widespread use of antibiotics in hospitals has provided a reservoir of antibiotic-resistant genes. The main focus on mechanisms of pathogenesis has been with foreign body infections and the role of specific adhesins and slime produced by Staphylococcus epidermidis. Slime can reduce the immune response and opsonophagocytosis, thereby interfering with host defense mechanisms. As we become more aware of the various strategies used by CNS, we will be in a better position to compromise their defense mechanisms and improve treatment. Images PMID:8118787

  12. Clinical Significance of the Humoral Immune Response to Modified LDL

    PubMed Central

    Lopes-Virella, MF; Virella, G

    2009-01-01

    Human low density lipoprotein (LDL) undergoes oxidation and glycation in vivo. By themselves, oxidized LDL (oxLDL) and AGE-LDL have proinflammatory properties and are considered atherogenic. But the atherogenicity of these lipoproteins are significantly increased as a consequence of the formation of immune complexes (IC) involving autoantibodies spontaneously formed. OxLDL and AGE antibodies have been shown to be predominantly of the IgG1 and IgG3 isotypes. OxLDL antibodies are able to activate the complement system by the classical pathway and to induce FcR-mediated phagocytosis. In vitro and ex vivo studies performed with modified LDL-IC have proven their pro-inflammatory and atherogenic properties. Clinical studies have demonstrated that the levels of circulating modified LDL-IC correlate with parameters indicative of cardiovascular and renal disease in diabetic patients and other patient populations. The possibility that spontaneously formed or induced modified LDL antibodies (particularly IgM oxLDL antibodies) may have a protective effect has been suggested, but the data is unclear and needs to be further investigated. PMID:19427818

  13. The pathogenesis and clinical significance of traumatic subdural hygroma.

    PubMed

    Lee, K S

    1998-07-01

    Subdural hygroma (SDG) is a common post-traumatic lesion. Despite its common occurrence, the pathogenesis and clinical significance are uncertain. The author reviewed the literature to clarify the present knowledge on the pathogenic, diagnostic and therapeutic aspects of this controversial lesion. A trivial trauma can cause a separation of the dura-arachnoid interface, which is the basic requirement for the development of a SDG. If the brain shrinks due to brain atrophy, excessive dehydration or decreased intracranial pressure, fluid collection may develop by a passive effusion. Most SDGs resolve when the brain is well expanded. However, a few SDGs become chronic subdural haematomas, when the necessary conditions persist over several weeks. Since the majority of patients with a SDG do not show a mass effect, surgery is rarely required. Outcome is closely related to the primary head injury not to the SDG itself. The complexity of SDG depends on various factors including the dynamics of absorption and expansion, duration of observation, and indication and rate of surgery, besides variety of the primary head injury in types and severity. SDG is a common epiphenomenon of head injury. PMID:9653522

  14. Construction of databases: advances and significance in clinical research.

    PubMed

    Long, Erping; Huang, Bingjie; Wang, Liming; Lin, Xiaoyu; Lin, Haotian

    2015-12-01

    Widely used in clinical research, the database is a new type of data management automation technology and the most efficient tool for data management. In this article, we first explain some basic concepts, such as the definition, classification, and establishment of databases. Afterward, the workflow for establishing databases, inputting data, verifying data, and managing databases is presented. Meanwhile, by discussing the application of databases in clinical research, we illuminate the important role of databases in clinical research practice. Lastly, we introduce the reanalysis of randomized controlled trials (RCTs) and cloud computing techniques, showing the most recent advancements of databases in clinical research. PMID:27215009

  15. Acute chorioamnionitis and funisitis: definition, pathologic features, and clinical significance.

    PubMed

    Kim, Chong Jai; Romero, Roberto; Chaemsaithong, Piya; Chaiyasit, Noppadol; Yoon, Bo Hyun; Kim, Yeon Mee

    2015-10-01

    -term complications (ie, sterile inflammation in fetuses, neonatal sepsis, bronchopulmonary dysplasia, periventricular leukomalacia, and cerebral palsy). This article reviews the definition, pathogenesis, grading and staging, and clinical significance of the most common lesions in placental disease. Illustrations of the lesions and diagrams of the mechanisms of disease are provided. PMID:26428501

  16. The Clinical Significance of Optimality Theory for Phonological Disorders

    ERIC Educational Resources Information Center

    Gierut, Judith A.; Morrisette, Michele L.

    2005-01-01

    Linguistic theory has made important contributions to the clinical assessment and treatment of children with functional phonological disorders. In this article, Optimality Theory (OT) is introduced as a new linguistic model of grammar. Basic assumptions of the model are described and extended to clinical assessment and treatment. The aim is (1) to…

  17. Identification and Clinical Significance of Helcococcus kunzii in Human Samples.

    PubMed

    Vergne, Anne; Guérin, François; Lienhard, Reto; Le Coustumier, Alain; Daurel, Claire; Isnard, Christophe; Marty, Nicole; Poyart, Claire; Cattoir, Vincent

    2015-08-01

    From 2008 to 2013, 39 Helcococcus kunzii strains were collected from human clinical specimens (79% from foot ulcers), and 85% of the 39 patients were infected. Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry and molecular methods accurately identified all isolates. This large study of clinical observations confirms the potential pathogenic role of H. kunzii. PMID:25994161

  18. Identification and Clinical Significance of Helcococcus kunzii in Human Samples

    PubMed Central

    Vergne, Anne; Guérin, François; Lienhard, Reto; Le Coustumier, Alain; Daurel, Claire; Isnard, Christophe; Marty, Nicole; Poyart, Claire

    2015-01-01

    From 2008 to 2013, 39 Helcococcus kunzii strains were collected from human clinical specimens (79% from foot ulcers), and 85% of the 39 patients were infected. Matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) mass spectrometry and molecular methods accurately identified all isolates. This large study of clinical observations confirms the potential pathogenic role of H. kunzii. PMID:25994161

  19. Athletic Training Students' Perception of Significant Clinical Instructor Demographic Characteristics

    ERIC Educational Resources Information Center

    Mulholland, Carlen; Martin, Malissa

    2010-01-01

    Context: Characteristics of a model clinical instructor (CI) continue to be defined. However, certain characteristics are still unknown. Objective: To more fully define and describe quality clinical instruction by examining the impact of employment status, years of experience as a certified athletic trainer (AT), and employment setting on athletic…

  20. [Clinical significance of urinary enzymes in diabetes mellitus].

    PubMed

    Morita, E; Kaizu, K; Uriu, K; Eto, S

    1990-06-01

    The aim of this study was to clarify the clinical significance of urinary enzyme activity in patients with diabetes mellitus. Patients were divided into two groups: group A - 102 outpatients, group B-23 inpatients. Spot urine samples before breakfast from group A and aliquots of 24-hours urine collections at 4 degrees C from group B were used. Urinary enzyme activities (N-acetyl- beta-D-glucosaminidase: NAG, alkaline phosphatase: ALP, leucine aminopeptidase: LAP, gamma-glutamyl transpeptidase: gamma-GTP) were determined by spectrophotometric assay, rate assay, Tuppy method and Orlowski method, respectively. 1) In group A, the percentage of the cases which showed higher than the normal range (NAG: 1.3-8.7, ALP: 4.2-17.7, LAP: 0-22.9 U/g. cer.) was 42.2% in NAG, 21.6% in ALP, and 8.8% in LAP. In a multiple regression analysis, the predictor variables which contributed to NAG were HbA1c, age, urinary protein and the one that contributed to ALP, LAP, gamma-GTP was urinary beta 2-microglobulin. 2) In group B, 87% of NAG was above the normal range (Mean +/- 2 SD; 4.8 +/- 3.9 U/day). There was no difference in the NAG activity between patients with and without nephropathy. The percent of high activities of ALP, LAP and gamma-GTP were 17%, 17%, 4%, respectively. Most of them were patients with nephropathy. There were correlations among ALP, LAP and gamma-GTP, though no correlation existed between NAG and the other three enzymes. These results suggested: 1) NAG reflects lysosomal dysfunction of both glomerular and proximal tubular epithelial cells which may be caused by poor glycemic control.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1975116

  1. TRP channels and temperature in airway disease—clinical significance

    PubMed Central

    Millqvist, Eva

    2015-01-01

    Temperatures above and below what is generally regarded as “comfortable” for the human being have long been known to induce various airway symptoms, especially in combination with exercise in cold climate with temperatures below 0°C, which is naturally since exercise is followed by enhanced ventilation and thus greater amounts of inhaled cold air. The aim was to highlight the knowledge we have today on symptoms from the airways (here also including the eyes) arisen from various temperatures; the mechanisms, the pathophysiology and their clinical significance. The most common eye and airway conditions related to temperature changes are dry eye disease, rhinitis, laryngeal dysfunction, asthma, chronic obstructive pulmonary disease and chronic cough. Transient receptor potential (TRP) ion channels are probably involved in all temperature induced airway symptoms but via different pathways, which are now beginning to be mapped out. In asthma, the most persuasive hypothesis today is that cold-induced asthmatic bronchoconstriction is induced by dehydration of the airway mucosa, from which it follows that provocations with osmotic stimuli like hypertonic saline and mannitol can be used as a surrogate for exercise provocation as well as dry air inhalation. In chronic unexplained cough there seems to be a direct influence of cold air on the TRP ion channels followed by coughing and increased cough sensitivity to inhaled capsaicin. Revelations in the last decades of the ability of several airway TRP ion channels to sense and react to ambient air temperature have opened new windows for the understanding of the pathogenesis in a diversity of airway reactions appearing in many common respiratory diseases. PMID:27227021

  2. Clinical significance of J-wave in elite athletes.

    PubMed

    Pelliccia, Antonio; Quattrini, Filippo M

    2015-01-01

    The J-wave pattern on 12-lead ECG is traditionally defined as a positive deflection at junction between the end of the QRS and the beginning of the ST-segment. This pattern has recently been associated with increased risk for idiopathic ventricular fibrillation in the absence of cardiovascular disease. The interest for the clinical significance of J-wave pattern as a potential ECG hallmark of high risk for cardiac arrest has recently been reinforced by the growing practice of ECG screening, such as occurs in large population of young competitive athletes. The available scientific evidence shows that the J-wave pattern is relatively common in trained athletes (ranging from 14% to 44%) and, differently from subjects who suffered from ventricular fibrillation, commonly localized in lateral leads while it is relatively rare to be found in inferior leads. Furthermore the J-wave pattern has been demonstrated to be a dynamic phenomenon related to the training status, with the larger prominence at the peak of training and with an inverse relation between magnitude of J-wave and heart rate. In addition the J-wave pattern is usually associated with other ECG changes, such as increased QRS voltages and ST-segment elevation, as well as LV remodeling, suggesting that it likely represents another expression of the physiologic athlete's heart. Finally the scientific data available demonstrated that during a medium follow-up period the J-wave pattern does not convey risk for adverse cardiac events, including sudden death or ventricular tachyarrhythmias. PMID:25796101

  3. TRP channels and temperature in airway disease-clinical significance.

    PubMed

    Millqvist, Eva

    2015-01-01

    Temperatures above and below what is generally regarded as "comfortable" for the human being have long been known to induce various airway symptoms, especially in combination with exercise in cold climate with temperatures below 0°C, which is naturally since exercise is followed by enhanced ventilation and thus greater amounts of inhaled cold air. The aim was to highlight the knowledge we have today on symptoms from the airways (here also including the eyes) arisen from various temperatures; the mechanisms, the pathophysiology and their clinical significance. The most common eye and airway conditions related to temperature changes are dry eye disease, rhinitis, laryngeal dysfunction, asthma, chronic obstructive pulmonary disease and chronic cough. Transient receptor potential (TRP) ion channels are probably involved in all temperature induced airway symptoms but via different pathways, which are now beginning to be mapped out. In asthma, the most persuasive hypothesis today is that cold-induced asthmatic bronchoconstriction is induced by dehydration of the airway mucosa, from which it follows that provocations with osmotic stimuli like hypertonic saline and mannitol can be used as a surrogate for exercise provocation as well as dry air inhalation. In chronic unexplained cough there seems to be a direct influence of cold air on the TRP ion channels followed by coughing and increased cough sensitivity to inhaled capsaicin. Revelations in the last decades of the ability of several airway TRP ion channels to sense and react to ambient air temperature have opened new windows for the understanding of the pathogenesis in a diversity of airway reactions appearing in many common respiratory diseases. PMID:27227021

  4. Distress Screening in a Multidisciplinary Lung Cancer Clinic: Prevalence and Predictors of Clinically-Significant Distress

    PubMed Central

    Graves, Kristi D.; Arnold, Susanne M.; Love, Celia L.; Kirsh, Kenneth L.; Moore, Pamela G.; Passik, Steven D.

    2007-01-01

    Summary Screening for distress in cancer patients is recommended by the National Comprehensive Cancer Network, and a Distress Thermometer has previously been developed and empirically-validated for this purpose. The present study sought to determine the rates and predictors of distress in a sample of patients being seen in a multidisciplinary lung cancer clinic. Consecutive patients (N = 333) were recruited from an outpatient multidisciplinary lung cancer clinic to complete the Distress Thermometer, an associated Problem Symptom List, and two questions about interest in receiving help for symptoms. Over half (61.6%) of patients reported distress at a clinically significant level, and 22.5% of patients indicated interest in receiving help with their distress and/or symptoms. Problems in the areas of family relationships, emotional functioning, lack of information about diagnosis/treatment, physical functioning, and cognitive functioning were associated with higher reports of distress. Specific symptoms of depression, anxiety, pain and fatigue were most predictive of distress. Younger age was also associated with higher levels of distress. Distress was not associated with other clinical variables, including stage of illness or medical treatment approach. Similar results were obtained when individuals who had not yet received a definitive diagnosis of lung cancer (n = 134) were excluded from analyses; however, family problems and anxiety were no longer predictive of distress. Screening for distress in a multidisciplinary lung cancer clinic is feasible and a significant number of patients can be expected to meet clinical criteria for distress. Results also highlight younger age and specific physical and psychosocial symptoms as predictive of clinically-significant distress. Identification of the presence and predictors of distress are the first steps toward appropriate referral and treatment of symptoms and problems that contribute to cancer patients’ distress. PMID

  5. Achieving the World Health Organization's vision for clinical pharmacology.

    PubMed

    Martin, Jennifer H; Henry, David; Gray, Jean; Day, Richard; Bochner, Felix; Ferro, Albert; Pirmohamed, Munir; Mörike, Klaus; Schwab, Matthias

    2016-02-01

    Clinical pharmacology is a medical specialty whose practitioners teach, undertake research, frame policy, give information and advice about the actions and proper uses of medicines in humans and implement that knowledge in clinical practice. It involves a combination of several activities: drug discovery and development, training safe prescribers, providing objective and evidence-based therapeutic information to ethics, regulatory and pricing bodies, supporting patient care in an increasingly subspecialized arena where co-morbidities, polypharmacy, altered pharmacokinetics and drug interactions are common and developing and contributing to medicines policies for Governments. Clinical pharmacologists must advocate drug quality and they must also advocate for sustainability of the Discipline. However for this they need appropriate clinical service and training support. This Commentary discusses strategies to ensure the Discipline is supported by teaching, training and policy organizations, to communicate the full benefits of clinical pharmacology services, put a monetary value on clinical pharmacology services and to grow the clinical pharmacology workforce to support a growing clinical, academic and regulatory need. PMID:26466826

  6. Identifying Adult Dengue Patients at Low Risk for Clinically Significant Bleeding

    PubMed Central

    Wong, Joshua G. X.; Thein, Tun Linn; Leo, Yee-Sin; Pang, Junxiong; Lye, David C.

    2016-01-01

    Background Clinically significant bleeding is important for subsequent optimal case management in dengue patients, but most studies have focused on dengue severity as an outcome. Our study objective was to identify differences in admission parameters between patients who developed clinically significant bleeding and those that did not. We sought to develop a model for discriminating between these patients. Methods We conducted a retrospective study of 4,383 adults aged >18 years who were hospitalized with dengue infection at Tan Tock Seng Hospital, Singapore from 2005 to 2008. Patients were divided into those with clinically significant bleeding (n = 188), and those without (n = 4,195). Demographic, clinical, and laboratory variables on admission were compared between groups to determine factors associated with clinically significant bleeding during hospitalization. Results On admission, female gender (p<0.001); temperature >38°C (p<0.001); nausea/vomiting (p = 0.009) and abdominal pain/tenderness (p = 0.005); lower systolic blood pressure (p<0.001); higher pulse rate (p<0.001); increased absolute neutrophil count (ANC; p<0.001); reduced absolute lymphocyte count (ALC; p<0.001), haematocrit percentage (p<0.001) and platelet count (p = 0.04), and increased prothrombin time (p = 0.003) were significantly associated with clinically significant bleeding on univariate analysis. Multivariate analysis showed that independent variables in the final model were female gender (aOR 2.85; 95% CI: 1.9–4.33); temperature >38°C (aOR 1.81; 95% CI: 1.27–2.61), nausea/vomiting (aOR 1.39; 95% CI: 0.94–2.12), ANC (aOR 1.3; 95% CI: 1.15–1.46), ALC (aOR 0.4; 95% CI: 0.25–0.64), hematocrit percentage (aOR 0.96; 95% CI: 0.92–1.002) and platelet count (aOR 0.993; 95% CI: 0.988–0.998). At the cutoff of -3.919, the model achieved an AUC of 0.758 (sensitivity:0.87, specificity: 0.38, PPV: 0.06, NPV: 0.98). Conclusion Clinical risk factors associated with clinically significant

  7. High-fidelity simulation: Assessment of student nurses' team achievements of clinical judgment.

    PubMed

    Hallin, Karin; Bäckström, Britt; Häggström, Marie; Kristiansen, Lisbeth

    2016-07-01

    Nursing educators have the challenge of preparing nursing students to handle complex patient care situations in real life, but much remains unknown about the ability to make clinical judgments. In this study, high-fidelity simulation (HFS) was used at a Swedish university to find answers about pre-licensure nursing students' success in clinical judgment in terms of team ability and relationships with theoretical achievements, and personal and scenario circumstances. The matrix Lasater Clinical Judgment Rubric (LCJR) was used to analyze and score the students' ability in teams to notice, interpret and respond to complex care situations. Overall, the results showed the student teams in their first meeting with HFS in a complex care situation achieved low clinical judgment points; most teams were in the stages of Beginning and Developing. For attaining high team achievements the majority of the students in the team should theoretically be "high performance". Being observers and having HFS experience before nursing education was significant too. However, age, health care experience, and assistant nurse degrees were of secondary importance. Further research at universities regionally, nationally, and internationally is needed. PMID:27428686

  8. The detection of clinically significant erythrocyte alloantibodies using a human mononuclear phagocyte assay

    SciTech Connect

    Schanfield, M.S.; Stevens, J.O.; Bauman, D.

    1981-01-01

    Red blood cell (RBC) allo- or autoantibodies, which markedly reduce the survival of transfused or autologous RBC, are considered to be clinically significant antibodies. The occurrence of antibodies against high-incidence antigens, which are occasionally associated with clinically significant RBC destruction or are of unknown clinical significance, often creates delays in providing blood to patients. In the majority of cases these antibodies are benign; however, clinically significant examples of these antibodies have been reported. An in vitro homologous human mononuclear phagocyte assay (MPA) was used to study antibodies directed against specificities associated with variable clinical significance. Two antibodies reported to be clinically significant and 25 antibodies known to be clinically insignificant were tested by MPA. The results indicate that clinically significant antibodies have a significantly higher score than do clinically insignificant antibodies, with no overlap observed between the two groups. An additional eight antibodies with unknown clinical significance were tested. None of these antibodies had scores in the clinically significant range.

  9. Granulocyte antigen systems and antibodies and their clinical significance

    SciTech Connect

    McCullough, J.

    1983-03-01

    Granulocyte alloantibodies and autoantibodies have a key role in the pathophysiology of several clinical problems. These include febrile transfusion reactions, severe pulmonary reactions to transfusion, isoimmune neonatal neutropenia, failure of effective granulocyte transfusion, autoimmune neutropenia, drug-induced neutropenia, and neutropenias secondary to many other diseases. Although many techniques are available for detecting granulocyte antibodies, the optimal in-vitro tests for predicting the antibodies' clinical effects are not established. Use of indium-111-labeled granulocytes may provide valuable information regarding the in-vivo effects of different granulocyte antibodies. Granulocyte transfusions continue to be used for a limited number of severely infected neutropenic patients who do not respond to antibiotic therapy.

  10. Clinical Significance of Microbial Infection and Adaptation in Cystic Fibrosis

    PubMed Central

    Hauser, Alan R.; Jain, Manu; Bar-Meir, Maskit; McColley, Susanna A.

    2011-01-01

    Summary: A select group of microorganisms inhabit the airways of individuals with cystic fibrosis. Once established within the pulmonary environment in these patients, many of these microbes adapt by altering aspects of their structure and physiology. Some of these microbes and adaptations are associated with more rapid deterioration in lung function and overall clinical status, whereas others appear to have little effect. Here we review current evidence supporting or refuting a role for the different microbes and their adaptations in contributing to poor clinical outcomes in cystic fibrosis. PMID:21233507

  11. Applications of the psychotherapy phase model to clinically significant deterioration.

    PubMed

    Swift, Joshua K; Callahan, Jennifer L; Heath, Christopher J; Herbert, Gregory L; Levine, Jason C

    2010-06-01

    While previous research on deterioration has focused on identifying individuals at risk for negative outcomes, little is known about the nature or pattern by which deterioration occurs. The problem of deterioration is especially salient in training clinics; a setting in which higher deterioration rates have been reported. Two studies were designed to test the applicability of the phase model to deterioration in a training clinic and to replicate the model with a training clinic referral-base sample. In Study 1, the course of therapy was monitored for 135 clients. For the 38 clients who deteriorated during therapy, a model where increased symptoms (demediation) reliably preceded both decreased functioning (dehabilitation) and decreased well-being (demoralization) was found. In Study 2, the same three phases were prospectively monitored for 914 undergraduate students on a weekly basis throughout a single semester. For the 158 individuals who deteriorated during this time, a model where demediation reliably preceded dehabilitation, which preceded demoralization was found. These results have clinical implications for the use of tailored intervention strategies focusing on the deterioration phases. PMID:22402050

  12. The significance of coronary reserve in clinical heart disease.

    PubMed

    Strauer, B E

    1990-03-15

    The clinical syndrome "coronary insufficiency with normal coronary arteriogram" is found in approximately 10% to 20% of patients with exercise-induced coronary insufficiency. In most of these cases, disturbances of the coronary microcirculation are present. They can appear in vascular diseases (arterial hypertension, systemic immunopathies, immune complex vasculitis), in rheologic diseases (paraproteinemia, hyperlipoproteinemia, polyglobulia) and in disturbances of transport and diffusion of oxygen (carbon monoxide intoxication, methemoglobinemia). The clinical diagnosis is based on the usual diagnostic procedures (electrocardiogram, exercise electrocardiogram, responsiveness to nitroglycerin), as well as on newer functionally oriented diagnostic procedures (determinations of coronary blood flow and coronary vascular reserve, production of lactate, serologic findings, histology and immune histology of peripheral arteries, measurements of viscosities in both plasma and blood). Many clinically relevant disturbances in the coronary microcirculation can thus be detected and treated on a rational basis by management of the underlying main disease, that is, by treatment of the vascular, rheologic and metabolic disorders. Persistent angina pectoris in the presence of a normal coronary arteriogram does not represent an end to coronary diagnostic procedures, but introduces the clinical task of using all diagnostic possibilities to enable functional and therapeutic assessment of the coronary microcirculation. PMID:2307786

  13. Social networking strategies that aim to reduce obesity have achieved significant although modest results.

    PubMed

    Ashrafian, Hutan; Toma, Tania; Harling, Leanne; Kerr, Karen; Athanasiou, Thanos; Darzi, Ara

    2014-09-01

    The global epidemic of obesity continues to escalate. Obesity accounts for an increasing proportion of the international socioeconomic burden of noncommunicable disease. Online social networking services provide an effective medium through which information may be exchanged between obese and overweight patients and their health care providers, potentially contributing to superior weight-loss outcomes. We performed a systematic review and meta-analysis to assess the role of these services in modifying body mass index (BMI). Our analysis of twelve studies found that interventions using social networking services produced a modest but significant 0.64 percent reduction in BMI from baseline for the 941 people who participated in the studies' interventions. We recommend that social networking services that target obesity should be the subject of further clinical trials. Additionally, we recommend that policy makers adopt reforms that promote the use of anti-obesity social networking services, facilitate multistakeholder partnerships in such services, and create a supportive environment to confront obesity and its associated noncommunicable diseases. PMID:25201670

  14. Clinical significance of microembolus detection by transcranial Doppler sonography in cardiovascular clinical conditions.

    PubMed

    Hudorović, Narcis

    2006-01-01

    Transcranial Doppler can detect microembolic signals, which are characterized by unidirectional high intensity increase, short duration, and random occurrence, producing a "whistling" sound. Microembolic signals have been proven to represent solid or gaseous particles within the blood flow. Microemboli have been detected in a number of clinical cardiovascular settings: carotid artery stenosis, aortic arch plaques, atrial fibrillation, myocardial infarction, prosthetic heart valves, patent foramen ovale, valvular stenosis, during invasive procedures (angiography, percutaneous transluminal angioplasty) and surgery (carotid, cardiopulmonary bypass). Despite numerous studies performed so far, clinical significance of microembolic signals is still unclear. This article provides an overview of the development and current state of technical and clinical aspects of microembolus detection. PMID:17462357

  15. Treatment-resistant panic disorder: clinical significance, concept and management.

    PubMed

    Chen, Mu-Hong; Tsai, Shih-Jen

    2016-10-01

    Panic disorder is commonly prevalent in the population, but the treatment response for panic disorder in clinical practice is much less effective than that in our imagination. Increasing evidence suggested existence of a chronic or remitting-relapsing clinical course in panic disorder. In this systematic review, we re-examine the definition of treatment-resistant panic disorder, and present the potential risk factors related to the treatment resistance, including the characteristics of panic disorder, other psychiatric and physical comorbidities, and psychosocial stresses. Furthermore, we summarize the potential pathophysiologies, such as genetic susceptibility, altered brain functioning, brain-derived neurotrophic factor, and long-term inflammation, to explain the treatment resistance. Finally, we conclude the current therapeutic strategies for treating treatment-resistant panic disorder from pharmacological and non-pharmacological views. PMID:26850787

  16. Molecular Analysis and Clinical Significance of Lactobacillus spp. Recovered from Clinical Specimens Presumptively Associated with Disease

    PubMed Central

    Martinez, Raquel M.; Hulten, Kristina G.; Bui, Uyen

    2014-01-01

    Lactobacillus spp. are part of the normal human flora and are generally assumed to be nonpathogenic. We determined the genotypic identification of >100 Lactobacillus isolates from clinical specimens in the context of presumed pathogenic potential (e.g., recovered as the single/predominant isolate from a sterile site or at ≥105 CFU/ml from urine). This study assessed the clinical significance and the frequency of occurrence of each Lactobacillus sp. We identified 16 species of Lactobacillus by 16S rRNA gene sequence analysis, 10 of which could not be associated with disease. While Lactobacillus rhamnosus, Lactobacillus gasseri, and Lactobacillus paracasei were associated with infections, L. gasseri was also a common colonizing/contaminating species. Lactobacillus casei, Lactobacillus johnsonii, and Lactobacillus delbrueckii were associated with at least one infection. Species commonly used in probiotic products (e.g., L. rhamnosus and L. casei) were identical, by 16S rRNA gene sequencing, to our isolates associated with disease. Human isolates of Lactobacillus spp. have differing site associations and levels of clinical significance. Knowing the niche and pathogenic potential of each Lactobacillus sp. can be of importance to both clinical microbiology and the food and probiotic supplement industry. PMID:24131686

  17. An exploration of comorbid symptoms and clinical correlates of clinically significant hoarding symptoms

    PubMed Central

    Hall, Brian J.; Tolin, David F.; Frost, Randy O.; Steketee, Gail

    2016-01-01

    Background Hoarding Disorder is currently being considered for inclusion in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, yet remains poorly understood. Consensus is building that hoarding may constitute a separate disorder, although comorbidity remains high and complicates the diagnostic picture. The purpose of this investigation was to explore patterns of comorbidity among people who engage in hoarding behavior in order to better understand its clinical presentation and phenomenology. Methods Data were collected from a large internet sample (N = 363) of people who self-identified as having hoarding problems, met criteria for clinically significant hoarding, and completed all measures for this study. Participants self-reported their symptoms of disorders commonly co-occurring with hoarding (obsessive compulsive disorder [OCD], depression, and attention deficit hyperactivity disorder [ADHD]), along with other clinical problems. Results: Latent class analysis results indicated that the participants were grouped into three classes: “non-comorbid” hoarding (42%), hoarding with depression (42%), and hoarding with depression and inattention (16%). Conclusions Depression symptoms were the most commonly co-occurring symptom in this sample. Contrary to previous theory relating to hoarding etiology, OCD symptoms were not significantly co-occurring and a large percentage of the study participants were free from comorbid symptoms of OCD, depression, and ADHD. This suggests that hoarding disorder is not primarily the consequence of other psychiatric conditions. Implications for DSM-5, clinical treatment, and future research directions are discussed. PMID:23213052

  18. [Persistent primitive trigeminal artery: critical review of the clinical significance].

    PubMed

    Oliveira, H A; Passos, J D; Barbosa, M B; Do Amorim, E A

    1991-09-01

    The authors report three cases of persistence of primitive trigeminal artery with no evidence of a relationship between its presence and any specific clinical syndrome. They discuss embryological aspects and establish the correlation between the presence of this malformation and other intracranial pathologies, such as "tic douloureux" and morphologic alteration of the circle of Willis. A critical review of the literature is also presented. PMID:1807233

  19. The clinical significance and management of microleakage. Part one.

    PubMed

    Larson, Thomas D

    2005-01-01

    This research reviews relevant articles related to microleakage from 1966 to the present. The review discusses what the sensation of microleakage is clinically; how dentin permeability is related to microleakage; how the quality of dentin affects permeability and microleakage; what the effects of bacterial infiltration from microleakage can be, as well as the body's defenses against bacterial infiltration within the tooth complex; how caries and microleakage are related; and how various materials and procedures can be used to limit microleakage. PMID:15807140

  20. Acrophialophora, a Poorly Known Fungus with Clinical Significance

    PubMed Central

    Sandoval-Denis, Marcelo; Sutton, Deanna A.; Wiederhold, Nathan P.; Guarro, Josep

    2015-01-01

    Acrophialophora fusispora is an emerging opportunistic fungus capable of causing human infections. The taxonomy of the genus is not yet resolved and, in order to facilitate identification of clinical specimens, we have studied a set of clinical and environmental Acrophialophora isolates by morphological and molecular analyses. This set included the available type strains of Acrophialophora species and similar fungi, some of which were considered by various authors to be synonyms of A. fusispora. Sequence analysis of the large subunit (LSU) and internal transcribed spacer (ITS) regions of the nuclear ribosomal DNA and a fragment of the β-tubulin (Tub) gene revealed that Acrophialophora belongs in the family Chaetomiaceae and comprises three different species, i.e., A. fusispora, Acrophialophora levis, and Acrophialophora seudatica; the latter was previously included in the genus Ampullifera. The most prevalent species among clinical isolates was A. levis (72.7%), followed by A. fusispora (27.3%), both of which were isolated mostly from respiratory specimens (72.7%), as well as subcutaneous and corneal tissue samples. In general, of the eight antifungal drugs tested, voriconazole had the greatest in vitro activity, while all other agents showed poor in vitro activity against these fungi. PMID:25716450

  1. Bacterial resistance to tetracycline: mechanisms, transfer, and clinical significance.

    PubMed Central

    Speer, B S; Shoemaker, N B; Salyers, A A

    1992-01-01

    Tetracycline has been a widely used antibiotic because of its low toxicity and broad spectrum of activity. However, its clinical usefulness has been declining because of the appearance of an increasing number of tetracycline-resistant isolates of clinically important bacteria. Two types of resistance mechanisms predominate: tetracycline efflux and ribosomal protection. A third mechanism of resistance, tetracycline modification, has been identified, but its clinical relevance is still unclear. For some tetracycline resistance genes, expression is regulated. In efflux genes found in gram-negative enteric bacteria, regulation is via a repressor that interacts with tetracycline. Gram-positive efflux genes appear to be regulated by an attenuation mechanism. Recently it was reported that at least one of the ribosome protection genes is regulated by attenuation. Tetracycline resistance genes are often found on transmissible elements. Efflux resistance genes are generally found on plasmids, whereas genes involved in ribosome protection have been found on both plasmids and self-transmissible chromosomal elements (conjugative transposons). One class of conjugative transposon, originally found in streptococci, can transfer itself from streptococci to a variety of recipients, including other gram-positive bacteria, gram-negative bacteria, and mycoplasmas. Another class of conjugative transposons has been found in the Bacteroides group. An unusual feature of the Bacteroides elements is that their transfer is enhanced by preexposure to tetracycline. Thus, tetracycline has the double effect of selecting for recipients that acquire a resistance gene and stimulating transfer of the gene. PMID:1423217

  2. Acrophialophora, a poorly known fungus with clinical significance.

    PubMed

    Sandoval-Denis, Marcelo; Gené, Josepa; Sutton, Deanna A; Wiederhold, Nathan P; Guarro, Josep

    2015-05-01

    Acrophialophora fusispora is an emerging opportunistic fungus capable of causing human infections. The taxonomy of the genus is not yet resolved and, in order to facilitate identification of clinical specimens, we have studied a set of clinical and environmental Acrophialophora isolates by morphological and molecular analyses. This set included the available type strains of Acrophialophora species and similar fungi, some of which were considered by various authors to be synonyms of A. fusispora. Sequence analysis of the large subunit (LSU) and internal transcribed spacer (ITS) regions of the nuclear ribosomal DNA and a fragment of the β-tubulin (Tub) gene revealed that Acrophialophora belongs in the family Chaetomiaceae and comprises three different species, i.e., A. fusispora, Acrophialophora levis, and Acrophialophora seudatica; the latter was previously included in the genus Ampullifera. The most prevalent species among clinical isolates was A. levis (72.7%), followed by A. fusispora (27.3%), both of which were isolated mostly from respiratory specimens (72.7%), as well as subcutaneous and corneal tissue samples. In general, of the eight antifungal drugs tested, voriconazole had the greatest in vitro activity, while all other agents showed poor in vitro activity against these fungi. PMID:25716450

  3. Clinical significance of treatment delay in status epilepticus

    PubMed Central

    2013-01-01

    Background Status epilepticus (SE) is a medical emergency that requires immediate action. The clinical and demographic features of SE are known to be highly variable. The objective of this study was to analyze the effect of treatment delays on patient recovery and different clinical factors that are important in the determination of the acute prognosis in SE. Methods This population-based study included 109 consecutive visits of patients with the diagnosis of SE in the emergency department (ED) of Tampere University Hospital. The clinical features of SE were compared with the discharge condition. Results The treatment delays were long; in half of the patients, the delay for paramedic arrival was over 30 min, and in one-third of the cases, the delay was over 24 h. ED patients who had less than 1 h of delay before the administration of an antiepileptic drug (AED) had better outcomes compared to patients with a greater than 1 h delay (p < 0.05). The two major etiologies for the SE were cerebrovascular disease and alcohol misuse. A good immediate outcome was found in 46% of the patients. Epileptiform activity on the EEG, a history of epilepsy or SE, presence of cardiovascular disease, and alcohol misuse were associated with a poor outcome. Conclusions The results of this study emphasize the importance of an urgent response by emergency services and proper recognition of atypical phenotypes of SE. PMID:23445821

  4. Expertise, Ethics Expertise, and Clinical Ethics Consultation: Achieving Terminological Clarity.

    PubMed

    Iltis, Ana S; Sheehan, Mark

    2016-08-01

    The language of ethics expertise has become particularly important in bioethics in light of efforts to establish the value of the clinical ethics consultation (CEC), to specify who is qualified to function as a clinical ethics consultant, and to characterize how one should evaluate whether or not a person is so qualified. Supporters and skeptics about the possibility of ethics expertise use the language of ethics expertise in ways that reflect competing views about what ethics expertise entails. We argue for clarity in understanding the nature of expertise and ethics expertise. To be an ethics expert, we argue, is to be an expert in knowing what ought to be done. Any attempt to articulate expertise with respect to knowing what ought to be done must include an account of ethics that specifies the nature of moral truth and the means by which we access this truth or a theoretical account of ethics such that expertise in another domain is linked to knowing or being better at judging what ought to be done and the standards by which this "knowing" or "being better at judging" is determined. We conclude with a discussion of the implications of our analysis for the literature on ethics expertise in CEC. We do think that there are clear domains in which a clinical ethics consultant might be expert but we are skeptical about the possibility that this includes ethics expertise. Clinical ethics consultants should not be referred to as ethics experts. PMID:27256848

  5. Clinical significance of immunohistochemically detected extracellular matrix proteins and their spatial distribution in primary cancer.

    PubMed

    Čunderlíková, B

    2016-09-01

    Our understanding of cancer has evolved mainly from results of studies utilizing experimental models. Simplification inherent to in vitro cell culture models enabled potential ways of cell behaviour in response to various external stimuli to be described, but it has led also to disappointments in clinical trials, presumably due to the lack of crucial tissue components, including extracellular matrix (ECM). ECM and its role in healthy and diseased tissues are being explored extensively and significance of ECM for cell behaviour has been evidenced experimentally. Part of the information gathered in such research that is relevant for natural conditions of a human body can be identified by carefully designed analyses of human tissue samples. This review summarizes published information on clinical significance of ECM in cancer and examines whether effects of ECM on cell behaviour evidenced in vitro, could be supported by clinically based data acquired from analysis of tissue samples. Based on current approaches of clinical immunohistochemical analyses, impact of ECM components on tumour cell behaviour is vague. Except of traditionally considered limitations, other reasons may include lack of stratification of analyzed cases based on clinicopathologic parameters, inclusion of patients treated postoperatively by different treatments or neglecting complexity of interactions among tumour constituents. Nevertheless, reliable immunohistochemical studies represent a source of crucial information for design of tumour models comprising ECM corresponding to real clinical situation. Knowledge gathered from such immunohistochemical studies combined with achievements in tissue engineering hold promise for reversal of the unfavourable trends in the current translational oncologic research. PMID:27443915

  6. The clinical significance and management of microleakage. Part two.

    PubMed

    Larson, Thomas D

    2005-01-01

    This research reviews relevant articles related to microleakage from 1966 to the present. The review discusses what the sensation of microleakage is clinically; how dentin permeability is related to microleakage; how the quality of dentin affects permeability and microleakage; what the effects of bacterial infiltration from microleakage can be, as well as the body's defenses against bacterial infiltration within the tooth complex; how caries and microleakage are related; and how various materials and procedures can be used to limit microleakage. Part Two reviews the use of materials, technique, and procedures to limit microleakage, and specifically how the use of various dentin and enamel bonding materials can be used to limit microleakage. PMID:15934228

  7. The clinical significance of creativity in bipolar disorder

    PubMed Central

    Murray, Greg; Johnson, Sheri L.

    2012-01-01

    Clinical implications of the high rates of creativity within bipolar disorder (BD) have not been explored. The aim of this review is to outline these implications by (i) reviewing evidence for the link between creativity and BD, (ii) developing a provisional model of mechanisms underpinning the creativity–BD link, (iii) describing unique challenges faced by creative-BD populations, and (iv) systematically considering evidence-based psychosocial treatments in the light of this review. While more research into the creativity–BD nexus is urgently required, treatment outcomes will benefit from consideration of this commonly occurring phenotype. PMID:20579791

  8. Anticoagulative strategies in reconstructive surgery – clinical significance and applicability

    PubMed Central

    Jokuszies, Andreas; Herold, Christian; Niederbichler, Andreas D.; Vogt, Peter M.

    2012-01-01

    Advanced strategies in reconstructive microsurgery and especially free tissue transfer with advanced microvascular techniques have been routinely applied and continously refined for more than three decades in day-to-day clinical work. Bearing in mind the success rates of more than 95%, the value of these techniques in patient care and comfort (one-step reconstruction of even the most complex tissue defects) cannot be underestimated. However, anticoagulative protocols and practices are far from general acceptance and – most importantly – lack the benchmark of evidence basis while the reconstructive and microsurgical methods are mostly standardized. Therefore, the aim of our work was to review the actual literature and synoptically lay out the mechanisms of action of the plethora of anticoagulative substances. The pharmacologic prevention and the surgical intervention of thrombembolic events represent an established and essential part of microsurgery. The high success rates of microvascular free tissue transfer as of today are due to treatment of patients in reconstructive centers where proper patient selection, excellent microsurgical technique, tissue transfer to adequate recipient vessels, and early anastomotic revision in case of thrombosis is provided. Whether the choice of antithrombotic agents is a factor of success remains still unclear. Undoubtedly however the lack of microsurgical experience and bad technique can never be compensated by any regimen of antithrombotic therapy. All the more, the development of consistent standards and algorithms in reconstructive microsurgery is absolutely essential to optimize clinical outcomes and increase multicentric and international comparability of postoperative results and complications. PMID:22294976

  9. Brain death in ICU patients: Clinical significance of endocrine changes

    PubMed Central

    Bajwa, Sukhminder Jit Singh; Haldar, Rudrashish

    2014-01-01

    Numerous studies have been carried out among patients admitted in intensive care unit (ICU) having primary endocrine pathology, endocrine manifestations of systemic diseases or post-endocrine tissue surgery. However, minimal literary evidence is available highlighting the endocrine changes occurring during brain death in critically ill patients. A precise and timely diagnosis of brain death is required to convey the relatives about the prognosis and also to possibly plan for organ retrieval for transplantation purposes. The diagnosis of this condition as of today remains largely a clinical one. Brain death is associated with a multitude of endocrinological alterations which are yet to be completely unraveled and understood. Evaluating these endocrinological modifications lends us an added vista to add to the existing clinical parameters which might help us to confirm the diagnosis of brain death with a higher degree of precision. Moreover, since the efficacy of hormone replacement therapy to benefit in organ retrieval remains yet unproven, newer diagnostic modalities and research studies are definitely called for to strategize the optimal dosage and duration of such therapies. PMID:24741523

  10. Clinical significance of multi-leaf collimator calibration errors.

    PubMed

    Norvill, Craig; Jenetsky, Guy

    2016-03-01

    This planning study investigates the clinical impact of multi-leaf collimator (MLC) calibration errors on three common treatment sites; head and neck (H&N), prostate and stereotactic body radiotherapy (SBRT) for lung. All plans used using either volumetric modulated adaptive therapy or dynamic MLC techniques. Five patient plans were retrospectively selected from each treatment site, and MLC errors intentionally introduced. MLC errors of 0.7, 0.4 and 0.2 mm were sufficient to cause major violations in the PTV planning criteria for the H&N, prostate and SBRT lung plans. Mean PTV dose followed a linear trend with MLC error, increasing at rates of 3.2-5.9 % per millimeter depending on treatment site. The results indicate that an MLC quality assurance program that provides sub-millimeter accuracy is an important component of intensity modulated radiotherapy delivery techniques. PMID:26819078

  11. Lipoprotein ratios: Physiological significance and clinical usefulness in cardiovascular prevention

    PubMed Central

    Millán, Jesús; Pintó, Xavier; Muñoz, Anna; Zúñiga, Manuel; Rubiés-Prat, Joan; Pallardo, Luis Felipe; Masana, Luis; Mangas, Alipio; Hernández-Mijares, Antonio; González-Santos, Pedro; Ascaso, Juan F; Pedro-Botet, Juan

    2009-01-01

    Low-density lipoprotein (LDL) cholesterol concentration has been the prime index of cardiovascular disease risk and the main target for therapy. However, several lipoprotein ratios or “atherogenic indices” have been defined in an attempt to optimize the predictive capacity of the lipid profile. In this review, we summarize their pathophysiological aspects, and highlight the rationale for using these lipoprotein ratios as cardiovascular risk factors in clinical practice, specifying their cut-off risk levels and a target for lipid-lowering therapy. Total/high-density lipoprotein (HDL) cholesterol and LDL/HDL cholesterol ratios are risk indicators with greater predictive value than isolated parameters used independently, particularly LDL. Future recommendations regarding the diagnosis and treatment of dyslipidemia, including instruments for calculating cardiovascular risk or action guidelines, should include the lipoprotein ratios with greater predictive power which, in view of the evidence-based results, are none other than those which include HDL cholesterol. PMID:19774217

  12. The significance of Candida pulcherrima findings in human clinical specimens.

    PubMed

    Pospisil, L

    1989-11-01

    From 1971 to 1976 the author examined by cultivation on Sabouraud glucose agar, 1720 specimens of the most varied materials--skin scales, nails, hair, beard, sputum--obtained from patients suffering from skin problems. In no one single case did he find Candida pulcherrima. However, since 1977 he has found C. pulcherrima to be on an increase. From 1977 to 1984 in 4644 specimens C. pulcherrima was found in 44 cases. 38 strains, i.e. 86%, were isolated from patients with clinical diagnosis of mycotic infection. The most frequent diagnosis was onychomycosis, 36%. Cultivation findings were mostly profuse and massive relative to the number of germs, in some patients even occurring repeatedly. In view of these findings it may be necessary to revise the views purporting the finding of C. pulcherrima from human material to be insignificant. PMID:2615783

  13. Studies in the radiobiology of osteoradionecrosis and their clinical significance

    SciTech Connect

    Marx, R.E.; Johnson, R.P.

    1987-10-01

    The radiobiology of osteoradionecrosis is a complex of cellular death and cellular functional impairments from radiation energy transfers. Four studies of irradiated patients and a data base from 536 patients with osteoradionecrosis revealed separate pathophysiologic conditions for osteoradionecrosis induced by early trauma, osteoradionecrosis induced by late trauma, and spontaneous osteoradionecrosis. A large body of data suggested useful clinical guidelines for the management of irradiated patients. The guidelines, in part, include a recommendation for deferring radiation treatment for 21 days after tissue wounding, if possible; a relative contraindication to wounding tissue during a radiation course; a recommendation for the use of hyperbaric oxygen before wounding; and a strong recommendation to provide comprehensive dental care to the irradiated patient.

  14. Adverse effects of acupuncture. Which are clinically significant?

    PubMed Central

    Chung, Ainee; Bui, Luke; Mills, Edward

    2003-01-01

    OBJECTIVE: To review potentially serious adverse events associated with acupuncture. QUALITY OF EVIDENCE: Studies in the medical literature primarily provide level II evidence from retrospective reviews, case reports, and prospective surveys of practitioners. MAIN MESSAGE: Both the general public and physicians are becoming more interested in the ancient Chinese medical practice of acupuncture. This paper discusses the basic philosophy of acupuncture and describes adverse events that might be associated with acupuncture treatment. Some events, such as nausea and syncope, can be mild and transient, but rare events, such as septicemia and hepatitis C infection, can be fatal. As the role of acupuncture in today's multidisciplinary clinics increases, the complications of acupuncture, although infrequent, cannot be overlooked. CONCLUSION: Responsible clinicians practising acupuncture and seeing patients who use acupuncture should be aware of the adverse events associated with it. PMID:12943357

  15. Predictors of treatment attrition among an outpatient clinic sample of youths with clinically significant anxiety.

    PubMed

    Gonzalez, Araceli; Weersing, V Robin; Warnick, Erin M; Scahill, Lawrence D; Woolston, Joseph L

    2011-09-01

    Predictors of treatment attrition were examined in a sample of 197 youths (ages 5-18) with clinically-significant symptoms of anxiety seeking psychotherapy services at a community-based outpatient mental health clinic (OMHC). Two related definitions of attrition were considered: (a) clinician-rated dropout (CR), and (b) CR dropout qualified by phase of treatment (pre, early, or late phases) (PT). Across both definitions, rates of attrition in the OMHC sample were higher than those for anxious youths treated in randomized controlled trials, and comorbid depression symptoms predicted dropout, with a higher rate of depressed youths dropping out later in treatment (after 6 sessions). Using the PT definition, minority status also predicted attrition, with more African-American youths lost pre-treatment. Other demographic (age, gender, single parent status) and clinical (externalizing symptoms, anxiety severity) characteristics were not significantly associated with attrition using either definition. Implications for services for anxious youths in public service settings are discussed. Results highlight the important role of comorbid depression in the treatment of anxious youth and the potential value of targeted retention efforts for ethnic minority families early in the treatment process. PMID:20976618

  16. Clinical significance of serum adipokines levels in lung cancer.

    PubMed

    Kerenidi, Theodora; Lada, Martha; Tsaroucha, Agori; Georgoulias, Panagiotis; Mystridou, Parthena; Gourgoulianis, Konstantinos I

    2013-06-01

    Adipokines have a significant effect on metabolism, immunoinflammatory responses as well as on carcinogenesis; therefore, we aimed at evaluating their potential predictive and prognostic significance in lung cancer. Eighty patients--mean age 62.9 ± 9.2 years--with previously untreated lung cancer (61 NSCLC and 19 SCLC) of all stages and 40 healthy individuals were enrolled in this study. Serum levels of leptin, adiponectin and ghrelin were measured using human Radioimmunoassay kits. Serum leptin levels in lung cancer patients were lower compared to control (p < 0.0001), while adiponectin and ghrelin levels were significantly increased in patients (p = 0.0003 and p = 0.0043, respectively). Additionally, the leptin/adiponectin ratio was significantly lower in the patients group compared to controls (p < 0.0001]. There was no association between serum levels of adipokines and any of the patient clinicopathological characteristics or response to therapy. Nevertheless, patients with lower values of serum leptin had shorter overall survival (p = 0.014), whereas multivariate analysis revealed leptin levels as an independent prognostic factor for survival (p = 0.024, HR 0.452, CI 95 % 0.232-0.899). These results suggest that adipokines may play a role in the pathogenesis of lung cancer, while leptin serum levels might provide useful prognostic information. PMID:23430445

  17. Ventricular arrhythmias in congestive heart failure: clinical significance and management.

    PubMed Central

    Khoshnevis, G R; Massumi, A

    1999-01-01

    The benefit of defibrillator therapy has been well established for patients with LV dysfunction (ejection fraction less than 35%), coronary artery disease, NSVT, and inducible and nonsuppressible ventricular tachycardia. Implantable cardioverter-defibrillator therapy is also indicated for all CHF patients in NYHA functional classes I, II, and III who present with aborted sudden cardiac death, or ventricular fibrillation, or hemodynamically unstable ventricular tachycardia--and also in patients with syncope with no documented ventricular tachycardia but with inducible ventricular tachycardia at electrophysiology study. The ongoing MADIT II trial was designed to evaluate the benefit of prophylactic ICD implantation in these patients (ejection fraction less than 30%, coronary artery disease, and NSVT) without prior risk stratification by PES. The CABG Patch trial concluded that prophylactic placement of an ICD during coronary artery bypass grafting in patients with low ejection fraction and abnormal SAECG is not justifiable. Except for the indications described above, ICD implantation has not been proved to be beneficial as primary or secondary therapy. Until more data are available, patients should be encouraged to enroll in the ongoing clinical trials. PMID:10217470

  18. Laboratory aspects of clinically significant rapidly growing mycobacteria.

    PubMed

    Set, R; Shastri, J

    2011-01-01

    The pathogenic potential of the rapidly growing mycobacteria (RGM) has started being recognized. This is due to more sensitive and specific techniques in the laboratory. The RGM are generally defined as nontuberculous species of mycobacteria that show visible growth on agar media within 7 days. RGM are widely distributed in nature and have been isolated from natural water, tap water, and soil. Several biochemical tests, high performance liquid chromatography, and molecular techniques have been developed for rapid identification of these species. The American Thoracic Society and the Infectious Disease Society of America recommend that RGM should be identified to the species level using a recognized acceptable methodology such as polymerase chain reaction restriction enzyme analysis or biochemical testing and routine susceptibility testing of RGM should include amikacin, imipenem, doxycycline, the fluorinated quinolones, a sulphonamide or trimethoprim-sulphamethoxazole, cefoxitin, clarithromycin, linezolid, and tobramycin. The diseases caused by these organisms have varied manifestations. They have been responsible for a number of healthcare-associated outbreaks and pseudo-outbreaks. For recognition of outbreaks, it is important to be familiar with the causative organisms like RGM which are most frequently involved in healthcare-associated outbreaks and pseudo outbreaks. It is essential to intervene as soon as possible to interrupt this transmission. Large gaps still exist in our knowledge of RGM. Unquestionably more studies are required. Through this review, we wish to emphasize that reporting of RGM from clinical settings along with their sensitivity patterns is an absolute need of the hour. PMID:22120792

  19. Left-sided gallbladder: Its clinical significance and imaging presentations

    PubMed Central

    Hsu, Sheng-Lung; Chen, Tai-Yi; Huang, Tung-Liang; Sun, Cheuk-Kwan; Concejero, Allan M; Tsang, Leo Leung-Chit; Cheng, Yu-Fan

    2007-01-01

    AIM: To assess the importance of preoperative diagnosis and presentation of left-sided gallbladder using ultrasound (US), CT and angiography. METHODS: Retrospective review of 1482 patients who underwent enhanced CT scanning was performed. Left-sided gallbladder was diagnosed if a right-sided ligamentum teres was present. The image presentations on US, CT and angiography were also reviewed. RESULTS: Left-sided gallbladder was diagnosed in nine patients. The associated abnormalities on CT imaging included portal vein anomalies, absence of umbilical portion of the portal vein in the left lobe of the liver, club-shaped portal vein in the right lobe of the liver, and difficulty in identifying segment IV. Angiography in six of nine patients demonstrated abnormal portal venous system (trifurcation type in four of six patients). The main hepatic arteries followed the portal veins in all six patients. The segment IV artery was identified in four of six patients using angiography, although segment IV was difficult to define on CT imaging. Hepatectomy was performed in three patients with concomitant liver tumor and the diagnosis of left-sided gallbladder was confirmed intraoperatively. CONCLUSION: Left-sided gallbladder is an important clinical entity in hepatectomy due to its associated portal venous and biliary anomalies. It should be considered in US, CT and angiography images that demonstrate no definite segment IV, absence of umbilical portion of the portal vein in the left lobe, and club-shaped right anterior portal vein. PMID:18081230

  20. Variations of Gonadal Veins: Embryological Prospective and Clinical Significance

    PubMed Central

    Gupta, Raman; Aggarwal, Navita

    2015-01-01

    Introduction: An adequate knowledge of anomalies of gonadal veins will help the radiologists and surgeons in recognition and protection of these veins which play major roles in thermo-regulation that is essential for the efficient functioning of testis on which the survival of the human species depends. Aim: The aim of this work is to present an analysis of the anatomical variations of gonadal veins. An effort has also been made to explicate the possible embryological model of development of such variants and to present the variable clinical aspects concerning them. Materials and Methods: Gonadal veins in 60 dissection room cadavers were examined for variations from the classic anatomic description. Result: In the present study, out of 60 cases, male: female ratio was 2:1(40:20) in which no variation was found in ovarian veins. In the 18 (45%) cases, testicular veins showed variations which consist of duplication and atypical drainage. Discussion: Variations of drainage of gonadal vein are due to error of embryological development in venous shift and alteration in anastomotic channel of post-cardinal, supra-cardinal and sub cardinal veins. Conclusion: The gonadal veins present numeric variations as well as variations in its site of drainage, which attributed to the various pathological conditions as varicocele and pelvic congestion syndrome, leading to infertility in patients. Hence, in -depth knowledge of these developmental anomalies of gonadal veins is important. PMID:25859438

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

    PubMed

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

    2016-01-01

    As a highly conserved signaling pathway, Wnt/β-catenin signal transduction pathway plays an important role in many processes. Either in the occurrence or development of tumor, activation of this pathway takes an important place. APC inhibits Wnt/β-catenin pathway to regulate cell proliferation and differentiation. This study aimed to investigate the function of cancer suppressor gene. PCR amplification and sequencing method was used to analyze APC mutations of human clinical specimens. The pathological specimens were collected for PCR and clear electrophoretic bands were obtained after electrophoresis. The gene sequence obtained after purification and sequencing analysis was compared with the known APC gene sequence (NM_000038.5). Base mutations at APC 1543 (T → C), APC-4564 (G → A), APC-5353 (T → G), APC-5550 (T → A) and APC-5969 (G → A) locus existed in 22 (27.5 %), 12 (15 %), 5 (6.25 %), 13 (16.25 %) and 12 patients (15 %), respectively. Gene mutations existed in ameloblastoma, and the mutation loci were 1543 locus (T → C), 4564 locus (G → A), 5353 locus (T → G), 5550 locus (T → A) and 5969 locus (G → A) 15 %, respectively. APC mutation plays a certain role in monitoring the tumor malignant degree as it may indicate the transition process of ameloblastoma malignant phenotype. PMID:27065015

  2. Clinical significance of hepatitis B surface antigen mutants

    PubMed Central

    Coppola, Nicola; Onorato, Lorenzo; Minichini, Carmine; Di Caprio, Giovanni; Starace, Mario; Sagnelli, Caterina; Sagnelli, Evangelista

    2015-01-01

    Hepatitis B virus (HBV) infection is a major public health problem in many countries, with nearly 300 million people worldwide carrying HBV chronic infection and over 1 million deaths per year due to cirrhosis and liver cancer. Several hepatitis B surface antigen (HBsAg) mutations have been described, most frequently due to a single amino acid substitution and seldom to a nucleotide deletion. The majority of mutations are located in the S region, but they have also been found in the pre-S1 and pre-S2 regions. Single amino acid substitutions in the major hydrophilic region of HBsAg, called the “a” determinant, have been associated with immune escape and the consequent failure of HBV vaccination and HBsAg detection, whereas deletions in the pre-S1 or pre-S2 regions have been associated with the development of hepatocellular carcinoma. This review article will focus on the HBsAg mutants and their biological and clinical implications. PMID:26644816

  3. Clinical significance of T cell metabolic reprogramming in cancer.

    PubMed

    Herbel, Christoph; Patsoukis, Nikolaos; Bardhan, Kankana; Seth, Pankaj; Weaver, Jessica D; Boussiotis, Vassiliki A

    2016-12-01

    Conversion of normal cells to cancer is accompanied with changes in their metabolism. During this conversion, cell metabolism undergoes a shift from oxidative phosphorylation to aerobic glycolysis, also known as Warburg effect, which is a hallmark for cancer cell metabolism. In cancer cells, glycolysis functions in parallel with the TCA cycle and other metabolic pathways to enhance biosynthetic processes and thus support proliferation and growth. Similar metabolic features are observed in T cells during activation but, in contrast to cancer, metabolic transitions in T cells are part of a physiological process. Currently, there is intense interest in understanding the cause and effect relationship between metabolic reprogramming and T cell differentiation. After the recent success of cancer immunotherapy, the crosstalk between immune system and cancer has come to the forefront of clinical and basic research. One of the key goals is to delineate how metabolic alterations of cancer influence metabolism-regulated function and differentiation of tumor resident T cells and how such effects might be altered by immunotherapy. Here, we review the unique metabolic features of cancer, the implications of cancer metabolism on T cell metabolic reprogramming during antigen encounters, and the translational prospective of harnessing metabolism in cancer and T cells for cancer therapy. PMID:27510264

  4. Iatrogenic QT Abnormalities and Fatal Arrhythmias: Mechanisms and Clinical Significance

    PubMed Central

    Cubeddu, Luigi X

    2009-01-01

    Severe and occasionally fatal arrhythmias, commonly presenting as Torsade de Pointes [TdP] have been reported with Class III-antiarrhythmics, but also with non-antiarrhythmic drugs. Most cases result from an action on K+ channels encoded by the HERG gene responsible for the IKr repolarizing current, leading to a long QT and repolarization abnormalities. The hydrophobic central cavity of the HERG-K+ channels, allows a large number of structurally unrelated drugs to bind and cause direct channel inhibition. Some examples are dofetilide, quinidine, sotalol, erythromycin, grepafloxacin, cisapride, dolasetron, thioridazine, haloperidol, droperidol and pimozide. Other drugs achieve channel inhibition indirectly by impairing channel traffic from the endoplasmic reticulum to the cell membrane, decreasing channel membrane density (pentamidine, geldalamicin, arsenic trioxide, digoxin, and probucol). Whereas, ketoconazole, fluoxetine and norfluoxetine induce both direct channel inhibition and impaired channel trafficking. Congenital long QT syndrome, subclinical ion-channel mutations, subjects and relatives of subjects with previous history of drug-induced long QT or TdP, dual drug effects on cardiac repolarization [long QT plus increased QT dispersion], increased transmural dispersion of repolarization and T wave abnormalities, use of high doses, metabolism inhibitors and/or combinations of QT prolonging drugs, hypokalemia, structural cardiac disease, sympathomimetics, bradycardia, women and older age, have been shown to increase the risk for developing drug-induced TdP. Because most of these reactions are preventable, careful evaluation of risk factors and increased knowledge of drugs use associated with repolarization abnormalities is strongly recommended. Future genetic testing and development of practical and simple provocation tests are in route to prevent iatrogenic TdP. PMID:20676275

  5. Clinical significance of lactate in acute cardiac patients

    PubMed Central

    Lazzeri, Chiara; Valente, Serafina; Chiostri, Marco; Gensini, Gian Franco

    2015-01-01

    Lactate, as a metabolite of easy and quick assessment, has been studied over time in critically ill patients in order to evaluate its prognostic ability. The present review is focused on the prognostic role of lactate levels in acute cardiac patients (that is with acute coronary syndrome, cardiogenic shock, cardiac arrest, non including post cardiac surgery patients). In patients with ST-elevation myocardial infarction treated with mechanical revascularization, hyperlactatemia identified a subset of patients at higher risk for early death and in-hospital complications, being strictly related mainly to hemodynamic derangement. The prognostic impact of hyperlactatemia on mortality has been documented in patients with cardiogenic shock and in those with cardiac arrest even if there is no cut-off value of lactate to be associated with worse outcome or to guide resuscitation or hemodynamic management. Therapeutic hypothermia seems to affect per se lactate values which have been shown to progressively decrease during hypothermia. The mechanism(s) accounting for lactate levels during hypothemia seem to be multiple ranging from the metabolic effects of reduced temperatures to the hemodynamic effects of hypothermia (i.e., reduced need of vasopressor agents). Serial lactate measurements over time, or lactate clearance, have been reported to be clinically more reliable than lactate absolute value also in acute cardiac patients. Despite differences in study design, timing of lactate measurements and type of acute cardiac conditions (i.e., cardiogenic shock, cardiac arrest, refractory cardiac arrest), available evidence strongly suggests that higher lactate levels can be observed on admission in non-survivors and that higher lactate clearance is associated with better outcome. PMID:26322188

  6. Feedback and assessment for clinical placements: achieving the right balance

    PubMed Central

    Burgess, Annette; Mellis, Craig

    2015-01-01

    During clinical placements, the provision of feedback forms an integral part of the learning process and enriches students’ learning experiences. The purpose of feedback is to improve the learner’s knowledge, skills, or behavior. Receipt of accurate feedback can help to narrow the gap between actual and desired performance. Effective and regular feedback has the potential to reinforce good practice and motivate the learner toward the desired outcome. Despite the obvious role of feedback in effective teaching and learning, a common complaint from students is that they do not receive adequate feedback. Unfortunately, skills in giving and receiving feedback are rarely taught to students or clinicians. This study aims to provide an understanding of the role of feedback within the learning process, consider consequences of inadequate or poorly given feedback, consider the barriers to the feedback process, provide practical guidelines for providing feedback, and consider the need for student and faculty development in feedback skills. PMID:26056511

  7. Clinical Significance of Microcytosis in Patients with Primary Myelofibrosis

    PubMed Central

    Strati, Paolo; Pemmaraju, Naveen; Estrov, Zeev; Cardenas-Turanzas, Marylou; Pierce, Sherry; Newberry, Kate J.; Daver, Naval; Cortes, Jorge; Kantarjian, Hagop; Verstovsek, Srdan

    2014-01-01

    Microcytosis is a relatively frequent finding in primary myelofibrosis (PMF); however its prognostic significance is unknown. We identified factors associated with microcytosis in PMF and measured its impact on outcomes. Among 725 patients with PMF, 140 (19%) showed microcytosis. In multivariate analysis, factors associated with microcytosis were absence of prior therapy, low iron, low transferrin saturation (satTF), and splenomegaly. Among 375 untreated patients, low satTF and splenomegaly were associated with microcytosis. Overall, microcytosis was associated with a higher risk of transformation to leukemia (p=0.03), but not shorter leukemia-free survival. Microcytosis in PMF may be related to dysregulation of iron homeostasis. PMID:25217891

  8. Clinical significance of lymphadenectomy in patients with gastric cancer.

    PubMed

    Tóth, Dezső; Plósz, János; Török, Miklós

    2016-02-15

    Approximately thirty percent of patients with gastric cancer undergo an avoidable lymph node dissection with a higher rate of postoperative complication. Comparing the D1 and D2 dissections, it was found that there is a significant difference in morbidity, favoured D1 dissection without any difference in overall survival. Subgroup analysis of patients with T3 tumor shows a survival difference favoring D2 lymphadenectomy, and there is a better gastric cancer-related death and non-statistically significant improvement of survival for node-positive disease in patients with D2 dissection. However, the extended lymphadenectomy could improve stage-specific survival owing to the stage migration phenomenon. The deployment of centralization and application of national guidelines could improve the surgical outcomes. The Japanese and European guidelines enclose the D2 lymphadenectomy as the gold standard in R0 resection. In the individualized, stage-adapted gastric cancer surgery the Maruyama computer program (MCP) can estimate lymph node involvement preoperatively with high accuracy and in addition the Maruyama Index less than 5 has a better impact on survival, than D-level guided surgery. For these reasons, the preoperative application of MCP is recommended routinely, with an aim to perform "low Maruyama Index surgery". The sentinel lymph node biopsy (SNB) may decrease the number of redundant lymphadenectomy intraoperatively with a high detection rate (93.7%) and an accuracy of 92%. More accurate stage-adapted surgery could be performed using the MCP and SNB in parallel fashion in gastric cancer. PMID:26909128

  9. Expression and clinical significance of Sirt1 in colorectal cancer

    PubMed Central

    YU, DENG-FENG; JIANG, SU-JUAN; PAN, ZHI-PENG; CHENG, WEI-DONG; ZHANG, WEN-JUN; YAO, XIAO-KUN; LI, YU-CHENG; LUN, YONG-ZHI

    2016-01-01

    The objective of the present study was to examine the expression of Silent information regulator 1 (Sirt1) in colorectal cancer and peritumoral normal mucosa tissue, and therefore analyze the role and molecular mechanism of Sirt1 in the pathogenesis of colorectal cancer. Colorectal cancer tissue specimens were employed as the experimental group, and adjacent normal mucosa tissues >5 cm from tumor lesions were used as the control group. The expression of Sirt1 was detected by the immunohistochemical streptavidin peroxidase detection method in paraffin-embedded sections, whilst Sirt1 protein expression was examined by western blot analysis in the fresh tissues. Sirt1 protein was primarily expressed in the nuclei of the tumor cells, and positive staining was brownish-yellow in color. The relative expression quantities of Sirt1 in the peritumoral normal rectal mucosa and rectal carcinoma were 1.15 and 2.62, and the differences between the two groups were statistically significant (P<0.05). The expression level of Sirt1 in colorectal carcinoma was significantly associated with the depth of tumor invasion, differentiation and tumor size (P<0.05). Sirt1 expression was also found to be associated with tumor tissue type, lymph node metastasis, Duke's stage and patient age. These characteristics combined may therefore be used as markers for the early diagnosis of colorectal cancer pathogenesis. PMID:26893713

  10. Clinical significance of HOTAIR expression in colon cancer

    PubMed Central

    Luo, Zhi-Fen; Zhao, Dan; Li, Xi-Qing; Cui, Yong-Xia; Ma, Ning; Lu, Chuang-Xin; Liu, Ming-Yue; Zhou, Yun

    2016-01-01

    AIM: To detect the expression of the long noncoding RNA HOTAIR in colon cancer and analyze its relationship with clinicopathological parameters of colon cancer. METHODS: Total RNA was extracted from 80 colon cancer tissues and matched tumor-adjacent normal colon tissues and reverse transcribed. Quantitative polymerase chain reaction was used to detect the expression of HOTAIR. The relationship between the expression of HOTAIR and clinicopathological parameters of colon cancer was analyzed. RESULTS: The expression of HOTAIR was significantly higher in colon cancer tissues than in matched tumor-adjacent normal colon tissues (P < 0.05). HOTAIR expression was significantly higher in cases with lymph node metastasis than in those without metastasis; in lowly differentiated and undifferentiated cases than in highly and moderately differentiated cases; and in stages III + IV cases than in stages I + II cases (P < 0.05). CONCLUSION: HOTAIR expression is upregulated in colon cancer, suggesting that HOTAIR plays an important role in the tumorigenesis, development and metastasis of colon cancer. HOTAIR may act as an oncogene and represents a new molecular target for the treatment of colon cancer. PMID:27298568

  11. [Clinical significance of gastrointestinal decontamination under protected environment].

    PubMed

    Nagao, T; Yonekura, S; Komatsuda, M; Nozaki, H; Arimori, S; Sawamura, S; Ozawa, A; Sasaki, S

    1991-01-01

    Many infections are caused by the patient's own oro-intestinal microbial flora under a protected environment. Thirty-eight patients with acute leukemia and two patients with blast crisis of chronic myelocytic leukemia were treated under a protected environment with or without prophylactic antibiotics. Antibiotics used for decontamination were vancomycin (V), polymyxin B (P) and nystatin (N). The number of patients in the VPN, PN and the no antibiotic group were 13, 13 and 14, respectively. While the intestinal microbial flora was almost completely eliminated in VPN group, the number of bacteria decreased slightly in PN group. The mean number of pharyngeal and anorectal bacterial species decreased most markedly in the VPN group, but there were no significant differences among the three groups. The number of febrile days was significantly lower in the VPN and PN group than the no antibiotics group with neutrophil counts of less than 100 microliters. The average number of episodes of infection per patient was lowest in VPN group and highest in the no antibiotic group. These data indicate that VPN administration is effective for eliminating intestinal bacterial flora and resultantly protecting endogenous infections. PMID:2066589

  12. Relative density of urine: methods and clinical significance.

    PubMed

    Pradella, M; Dorizzi, R M; Rigolin, F

    1988-01-01

    The physical properties and chemical composition of urine are highly variable and are determined in large measure by the quantity and the type of food consumed. The specific gravity is the ratio of the density to that of water, and it is dependent on the number and weight of solute particles and on the temperature of the sample. The weight of solute particles is constituted mainly of urea (73%), chloride (5.4%), sodium (5.1%), potassium (2.4%), phosphate (2.0%), uric acid (1.7%), and sulfate (1.3%). Nevertheless, urine osmolality depends only on the number of solute particles. The renal production of maximally concentrated urine and formation of dilute urine may be reduced to two basic elements: (1) generation and maintenance of a renal medullary solute concentration hypertonic to plasma and (2) a mechanism for osmotic equilibration between the inner medulla and the collecting duct fluid. The interaction of the renal medullary countercurrent system, circulating levels of antidiuretic hormone, and thirst regulates water metabolism. Renin, aldosterone, prostaglandins, and kinins also play a role. Clinical estimation of the concentrating and diluting capacity can be performed by relatively simple provocative tests. However, urinary specific gravity after taking no fluids for 12 h overnight should be 1.025 or more, so that the second urine in the morning is a useful sample for screening purposes. Many preservation procedures affect specific gravity measurements. The concentration of solids (or water) in urine can be measured by weighing, hydrometer, refractometry, surface tension, osmolality, a reagent strip, or oscillations of a capillary tube. These measurements are interrelated, not identical. Urinary density measurement is useful to assess the disorders of water balance and to discriminate between prerenal azotemia and acute tubular necrosis. The water balance regulates the serum sodium concentration, therefore disorders are revealed by hypo- and hypernatremia. The

  13. Occult breast tumor reservoir: biological properties and clinical significance.

    PubMed

    Santen, Richard J; Yue, Wei; Heitjan, Daniel F

    2013-08-01

    Small, occult, undiagnosed breast cancers are found at autopsy in up to 15.6 % of women dying from unrelated causes with an average of 7 % from eight separate studies. The mammographic detection threshold of breast tumors ranges from 0.88 to 1.66 cm in diameter based on the patient's age. Tumor growth rates, expressed as "effective doubling times," vary from 10 to >700 days. We previously reported two models, based on iterative analysis of these parameters, to describe the biologic behavior of undiagnosed, occult breast tumors. Our models facilitate interpretation of the Women's Health Initiative (WHI) and antiestrogen breast cancer prevention studies. A nude mouse xenograft model was used to validate our assumption that breast tumors grow in a log-linear fashion. We then used our previously reported occult tumor growth (OTG) and computer-simulated tumor growth models to analyze various clinical trial data. Parameters used in the OTG model included a 200-day effective doubling time, 7 % prevalence of occult tumors, and 1.16 cm detection threshold. These models had been validated by comparing predicted with observed incidence of breast cancer in eight different populations of women. Our model suggests that menopausal hormone therapy with estrogens plus a progestogen (E + P) in the WHI trial primarily promoted the growth of pre-existing, occult lesions and minimally initiated de novo tumors. We provide a potential explanation for the lack of an increase in breast cancer incidence in the subgroup of women in the WHI who had not received E + P prior to randomization. This result may have reflected a leftward skew in the distribution of occult tumor doublings and insufficient time for stimulated tumors to reach the detection threshold. Our model predicted that estrogen alone reduced the incidence of breast cancer as a result of apoptosis. Understanding of the biology of occult tumors suggests that breast cancer "prevention" with antiestrogens or aromatase

  14. TRP channels in skin: from physiological implications to clinical significances.

    PubMed

    Ho, Ji-Chen; Lee, Chih-Hung

    2015-01-01

    TRP channels are expressed in various cells in skin. As an organ system to border the host and environment, many nonneuronal cells, including epidermal keratinocytes and melanocytes, express several TRP channels functionally distinct from sensory processing. TRPV1 and TRPV3 in keratinocytes of the epidermis and hair apparatus inhibit proliferation, induce terminal differentiation, induce apoptosis, and promote inflammation. Activation of TRPV4, 6, and TRPA1 promotes regeneration of the severed skin barriers. TRPA1 also enhances responses in contact hypersensitivity. TRPCs in keratinocytes regulate epidermal differentiation. In human diseases with pertubered epidermal differentiation, the expression of TRPCs are altered. TRPMs, which contribute to melanin production in melanocytes, serve as significant prognosis markers in patients with metastatic melanoma. In summary, not only act in sensory processing, TRP channels also contribute to epidermal differentiation, proliferation, barrier integration, skin regeneration, and immune responses. In diseases with aberrant TRP channels, TRP channels might be good therapeutic targets. PMID:27493510

  15. Cohesin gene mutations in tumorigenesis: from discovery to clinical significance

    PubMed Central

    Solomon, David A.; Kim, Jung-Sik; Waldman, Todd

    2014-01-01

    Cohesin is a multi-protein complex composed of four core subunits (SMC1A, SMC3, RAD21, and either STAG1 or STAG2) that is responsible for the cohesion of sister chromatids following DNA replication until its cleavage during mitosis thereby enabling faithful segregation of sister chromatids into two daughter cells. Recent cancer genomics analyses have discovered a high frequency of somatic mutations in the genes encoding the core cohesin subunits as well as cohesin regulatory factors (e.g. NIPBL, PDS5B, ESPL1) in a select subset of human tumors including glioblastoma, Ewing sarcoma, urothelial carcinoma, acute myeloid leukemia, and acute megakaryoblastic leukemia. Herein we review these studies including discussion of the functional significance of cohesin inactivation in tumorigenesis and potential therapeutic mechanisms to selectively target cancers harboring cohesin mutations. [BMB Reports 2014; 47(6): 299-310] PMID:24856830

  16. Clinical and biological significance of precursor lesions of intrahepatic cholangiocarcinoma.

    PubMed

    Ettel, Mark; Eze, Ogechukwu; Xu, Ruliang

    2015-11-01

    Cholangiocarcinoma (CC) is primarily a malignant tumor of older adults most prevalent in Southeast Asia, where liver fluke infestation is high. However the etiology in western countries is unknown. Although the incidence of extrahepatic cholangiocarcinoma has remained constant, incidence of intrahepatic CC (ICC) which differs in morphology, pathogenesis, risk factors, treatment and prognosis is increasing. While this increase is associated with hepatitis C virus infection, chronic nonalcoholic liver disease, obesity, and smoking, the pathogenesis of ICC and molecular alterations underlying the carcinogenesis are not completely elucidated. Benign biliary lesions such as biliary intraepithelial neoplasia, intraductal papillary neoplasm of the bile duct, von Meyenburg complex or bile duct hamartoma, and bile duct adenoma have been associated with ICC. For each of these entities, evidence suggests or supports a role as premalignant lesions. This article summarized the important biological significance of the precursor lesions of ICC and the molecular mechanisms that may be involved in intrahepatic cholangiocarcinogenesis. PMID:26557948

  17. Clinical and biological significance of precursor lesions of intrahepatic cholangiocarcinoma

    PubMed Central

    Ettel, Mark; Eze, Ogechukwu; Xu, Ruliang

    2015-01-01

    Cholangiocarcinoma (CC) is primarily a malignant tumor of older adults most prevalent in Southeast Asia, where liver fluke infestation is high. However the etiology in western countries is unknown. Although the incidence of extrahepatic cholangiocarcinoma has remained constant, incidence of intrahepatic CC (ICC) which differs in morphology, pathogenesis, risk factors, treatment and prognosis is increasing. While this increase is associated with hepatitis C virus infection, chronic nonalcoholic liver disease, obesity, and smoking, the pathogenesis of ICC and molecular alterations underlying the carcinogenesis are not completely elucidated. Benign biliary lesions such as biliary intraepithelial neoplasia, intraductal papillary neoplasm of the bile duct, von Meyenburg complex or bile duct hamartoma, and bile duct adenoma have been associated with ICC. For each of these entities, evidence suggests or supports a role as premalignant lesions. This article summarized the important biological significance of the precursor lesions of ICC and the molecular mechanisms that may be involved in intrahepatic cholangiocarcinogenesis. PMID:26557948

  18. TRP channels in skin: from physiological implications to clinical significances

    PubMed Central

    Ho, Ji-Chen; Lee, Chih-Hung

    2015-01-01

    TRP channels are expressed in various cells in skin. As an organ system to border the host and environment, many nonneuronal cells, including epidermal keratinocytes and melanocytes, express several TRP channels functionally distinct from sensory processing. TRPV1 and TRPV3 in keratinocytes of the epidermis and hair apparatus inhibit proliferation, induce terminal differentiation, induce apoptosis, and promote inflammation. Activation of TRPV4, 6, and TRPA1 promotes regeneration of the severed skin barriers. TRPA1 also enhances responses in contact hypersensitivity. TRPCs in keratinocytes regulate epidermal differentiation. In human diseases with pertubered epidermal differentiation, the expression of TRPCs are altered. TRPMs, which contribute to melanin production in melanocytes, serve as significant prognosis markers in patients with metastatic melanoma. In summary, not only act in sensory processing, TRP channels also contribute to epidermal differentiation, proliferation, barrier integration, skin regeneration, and immune responses. In diseases with aberrant TRP channels, TRP channels might be good therapeutic targets. PMID:27493510

  19. Epidemiology and clinical significance of cervical erosion in women attending a family planning clinic.

    PubMed

    Goldacre, M J; Loudon, N; Watt, B; Grant, G; Loudon, J D; McPherson, K; Vessey, M P

    1978-03-25

    Women attending a family planning clinic were studied to determine the relation between cervical erosion and clinical and social characteristics. The appearance of the cervix was recorded without knowledge of the women's symptoms. The prevalence of erosion increased with parity but, when the effects of other factors were controlled, decreased in women aged 35 and over. Erosion was significantly more common in women taking the "pill" and less common in women using barrier methods of contraception than in others. There was considerable variation between doctors in the reporting of erosion. No association was found between erosion and postcoital bleeding, dyspareunia, backache, or dysuria. There was a significant but modest association between erosion and vaginal discharge and a suggestion that erosion may sometimes be associated with nocturia and frequency of micturition. Vaginal flora was similar in women with and without erosion. Cervical erosion should not be regarded as pathological in asymptomatic women, nor should it be assumed necessarily to be the cause of symptoms in women with genitourinary complaints. PMID:630328

  20. Asbestos and other ferruginous bodies: their formation and clinical significance.

    PubMed Central

    Churg, A. M.; Warnock, M. L.

    1981-01-01

    Analyses of asbestos bodies from the general population have confirmed that these structures, like asbestos bodies from the lungs of asbestos workers, contain an asbestos core. In members of the general population this core is almost always an amphibole, whereas asbestos workers may have bodies formed on either amphibole or chrysotile. Most adults have a few bodies, and increasing numbers are seen in blue collar workers and others who handle small amounts of the fiber, with the highest levels being seen in asbestos workers. In men with minimal or extensive occupational exposure, asbestos bodies are formed on the commercial fibers, amosite and crocidolite, whereas women also form a significant number of bodies on the noncommercial fibers, anthophyllite and tremolite. These findings suggest that women may be exposed to specific asbestos-containing products, eg, cosmetic talc. The commercial fibers found in women and white collar men probably reflect atmospheric pollution with asbestos. At the highest levels of exposure, numbers of asbestos bodies correlate in a general way with the presence of asbestosis, although no precise value has been determined above which asbestosis is always found. In persons with much lower or environmental exposure, there does not appear to be any correlation between numbers of bodies and disease, in particular between numbers of bodies and carcinoma of the lung or gastrointestinal tract. The situation for mesothelioma is uncertain. Images Figure 1 Figure 2 Figure 3 PMID:6101235

  1. Clinical significance of acquired somatic mutations in aplastic anaemia.

    PubMed

    Marsh, J C W; Mufti, G J

    2016-08-01

    Aplastic anaemia (AA) is frequently associated with other disorders of clonal haemopoiesis such as paroxysmal nocturnal haemoglobinuria (PNH), myelodysplastic syndrome (MDS) and T-large granular lymphocytosis. Certain clones may escape the immune attack within the bone marrow environment and proliferate and attain a survival advantage over normal haemopoietic stem cells, such as trisomy 8, loss of heterozygosity of short arm of chromosome 6 and del13q clones. Recently acquired somatic mutations (SM), excluding PNH clones, have been reported in around 20-25 % of patients with AA, which predispose to a higher risk of later malignant transformation to MDS/acute myeloid leukaemia. Furthermore, certain SM, such as ASXL1 and DNMT3A are associated with poor survival following immunosuppressive therapy, whereas PIGA, BCOR/BCORL1 predict for good response and survival. Further detailed and serial analysis of the immune signature in AA is needed to understand the pathogenetic basis for the presence of clones with SM in a significant proportion of patients. PMID:27084249

  2. Clinical Significance of Enteric Protozoa in the Immunosuppressed Human Population

    PubMed Central

    Stark, D.; Barratt, J. L. N.; van Hal, S.; Marriott, D.; Harkness, J.; Ellis, J. T.

    2009-01-01

    Summary: Globally, the number of immunosuppressed people increases each year, with the human immunodeficiency virus (HIV) pandemic continuing to spread unabated in many parts of the world. Immunosuppression may also occur in malnourished persons, patients undergoing chemotherapy for malignancy, and those receiving immunosuppressive therapy. Components of the immune system can be functionally or genetically abnormal as a result of acquired (e.g., caused by HIV infection, lymphoma, or high-dose steroids or other immunosuppressive medications) or congenital illnesses, with more than 120 congenital immunodeficiencies described to date that either affect humoral immunity or compromise T-cell function. All individuals affected by immunosuppression are at risk of infection by opportunistic parasites (such as the microsporidia) as well as those more commonly associated with gastrointestinal disease (such as Giardia). The outcome of infection by enteric protozoan parasites is dependent on absolute CD4+ cell counts, with lower counts being associated with more severe disease, more atypical disease, and a greater risk of disseminated disease. This review summarizes our current state of knowledge on the significance of enteric parasitic protozoa as a cause of disease in immunosuppressed persons and also provides guidance on recent advances in diagnosis and therapy for the control of these important parasites. PMID:19822892

  3. Clinical significance of midkine expression in sporadic desmoid tumors

    PubMed Central

    KIM, HEE SUNG; KIM, JIN; NAM, KYUNG HAN; KIM, WOO HO

    2016-01-01

    The aim of the present study was to identify the prognostic factors for the propensity for recurrence in sporadic desmoid tumors. The catenin (cadherin-associated protein) β1 (CTNNB1) genotypes and expression of Wnt pathway proteins and midkine (also termed neurite growth-promoting factor 2) were investigated in 159 patients with sporadic desmoid tumors. Formalin-fixed paraffin-embedded tissues of the surgically resected desmoid tumors were examined by direct sequencing of CTNNB1 exon 3, and immunostained for the expression of β-catenin, T-cell factor 4 (TCF-4), phosphorylated protein kinase B (pAkt), midkine and menin using a tissue microarray method. Among the samples, 70% (111/159) exhibited point mutations of the CTNNB1 gene, including T41A (56%), S45F (8%), S45P (2%), S45N (2%) and T42A (1%). In addition, 100, 57, 24, 15 and 92% of the tumors expressed β-catenin, TCF-4, midkine, pAkt and menin, respectively. Positive midkine expression was significantly associated with the recurrence of tumors (P=0.001). The multivariate analysis of recurrence demonstrated that an extra-abdominal tumor site [hazard ratio (HR), 2.625; P=0.001] and midkine expression (HR, 2.077; P<0.009) were independent prognostic factors of tumor recurrence. In conclusion, the present results suggest that the tumor site and midkine expression may be predictive markers for the recurrence of sporadic desmoid tumors. PMID:26998061

  4. N-Cadherin in Neuroblastoma Disease: Expression and Clinical Significance

    PubMed Central

    Derycke, Lara; De Craemer, Annemie; De Brouwer, Sara; De Preter, Katleen; Van Roy, Nadine; Vandesompele, Jo; Speleman, Frank; Philippé, Jan; Benoit, Yves; Beiske, Klaus; Bracke, Marc; Laureys, Geneviève

    2012-01-01

    One of the first and most important steps in the metastatic cascade is the loss of cell-cell and cell-matrix interactions. N-cadherin, a crucial mediator of homotypic and heterotypic cell-cell interactions, might play a central role in the metastasis of neuroblastoma (NB), a solid tumor of neuroectodermal origin. Using Reverse Transcription Quantitative PCR (RT-qPCR), Western blot, immunocytochemistry and Tissue MicroArrays (TMA) we demonstrate the expression of N-cadherin in neuroblastoma tumors and cell lines. All neuroblastic tumors (n = 356) and cell lines (n = 10) expressed various levels of the adhesion protein. The N-cadherin mRNA expression was significantly lower in tumor samples from patients suffering metastatic disease. Treatment of NB cell lines with the N-cadherin blocking peptide ADH-1 (Exherin, Adherex Technologies Inc.), strongly inhibited tumor cell proliferation in vitro by inducing apoptosis. Our results suggest that N-cadherin signaling may play a role in neuroblastoma disease, marking involvement of metastasis and determining neuroblastoma cell viability. PMID:22355346

  5. Clinical significance of estrogen receptor beta in breast cancer.

    PubMed

    Saji, Shigehira; Hirose, Makiko; Toi, Masakazu

    2005-11-01

    Ever since the estrogen receptor (ER) beta was discovered in 1996, we have been trying to determine its value as a prognostic and/or predictive factor in breast cancer and its potential as a novel target for pharmacological intervention. Recent progress in cellular experiments has shown that ERbeta works as counter partner of ERalpha through inhibition of the transactivating function of ERalpha by heterodimerization, distinct regulation on several specific promoters by ERalpha or ERbeta, and ERbeta-specific regulated genes which are probably related to its anti-proliferative properties. Accumulated data from protein studies in breast cancer tissues indicate that positive expression of ERbeta appears to correlate with a favorable prognosis. Although the number of studies is small, a positive response to tamoxifen treatment is observed in both ERalpha- and ERbeta-positive populations. The significance of ERbeta2/cx, a splicing variant of ERbeta, remains controversial and needs to be analyzed in further studies. We postulate that a combined evaluation of ERbetacx with progesterone receptor may help the stratification of ERalpha-positive breast cancer. Epidemiological studies of hormone replacement therapy and isoflavone (genistein) consumption indicate the possible contribution of ERbeta-specific signaling in breast cancer prevention. A selective estrogen receptor modulator, which works as an antagonist of ERalpha and an agonist of ERbeta, may be a promising chemo-preventive treatment. PMID:16273360

  6. The relationship between medical students’ epistemological beliefs and achievement on a clinical performance examination

    PubMed Central

    Oh, Sun-A; Chung, Eun-Kyung; Han, Eui-Ryoung; Woo, Young-Jong; Kevin, Deiter

    2016-01-01

    Purpose: This study was to explore the relationship between clinical performance examination (CPX) achievement and epistemological beliefs to investigate the potentials of epistemological beliefs in ill-structured medical problem solving tasks. Methods: We administered the epistemological beliefs questionnaire (EBQ) to fourth-year medical students and correlated the results with their CPX scores. The EBQ comprised 61 items reflecting five belief systems: certainty of knowledge, source of knowledge, rigidity of learning, ability to learn, and speed of knowledge acquisition. The CPX included scores for history taking, physical examination, and patient-physician interaction. Results: The higher epistemological beliefs group obtained significantly higher scores on the CPX with regard to history taking and patient-physician interaction. The epistemological beliefs scores on certainty of knowledge and source of knowledge were significantly positively correlated with patient-physician interaction. The epistemological beliefs scores for ability to learn were significantly positively correlated with those for history taking, physical examination, and patient-physician interaction. Conclusion: Students with more sophisticated and advanced epistemological beliefs stances used more comprehensive and varied approaches in the patient-physician interaction. Therefore, educational efforts that encourage discussions pertaining to epistemological views should be considered to improve clinical reasoning and problem-solving competence in the clinic setting. PMID:26838566

  7. CLINICALLY SIGNIFICANT PSYCHOTROPIC DRUG-DRUG INTERACTIONS IN THE PRIMARY CARE SETTING

    PubMed Central

    English, Brett A.; Dortch, Marcus; Ereshefsky, Larry; Jhee, Stanford

    2014-01-01

    In recent years, the growing numbers of patients seeking care for a wide range of psychiatric illnesses in the primary care setting has resulted in an increase in the number of psychotropic medications prescribed. Along with the increased utilization of psychotropic medications, considerable variability is noted in the prescribing patterns of primary care providers and psychiatrists. Because psychiatric patients also suffer from a number of additional medical comorbidities, the increased utilization of psychotropic medications presents an elevated risk of clinically significant drug interactions in these patients. While life-threatening drug interactions are rare, clinically significant drug interactions impacting drug response or appearance of serious adverse drug reactions have been documented and can impact long-term outcomes. Additionally, the impact of genetic variability on the psychotropic drug’s pharmacodynamics and/or pharmacokinetics may further complicate drug therapy. Increased awareness of clinically relevant psychotropic drug interactions can aid clinicians to achieve optimal therapeutic outcomes in patients in the primary care setting. PMID:22707017

  8. Embracing the complexity of matricellular proteins: the functional and clinical significance of splice variation.

    PubMed

    Viloria, Katrina; Hill, Natasha J

    2016-05-01

    Matricellular proteins influence wide-ranging fundamental cellular processes including cell adhesion, migration, growth and differentiation. They achieve this both through interactions with cell surface receptors and regulation of the matrix environment. Many matricellular proteins are also associated with diverse clinical disorders including cancer and diabetes. Alternative splicing is a precisely regulated process that can produce multiple isoforms with variable functions from a single gene. To date, the expression of alternate transcripts for the matricellular family has been reported for only a handful of genes. Here we analyse the evidence for alternative splicing across the matricellular family including the secreted protein acidic and rich in cysteine (SPARC), thrombospondin, tenascin and CCN families. We find that matricellular proteins have double the average number of splice variants per gene, and discuss the types of domain affected by splicing in matricellular proteins. We also review the clinical significance of alternative splicing for three specific matricellular proteins that have been relatively well characterised: osteopontin (OPN), tenascin-C (TNC) and periostin. Embracing the complexity of matricellular splice variants will be important for understanding the sometimes contradictory function of these powerful regulatory proteins, and for their effective clinical application as biomarkers and therapeutic targets. PMID:27135623

  9. Significant Increase in Ecosystem C Can Be Achieved with Sustainable Forest Management in Subtropical Plantation Forests

    PubMed Central

    Wei, Xiaohua; Blanco, Juan A.

    2014-01-01

    Subtropical planted forests are rapidly expanding. They are traditionally managed for intensive, short-term goals that often lead to long-term yield decline and reduced carbon sequestration capacity. Here we show how it is possible to increase and sustain carbon stored in subtropical forest plantations if management is switched towards more sustainable forestry. We first conducted a literature review to explore possible management factors that contribute to the potentials in ecosystem C in tropical and subtropical plantations. We found that broadleaves plantations have significantly higher ecosystem C than conifer plantations. In addition, ecosystem C increases with plantation age, and reaches a peak with intermediate stand densities of 1500–2500 trees ha−1. We then used the FORECAST model to simulate the regional implications of switching from traditional to sustainable management regimes, using Chinese fir (Cunninghamia lanceolata) plantations in subtropical China as a study case. We randomly simulated 200 traditional short-rotation pure stands and 200 sustainably-managed mixed Chinese fir – Phoebe bournei plantations, for 120 years. Our results showed that mixed, sustainably-managed plantations have on average 67.5% more ecosystem C than traditional pure conifer plantations. If all pure plantations were gradually transformed into mixed plantations during the next 10 years, carbon stocks could rise in 2050 by 260.22 TgC in east-central China. Assuming similar differences for temperate and boreal plantations, if sustainable forestry practices were applied to all new forest plantation types in China, stored carbon could increase by 1,482.80 TgC in 2050. Such an increase would be equivalent to a yearly sequestration rate of 40.08 TgC yr−1, offsetting 1.9% of China’s annual emissions in 2010. More importantly, this C increase can be sustained in the long term through the maintenance of higher amounts of soil organic carbon and the production of timber

  10. Biomarkers of treatment outcome in schizophrenia: Defining a benchmark for clinical significance.

    PubMed

    Levine, Stephen Z; Rabinowitz, Jonathan; Uher, Rudolf; Kapur, Shitij

    2015-10-01

    Emerging data from on imaging and genetic studies have generated interest in "clinically significant" biomarkers to predict response and prognosis. What constitutes "clinical significance" and how a biomarker would reach that threshold are unclear. To develop a benchmark we reviewed different approaches for defining "clinical significance" applied in schizophrenia research and identified that an improvement of 15 points on the PANSS Total is considered meaningful in clinical settings. Using this benchmark and we simulated thousands of schizophrenia trials, using characteristics derived from the NEWMEDS database with over 8000 patients with schizophrenia, to the kind of imaging, genetic, and other biomarkers that could attain clinical significance. We plotted the interaction between frequency-of-occurrence, the effect size of biomarkers and their relationship to the clinical significance threshold. Results show that categorical biomarkers are likely to attain clinical significance when they occur in 20-50% of the clinical population, and can predict at least a 8-10 point PANSS scale difference. Genetic markers are likely to have clinical significance when they occur in 20-50% of the population and can predict 7-9 points on the PANSS scale. A marker with a lower frequency or lesser effect size would find it hard to meet clinical significance thresholds for schizophrenia. The assumptions and limitations of this approach are discussed. Compared with standards in the rest of medicine, biomarkers that can attain this benchmark will be cost-effective and are likely to be adopted by clinical systems. PMID:26145487

  11. Factors significantly related to science achievement of Malaysian middle school students: An analysis of TIMSS 1999 data

    NASA Astrophysics Data System (ADS)

    Mokshein, Siti Eshah

    The importance of science and technology in the global economy has led to growing emphasis on math and science achievement all over the world. In this study, I seek to identify variables at the student-level and school-level that account for the variation in science achievement of the eighth graders in Malaysia. Using the Third International Math and Science Study (TIMSS) 1999 for Malaysia, a series of HLM analysis was performed. Results indicate that (1) variation in overall science achievement is greater between schools than within schools; (2) both the selected student-level and school-level factors are Important in explaining the variation in the eight graders' achievement In science; (3) the selected student-level variables explain about 13% of the variation in students' achievement within schools, but as an aggregate, they account for a much larger proportion of the between-school variance; (4) the selected school-level variables account for about 55% of the variation between schools; (5) within schools, the effects of self-concept In science, awareness of the social implications of science, gender, and home educational resources are significantly related to achievement; (6) the effects of self-concept in science and awareness of social implications of science are significant even after controlling for the effects of SES; (7) between schools, the effects of the mean of home educational resources, mean of parents' education, mean of awareness of the social implications of science, and emphasis on conducting experiments are significantly related to achievement; (8) the effects of SES variables explain about 50% of the variation in the school means achievement; and (9) the effects of emphasis on conducting experiments on achievement are significant even after controlling for the effects of SES. Since it is hard to change the society, it is recommended that efforts to Improve science achievement be focused more at the school-level, concentrating on variables that

  12. Clinical relevance vs. statistical significance: Using neck outcomes in patients with temporomandibular disorders as an example.

    PubMed

    Armijo-Olivo, Susan; Warren, Sharon; Fuentes, Jorge; Magee, David J

    2011-12-01

    Statistical significance has been used extensively to evaluate the results of research studies. Nevertheless, it offers only limited information to clinicians. The assessment of clinical relevance can facilitate the interpretation of the research results into clinical practice. The objective of this study was to explore different methods to evaluate the clinical relevance of the results using a cross-sectional study as an example comparing different neck outcomes between subjects with temporomandibular disorders and healthy controls. Subjects were compared for head and cervical posture, maximal cervical muscle strength, endurance of the cervical flexor and extensor muscles, and electromyographic activity of the cervical flexor muscles during the CranioCervical Flexion Test (CCFT). The evaluation of clinical relevance of the results was performed based on the effect size (ES), minimal important difference (MID), and clinical judgement. The results of this study show that it is possible to have statistical significance without having clinical relevance, to have both statistical significance and clinical relevance, to have clinical relevance without having statistical significance, or to have neither statistical significance nor clinical relevance. The evaluation of clinical relevance in clinical research is crucial to simplify the transfer of knowledge from research into practice. Clinical researchers should present the clinical relevance of their results. PMID:21658987

  13. Achievable Convergence Angle and the Effect of Preparation Design on the Clinical Outcome of Full Veneer Crowns in Dogs

    PubMed Central

    Soukup, Jason W.; Snyder, Christopher J.; Karls, Tina L.; Riehl, Jessica

    2012-01-01

    Summary It is widely accepted that the convergence angle of a full veneer crown preparation should be as close to parallel as possible to attain adequate retention/resistance. The shape of the dog’s canine tooth limits the veterinary dentists’ ability to achieve the recommended convergence angle. However, the clinically achievable convergence angle of the canine tooth in dogs has not been evaluated. In addition, the convergence angle and other physical properties of a preparation, such as height and base diameter, have been shown to affect the retention/resistance of full veneer crowns, in vitro. This effect has not been evaluated clinically in the dog. Physical properties of 32 stone dies from full veneer crowns of canine teeth were studied to evaluate the clinically achievable convergence angle and the potential effect physical properties of the preparation had on the clinical outcome of the restoration. The clinically achievable convergence angle was much higher than the current recommendation. There was an association, albeit not statistically significant, between physical properties of a preparation (convergence angle, height, base diameter) and the clinical outcome of the restoration. PMID:21916370

  14. Achieving progress through clinical governance? A national study of health care managers' perceptions in the NHS in England

    PubMed Central

    Freeman, T; Walshe, K

    2004-01-01

    Background: A national cross sectional study was undertaken to explore the perceptions concerning the importance of, and progress in, aspects of clinical governance among board level and directorate managers in English acute, ambulance, and mental health/learning disabilities (MH/LD) trusts. Participants: A stratified sample of acute, ambulance, and mental health/learning disabilities trusts in England (n = 100), from each of which up to 10 board level and 10 directorate level managers were randomly sampled. Methods: Fieldwork was undertaken between April and July 2002 using the Organisational Progress in Clinical Governance (OPCG) schedule to explore managers' perceptions of the importance of, and organisational achievement in, 54 clinical governance competency items in five aggregated domains: improving quality; managing risks; improving staff performance; corporate accountability; and leadership and collaboration. The difference between ratings of importance and achievement was termed a shortfall. Results: Of 1916 individuals surveyed, 1177 (61.4%) responded. The competency items considered most important and recording highest perceived achievement related to corporate accountability structures and clinical risks. The highest shortfalls between perceived importance and perceived achievement were reported in joint working across local health communities, feedback of performance data, and user involvement. When aggregated into domains, greatest achievement was perceived in the assurance related areas of corporate accountability and risk management, with considerably less perceived achievement and consequently higher shortfalls in quality improvement and leadership and collaboration. Directorate level managers' perceptions of achievement were found to be significantly lower than those of their board level colleagues on all domains other than improving performance. No differences were found in perceptions of achievement between different types of trusts, or between

  15. The negative influence of significant others on high academic achieving school pupils' choice of nursing as a career.

    PubMed

    Neilson, Gavin R; McNally, Jim

    2013-03-01

    The International Council of Nurses proposes that the shortage of nurses is global in scale and is expected to become much worse in the years ahead. A major factor impacting on the worldwide nursing shortage is the diminishing number of young people choosing nursing as a career (International Council of Nurses, 2008). One important dimension of the school pupils' career choice process is their interactions with significant others and the influence of these significant others (Hodkinson and Sparkes, 1997). As Schools/Departments of Nursing endeavour to attract more intellectual school leavers it is important to examine what advice and opinions are significant others giving regarding nursing as a career choice and how influential is this advice. This paper is based on interview data from 20 high academic achieving 5th and 6th year school pupils in Scotland, paradigmatic cases from a larger sample, who had considered nursing as a possible career choice within their career preference cluster, but then later disregarded nursing and decided to pursue medicine or another health care profession. The data was particularly striking in revealing the negative influence of significant others on high academic achieving school pupils' choice of nursing as a career. The influence of significant others, these being specifically parents, guardians, guidance teachers and career advisors was very apparent in the data in that they had a very negative view regarding nursing as a career choice for high academic achieving school pupils. PMID:22464633

  16. Calculating Clinically Significant Change: Applications of the Clinical Global Impressions (CGI) Scale to Evaluate Client Outcomes in Private Practice

    ERIC Educational Resources Information Center

    Kelly, Peter James

    2010-01-01

    The Clinical Global Impressions (CGI) scale is a therapist-rated measure of client outcome that has been widely used within the research literature. The current study aimed to develop reliable and clinically significant change indices for the CGI, and to demonstrate its application in private psychological practice. Following the guidelines…

  17. Body Dysmorphic Disorder and Other Clinically Significant Body Image Concerns in Adolescent Psychiatric Inpatients: Prevalence and Clinical Characteristics

    ERIC Educational Resources Information Center

    Dyl, Jennifer; Kittler, Jennifer; Phillips, Katharine A.; Hunt, Jeffrey I.

    2006-01-01

    Background: This study assessed prevalence and clinical correlates of body dysmorphic disorder (BDD), eating disorders (ED), and other clinically significant body image concerns in 208 consecutively admitted adolescent inpatients. It was hypothesized that adolescents with BDD would have higher levels of depression, anxiety, and suicidality.…

  18. Confidence Intervals for Effect Sizes: Compliance and Clinical Significance in the "Journal of Consulting and Clinical Psychology"

    ERIC Educational Resources Information Center

    Odgaard, Eric C.; Fowler, Robert L.

    2010-01-01

    Objective: In 2005, the "Journal of Consulting and Clinical Psychology" ("JCCP") became the first American Psychological Association (APA) journal to require statistical measures of clinical significance, plus effect sizes (ESs) and associated confidence intervals (CIs), for primary outcomes (La Greca, 2005). As this represents the single largest…

  19. Pre-operative Thresholds for Achieving Meaningful Clinical Improvement after Arthroscopic Treatment of Femoroacetabular Impingement

    PubMed Central

    Nwachukwu, Benedict U.; Fields, Kara G.; Nawabi, Danyal H.; Kelly, Bryan T.; Ranawat, Anil S.

    2016-01-01

    Objectives: Knowledge of the thresholds and determinants for successful femoroacetabular impingement (FAI) treatment is evolving. The primary purpose of this study was to define pre-operative outcome score thresholds that can be used to predict patients most likely to achieve meaningful clinically important difference (MCID) after arthroscopic FAI treatment. Secondarily determinants of achieving MCID were evaluated. Methods: A prospective institutional hip arthroscopy registry was reviewed to identify patients with FAI treated with arthroscopic labral surgery, acetabular rim trimming, and femoral osteochondroplasty. The modified Harris Hip Score (mHHS), the Hip Outcome Score (HOS) and the international Hip Outcome Tool (iHOT-33) tools were administered at baseline and at one year post-operatively. MCID was calculated using a distribution-based method. A receiver operating characteristic (ROC) analysis was used to calculate cohort-based threshold values predictive of achieving MCID. Area under the curve (AUC) was used to define predictive ability (strength of association) with AUC >0.7 considered acceptably predictive. Univariate and multivariable analyses were used to analyze demographic, radiographic and intra-operative factors associated with achieving MCID. Results: There were 374 patients (mean + SD age, 32.9 + 10.5) and 56.4% were female. The MCID for mHHS, HOS activities of daily living (HOS-ADL), HOS Sports, and iHOT-33 was 8.2, 8.4,14.5, and 12.0 respectively. ROC analysis (threshold, % achieving MCID, strength of association) for these tools in our population was: mHHS (61.6, 78%, 0.68), HOS-ADL (83.8, 68%, 0.84), HOS-Sports (63.9, 64%, 0.74), and iHOT-33 (54.3, 82%, 0.65). Likelihood for achieving MCID declined above and increased below these thresholds. In univariate analysis female sex, femoral version, lower acetabular outerbridge score and increasing CT sagittal center edge angle (CEA) were predictive of achieving MCID. In multivariable analysis

  20. Expression and clinical significance of Beclin-1 in gastric cancer tissues of various clinical stages

    PubMed Central

    FEI, BINGYUAN; JI, FUJIAN; CHEN, XUEBO; LIU, ZHUO; LI, SHUO; MO, ZHANHAO; FANG, XUEDONG

    2016-01-01

    Autophagy is a common phenomenon in cancer metabolism. However the mechanism and guiding significance of autophagy in the development of gastric cancer has remained to be elucidated. In the present study, 75 gastric cancer tissue specimens were collected at The China Japan Union Hospital of Jilin University (Changchun, China). Of these samples, 16 cases were stage 1, 40 stage 2 and 19 stage 3. Polymerase chain reaction and western blotting were used to detect the messenger RNA and protein expression of Beclin-1, a significant protein associated with cellular autophagy. It was found that expression of Beclin-1 in cancer tissues from stages 1 and 2 was higher, while in stage 3 cases levels were significantly lower than that of adjacent normal tissues. In addition, the infiltration of inflammatory cytokines was also increased in stage 1 and 2 cases. In vitro studies revealed that following stimulation with interferon-γ (IFN-γ), autophagy-associated proteins Beclin-1 and microtubule-associated protein light chain 3 were activated. Furthermore, activation of autophagy inhibited xenograft growth in nude mice. The results of these in vivo and in vitro experiments indicated that in gastric cancer tissues, autophagy was downregulated following the development of cancer tissue and that inflammation may be a significant factor in this process. IFN-γ may be involved in the mediation of this process and thus present a novel target for the treatment of gastric cancer. PMID:26998161

  1. Graduate-Entry Medical Student Variables that Predict Academic and Clinical Achievement

    ERIC Educational Resources Information Center

    Blackman, Ian; Darmawan, I Gusti Ngurah

    2004-01-01

    A hypothetical model was formulated to explore factors that influenced academic and clinical achievement for graduate-entry medical students completing their third year of university studies. Nine latent variables were considered including the students' background, previous successes with their undergraduate and postgraduate studies and their…

  2. Undergraduate Nurse Variables that Predict Academic Achievement and Clinical Competence in Nursing

    ERIC Educational Resources Information Center

    Blackman, Ian; Hall, Margaret; Darmawan, I Gusti Ngurah.

    2007-01-01

    A hypothetical model was formulated to explore factors that influenced academic and clinical achievement for undergraduate nursing students. Sixteen latent variables were considered including the students' background, gender, type of first language, age, their previous successes with their undergraduate nursing studies and status given for…

  3. Cultural Competency and Achieving Styles in Clinical Social Work: A Conceptual and Empirical Exploration.

    ERIC Educational Resources Information Center

    Lu, Yuhwa Eva; Lum, Doman; Chen, Sheying

    2001-01-01

    A study explored the relationship between linguistic/cultural differences and individual achieving styles among 900 clinical social workers, including Asian Americans, Latinos, American Indians, African Americans, Jewish Americans, and Whites. Findings are related to a model of cultural competency in which cross-cultural counselor-client…

  4. Lead Clinical and Preclinical Antimalarial Drugs Can Significantly Reduce Sporozoite Transmission to Vertebrate Populations

    PubMed Central

    Upton, L. M.; Brock, P. M.; Churcher, T. S.; Ghani, A. C.; Gething, P. W.; Delves, M. J.; Sala, K. A.; Leroy, D.; Sinden, R. E.

    2014-01-01

    To achieve malarial elimination, we must employ interventions that reduce the exposure of human populations to infectious mosquitoes. To this end, numerous antimalarial drugs are under assessment in a variety of transmission-blocking assays which fail to measure the single crucial criteria of a successful intervention, namely impact on case incidence within a vertebrate population (reduction in reproductive number/effect size). Consequently, any reduction in new infections due to drug treatment (and how this may be influenced by differing transmission settings) is not currently examined, limiting the translation of any findings. We describe the use of a laboratory population model to assess how individual antimalarial drugs can impact the number of secondary Plasmodium berghei infections over a cycle of transmission. We examine the impact of multiple clinical and preclinical drugs on both insect and vertebrate populations at multiple transmission settings. Both primaquine (>6 mg/kg of body weight) and NITD609 (8.1 mg/kg) have significant impacts across multiple transmission settings, but artemether and lumefantrine (57 and 11.8 mg/kg), OZ439 (6.5 mg/kg), and primaquine (<1.25 mg/kg) demonstrated potent efficacy only at lower-transmission settings. While directly demonstrating the impact of antimalarial drug treatment on vertebrate populations, we additionally calculate effect size for each treatment, allowing for head-to-head comparison of the potential impact of individual drugs within epidemiologically relevant settings, supporting their usage within elimination campaigns. PMID:25385107

  5. Evidence of clinically significant change: the therapeutic alliance and the possibilities of outcomes-informed care.

    PubMed

    Manning, Walter H

    2010-11-01

    This article addresses the issue of clinically significant (or meaningful) change resulting from treatment for stuttering. Research in both medical and behavioral fields indicates that clients often have their own unique perspective of meaningful clinical change and that this perspective is often different from that of the professional administering the treatment. Among the variables that the client brings to the treatment session are their progression through stages of therapeutic change and the ways in which they believe they are capable of coping with their problem. Research has shown that how an individual interprets the meaning his or her therapeutic experience is central to clinically significant change. Procedures for obtaining feedback from clients concerning clinically significant change and the quality of the therapeutic alliance are described. PMID:21080293

  6. [Clinical efficacy and achievement of a complete remission in depression: increasing interest in treatment with escitalopram].

    PubMed

    Favré, P

    2012-02-01

    Such a prevalent disease as Major Depressive Disorder (MDD), associated with prominent impairment in physical and social functioning, implies as well an increased morbidity and mortality. Long-term treatments are required due to the frequent occurrence of relapses. Patient compliance is a core factor in both acute and continuation treatment, closely related to tolerability issues. We have partially reviewed the literature published on PubMed since 2004 which assess the relative antidepressant efficacy of escitalopram and comparator antidepressants in adult patients who met DSM-IV criteria for major depressive disorder (MDD). Clinically important differences exist between commonly prescribed antidepressants. These analyses are in favor of a superior efficacy and tolerability of long-term escitalopram treatment (10 to 20mg/day) compared with active controls, including selective serotonin re-uptake inhibitors (SSRIs) (paroxetine, citalopram, bupropion, fluoxetine, fluvoxamine, sertraline), serotonin/noradrenaline reuptake inhibitors (SNRIs) (venlafaxine, milnacipran and duloxetine) and noradrenergic and specific serotonergic antidepressants (NaSSAs) (mirtazapine). Cipriani et al. (2009) have performed a network meta-analysis of 12 new generation antidepressants. They have shown that clinically important differences exist between commonly prescribed antidepressants for both efficacy and acceptability in favor of escitalopram and sertraline in acute treatment, defined as 8-week treatment. Kasper et al. (2009) conducted a post-hoc pooled analysis of data from two 6-month randomized controlled trials that revealed superior efficacy and tolerability of escitalopram when compared with paroxetine. The pooled analysis of four randomized, double-blind, active comparator, 6-month trials in MDD, by Wade et al. (2009), showed that short-term outcomes may predict long-term treatment compliance and outcomes. A higher probability of achieving remission was associated with responding

  7. Gut-directed hypnotherapy significantly augments clinical remission in quiescent ulcerative colitis

    PubMed Central

    Keefer, Laurie; Taft, Tiffany H; Kiebles, Jennifer L; Martinovich, Zoran; Barrett, Terrence A; Palsson, Olafur S

    2013-01-01

    Summary Background Psychotherapy is not routinely recommended for in ulcerative colitis (UC). Gut-directed hypnotherapy (HYP) has been linked to improved function in the gastrointestinal tract and may operate through immune-mediated pathways in chronic diseases. Aims To determine the feasibility and acceptability of hypnotherapy and estimate the impact of hypnotherapy on clinical remission status over a 1 year period in patients with an historical flare rate of 1.3 times per year. Methods 54 patients were randomized at a single site to 7 sessions of gut-directed hypnotherapy (N = 26) or attention control (CON; N = 29) and followed for 1 year. The primary outcome was the proportion of participants in each condition that had remained clinically asymptomatic (clinical remission) through 52 weeks post-treatment. Results One-way ANOVA comparing hypnotherapy and control subjects on number of days to clinical relapse favored the hypnotherapy condition [F = 4.8 (1, 48), p = .03] by 78 days. Chi square analysis comparing the groups on proportion maintaining remission at 1 year was also significant [X2(1) = 3.9, p = .04], with 68% of hypnotherapy and 40% of control patients maintaining remission for 1 year. There were no significant differences between groups over time in quality of life, medication adherence, perceived stress or psychological factors. Conclusions This is the first prospective study that has demonstrated a significant effect of a psychological intervention on prolonging clinical remission in patients with quiescent UC. Clinical Trial # NCT00798642 PMID:23957526

  8. Body Dysmorphic Disorder and Other Clinically Significant Body Image Concerns in Adolescent Psychiatric Inpatients: Prevalence and Clinical Characteristics

    PubMed Central

    Dyl, Jennifer; Kittler, Jennifer; Phillips, Katharine A.; Hunt, Jeffrey I.

    2006-01-01

    Background This study assessed prevalence and clinical correlates of body dysmorphic disorder (BDD), eating disorders (ED), and other clinically significant body image concerns in 208 consecutively admitted adolescent inpatients. It was hypothesized that adolescents with BDD would have higher levels of depression, anxiety, and suicidality. Adolescents with eating disorders were expected to have higher levels of depression, anxiety, and trauma-related symptoms. Trauma-related symptoms were also examined in relation to BDD, in the absence of specific hypotheses. Method Participants completed the Body Dysmorphic Disorder Questionnaire (BDDQ) and reliable and valid self-report measures of suicidality, depression, anxiety, post-traumatic stress disorder (PTSD), dissociation, and sexual preoccupation/distress. Prevalence of BDD, eating disorders, and other clinically significant body image concerns was determined, and clinical correlates were examined. Results 6.7% (n = 14) of participants met DSM-IV criteria for definite (n = 10) or probable (n = 4) DSM-IV BDD, 3.8% (n = 8) met criteria for an eating disorder, and 22.1% (n = 46) had clinically significant shape/weight concerns (SWC) that did not clearly meet criteria for BDD or an eating disorder. Both the BDD and SWC groups scored significantly higher than the group with no significant body image concerns (no BDD/ED/SWC group) on measures of anxiety and suicidality. The BDD, SWC, and ED groups all had significantly higher levels of depression than the no BDD/ED/SWC group. Only the SWC group scored significantly higher than the no BDD/ED/SWC group on measures of PTSD, dissociation, and sexual preoccupation/distress. Conclusions A high proportion of participants had clinically significant body image concerns or a body image disorder. These concerns/disorders were associated with higher levels of depression, anxiety, and suicidality. In addition, the group concerned with body shape or weight had significantly greater

  9. Clinical importance of achieving biochemical control with medical therapy in adult patients with acromegaly

    PubMed Central

    Christofides, Elena A

    2016-01-01

    In acromegaly, achieving biochemical control (growth hormone [GH] level <1.0 ng/mL and age- and sex-normalized levels of insulin-like growth factor 1 [IGF-1]) through timely diagnosis and appropriate treatment provides an opportunity to improve patient outcomes. Diagnosis of acromegaly is challenging because it is rooted in observing subtle clinical manifestations, and it is typical for acromegaly to evolve for up to 10 years before it is recognized. This results in chronic exposure to elevated levels of GH and IGF-1 and delay in patients receiving appropriate treatment, which consequently increases mortality risk. In this review, the clinical impact of elevated GH and IGF-1 levels, the effectiveness of current therapies, and the potential role of novel treatments for acromegaly will be discussed. Clinical burden of acromegaly and benefits associated with management of GH and IGF-1 levels will be reviewed. Major treatment paradigms in acromegaly include surgery, medical therapy, and radiotherapy. With medical therapies, such as somatostatin analogs, dopamine agonists, and GH receptor antagonists, a substantial proportion of patients achieve reduced GH and normalized IGF-1 levels. In addition, signs and symptoms, quality of life, and comorbidities have also been reported to improve to varying degrees in patients who achieve biochemical control. Currently, there are several innovative therapies in development to improve patient outcomes, patient use, and access. Timely biochemical control of acromegaly ensures that the patient can ultimately improve morbidity and mortality from this disease and its extensive consequences. PMID:27471378

  10. Inpatient Treatment for Adolescents with Anorexia Nervosa: Clinical Significance and Predictors of Treatment Outcome.

    PubMed

    Schlegl, Sandra; Diedrich, Alice; Neumayr, Christina; Fumi, Markus; Naab, Silke; Voderholzer, Ulrich

    2016-05-01

    This study evaluated the clinical significance as well as predictors of outcome for adolescents with severe anorexia nervosa (AN) treated in an inpatient setting. Body mass index (BMI), eating disorder (ED) symptoms [Eating Disorder Inventory-2 (EDI-2)], general psychopathology and depression were assessed in 238 patients at admission and discharge. BMI increased from 14.8 + 1.2 to 17.3 + 1.4 kg/m(2). Almost a fourth (23.6%) of the patients showed reliable changes, and 44.7% showed clinically significant changes (EDI-2). BMI change did not significantly differ between those with reliable or clinically significant change or no reliable change in EDI-2. Length of stay, depression and body dissatisfaction were negative predictors of a clinically significant change. Inpatient treatment is effective in about two thirds of adolescents with AN and should be considered when outpatient treatment fails. About one third of patients showed significant weight gain, but did not improve regarding overall ED symptomatology. Future studies should focus on treatment strategies for non-responders. PMID:26603278

  11. Clinical decision support systems for improving diagnostic accuracy and achieving precision medicine.

    PubMed

    Castaneda, Christian; Nalley, Kip; Mannion, Ciaran; Bhattacharyya, Pritish; Blake, Patrick; Pecora, Andrew; Goy, Andre; Suh, K Stephen

    2015-01-01

    As research laboratories and clinics collaborate to achieve precision medicine, both communities are required to understand mandated electronic health/medical record (EHR/EMR) initiatives that will be fully implemented in all clinics in the United States by 2015. Stakeholders will need to evaluate current record keeping practices and optimize and standardize methodologies to capture nearly all information in digital format. Collaborative efforts from academic and industry sectors are crucial to achieving higher efficacy in patient care while minimizing costs. Currently existing digitized data and information are present in multiple formats and are largely unstructured. In the absence of a universally accepted management system, departments and institutions continue to generate silos of information. As a result, invaluable and newly discovered knowledge is difficult to access. To accelerate biomedical research and reduce healthcare costs, clinical and bioinformatics systems must employ common data elements to create structured annotation forms enabling laboratories and clinics to capture sharable data in real time. Conversion of these datasets to knowable information should be a routine institutionalized process. New scientific knowledge and clinical discoveries can be shared via integrated knowledge environments defined by flexible data models and extensive use of standards, ontologies, vocabularies, and thesauri. In the clinical setting, aggregated knowledge must be displayed in user-friendly formats so that physicians, non-technical laboratory personnel, nurses, data/research coordinators, and end-users can enter data, access information, and understand the output. The effort to connect astronomical numbers of data points, including '-omics'-based molecular data, individual genome sequences, experimental data, patient clinical phenotypes, and follow-up data is a monumental task. Roadblocks to this vision of integration and interoperability include ethical, legal

  12. [Clinical significance of prostate specific antigen and gamma-seminoprotein ratio for diagnosing prostate cancer].

    PubMed

    Akino, H; Suzuki, Y; Okada, K

    1998-08-01

    It has been reported that prostate specific antigen and gamma-seminoprotein ratio (PSA/gamma-Sm ratio) is an useful means for distinguishing benign prostatic hyperplasia and prostate cancer if serum PSA is measured by Eiken-PSA method. We studied the clinical significance of PSA/gamma-Sm ratio when using Markit-M-PSA method. PSA/gamma-Sm ratio had no superiority over PSA alone for detecting prostate cancer. The present results suggest that the clinical significance of PSA/gamma-Sm ratio can be varied by various PSA-assay kits. PMID:9750496

  13. Evaluating research for clinical significance: using critically appraised topics to enhance evidence-based neuropsychology.

    PubMed

    Bowden, Stephen C; Harrison, Elise J; Loring, David W

    2014-01-01

    Meehl's (1973, Psychodiagnosis: Selected papers. Minneapolis: University of Minnesota Press) distinction between statistical and clinical significance holds special relevance for evidence-based neuropsychological practice. Meehl argued that despite attaining statistical significance, many published findings have limited practical value since they do not inform clinical care. In the context of an ever expanding clinical research literature, accessible methods to evaluate clinical impact are needed. The method of Critically Appraised Topics (Straus, Richardson, Glasziou, & Haynes, 2011, Evidence-based medicine: How to practice and teach EBM (4th ed.). Edinburgh: Elsevier Churchill-Livingstone) was developed to provide clinicians with a "toolkit" to facilitate implementation of evidence-based practice. We illustrate the Critically Appraised Topics method using a dementia screening example. We argue that the skills practiced through critical appraisal provide clinicians with methods to: (1) evaluate the clinical relevance of new or unfamiliar research findings with a focus on patient benefit, (2) help focus of research quality, and (3) incorporate evaluation of clinical impact into educational and professional development activities. PMID:23463942

  14. Evaluation of preceptors and skills achievement by clinical pharmacy clerkship students during their clinical rotations at University of Gondar, Ethiopia

    PubMed Central

    Belachew, Sewunet Admasu; Abegaz, Tadesse Melaku; Bhagavathula, Akshaya Srikanth; Getachew, Henok; Tefera, Yonas Getaye

    2016-01-01

    Aim To investigate the overall experiences of clinical pharmacy students during their clinical attachments and to understand the breadth and depth of clinical skills provided by their preceptors. Methods A cross-sectional study using a self-administered questionnaire containing 34 items to obtain feedback from the clerkship students from June to July 2015. Data analysis was performed to calculate mean, standard deviation, percentages, and multiple logistic regression using Statistical Package for the Social Sciences (SPSS) software Version 22. Statistical significance was set at P<0.01. Results All 58 clerkship students actively participated in the study, yielding a response rate of 100%. While students ranked their clerkship experience as moderate, >15% remarked that they did not receive enough opportunities to hone their pharmaceutical care documentation skills. A relatively high percentage of students (32.8%) strongly agreed that their preceptors had provided ample opportunity to discuss the patient problems at the bedside and encouraged them to express their opinions regarding patients’ drug therapeutic issues. This study also revealed that students’ continuity in developing their therapeutic and disease process knowledge was significantly associated with the preceptor’s ability to provide adequate training and orientation (P =0.01), engagement in clinical pharmacy activities (P =0.01), regular review of students’ work (P =0.01), and instruction to students before entering clinical sites (P =0.00). Conclusion The findings of this study reveal that a majority of the students were moderately satisfied with the clinical training program and preceptors need to demonstrate effective pharmaceutical care processes in their clinical sites. PMID:27099540

  15. Elizabethkingia anophelis bacteremia is associated with clinically significant infections and high mortality

    PubMed Central

    Lau, Susanna K. P.; Chow, Wang-Ngai; Foo, Chuen-Hing; Curreem, Shirly O. T.; Lo, George Chi-Shing; Teng, Jade L. L.; Chen, Jonathan H. K.; Ng, Ricky H. Y.; Wu, Alan K. L.; Cheung, Ingrid Y. Y.; Chau, Sandy K. Y.; Lung, David C.; Lee, Rodney A.; Tse, Cindy W. S.; Fung, Kitty S. C.; Que, Tak-Lun; Woo, Patrick C. Y.

    2016-01-01

    Unlike Elizabethkingia meningoseptica, the clinical importance of E. anophelis is poorly understood. We determined the clinical and molecular epidemiology of bacteremia caused by Elizabethkingia-like species from five regional hospitals in Hong Kong. Among 45 episodes of Elizabethkingia-like bacteremia, 21 were caused by Elizabethkingia, including 17 E. anophelis, three E. meningoseptica and one E. miricola; while 24 were caused by other diverse genera/species, as determined by 16S rRNA gene sequencing. Of the 17 cases of E. anophelis bacteremia, 15 (88%) were clinically significant. The most common diagnosis was pneumonia (n = 5), followed by catheter-related bacteremia (n = 4), neonatal meningitis (n = 3), nosocomial bacteremia (n = 2) and neutropenic fever (n = 1). E. anophelis bacteremia was commonly associated with complications and carried 23.5% mortality. In contrast, of the 24 episodes of bacteremia due to non-Elizabethkingia species, 16 (67%) were clinically insignificant. Compared to non-Elizabethkingia bacteremia, Elizabethkingia bacteremia was associated with more clinically significant infections (P < 0.01) and positive cultures from other sites (P < 0.01), less polymicrobial bacteremia (P < 0.01), and higher complication (P < 0.05) and mortality (P < 0.05) rates. Elizabethkingia bacteremia is predominantly caused by E. anophelis instead of E. meningoseptica. Elizabethkingia bacteremia, especially due to E. anophelis, carries significant morbidity and mortality, and should be considered clinically significant unless proven otherwise. PMID:27185741

  16. 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…

  17. Clinically Significant Change to Establish Benchmarks in Residential Drug and Alcohol Treatment Services

    ERIC Educational Resources Information Center

    Billingham, Daniel D.; Kelly, Peter J.; Deane, Frank P.; Crowe, Trevor P.; Buckingham, Mark S.; Craig, Fiona L.

    2012-01-01

    There is increasing emphasis on the use routine outcome assessment measures to inform quality assurance initiatives. The calculation of reliable and clinically significant change indices is one strategy that organizations could use to develop both internal and externally focused benchmarking processes. The current study aimed to develop reliable…

  18. Clinical Significance: A Statistical Approach to Defining Meaningful Change in Psychotherapy Research.

    ERIC Educational Resources Information Center

    Jacobson, Neil S.; Truax, Paula

    1991-01-01

    Describes ways of operationalizing clinically significant change, defined as extent to which therapy moves someone outside range of dysfunctional population or within range of functional population. Uses examples to show how clients can be categorized on basis of this definition. Proposes reliable change index (RC) to determine whether magnitude…

  19. Reliability and Clinical Significance of Mobility and Balance Assessments in Multiple Sclerosis

    ERIC Educational Resources Information Center

    Learmonth, Yvonne C.; Paul, Lorna; McFadyen, Angus K.; Mattison, Paul; Miller, Linda

    2012-01-01

    The aim of the study was to establish the test-retest reliability, clinical significance and precision of four mobility and balance measures--the Timed 25-Foot Walk, Six-minute Walk, Timed Up and Go and the Berg Balance Scale--in individuals moderately affected by multiple sclerosis. Twenty four participants with multiple sclerosis (Extended…

  20. Expression and clinical significance of cytochrome c oxidase subunit IV in colorectal cancer patients

    PubMed Central

    Zhang, Kun; Chen, Yibing; Huang, Xiaojun; Qu, Ping; Pan, Qiuzhong; Lü, Lin; Jiang, Shanshan; Su, Haichuan

    2016-01-01

    Introduction Previous studies have demonstrated that the expression of cytochrome c oxidase (COX) subunits encoded by mitochondrial DNA is elevated in colorectal cancer (CRC). However, the expression of nuclear DNA-encoded COX IV and its clinical significance have not yet been investigated in CRC. Material and methods We examined COX IV expression in paired CRC samples (cancer and pericancerous tissues) by quantitative real-time polymerase chain reaction (qPCR), Western blot and immunohistochemical staining and analyzed its clinical significance. Results qPCR and Western blot analyses showed that COX IV expression was significantly elevated at both the mRNA (p = 0.05) and protein levels in CRC tissue samples when compared with those in paired pericancerous tissues. Immunohistochemistry also revealed that COX IV expression was significantly increased in CRC tissues (p < 0.001). Association analyses showed that there was no significant association between COX IV expression and clinical parameters of CRC patients except for gender (p = 0.017). Moreover, we did not find any association between COX IV expression and overall survival or recurrence-free survival of CRC patients. Further analysis showed no significant relationship between the expression of COX IV and proliferating cell nuclear antigen (PCNA), a marker of cell proliferation. Conclusions Our findings suggest that elevated COX IV expression may play an important role in colorectal carcinogenesis, but not in progression, which warrants further investigation in future studies. PMID:26925120

  1. Group cognitive behavioural treatment of youth anxiety in community based clinical practice: Clinical significance and benchmarking against efficacy.

    PubMed

    Jónsson, H; Thastum, M; Arendt, K; Juul-Sørensen, M

    2015-10-01

    The efficacy of a group cognitive behavioural therapy (CBT) programme (Cool Kids) of youth anxiety has been demonstrated at university clinics in Australia and Denmark and similar CBT programmes have been found effective within community settings in other countries. However, most effectiveness studies of CBT for youth anxiety have either used a mixture of CBT guidelines, or translated protocols not previous tested in an efficacy trial. This study used a benchmarking strategy to compare outcomes from the same CBT programme used at a university research clinic (N=87) and community centres (N=82). There was a significant reduction on both clinical and self-report measures of youth anxiety over time with medium to large effect sizes within both samples. Treatment effects on self-report measures of youth anxiety were significantly larger within the university sample, while changes in clinical measures of youth anxiety were similar in the two samples. Overall these findings suggest that an efficacious CBT group treatment programme developed within research contexts is transportable to community centres. Despite being effective within the community, the results indicate that the treatment may lose some of its efficacy when disseminated to the community. PMID:26283461

  2. Laser thermokeratoplasty: analysis of in-vitro results and refractive changes achieved in a first clinical study

    NASA Astrophysics Data System (ADS)

    Brinkmann, Ralf; Geerling, Gerd; Kampmeier, Juergen; Koop, Norbert; Radt, Benno; Birngruber, Reginald

    1997-12-01

    Laser thermokeratoplasty (LTK) is a minimally invasive method to correct hyperopia and astigmatism. A cw mid-IR laser diode emitting at wavelengths around 1.86 micrometers was used to perform LTK on a first clinical trial. The coagulations were applied to the cornea by means of a specially designed focusing handpiece which was introduced into a corneal application mask fixed by a suction ring. Coagulation patterns consisting of 8 spots per ring were performed with a laser power between 100 - 150 mW and an irradiation time of 10 seconds both on single and on double rings. Significant refractive changes up to 19 D could initially be achieved followed by a strong regression within the first month. Three months post LTK, refractive changes achieved with the single and double ring have stabilized, yielding 1.2 and 1.8 D on the average, respectively. The method reveals only little adverse effects limited to the first days post-op. Force measurements were performed on corneal stripes, which were submerged for 10 s into an oil bath of constant temperature in order to investigate the absolute temperatures required for corneal collagen contraction. Only temperatures exceeding 90 degree(s)C induced a significant force. Analyzing the clinically used LTK parameters by temperature calculations revealed that only a small part of the heated stromal volume experienced sufficient high temperatures to induce significant collagen shrinkage.

  3. Detection of Clinically Significant Retinopathy of Prematurity Using Wide-angle Digital Retinal Photography

    PubMed Central

    Chiang, Michael F.; Melia, Michele; Buffenn, Angela N.; Lambert, Scott R.; Recchia, Franco M.; Simpson, Jennifer L.; Yang, Michael B.

    2013-01-01

    Objective To evaluate the accuracy of detecting clinically significant retinopathy of prematurity (ROP) using wide-angle digital retinal photography. Methods Literature searches of PubMed and the Cochrane Library databases were conducted last on December 7, 2010, and yielded 414 unique citations. The authors assessed these 414 citations and marked 82 that potentially met the inclusion criteria. These 82 studies were reviewed in full text; 28 studies met inclusion criteria. The authors extracted from these studies information about study design, interventions, outcomes, and study quality. After data abstraction, 18 were excluded for study deficiencies or because they were superseded by a more recent publication. The methodologist reviewed the remaining 10 studies and assigned ratings of evidence quality; 7 studies were rated level I evidence and 3 studies were rated level III evidence. Results There is level I evidence from ≥5 studies demonstrating that digital retinal photography has high accuracy for detection of clinically significant ROP. Level III studies have reported high accuracy, without any detectable complications, from real-world operational programs intended to detect clinically significant ROP through remote site interpretation of wide-angle retinal photographs. Conclusions Wide-angle digital retinal photography has the potential to complement standard ROP care. It may provide advantages through objective documentation of clinical examination findings, improved recognition of disease progression by comparing previous photographs, and the creation of image libraries for education and research. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references. PMID:22541632

  4. [Further understanding on myocardial damage in the early stage post severe burn and its clinical significance].

    PubMed

    Huang, Y S

    2016-05-20

    A series of studies demonstrated that myocardial damage and cardiac dysfunction occurs immediately following severe burn, even before significant reduction in blood volume due to increased capillary permeability. Such myocardial damage and cardiac dysfunction leads to cardiac deficiency, and it is a precipitating factor for burn shock and ischemic/hypoxic injury. In recent years, many experimental and clinical studies elucidated the pathogenesis and confirmed the clinical importance of prevention and treatment of"shock heart"in the early stage post severe burn. PMID:27188482

  5. HyperModules: identifying clinically and phenotypically significant network modules with disease mutations for biomarker discovery

    PubMed Central

    Leung, Alvin; Bader, Gary D.; Reimand, Jüri

    2014-01-01

    Summary: Correlating disease mutations with clinical and phenotypic information such as drug response or patient survival is an important goal of personalized cancer genomics and a first step in biomarker discovery. HyperModules is a network search algorithm that finds frequently mutated gene modules with significant clinical or phenotypic signatures from biomolecular interaction networks. Availability and implementation: HyperModules is available in Cytoscape App Store and as a command line tool at www.baderlab.org/Sofware/HyperModules. Contact: Juri.Reimand@utoronto.ca or Gary.Bader@utoronto.ca Supplementary information: Supplementary data are available at Bioinformatics online PMID:24713437

  6. Using Visual and Narrative Methods to Achieve Fair Process in Clinical Care

    PubMed Central

    2011-01-01

    The Institute of Medicine has targeted patient-centeredness as an important area of quality improvement. A major dimension of patient-centeredness is respect for patient's values, preferences, and expressed needs. Yet specific approaches to gaining this understanding and translating it to quality care in the clinical setting are lacking. From a patient perspective quality is not a simple concept but is best understood in terms of five dimensions: technical outcomes; decision-making efficiency; amenities and convenience; information and emotional support; and overall patient satisfaction. Failure to consider quality from this five-pronged perspective results in a focus on medical outcomes, without considering the processes central to quality from the patient's perspective and vital to achieving good outcomes. In this paper, we argue for applying the concept of fair process in clinical settings. Fair process involves using a collaborative approach to exploring diagnostic issues and treatments with patients, explaining the rationale for decisions, setting expectations about roles and responsibilities, and implementing a core plan and ongoing evaluation. Fair process opens the door to bringing patient expertise into the clinical setting and the work of developing health care goals and strategies. This paper provides a step by step illustration of an innovative visual approach, called photovoice or photo-elicitation, to achieve fair process in clinical work with acquired brain injury survivors and others living with chronic health conditions. Applying this visual tool and methodology in the clinical setting will enhance patient-provider communication; engage patients as partners in identifying challenges, strengths, goals, and strategies; and support evaluation of progress over time. Asking patients to bring visuals of their lives into the clinical interaction can help to illuminate gaps in clinical knowledge, forge better therapeutic relationships with patients living

  7. Using visual and narrative methods to achieve fair process in clinical care.

    PubMed

    Lorenz, Laura S; Chilingerian, Jon A

    2011-01-01

    The Institute of Medicine has targeted patient-centeredness as an important area of quality improvement. A major dimension of patient-centeredness is respect for patient's values, preferences, and expressed needs. Yet specific approaches to gaining this understanding and translating it to quality care in the clinical setting are lacking. From a patient perspective quality is not a simple concept but is best understood in terms of five dimensions: technical outcomes; decision-making efficiency; amenities and convenience; information and emotional support; and overall patient satisfaction. Failure to consider quality from this five-pronged perspective results in a focus on medical outcomes, without considering the processes central to quality from the patient's perspective and vital to achieving good outcomes. In this paper, we argue for applying the concept of fair process in clinical settings. Fair process involves using a collaborative approach to exploring diagnostic issues and treatments with patients, explaining the rationale for decisions, setting expectations about roles and responsibilities, and implementing a core plan and ongoing evaluation. Fair process opens the door to bringing patient expertise into the clinical setting and the work of developing health care goals and strategies. This paper provides a step by step illustration of an innovative visual approach, called photovoice or photo-elicitation, to achieve fair process in clinical work with acquired brain injury survivors and others living with chronic health conditions. Applying this visual tool and methodology in the clinical setting will enhance patient-provider communication; engage patients as partners in identifying challenges, strengths, goals, and strategies; and support evaluation of progress over time. Asking patients to bring visuals of their lives into the clinical interaction can help to illuminate gaps in clinical knowledge, forge better therapeutic relationships with patients living

  8. Cell and tissue interactions in carcinogenesis and metastasis and their clinical significance.

    PubMed

    Tarin, David

    2011-04-01

    This review describes a new vision for future directions in the study of metastatic cancer biology and pathology. It is based upon clinical and experimental observations on the constituent cell lineages within a neoplasm and on tumour-host interactions. The vision incorporates information from studies in population biology, developmental biology and experimental pathology as well as investigations upon human malignant disease. The assembled information reveals that invasion and metastasis are supra-cellular manifestations of "emergent behavior" among combinations of normal and malignant cell lineages in vivo. Emergent behavior is a combinatorial interactive process in which a population displays new traits which cannot be achieved by individuals acting separately and which subside when the specific population mix disaggregates. Disruption of such pathological interactions in the field of a developing primary or secondary tumour is, therefore, required to disable the malignant population and arrest progression without tissue destruction. These conclusions originate, in part, from principles which govern the sociobiology and group behavior of bees, ants, fish, birds and human societies. In all these social organisms, external factors can disrupt signaling mechanisms and induce expanding self-perpetuating rogue behavior, leading to social disintegration. These principles also apply to cellular societies composing higher animals, which likewise need intrinsic rules to maintain social order and avoid anarchy, and recognition of this is essential for advancing future research on the mechanisms involved in carcinogenesis and metastasis. Summarised evidence is presented here to support the conclusion that miscommunications between cells and tissues in the region of the developing tumour and its metastases are the main direct perpetrators of malignant disease. Genetic lesions (mutations, deletions, translocations, reduplications, etc.), commonly seen in cancers, can

  9. Diabetic gastrointestinal autonomic neuropathy: current status and new achievements for everyday clinical practice.

    PubMed

    Gatopoulou, A; Papanas, N; Maltezos, E

    2012-09-01

    Gastrointestinal symptoms occur frequently among patients with diabetes mellitus and are associated with considerable morbidity. Diabetic gastrointestinal autonomic neuropathy represents a complex disorder with multifactorial pathogenesis, which is still not well understood. It appears to involve a spectrum of metabolic and cellular changes that affect gastrointestinal motor and sensory control. It may affect any organ in the digestive system. Clinical manifestations are often underestimated, and therefore autonomic neuropathy should be suspected in all diabetic patients with unexplained gastrointestinal symptoms. Advances in technology have now enabled assessment of gastrointestinal motor function. Moreover, novel pharmacological approaches, along with endoscopic and surgical treatment options, contribute to improved outcomes. This review summarises the progress achieved in diabetic gastrointestinal autonomic neuropathy during the last years, focusing on clinical issues of practical importance to the everyday clinician. PMID:22863425

  10. Clinical significance of Angiopoietin-1 in Behcet's disease patients with vascular involvement.

    PubMed

    Bassyouni, Iman H; Sharaf, Mohammed; Wali, Iman E; Mansour, Hossam M

    2016-06-01

    Behcet's disease (BD) is a chronic multisystem inflammatory disorder of unclear etiology. Vascular inflammation, endothelial dysfunction and angiogenesis may be in part responsible for the pathogenesis of BD. Angiopoietin-1 (Ang-1) is a recent angiogenic mediator. The aim of the present study was to assess Ang-1 in the plasma of BD patients as well as to analyze its association with clinical, and laboratory parameters of the disease. The present study included 47 BD patients and 30 age- and gender-matched healthy controls. Demographic, clinical, disease activity and severity were prospectively assessed. Plasma Ang-1 levels were measured using enzyme-linked immunosorbent assay. The plasma level of Ang-1 in BD patients was significantly lower than healthy controls (p = 0.005). Plasma Ang-1 level in patients with vascular affection was significantly lower than those without vascular affection (p = 0.045). Levels of Ang-1 showed a significant positive correlation with steroid dose. Patients who received cyclophosphamide or steroids showed a significant increase in plasma Ang-1 level. This was further confirmed by the results of the multivariate analysis. There was no significant association between plasma Ang-1 levels and other clinical manifestations or disease activity and severity. Plasma Ang-1 levels were diminished in our BD patients especially in patients with vascular involvement. Larger studies with further investigations of the precise role of Ang-1 in the pathogenesis of BD are needed and might lead to novel therapies for the clinical management of BD. PMID:25964071

  11. Cross-reactivity of steroid hormone immunoassays: clinical significance and two-dimensional molecular similarity prediction

    PubMed Central

    2014-01-01

    Background Immunoassays are widely used in clinical laboratories for measurement of plasma/serum concentrations of steroid hormones such as cortisol and testosterone. Immunoassays can be performed on a variety of standard clinical chemistry analyzers, thus allowing even small clinical laboratories to do analysis on-site. One limitation of steroid hormone immunoassays is interference caused by compounds with structural similarity to the target steroid of the assay. Interfering molecules include structurally related endogenous compounds and their metabolites as well as drugs such as anabolic steroids and synthetic glucocorticoids. Methods Cross-reactivity of a structurally diverse set of compounds were determined for the Roche Diagnostics Elecsys assays for cortisol, dehydroepiandrosterone (DHEA) sulfate, estradiol, progesterone, and testosterone. These data were compared and contrasted to package insert data and published cross-reactivity studies for other marketed steroid hormone immunoassays. Cross-reactivity was computationally predicted using the technique of two-dimensional molecular similarity. Results The Roche Elecsys Cortisol and Testosterone II assays showed a wider range of cross-reactivity than the DHEA sulfate, Estradiol II, and Progesterone II assays. 6-Methylprednisolone and prednisolone showed high cross-reactivity for the cortisol assay, with high likelihood of clinically significant effect for patients administered these drugs. In addition, 21-deoxycortisol likely produces clinically relevant cross-reactivity for cortisol in patients with 21-hydroxylase deficiency, while 11-deoxycortisol may produce clinically relevant cross-reactivity in 11β-hydroxylase deficiency or following metyrapone challenge. Several anabolic steroids may produce clinically significant false positives on the testosterone assay, although interpretation is limited by sparse pharmacokinetic data for some of these drugs. Norethindrone therapy may impact immunoassay measurement

  12. Clinical significance of RET mutation screening in a pedigree of multiple endocrine neoplasia type 2A.

    PubMed

    Ying, Rongbiao; Feng, Jun

    2016-08-01

    The clinical characteristics and RET proto-oncogene (RET‑PO) mutation status of a patient with multiple endocrine neoplasia type 2A pedigree (MEN2A) was analyzed with the aim of preliminarily exploring the molecular mechanisms and clinical significance of the disease. Clinical characteristics of a single MEN2A patient were analyzed. Genomic DNA was extracted from the peripheral blood of the proband and 10 family members. The 21 exons of RET‑PO were PCR amplified and the amplified products were sequenced. Of the family members, 5 exhibited a C634Y (TGC→TAC) missense mutation in exon 11 of RET‑PO, among which 2 family members were screened as mutation carriers, while the others did not exhibit clinical symptoms of the mutation. The screening and analysis of RET‑PO mutations for the MEN2A proband and the family members suggests potential clinical phenotypes and enables assessment of the risk of disease development, thus providing useful information for determining the surgical timing of preventive thyroid gland removal. PMID:27277749

  13. Clinical Significance of Histological Features of Thrombi in Patients with Myocardial Infarction

    PubMed Central

    Sebben, Juliana Canedo; Cambruzzi, Eduardo; Avena, Luisa Martins; Gazeta, Cristina do Amaral; Gottschall, Carlos Antonio Mascia; de Quadros, Alexandre Schaan

    2013-01-01

    Background Percutaneous Coronary Intervention (PCI) is the most common strategy for the treatment of Acute ST segment elevation Myocardial Infarction (STEMI), and thromboaspiration has been increasingly utilized for removal of occlusive thrombi. Objectives To analyze the influence of histopathological features of coronary thrombi in clinical outcomes of patients with STEMI, and the association of these variables with clinical, angiographic, and laboratory features and medications used in hospitalization. Methods Prospective cohort study. All patients were monitored during hospitalization and thirty days after the event. Aspirated thrombi were preserved in formalin and subsequently stained with hematoxylin-eosin and embedded in paraffin. Thrombi were classified as recent and old. The primary outcome was the occurrence of major cardiovascular events within thirty days. Results During the study period, 1,149 patients were evaluated with STEMI, and 331 patients underwent thrombi aspiration, leaving 199 patients available for analysis. It was identified recent thrombi in 116 patients (58%) and old thrombi in 83 patients (42%). Recent thrombi have greater infiltration of red blood cells than old thrombi (p = 0.02), but there were no statistically significant differences between other clinical, angiographic, laboratory, and histopathological features and medications in both group of patients. The rates of clinical outcomes were similar in both groups. Conclusions Recent thrombi were identified in 58% of patients with STEMI and it was observed an association with infiltration of red blood cells. There was no association between histopathological features of thrombi and clinical variables and cardiovascular outcomes. PMID:24162472

  14. Review of Ingested and Aspirated Foreign Bodies in Children and Their Clinical Significance for Radiologists.

    PubMed

    Pugmire, Brian S; Lim, Ruth; Avery, Laura L

    2015-01-01

    Ingested and aspirated foreign bodies are a common occurrence in children and are important causes of morbidity and mortality in the pediatric population. Imaging plays an important role in the diagnosis of ingested and aspirated foreign bodies in children and can be crucial to guiding the clinical management of these patients. Prompt identification and localization of ingested foreign bodies is essential to determining the appropriate treatment, as several types of commonly ingested foreign bodies require urgent removal and others can be managed conservatively. In particular, disk batteries impacted in the esophagus carry a high risk of esophageal injury or perforation; multiple ingested magnets can become attracted to each other across bowel walls and cause bowel perforation and fistula formation; and sharp objects commonly cause complications as they pass through the gastrointestinal tract. Accordingly, these ingested foreign bodies warrant aggressive clinical management and therefore radiologists must be familiar with their imaging appearances and clinical implications. Prompt recognition of secondary radiographic signs of foreign-body aspiration is also crucial, as clinical symptoms can sometimes be nonspecific and most aspirated foreign bodies are radiolucent. Overall, radiography is the most important modality in the evaluation of ingested or aspirated foreign bodies; however, fluoroscopy and computed tomography play an ancillary role in complicated cases. It is essential that every radiologist who interprets imaging examinations of children be aware of the imaging appearances of commonly ingested and aspirated foreign bodies and their clinical significance. PMID:26295734

  15. [Expression and clinical significance of Ki-67 in diffuse large B cell lymphoma].

    PubMed

    Zhou, Ying; Zhao, Yu; Bo, Jian; Li, Yan-Fen; Ma, Chao; Shi, Ya-Nan

    2013-10-01

    This study was aimed to evaluate the proliferation-associated antigen Ki-67 expression in diffuse large B cell lymphoma (DLBCL) and its clinical significance. The Ki-67 expression and its correlation with prognosis in 50 patients with DLBCL treated with rituximab plus CHOP (R-CHOP) between January 2008 and December 2010 were analyzed retrospectively. The results indicated that there was no significant relationship between Ki-67 expression and clinical features, including age, sex, staging, B symptoms, LDH level, IPI, extranodal site involvement, presence of bulky tumors (>10 cm in diameter), bone marrow involvement, GCG nor GCB type, or response to first line treatment. The median survival was 50 months and 15 months in low Ki-67 expression group (<85%) and in high Ki-67 expression group ( ≥ 85%) respectively. The overall survival (OS) and progress-free survival (PFS) in low Ki-67 expression group were obviously longer than that in high Ki-67 expression group (P = 0.001; P = 0.027). In univariate analysis, the clinical factors associated with OS included Ann Arbor staging and Ki-67 expression. The clinical factors associated with PFS included Ann Arbor staging. IPI and Ki-67 expression. In multivariate analysis. The Ki-67 expression level was an independent prognostic factor for OS (HR = 4.90; 95% CI, 1.456-16.511; P = 0.0103). It is concluded that Ki-67 expression level seems to be an effective marker for evaluation of DLBCL prognosis. PMID:24156426

  16. Achieving consensus for clinical trials: the REiNS International Collaboration.

    PubMed

    Plotkin, Scott R; Blakeley, Jaishri O; Dombi, Eva; Fisher, Michael J; Hanemann, C Oliver; Walsh, Karin S; Wolters, Pamela L; Widemann, Brigitte C

    2013-11-19

    The neurofibromatoses (NF)--including neurofibromatosis 1 (NF1), neurofibromatosis 2 (NF2), and schwannomatosis--are related tumor-suppressor syndromes characterized by a predisposition to multiple tumor types and other disease manifestations, which often result in functional disability, reduced quality of life, pain, and, in some cases, malignancy. With increasing knowledge of the biology and pathogenesis of NF, clinical trials with targeted agents directed at NF tumors have become available. Most clinical trials for patients with NF have used designs and endpoints similar to oncology trials. However, differences in the disease manifestations and natural history of NF (compared to cancers) require the development of new designs and endpoints to perform meaningful NF clinical trials. The Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) International Collaboration was established in 2011 at the Children's Tumor Foundation meeting to achieve consensus within the NF community about the design of future clinical trials, with a specific emphasis on endpoints. The REiNS Collaboration includes 7 working groups that focus on imaging of tumor response; functional, visual, patient-reported, and neurocognitive outcomes; whole-body MRI; and disease biomarkers. This supplement includes the first series of recommendations by the REiNS Collaboration. The hope is that these recommendations will be used by members of the group and by researchers outside of the REiNS International Collaboration to standardize the measurement of outcomes and thus improve clinical trials for patients with NF. Ultimately, we plan to engage industry partners and national regulatory agencies in this process to facilitate the approval of drugs for patients with NF. PMID:24249801

  17. Quantifying clinically significant change: a brief review of methods and presentation of a hybrid approach.

    PubMed

    Mann, Barton J; Gosens, Taco; Lyman, Stephen

    2012-10-01

    Treatment outcome researchers in orthopaedics frequently report only tests of statistical significance between group means to evaluate the effectiveness of a given intervention. Although important in establishing that mean differences are not caused by chance, these methods do not reflect the extent to which an intervention produces improvements that are meaningful and represent a return to health. This is an issue that is often of great interest to patients and clinicians. Other methods use a percentage change in an outcome measure (eg, 25% reduction in pain score) to classify treatment responders but often do not indicate whether the treatment restored a patient to normal. Researchers have developed several indices that provide a metric for statistically defining the amount of change that patients consider to be important. In this article, we focus on the concept of "clinical significance" and the different methods that have been developed to define clinically significant change using statistics. We then present a hybrid method that can classify whether a patient has returned to normal function. We apply this method to real patient data to illustrate its use with different outcome instruments commonly used in orthopaedic sports medicine. We advocate that the addition of these methods to reports from clinical outcome studies can deepen our understanding of the impact of interventions on patients' lives. PMID:22962295

  18. Clinical Significance of Additional Ablation of Atrial Premature Beats after Catheter Ablation for Atrial Fibrillation

    PubMed Central

    Kim, In-Soo; Yang, Pil-Sung; Kim, Tae-Hoon; Park, Junbeum; Park, Jin-Kyu; Uhm, Jae Sun; Joung, Boyoung; Lee, Moon Hyoung

    2016-01-01

    Purpose The clinical significance of post-procedural atrial premature beats immediately after catheter ablation for atrial fibrillation (AF) has not been clearly determined. We hypothesized that the provocation of immediate recurrence of atrial premature beats (IRAPB) and additional ablation improves the clinical outcome of AF ablation. Materials and Methods We enrolled 200 patients with AF (76.5% males; 57.4±11.1 years old; 64.3% paroxysmal AF) who underwent catheter ablation. Post-procedure IRAPB was defined as frequent atrial premature beats (≥6/min) under isoproterenol infusion (5 µg/min), monitored for 10 min after internal cardioversion, and we ablated mappable IRAPBs. Post-procedural IRAPB provocations were conducted in 100 patients. We compared the patients who showed IRAPB with those who did not. We also compared the IRAPB provocation group with 100 age-, sex-, and AF-type-matched patients who completed ablation without provocation (No-Test group). Results 1) Among the post-procedural IRAPB provocation group, 33% showed IRAPB and required additional ablation with a longer procedure time (p=0.001) than those without IRAPB, without increasing the complication rate. 2) During 18.0±6.6 months of follow-up, the patients who showed IRAPB had a worse clinical recurrence rate than those who did not (27.3% vs. 9.0%; p=0.016), in spite of additional IRAPB ablation. 3) However, the clinical recurrence rate was significantly lower in the IRAPB provocation group (15.0%) than in the No-Test group (28.0%; p=0.025) without lengthening of the procedure time or raising complication rate. Conclusion The presence of post-procedural IRAPB was associated with a higher recurrence rate after AF ablation. However, IRAPB provocation and additional ablation might facilitate a better clinical outcome. A further prospective randomized study is warranted. PMID:26632385

  19. Evolving approach and clinical significance of detecting DNA mismatch repair deficiency in colorectal carcinoma

    PubMed Central

    Shia, Jinru

    2016-01-01

    The last two decades have seen significant advancement in our understanding of colorectal tumors with DNA mismatch repair (MMR) deficiency. The ever-emerging revelations of new molecular and genetic alterations in various clinical conditions have necessitated constant refinement of disease terminology and classification. Thus, a case with the clinical condition of hereditary non-polyposis colorectal cancer as defined by the Amsterdam criteria may be one of Lynch syndrome characterized by a germline defect in one of the several MMR genes, one of the yet-to-be-defined “Lynch-like syndrome” if there is evidence of MMR deficiency in the tumor but no detectable germline MMR defect or tumor MLH1 promoter methylation, or “familial colorectal cancer type X” if there is no evidence of MMR deficiency. The detection of these conditions carries significant clinical implications. The detection tools and strategies are constantly evolving. The Bethesda guidelines symbolize a selective approach that uses clinical information and tumor histology as the basis to select high-risk individuals. Such a selective approach has subsequently been found to have limited sensitivity, and is thus gradually giving way to the alternative universal approach that tests all newly diagnosed colorectal cancers. Notably, the universal approach also has its own limitations; its cost-effectiveness in real practice, in particular, remains to be determined. Meanwhile, technological advances such as the next-generation sequencing are offering the promise of direct genetic testing for MMR deficiency at an affordable cost probably in the near future. This article reviews the up-to-date molecular definitions of the various conditions related to MMR deficiency, and discusses the tools and strategies that have been used in detecting these conditions. Special emphasis will be placed on the evolving nature and the clinical importance of the disease definitions and the detection strategies. PMID:25716099

  20. A Pharmacist-Staffed, Virtual Gout Management Clinic for Achieving Target Serum Uric Acid Levels: A Randomized Clinical Trial

    PubMed Central

    Goldfien, Robert; Pressman, Alice; Jacobson, Alice; Ng, Michele; Avins, Andrew

    2016-01-01

    Context: Relatively few patients with gout receive appropriate treatment. Objective: To determine whether a pharmacist-staffed gout management program is more effective than usual care in achieving target serum uric acid (sUA) levels in gout patients. Design: A parallel-group, randomized controlled trial of a pharmacist-staffed, telephone-based program for managing hyperuricemia vs usual care. Trial duration was 26 weeks. Main Outcome Measures: Primary outcome measure was achieving sUA levels at or below 6 mg/dL at the 26-week visit. Secondary outcome was mean change in sUA levels in the control and intervention groups. Participants were adults with recurrent gout and sUA levels above 6.0 mg/dL. Participants were randomly assigned to management by a clinical pharmacist following protocol or to monitoring of sUA levels but management of their gout by their usual treating physician. Results: Of 102 patients who met eligibility criteria, 77 subjects obtained a baseline sUA measurement and were entered into the trial. Among 37 participants in the intervention group, 13 (35%) had sUA levels at or below 6.0 mg/dL at 26 weeks, compared with 5 (13%) of 40 participants in the control group (risk ratio = 2.8, 95% confidence interval [CI] = 1.1 to 7.1, p = 0.03). The mean change in sUA levels among controls was +0.1 mg/dL compared with −1.5 mg/dL in the intervention group (sUA difference = −1.6, 95% CI = −0.9 to −2.4, p < 0.001). Conclusions: A structured pharmacist-staffed program was more effective than usual care for achieving target sUA levels. These results suggest a structured program could greatly improve gout management. PMID:27352414

  1. Role of Barium Swallow in Diagnosing Clinically Significant Anastomotic Leak following Esophagectomy

    PubMed Central

    Roh, Simon; Iannettoni, Mark D.; Keech, John C.; Bashir, Mohammad; Gruber, Peter J.; Parekh, Kalpaj R.

    2016-01-01

    Background Barium swallow is performed following esophagectomy to evaluate the anastomosis for detection of leaks and to assess the emptying of the gastric conduit. The aim of this study was to evaluate the reliability of the barium swallow study in diagnosing anastomotic leaks following esophagectomy. Methods Patients who underwent esophagectomy from January 2000 to December 2013 at our institution were investigated. Barium swallow was routinely done between days 5–7 to detect a leak. These results were compared to clinically determined leaks (defined by neck wound infection requiring jejunal feeds and or parenteral nutrition) during the postoperative period. The sensitivity and specificity of barium swallow in diagnosing clinically significant anastomotic leaks was determined. Results A total of 395 esophagectomies were performed (mean age, 62.2 years). The indications for the esophagectomy were as follows: malignancy (n=320), high-grade dysplasia (n=14), perforation (n=27), benign stricture (n=7), achalasia (n=16), and other (n=11). A variety of techniques were used including transhiatal (n=351), McKeown (n=35), and Ivor Lewis (n=9) esophagectomies. Operative mortality was 2.8% (n=11). Three hundred and sixty-eight patients (93%) underwent barium swallow study after esophagectomy. Clinically significant anastomotic leak was identified in 36 patients (9.8%). Barium swallow was able to detect only 13/36 clinically significant leaks. The sensitivity of the swallow in diagnosing a leak was 36% and specificity was 97%. The positive and negative predictive values of barium swallow study in detecting leaks were 59% and 93%, respectively. Conclusion Barium swallow is an insensitive but specific test for detecting leaks at the cervical anastomotic site after esophagectomy. PMID:27066433

  2. Cortical superficial siderosis: detection and clinical significance in cerebral amyloid angiopathy and related conditions.

    PubMed

    Charidimou, Andreas; Linn, Jennifer; Vernooij, Meike W; Opherk, Christian; Akoudad, Saloua; Baron, Jean-Claude; Greenberg, Steven M; Jäger, Hans Rolf; Werring, David J

    2015-08-01

    Cortical superficial siderosis describes a distinct pattern of blood-breakdown product deposition limited to cortical sulci over the convexities of the cerebral hemispheres, sparing the brainstem, cerebellum and spinal cord. Although cortical superficial siderosis has many possible causes, it is emerging as a key feature of cerebral amyloid angiopathy, a common and important age-related cerebral small vessel disorder leading to intracerebral haemorrhage and dementia. In cerebral amyloid angiopathy cohorts, cortical superficial siderosis is associated with characteristic clinical symptoms, including transient focal neurological episodes; preliminary data also suggest an association with a high risk of future intracerebral haemorrhage, with potential implications for antithrombotic treatment decisions. Thus, cortical superficial siderosis is of relevance to neurologists working in neurovascular, memory and epilepsy clinics, and neurovascular emergency services, emphasizing the need for appropriate blood-sensitive magnetic resonance sequences to be routinely acquired in these clinical settings. In this review we focus on recent developments in neuroimaging and detection, aetiology, prevalence, pathophysiology and clinical significance of cortical superficial siderosis, with a particular emphasis on cerebral amyloid angiopathy. We also highlight important areas for future investigation and propose standards for evaluating cortical superficial siderosis in research studies. PMID:26115675

  3. Significant alterations in reported clinical practice associated with increased oversight of organ transplant center performance.

    PubMed

    Schold, Jesse D; Arrington, Charlotte J; Levine, Greg

    2010-09-01

    In the past several years, emphasis on quality metrics in the field of organ transplantation has increased significantly, largely because of the new conditions of participation issued by the Centers for Medicare and Medicaid Services. These regulations directly associate patients' outcomes and measured performance of centers with the distribution of public funding to institutions. Moreover, insurers and marketing ventures have used publicly available outcomes data from transplant centers for business decision making and advertisement purposes. We gave a 10-question survey to attendees of the Transplant Management Forum at the 2009 meeting of the United Network for Organ Sharing to ascertain how centers have responded to the increased oversight of performance. Of 63 responses, 55% indicated a low or near low performance rating at their center in the past 3 years. Respondents from low-performing centers were significantly more likely to indicate increased selection criteria for candidates (81% vs 38%, P = .001) and donors (77% vs 31%, P < .001) as well as alterations in clinical protocols (84% vs 52%, P = .007). Among respondents indicating lost insurance contracts (31%), these differences were also highly significant. Based on respondents' perceptions, outcomes of performance evaluations are associated with significant changes in clinical practice at transplant centers. The transplant community and policy makers should practice vigilance that performance evaluations and regulatory oversight do not inadvertently lead to diminished access to care among viable candidates or decreased transplant volume. PMID:20929114

  4. Clinical significance of patterns of incidental thyroid uptake at (18)F-FDG PET/CT.

    PubMed

    Agrawal, K; Weaver, J; Ngu, R; Krishnamurthy Mohan, H

    2015-05-01

    Incidental uptake of 2-[(18)F]-fluoro-2-deoxy-d-glucose ((18)F-FDG) in the thyroid gland is not uncommonly encountered in day-to-day practice of oncological (18)F-FDG positron-emission tomography/computed tomography (PET/CT). These are often felt to be "nuisance lesions" by referring clinicians and radiologists alike. However, recognition of the importance of different patterns of FDG uptake in the thyroid gland and knowledge of the possible underlying aetiologies are crucial in ensuring that patients are managed appropriately in the clinical context of their primary diagnosis, as the underlying pathological condition may be clinically important in a significant minority of such cases. This review describes the various patterns of (18)F-FDG uptake within the thyroid and discusses the clinical significance and possible impact on patient management. Incidental low-grade homogeneous diffuse increased thyroid (18)F-FDG uptake is usually seen in the patients with chronic thyroiditis, Grave's disease, and hypothyroidism. Thyroid function tests and antibody profiling are advised in these patients. Incidental focal (18)F-FDG thyroid uptake should raise the possibility of underlying malignancy. Ultrasound with or without fine-needle aspiration cytology is usually recommended for the evaluation of these lesions. Heterogeneous uptake with prominent focal uptake in the thyroid should be further evaluated to exclude malignancy. PMID:25687827

  5. Clinical significance of B7-H6 protein expression in astrocytoma

    PubMed Central

    Guo, Jian-gui; Guo, Cheng-cheng; He, Zhen-qiang; Liu, Zhi-gang; Wang, Yang; Mou, Yong-gao

    2016-01-01

    Currently, immunotherapy by blocking the immune checkpoint inhibitors, such as anti-PD-1, has been carried out in many clinical studies on recurrent glioma, and the preliminary results are satisfactory, which provides a rationale for the exploration of immune checkpoint inhibitors in glioma. B7-H6 is a newly discovered member of the B7 family, which triggers antitumor of natural killer cell cytotoxicity and cytokine secretion by binding the NKp30 receptor. B7-H6 mRNA and protein expressions, which are not detected in normal tissues, are expressed mainly on the cell surface of various primary tumors and cell lines. However, up until now, there is no data about the clinical significance of B7-H6 expression in astrocytoma patients. The present study provides an investigation on the relationship between prognostic and clinical value of B7-H6 protein in astrocytoma tissues. All the astrocytic glioma tissues were stained for B7-H6. Immunohistochemistry stain of 122 astrocytoma samples showed that immunoreactivity of B7-H6 was seen predominantly in the cytoplasm. The B7-H6 expression did not show significant relevance with patient age, sex distribution, Karnofsky performance status score, extent of resection, and tumor location in astrocytoma patients, but B7-H6 positive expression is significantly associated with World Health Organization grade (P=0.046). However, the survival rate after operation presented no significant difference of B7-H6 expression in astrocytoma patients. Kaplan–Meier analysis and the log-rank test revealed that B7-H6 expression cannot predict the overall survival. In all, it seems that the B7-H6 expression might be a marker to differentiate the World Health Organization grade level of astrocytoma, but the prognosis value of B7-H6 in astrocytoma should be studied in detail. PMID:27330308

  6. Navajo Culture and Family Influences on Academic Success: Traditionalism Is Not a Significant Predictor of Achievement among Navajo Youth.

    ERIC Educational Resources Information Center

    Willeto, Angela A. A.

    1999-01-01

    A study of 451 Navajo youths attending 11 high schools in the Navajo Nation found no relationship between their academic achievement and their cultural attachments and practices. Families modestly influenced educational outcomes, but being female was a stronger predictor of academic success. An appendix describes study variables. (Contains 42…

  7. Largest Producer of Steel Products in the United States Achieves Significant Energy Savings at its Minntac Plant

    SciTech Connect

    2008-09-01

    The U. S. Steel Minntac plant in Mt. Iron, MN, achieved annual savings of $760,000 and 95,000 MMBtu after receiving a DOE Save Energy Now energy assessment and implementing recommendations to improve the efficiency of its process heating system.

  8. Largest Producer of Steel Products in the United States Achieves Significant Energy Savings at its Minntac Plant

    SciTech Connect

    Not Available

    2008-09-01

    This case study describes how the U. S. Steel Minntac plant in Mt. Iron, Minnesota, achieved annual savings of $760,000 and 95,000 MMBtu after receiving a DOE Save Energy Now energy assessment and implementing recommendations to improve the efficiency of its process heating system.

  9. Practice Guidelines for the Assessment of Clinically Significant Treatment Outcomes in the Children's Mental Health System.

    PubMed

    Chomycz, Suzanne; Schmidt, Fred

    2016-01-01

    The use of program evaluation to monitor client change and improve intervention effectiveness is gaining increasing importance in the mental health field. However, there is a lack of literature available in community-based clinics for those who desire to evaluate the effectiveness of services. Through this article the authors review the literature on the best methods to assess clinically significant treatment outcomes in community-based children's mental health services. The strengths and weaknesses of commonly recommended methods of evaluating change are discussed (i.e., reliable change index, percentage of improvement, normative comparisons, and effect size) using a dataset from a community-based parenting program (N = 308). PMID:26086975

  10. The clinical significance of autoantibodies to the proliferating cell nuclear antigen (PCNA).

    PubMed

    Mahler, Michael; Miyachi, Kiyomitsu; Peebles, Carol; Fritzler, Marvin J

    2012-08-01

    Autoantibodies targeting the proliferating cell nuclear antigen (PCNA) were first described over 30 years ago and are historically most commonly associated with systemic lupus erythematosus (SLE). The primary antigenic target is a 34 kDa protein that is part of the DNA polymerase delta multi-protein complex. A number of diagnostic platforms have incorporated PCNA into their diagnostic assays and algorithms. However, little is known about the clinical utility of autoantibodies to PCNA, especially with novel detection systems. This review will focus on the history of the discovery of the PCNA autoantigen and the current status of the diagnostic significance of anti-PCNA and suggest future studies that are required to strengthen our understanding of their clinical utility. PMID:22381917

  11. Disturbed eating behaviors and eating disorders in type 1 diabetes: clinical significance and treatment recommendations.

    PubMed

    Goebel-Fabbri, Ann E

    2009-04-01

    Girls and women with type 1 diabetes have increased rates of disturbed eating behaviors and clinically significant eating disorders than their nondiabetic peers. Type 1 diabetes is strongly associated with several empirically supported eating disorder risk factors (eg, higher body mass index, increased body weight and shape dissatisfaction, low self-esteem and depression, and dietary restraint). It may be that specific aspects of diabetes treatment increase the risk for developing disordered eating. Disturbed eating behaviors and clinical eating disorders predispose women with diabetes to many complex medical risks and increase risk of morbidity and mortality. For this reason, it is critical that diabetes clinicians understand more about eating disorders to improve the likelihood of early risk detection and access to appropriate treatment. This article presents a review of the current scientific literature on eating disturbances in type 1 diabetes and synthesizes the existent findings into recommendations for screening and treatment. PMID:19323958

  12. Incidence and Clinical Significance of De Novo Donor Specific Antibodies after Kidney Transplantation

    PubMed Central

    Panagiotellis, Konstantinos; Iniotaki, Aliki; Boletis, John N.

    2013-01-01

    Kidney transplantation has evolved over more than half a century and remarkable progress has been made in patient and graft outcomes. Despite these advances, chronic allograft dysfunction remains a major problem. Among other reasons, de novo formation of antibodies against donor human leukocyte antigens has been recognized as one of the major risk factors for reduced allograft survival. The type of treatment in the presence of donor specific antibodies (DSA) posttransplantation is largely related to the clinical syndrome the patient presents with at the time of detection. There is no consensus regarding the treatment of stable renal transplant recipients with circulating de novo DSA. On the contrast, in acute or chronic allograft dysfunction transplant centers use various protocols in order to reduce the amount of circulating DSA and achieve long-term graft survival. These protocols include removal of the antibodies by plasmapheresis, intravenous administration of immunoglobulin, or depletion of B cells with anti-CD20 monoclonal antibodies along with tacrolimus and mycophenolate mofetil. This review aims at the comprehension of the clinical correlations of de novo DSA in kidney transplant recipients, assessment of their prognostic value, and providing insights into the management of these patients. PMID:24348683

  13. Clinical and prognostic significance of HIF-1α in glioma patients: a meta-analysis

    PubMed Central

    Liu, Qi; Cao, Peicheng

    2015-01-01

    Gliomas are the most common brain tumors, leading to significant cancer-related mortality worldwide. Hypoxia-inducible factor 1-alpha (HIF-1α) was shown to be involved in the pathophysiology and management of glioma, and might offer a therapeutic target. However, the results remain inconclusive. The purpose of this study was to systematically investigate the clinical and prognostic significance of HIF-1α expression in patients with glioma. Relevant studies published between 2000 and 2015 were searched in the electronic databases. The odds ratio (OR), risk ratio (RR) and mean difference (MD) with their 95% confidence intervals (CI) were employed to calculate the strength of significance. Finally, a total of 24 articles were retrieved, including 1422 glioma patients. No significant heterogeneity was presented between studies (I2<50%, P>0.01). Overall, our results showed that HIF-1α expression was significantly associated with high WHO grade (III+IV) of glioma (OR=8.59, 95% CI=6.56-11.24, P<0.00001). This significant relationship was also found between HIF-1α expression and microvascular density (MD=26.32, 95% CI=14.48-38.16, P<0.0001), overall survival (OS) (3-year OS: RR=0.48, 95% CI=0.35-0.66, P<0.00001; 2-year OS: RR=0.53, 95% CI=0.38-0.73, P<0.0001; 1-year OS: RR=0.79, 95% CI=0.66-0.95, P=0.01), and the cumulative survival time. However, HIF-1α expression was not associated with age and gender of glioma patients (P>0.05). In conclusions, our results suggested that HIF-1α expression was associated with high grade of glioma and OS, indicating that HIF-1α could predict prognosis and provide clinical insights into the therapeutic strategy for patients with glioma. More studies concerning other populations are also needed in the future research. PMID:26885182

  14. Incidental and Isolated Follicular Lymphoma In Situ and Mantle Cell Lymphoma In Situ Lack Clinical Significance.

    PubMed

    Bermudez, Glenda; González de Villambrosía, Sonia; Martínez-López, Azahara; Batlle, Ana; Revert-Arce, José B; Cereceda Company, Laura; Ortega Bezanilla, César; Piris, Miguel A; Montes-Moreno, Santiago

    2016-07-01

    Follicular lymphoma in situ (FLIS) and mantle cell lymphoma in situ (MCLIS) are histopathologic findings of undetermined clinical significance. We studied a series of 341 consecutive lymph node resection specimens from patients diagnosed with colorectal (201 cases) and breast (140 cases) adenocarcinoma between 1998 and 2000. Incidental and isolated FLIS was identified in 11/341 patients (3.23%), whereas incidental and isolated MCLIS was found in 2/341 patients (0.59%). None of these cases developed overt lymphoma. A second series of 17 cases of FLIS (16 cases) and MCLIS (1 case) from consultation files was analyzed. Five cases with incidental and isolated FLIS were identified. None of these cases developed overt lymphoma. Overall, none of the 16 cases with incidental and isolated FLIS in both series developed overt FL after a median follow-up of 54 months (range, 7 to 187 mo). However, 12 of these cases with a clinical suspicion of lymphoproliferative disorder showed the association (in different lymph nodes) or combination (in the same sample) of FLIS or MCLIS with other lymphoid neoplasms (FL, splenic marginal zone lymphoma, nodal marginal zone lymphoma, Hodgkin lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, multiple myeloma). In conclusion, the clinical relevance of FLIS and MCLIS seems to strictly depend on the clinical context. Incidental FLIS or MCLIS seem to have a very low risk for transformation, which recommends careful clinical examination after histopathologic diagnosis and conservative management with follow-up for a limited period of time. PMID:26945339

  15. Clinical Significance of Auditory Target P300 Subcomponents in Psychosis: Differential Diagnosis, Symptom Profiles, and Course

    PubMed Central

    Perlman, Greg; Foti, Dan; Jackson, Felicia; Kotov, Roman; Constantino, Eduardo; Hajcak, Greg

    2015-01-01

    Background Reduced auditory target P300 amplitude is a leading biomarker for psychotic disorders, although its relevance for differential diagnosis and link to specific clinical features (symptom profiles, functional impairment, and course) is unclear. This study aims to clarify the clinical significance of auditory target P300 using concurrent and retrospective clinical data from a longitudinal cohort with psychosis. Methods 92 cases from an epidemiological study of first-admission psychosis were assessed using an auditory oddball paradigm at 15-year follow-up along with 44 never-psychotic adults. Subcomponents of auditory target P300 amplitude (i.e., a central positive P3a, a parietal positive P3b, and a frontal negative slow wave) were isolated using temporal-spatial principal components analysis. Results P3a amplitude was blunted across psychotic disorders relative to non-psychotic adults. P3b amplitude was reduced in schizophrenia specifically, including cases initially misclassified at baseline. The frontal negative slow wave did not distinguish among groups. P3b amplitude reduction was associated with several clinical features at the concurrent assessment, as well as previous time points, including recovery from psychosis even 5 years earlier and functioning even 15 years earlier. Conclusions Auditory target P300 amplitude yields both a schizophrenia-specific component (i.e., P3b) and a transdiagnostic psychosis component (i.e., P3a). The P3b component may also shed light on prognosis, real-world functioning, and course, as well as help to reduce misdiagnosis of psychotic disorders. Prospective studies are needed to test whether P3b tracks or predicts clinical status. PMID:25934167

  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. Expression of HIF-2α and VEGF in Cervical Squamous Cell Carcinoma and Its Clinical Significance

    PubMed Central

    Zhang, Lixia; Chen, Qiang; Hu, Jing; Chen, Yue; Liu, Chenglong; Xu, Changshui

    2016-01-01

    CSCC is a systemic disease involving polygenic alteration and multiple steps, and HIF and VEGF are closely associated with tumorigenesis. Specimens surgically resected from 64 cases of CSCC and 22 cases of normal cervical tissue were selected randomly to detect the expression of HIF-2α and VEGF in CSCC for exploring their clinical significance; information regarding the age, lymph node metastasis, and FIGO staging were collected as well; expression of HIF-2α and VEGF was detected by qPCR and immunohistochemistry. We found that the expression of HIF-2α and VEGF mRNA in CSCC was significantly higher than that of normal cervical tissues and showed a positive correlation between them. The positive rates of HIF-2α and VEGF protein expression in CSCC and normal cervical tissues were 93.8% and 18.2%, respectively, with correlation between them. The expression of both HIF-2α and VEGF mRNA did not relate closely to age but the FIGO staging and lymph node metastasis. Compared with the counterpart control group, CSCC tissues with high FIGO staging and lymph node metastasis had a higher level of HIF-2α and VEGF mRNA expression. So, HIF-2α and VEGF were overexpressed in CSCC, which has a great clinical significance for its diagnosis. PMID:27413748

  18. [The major achievements of medicine in XX-early XXI centuries and their significance for the near future].

    PubMed

    Lisitsyn, Iu P; Zhuravleva, T V

    2012-01-01

    Among major achievements of medicine in XX-early XXI centuries considered as the most outstanding contribution are the development of theory of system of control of functions of organism and its integrity by I.P. Pavlov and his disciples and followers: the concept of psycho-somatic medicine by Z. Freud and social psychology; the theory of stress and general adaptive syndrome by H. Selye and the discovering of nature of many infectious and parasitic diseases. Then establishment of pathogenic impact of extra-environmental factors, decoding of gene chromosomal structure of organism, development of genetic engineering, effective pharmaceuticals, and techniques of treatment and prevention of various inherent and acquired diseases also can be put into this category. The achievements and discoveries in the area of public health, social medicine and hygiene and development of concept of healthy life-style are discussed too. PMID:23350086

  19. Prevalence and Clinical Significance of Night Eating Syndrome in University Students

    PubMed Central

    Runfola, Cristin D.; Allison, Kelly C.; Hardy, Kristina K.; Lock, James; Peebles, Rebecka

    2014-01-01

    Purpose Most studies of night eating syndrome (NES) fail to control for binge eating, despite moderate overlap between the two conditions. Establishing the independent clinical significance of NES is imperative for it to be considered worthy of clinical attention. We compared students with and without NES on eating disorder symptomatology, quality of life, and mental health, while exploring the role of binge eating in associations. Methods Students (N=1636) ages 18 to 26 (M=20.9) recruited from ten U.S. universities completed an online survey including the Night Eating Questionnaire (NEQ), Eating Disorder Examination-Questionnaire (EDE-Q), Project Eating Among Teens, and the Health-Related Quality of Life-4. NES was diagnosed according to endorsement of proposed diagnostic criteria on the NEQ. Groups (NES vs. non-NES) were compared on all dependent variables and stratified by binge eating status in secondary analyses. Results The prevalence of NES in our sample was 4.2%; it was 2.9% after excluding those with binge eating. Body mass index did not differ between groups, but students with NES were significantly more likely to have histories of underweight and anorexia nervosa. In students with NES, EDE-Q scores were significantly higher; purging, laxative use, and compulsive exercise were more frequent; quality of life was reduced; and histories of depression, attention-deficit/hyperactivity disorder, and self-injury were more common. Binge eating did not account for all of these differences; the presence of it and NES was associated with additive risk for psychopathology on some items. Conclusions NES may be a distinct clinical entity from other DSM-5 eating disorders. PMID:24485551

  20. [The pathogenetic and clinical significance of disorders in hemostatic homeostasis in diabetics].

    PubMed

    Lapchyns'ka, I I; Bielits'ka, H O; Kovalenko, S O

    1997-01-01

    DM patients who do not present with clinical manifestations of nephropathy exhibited significant reduction of urine fibrinolytic activity which is regarded as suggesting a preclinical stage of renal lesion in DM as well as hyperaggregation of platelets, enhanced activity of coagulative link of hemostasis and changes of different directions in the system of fibrinolysis. Among coagulologic methods, of most informative value is the turbidimetric method. In DM and low tolerability to glucosa, there is an increased incidence of gastroduodenal abnormalities, ulcer disease included, which fact warrants a gastroenterologic evaluation to be done in this patient population prior to prescribing anticoagulants. PMID:9491703

  1. The Clinical Significance and Potential Therapeutic Role of GPx3 in Tumor Recurrence after Liver Transplantation

    PubMed Central

    Qi, Xiang; Ng, Kevin Tak-Pan; Shao, Yan; Li, Chang Xian; Geng, Wei; Ling, Chang Chun; Ma, Yuen Yuen; Liu, Xiao Bing; Liu, Hui; Liu, Jiang; Yeung, Wai Ho; Lo, Chung Mau; Man, Kwan

    2016-01-01

    Background and Aims: Our previous study showed that small-for-size liver graft may provide favorable micro-environment for tumor growth. GPx3, an anti-oxidant, not only attenuates oxidative stress, but also suppresses liver tumor growth in our recent study. Here, we aimed to characterize the clinical significance and explore the functional role of GPx3 in HCC recurrence after liver transplantation. Methods: To explore the association between GPx3 expression and HCC invasiveness, a rat orthotopic liver transplantation model with tumor development was established. To investigate the clinical relevance of GPx3, 105 HCC patients who underwent liver transplantation were recruited. The suppressive role of GPx3 in HCC cells was studied using wound healing, Matrigel invasion assay and lung metastasis model. The real-time intravital imaging system was applied to directly visualize the tumor cells invasion in a living animal. The underlying mechanism was further explored. Results: GPx3 was identified as a down-regulated protein in small-for-size liver graft and significantly associated with invasive phenotype of tumor growth in a rat model. Plasma GPx3 was significantly lower in small-for-size graft group post-transplantation (day1: 33 vs 1147; day3: 3209 vs 4459; day7: 303 vs 2506; mU/mL, P<0.05) in rat model. Clinically, the plasma GPx3 was significantly lower in the recipients with HCC recurrence post-transplantation (day1: 4.16 vs 8.99 µg/mL, P<0.001; day7: 3.86 vs 9.99 µg/mL, P<0.001). Furthermore, lower plasma GPx3 was identified as an independent predictor (HR=4.528, P=0.046) for poor overall survival post-transplantation. Over-expression of GPx3 significantly suppressed migration, invasiveness and metastasis of HCC cells. Real-time intravital imaging showed that GPx3 significantly suppressed HCC invasiveness in a live animal. GPx3 suppressed the tumor invasiveness through inhibition of JNK-cJun-MMP2 pathway. Conclusion: GPx3 may possess prognostic and therapeutic

  2. Angiostrongylus cantonensis: a review of its distribution, molecular biology and clinical significance as a human pathogen.

    PubMed

    Barratt, Joel; Chan, Douglas; Sandaradura, Indy; Malik, Richard; Spielman, Derek; Lee, Rogan; Marriott, Deborah; Harkness, John; Ellis, John; Stark, Damien

    2016-08-01

    Angiostrongylus cantonensis is a metastrongyloid nematode found widely in the Asia-Pacific region, and the aetiological agent of angiostrongyliasis; a disease characterized by eosinophilic meningitis. Rattus rats are definitive hosts of A. cantonensis, while intermediate hosts include terrestrial and aquatic molluscs. Humans are dead-end hosts that usually become infected upon ingestion of infected molluscs. A presumptive diagnosis is often made based on clinical features, a history of mollusc consumption, eosinophilic pleocytosis in cerebral spinal fluid, and advanced imaging such as computed tomography. Serological tests are available for angiostrongyliasis, though many tests are still under development. While there is no treatment consensus, therapy often includes a combination of anthelmintics and corticosteroids. Angiostrongyliasis is relatively rare, but is often associated with morbidity and sometimes mortality. Recent reports suggest the parasites' range is increasing, leading to fatalities in regions previously considered Angiostrongylus-free, and sometimes, delayed diagnosis in newly invaded regions. Increased awareness of angiostrongyliasis would facilitate rapid diagnosis and improved clinical outcomes. This paper summarizes knowledge on the parasites' life cycle, clinical aspects and epidemiology. The molecular biology of Angiostrongylus spp. is also discussed. Attention is paid to the significance of angiostrongyliasis in Australia, given the recent severe cases reported from the Sydney region. PMID:27225800

  3. Clinical Significance of Community- and Healthcare-Acquired Carbapenem-Resistant Enterobacteriaceae Isolates

    PubMed Central

    Tang, Hung-Jen; Hsieh, Cheng-Fang; Chang, Ping-Chin; Chen, Jyh-Jou; Lin, Yu-Hsiu; Lai, Chih-Cheng; Chao, Chien-Ming; Chuang, Yin-Ching

    2016-01-01

    This study was conducted to investigate the clinical significance, manifestations, microbiological characteristics and outcomes of carbapenem-resistant Enterobacteriaceae (CRE) isolates, and compare the clinical features of community- and healthcare-acquired CRE isolates. A total of 78 patients were identified to have CRE. Klebsiella pneumoniae was the most common pathogens (n = 42, 53.8%), followed by Enterobacter cloacae (n = 24, 30.8%), and Escherichia coli (n = 11, 14.1%). Most of the patients acquired CRE from healthcare settings (n = 55, 70.5%), and other cases got CRE from community settings (n = 23, 29.5%). Nine cases (11.5%) were classified as CRE colonization. Among the remaining 69 cases of CRE infections, pneumonia (n = 28, 40.6%) was the most common type of infections, followed by urinary tract infection (n = 24, 34.8%), and intra-abdominal infection (n = 16, 23.2%). The patients acquired CRE from community settings were more likely to be elderly, female, and had more urinary tract infections than from healthcare settings. In contrast, the patients acquired CRE from healthcare settings had more intra-abdominal infections, intra-abdominal surgery, and presence of indwelling device than from community settings. In conclusion, community-acquired CRE are not rare, and their associated clinical presentations are different from healthcare-acquired CRE. PMID:26999356

  4. The clinical significance of dipstick-negative, culture-positive urines in a veterans population.

    PubMed

    Gutman, S I; Solomon, R R

    1987-08-01

    The consequences of omitting cultures in dipstick-negative urines submitted to the authors' microbiology laboratory were evaluated retrospectively in 1,079 clean-catch midstream samples. Using positive dipstick readings for leukocyte esterase, nitrite, and/or protein as evidence of a positive screen, the sensitivity, specificity, positive predictive value, and negative predictive value for specimens containing more than or 10(3) CFUs/mL (10(6)/L) were 80%, 71%, 48%, and 91%, respectively. Clinical data were reviewed in 38 patients with one or more dipstick-negative, culture-positive urines. Most of these patients lacked clinical or other laboratory evidence suggesting urinary tract infection. Problems with specimen collection were suspected in 19 neurologically compromised patients. Only two patients with dipstick-negative urines received treatment based on the culture reports. Symptoms persisted in both. The authors conclude that in their predominantly male veteran population, clinically significant bacteriuria is an unlikely finding in a dipstick-negative urine. PMID:3618553

  5. Detection methods and clinical significance of free peritoneal tumor cells found during colorectal cancer surgery

    PubMed Central

    Sibio, Simone; Fiorani, Cristina; Stolfi, Carmine; Divizia, Andrea; Pezzuto, Roberto; Montagnese, Fabrizio; Bagaglini, Giulia; Sammartino, Paolo; Sica, Giuseppe Sigismondo

    2015-01-01

    Peritoneal washing is now part of the standard clinical practice in several abdominal and pelvic neoplasias. However, in colorectal cancer surgery, intra-peritoneal free cancer cells (IFCC) presence is not routinely investigated and their prognostic meaning is still unclear. When peritoneal washing results are positive for the presence of IFCC a worse outcome is usually expected in these colorectal cancer operated patients, but it what is not clear is whether it is associated with an increased risk of local recurrence. It is authors’ belief that one of the main reasons why IFCC are not researched as integral part of the routine staging system for colon cancer is that there still isn’t a diagnostic or detection method with enough sensibility and specificity. However, the potential clinical implications of a routine research for the presence IFCC in colon neoplasias are enormous: not only to obtain a more accurate clinical staging but also to offer different therapy protocols, based on the presence of IFCC. Based on this, adjuvant chemotherapy could be offered to those patients found to be positive for IFCC; also, protocols of proactive intraperitoneal chemotherapy could be applied. Although presence of IFCC appears to have a valid prognostic significance, further studies are needed to standardize detection and examination procedures, to determine if there are and which are the stages more likely to benefit from routine search for IFCC. PMID:26425265

  6. Clinical significance of surgical margin status in patients subjected to radical prostatectomy.

    PubMed

    Dobruch, Jakub; Nyk, Lukasz; Skrzypczyk, Michał; Chłosta, Piotr; Dzik, Tomasz; Borówka, Andrzej

    2012-01-01

    The aim of this study is to evaluate the clinical value of positive surgical margins (PSM) in patients subjected to radical prostatectomy (RP). The data of men who were subjected to RP from the 1st of January, 2001 to the 30th of May, 2010 were analyzed. Specimens with PSM were again evaluated to confirm the presence of positive margins. PSM were found in 64 (25%) out of 255 analyzed patients. Out of all clinical features, only biopsy Gleason score and clinical stage of the disease were found to be predictive of PSM. Biochemical recurrence (BR) was found in 42 (16.5%) men, among them 17 (26.6%) had PSM and 25 (13.1%) had negative margins. The risk of BR in those with "focal" PSM (<3 mm) did not differ from the risk of BR observed in patients without PSM. In contrast, the likelihood of BR was significantly greater in cases of PSM in which maximum longitude exceeded 3 mm. Reevaluation of the PSM specimens revealed equivocal margins status in six cases. PSM are not inevitably associated with BR. The risk of failure is influenced by their length. Reevaluation of the prostate specimen may lead to surgical margins status modification. PMID:24578961

  7. Significance of Image Guidance to Clinical Outcomes for Localized Prostate Cancer

    PubMed Central

    Zhong, Qiuzi; Gao, Hong; Li, Gaofeng; Xiu, Xia; Wu, Qinhong; Li, Ming; Xu, Yonggang

    2014-01-01

    Purpose. To compare toxicity profiles and biochemical tumor control outcomes between patients treated with image-guided intensity-modulated radiotherapy (IG-IMRT) and non-IGRT intensity-modulated radiotherapy (IMRT) for clinically localized prostate cancer. Materials and Methods. Between 2009 and 2012, 65 patients with localized prostate cancer were treated with IG-IMRT. This group of patients was retrospectively compared with a similar cohort of 62 patients who were treated between 2004 and 2009 with IMRT to the same dose without image guidance. Results. The median follow-up time was 4.8 years. The rectal volume receiving ≥40 and ≥70 Gy was significantly lower in the IG-IMRT group. Grade 2 and higher acute and late GI and GU toxicity rates were lower in IG-IMRT group, but there was no statistical difference. No significant improvement in biochemical control at 5 years was observed in two groups. In a Cox regression analysis identifying predictors for PSA relapse-free survival, only preradiotherapy PSA was significantly associated with biochemical control; IG-IMRT was not a statistically significant indicator. Conclusions. The use of image guidance in the radiation of prostate cancer at our institute did not show significant reduction in the rates of GI and GU toxicity and did not improve the biochemical control compared with IMRT. PMID:25110701

  8. Guided self-help CBT treatment for bulimic disorders: effectiveness and clinically significant change.

    PubMed

    Vaz, Ana Rita; Conceição, Eva; Machado, Paulo P P

    2013-01-01

    The aim of this study was to test the effectiveness of a cognitive-behavioral guided self-help treatment program for bulimia nervosa and similar disorders. Participants were assessed at the beginning and end of treatment, and at 6 months follow-up, using the Eating Disorder Examination Questionnaire (EDE-Q), the Outcome-Questionnaire-45 (OQ-45), and the Beck Depression Inventory (BDI). Forty-two participants from an eating disorders treatment service participated in this study. This study followed a one-group repeated measures naturalistic design with no control group. Results showed a significant reduction in EDE scores, OQ-45 and BDI. Clinically significant change occurred for the majority of participants. Cognitive-behavioral self-help treatment may be of value as an initial treatment for bulimia nervosa and similar disorders such as binge eating disorder. PMID:23701428

  9. Multiple mechanisms contribute to the development of clinically significant azole resistance in Aspergillus fumigatus

    PubMed Central

    Moye-Rowley, W. S.

    2015-01-01

    Infections caused by the filamentous fungus Aspergillus fumigatus are a significant clinical issue and represent the second most-common form of fungal infection. Azole drugs are effective against this pathogen but resistant isolates are being found more frequently. Infections associated with azole resistant A. fumigatus have a significantly increased mortality making understanding drug resistance in this organism a priority. The target of azole drugs is the lanosterol α-14 demethylase enzyme encoded by the cyp51A gene in A. fumigatus. Mutations in cyp51A have been described that give rise to azole resistance and been argued to be the primary, if not sole, contributor to azole resistance. Here, I discuss recent developments that indicate multiple mechanisms, including increased expression of ATP-binding cassette (ABC) transporter proteins, contribute to azole resistance. ABC transporters are well-established determinants of drug resistance in other fungal pathogens and seem likely to play a similar role in A. fumigatus. PMID:25713565

  10. The Clinical Significance of HbA1c in Operable Chronic Thromboembolic Pulmonary Hypertension

    PubMed Central

    Richter, Manuel Jonas; Milger, Katrin; Haase, Sarah; Sommer, Natascha; Tello, Khodr; Seeger, Werner; Mayer, Eckhard; Wiedenroth, Christoph Benjamin; Grimminger, Friedrich; George, Wolfgang; Ghofrani, Hossein Ardeschir; Guth, Stefan; Gall, Henning

    2016-01-01

    Background Glycosylated hemoglobin A1c (HbA1c) has been proposed as an independent predictor of long-term prognosis in pulmonary arterial hypertension. However, the clinical relevance of HbA1c in patients with operable chronic thromboembolic pulmonary hypertension (CTEPH) remains unknown. The aim of the present study was to investigate the clinical significance of HbA1c as a biomarker in CTEPH. Methods Prospectively, 102 patients underwent pulmonary endarterectomy (PEA) in our national referral center between March 2013 and March 2014, of which after exclusion 45 patients were analyzed. HbA1c- levels, hemodynamic and exercise parameters were analyzed prior and one-year post-PEA. Results 45 patients (BMI: 27.3 ± 6.0 kg/m2; age: 62.7 ± 12.3 years) with a mean pulmonary arterial pressure (mPAP) of 43.6 ± 9.4 mmHg, a pulmonary vascular resistance (PVR) of 712.1 ± 520.4 dyn*s/cm5, a cardiac index (CI) of 2.4 ± 0.5 l/min/m2 and a mean HbA1c-level of 39.8 ± 5.6 mmol/mol were included. One-year post-PEA pulmonary hemodynamic and functional status significantly improved in our cohort. Baseline HbA1c-levels were significantly associated with CI, right atrial pressure, peak oxygen uptake and the change of 6-minute walking distance using linear regression analysis. However, using logistic regression analysis baseline HbA1c-levels were not significantly associated with residual post-PEA PH. Conclusions This is the first prospective study to describe an association of HbA1c-levels with pulmonary hemodynamics and exercise capacity in operable CTEPH patients. Our preliminary results indicate that in these patients impaired glucose metabolism as assessed by HbA1c is of clinical significance. However, HbA1c failed as a predictor of the hemodynamic outcome one-year post-PEA. PMID:27031508

  11. Difference, significant difference and clinically meaningful difference: The meaning of change in rehabilitation

    PubMed Central

    Dvir, Zeevi

    2015-01-01

    The valid confirmation of a positive change (improvement) in a patient’s health status due to intervention has been at the core of medicine and rehabilitation since their very inception as clinicians always aspired to ensure that treating their patients had led to successful outcomes both in acute and chronic conditions. However what is change: either improvement or worsening (aggravation), is a complicated issue which involves clinical as well as statistical considerations. Change invariably relates to a difference in some measurable entity and almost always it relates to a time span. The confirmation of clinical change is important both for varying the treatment course (if necessary) and for the termination of treatment when the latter has reached wither its prescribed objective or a plateau. Since in the context of rehabilitation, the outcome measures (OM) are strongly linked to performance, determination of change in the latter is confounded by many factors, collectively known as the error of measurement, which render a decision regarding clinically meaningful change, highly involved. This is further complicated by the stability of the observed OM, the so-called reproducibility of the OM, and the accuracy of the measurement instrument. The higher the reproducibility the lower is the error. Moreover, in order to proclaim change, in most cases a positive one, it is necessary for the difference in outcome scores (i.e. the change) to surpass the error of measurement, in varying degree of rigor. This paper describes selected methods associated with determination of change and focuses predominantly on the difference between a simple difference in scores (‘simple change’), a significant difference in scores and the so-called clinically meaningful change in scores which is considered today as the benchmark for confirmation of a real change. PMID:25960978

  12. Posterior cerebral artery--variation in the origin and clinical significance.

    PubMed

    Dodevski, Ace; Tosovska Lazarova, Dobrila; Mitreska, Nadica; Aliji, Vjolca; Stojovska Jovanovska, Elizabeta

    2014-01-01

    With the introduction of new techniques in diagnostic and interventional radiology and progress in micro-neurosurgery, accurate knowledge of the brain blood vessels is essential in daily clinical work. The aim of this study was to describe the different types of PCA origin, their diameter, and to emphasize their clinical significance. In this study we examined radiographs of 53 patients who had CT angiography undertaken for a variety of clinical reasons, performed as a part of their medical treatment at the University Radiology Clinic in Skopje, R. Macedonia. This study included 24 females and 29 males, ranging in age from 32 to 73 years; mean age 55.3±11.5 years. The results showed that the diameter of the posterior cerebral artery was 1.74±0.317 mm on the right side and 1.98±0.408 mm on the left side. The adult configuration was present in 37 (69.81%); foetal configuration was present in 12 (22.64%) and transitional configuration was present in 4 (7.54%) of the patients. We found two patients with bilateral foetal type and ten with unilateral foetal type (six on the right side and four on the left side). Despite the limitations of the study, we found that the foetal variant was presented in 22.64% of patients. Thorough knowledge of the anatomy of the intracranial vessels is important to clinicians as well as basic scientists who deal with problems related to intracranial vasculature on a daily basis. PMID:24798602

  13. Clinical, Functional and Health-Related Quality of Life Correlates of Clinically Significant Symptoms of Anxiety and Depression in Patients with Systemic Sclerosis: A Cross-Sectional Survey

    PubMed Central

    Nguyen, Christelle; Ranque, Brigitte; Baubet, Thierry; Bérezné, Alice; Mestre-Stanislas, Caroline; Rannou, François; Papelard, Agathe; Morell-Dubois, Sandrine; Revel, Michel; Moro, Marie-Rose; Guillevin, Loïc; Poiraudeau, Serge; Mouthon, Luc

    2014-01-01

    Objectives To identify clinical, functional and health-related quality of life (HRQoL) correlates of clinically significant symptoms of anxiety and depression in patients with systemic sclerosis (SSc). Methods Three-hundred-and-eighty-one patients fulfilling the American College of Rheumatology and/or the Leroy and Medsger criteria for SSc were assessed for visceral involvement, disability and HRQoL (assessed by SF-36). Clinically significant symptoms of anxiety and depression were evaluated with the Hospital Anxiety Depression Scale (HAD) (defined cut-off≥8). Results 9.2% the patients had limited SSc, 50.5% limited cutaneous SSc (lcSSc), and 40.3% diffuse cutaneous SSc (dcSSc). Overall, 40.4% and 58.8% of the patients had clinically significant symptoms of depression and anxiety, respectively. Compared to patients without clinically significant symptoms of depression, patients with clinically significant symptoms of depression had poorer health status, HRQoL mental and physical component, and greater global disability, hand disability and aesthetic impairment. Compared to patients without clinically significant symptoms of anxiety, patients with clinically significant symptoms of anxiety had poorer SF-36 mental and physical component scores. On multivariable analysis, excluding mental component score of SF-36, variables independently associated with clinically significant symptoms of depression and anxiety were global disability and physical component of SF-36, plus female gender for clinically significant symptoms of anxiety only. Remarkably, patients with and without clinically significant psychiatric symptoms were comparable for all disease-related clinical features assessed. Conclusion High levels of clinically significant symptoms of anxiety and depression are observed among SSc patients. Clinically significant psychiatric symptoms are rather associated with increased disability and altered HRQoL, than with disease-specific organ manifestations. PMID

  14. Relevance and clinical significance of serum resistin level in obese T2DM rhesus monkey models.

    PubMed

    Qi, S-D; He, Z-L; Chen, Y; Ma, J; Yu, W-H; Li, Y-Y; Yang, F-M; Wang, J-B; Chen, L-X; Zhao, Y; Lu, S-Y

    2015-09-01

    Resistin is a type of hormone-like adipocytokines, which is secreted specifically by adipocytes. It may be a key factor in the development of type 2 diabetes mellitus (T2DM) from obesity- associated insulin resistance due to results that show that it has a close relationship with insulin resistance in rodents. We utilized the rhesus monkeys as study objects to preliminarily test the association with glucose metabolism and to conduct a correlation analysis for clinical parameters and serum resistin levels in obese rhesus monkey models of T2DM. The results suggested that resistin was significantly increased in T2DM monkeys (P <0.01), and that resistin had a positive correlation respectively with total cholesterol (TC), low-density lipoprotein (LDL-C), fasting plasma glucose (FPG), fasting insulin (FPI) and glycated hemoglobin (HbA1c), Insulin resistance index (HOA-IR), but a negative correlation with islet β-cell function (HOMA-β). In the course of glucose metabolism, reverse release change of resistin and insulin in T2DM monkeys occurred, but the phenomenon that was not observed in the control group, these findings indicated that resistin negatively regulated and interfered with carbohydrate metabolism in T2DM monkey models. The character of the releasing change of resistin might be a unique process in T2DM. Therefore, all of the results could provide references for clinical diagnostic criteria for human cases of T2DM, and could have clinical significance for obese T2DM diagnosis and degree of insulin resistance. PMID:26069076

  15. Clinical significance of programmed death ligand-1 (PD-L1) in colorectal serrated adenocarcinoma

    PubMed Central

    Zhu, Hailong; Qin, Huali; Huang, Ziling; Li, Shuai; Zhu, Xuyou; He, Jian; Yang, Jing; Yu, Xiaoting; Yi, Xianghua

    2015-01-01

    Preliminary research results with antibody of the negative costimulatory molecule programmed cell death ligand-1 (PD-L1) suggested its expression on tumor cells associated with various tumor grade and postoperative prognosis. However, to date, there is no information of PD-L1 expression in colorectal serrated adenocarcinoma (SAC) and its clinical relevance. Therefore, the purpose of this study is to investigate the clinical significance of PD-L1 expression in a large cohort of patients with SAC. Here, we first retrospectively identified all SAC collected at our institution between August 2008 and May 2013. The expression levels of PD-L1 were examined by immunohistochemistry in 120 patients with SAC. We further evaluated the correlation between expression data and clinical parameters, including patient age, sex, tumor size, location, grade, primary tumor classification (pT), lymph node metastasis (pN), distant metastases (pM), and vascular invasion. Strong PD-L1 expression was detected in 25% of SAC. Higher expression of PD-L1 was significantly associated with pN (P=0.003) and pM (P=0.014). Survival analysis showed that patients with higher expression of PD-L1 had a poorer prognosis (P=0.045). However, multivariate regression analysis did not support PD-L1 as an independent prognostic factor (P=0.430). Our data suggest that PD-L1 may represent a new biomarker of metastasis and prognosis for patients with SAC, but as a target in the treatment of SAC is less certain. PMID:26464688

  16. Clinical significance of incidental FDG uptake in the prostate gland detected by PET/CT

    PubMed Central

    Sahin, Ertan; Elboga, Umut; Kalender, Ebuzer; Basıbuyuk, Mustafa; Demir, Hasan Deniz; Celen, Yusuf Zeki

    2015-01-01

    The value of FDG-positron emission tomography/computed tomography (PET/CT) for detecting prostate cancer is unknown. We aimed to investigate the clinical value of incidental prostate FDG uptake on PET/CT scans. We reviewed 6128 male patients who underwent FDG-PET/CT scans and selected cases that reported hypermetabolic lesion in the prostate. The patients who have prior history of prostate carcinoma or prostate surgery were excluded from the study. We have analyzed the correlation between PET/CT findings and serum prostate-specific antigen (PSA) levels, imaging (USG), urological examinations and biopsy. Incidental 18F-FDG uptake of the prostate gland was observed in 79 patients (1.3%). While sixteen of them were excluded due to inadequate clinical data, the remaining 63 patients were included for further analysis. The patients were divided into two groups; 8 patients (12.7%) in the malignant group and 55 patients (87.3%) in the benign group. The SUVmax values were not significantly different between the two groups. In 6 (75%) patients with prostate cancer, FDG uptake was observed focally in the peripheral zone of the prostate glands. There was no significant correlation between the SUVmax and the PSA levels. Incidental 18F-FDG uptake in the prostate gland is a rare condition, but a substantial portion of it is associated with the cancer. Benign and malignant lesions of the prostate gland in FDG-PET/CT imaging could not be reliably distinguished. The peripheral focally FDG uptake of prostate glands should be further examined with the clinical and labaratory evaluations. PMID:26379847

  17. Frequency and clinical significance of placental histological lesions in an unselected population at or near term.

    PubMed

    Pathak, Sangeeta; Lees, Christoph C; Hackett, Gerald; Jessop, Flora; Sebire, Neil J

    2011-12-01

    Associations between specific placental histological abnormalities and obstetric outcomes are reported. However, most data are based either on high-risk cases or relate to case-control studies selected from those with abnormal placental histology findings, with the unavoidable biases that these approaches entail. This study reports the frequency of the several common, objective and predefined histological abnormalities of the placenta as identified by pathologists blinded to all clinical information. A total 1,153 women were recruited from an unselected population delivering at 34-43 weeks. Histological findings in common obstetric outcome groups were compared to those of the unselected population, and odds ratios and predictive values were calculated. Normal histological findings were present in 72.1% of pregnancies with normal outcomes and in 79.1%, 66.6%, 80%, and 74.8% of pregnancies affected by pre-eclampsia (PET), pregnancy-induced hypertension (PIH), gestational diabetes (GDM), and small for gestational age (SGA), respectively. Chronic placental underperfusion was seen more frequently in PIH (odds ratio (OR) 2) and SGA (OR 1.4), while villitis of unknown aetiology was observed more commonly in cases with PIH (OR 3.2). Fetal thrombotic vasculopathy was twice as common in cases with GDM whilst massive perivillous fibrin deposition was much more frequent in those with PET (OR 20.2) and SGA (OR 8.9). Chorangiomata were 13 times more common in pregnancies with PET. However, in all cases, positive predictive values were low, with the majority of cases with histological abnormalities being associated with normal outcome. At term, specific placental histological lesions are significantly more common in complicated pregnancies, but the clinical significance of such lesions in a specific case remains uncertain, since the majority will be identified from clinically uncomplicated normal pregnancies. PMID:22038509

  18. Detection and Classification of Cancer from Microscopic Biopsy Images Using Clinically Significant and Biologically Interpretable Features

    PubMed Central

    Kumar, Rajesh; Srivastava, Subodh

    2015-01-01

    A framework for automated detection and classification of cancer from microscopic biopsy images using clinically significant and biologically interpretable features is proposed and examined. The various stages involved in the proposed methodology include enhancement of microscopic images, segmentation of background cells, features extraction, and finally the classification. An appropriate and efficient method is employed in each of the design steps of the proposed framework after making a comparative analysis of commonly used method in each category. For highlighting the details of the tissue and structures, the contrast limited adaptive histogram equalization approach is used. For the segmentation of background cells, k-means segmentation algorithm is used because it performs better in comparison to other commonly used segmentation methods. In feature extraction phase, it is proposed to extract various biologically interpretable and clinically significant shapes as well as morphology based features from the segmented images. These include gray level texture features, color based features, color gray level texture features, Law's Texture Energy based features, Tamura's features, and wavelet features. Finally, the K-nearest neighborhood method is used for classification of images into normal and cancerous categories because it is performing better in comparison to other commonly used methods for this application. The performance of the proposed framework is evaluated using well-known parameters for four fundamental tissues (connective, epithelial, muscular, and nervous) of randomly selected 1000 microscopic biopsy images. PMID:27006938

  19. Clinical Significance and Characterization of Streptococcus tigurinus Isolates in an Adult Population.

    PubMed

    Bourassa, Lori; Clarridge, J E

    2015-11-01

    Streptococcus tigurinus is a newly described member of the Streptococcus mitis group. Due to the difficulty in distinguishing viridans group streptococci (VGS) by phenotype, analysis of 16S rRNA sequences is necessary for the accurate identification of most species. Through a laboratory policy of analyzing all clinically significant isolates from the VGS group by16S rRNA gene sequencing, we identified 14 S. tigurinus isolates from 11 patients. The Vitek 2 system most commonly gave an excellent rating to an incorrect identification (e.g., Streptococcus mitis), as did matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) (e.g., Streptococcus oralis). S. tigurinus strains were recovered from numerous body sites, including the blood, peritoneal fluid, bone, synovial fluid, a perianal abscess, and an arm wound. Retrospective chart review indicated that most isolates were clinically significant, with bacteremia (n = 5), soft tissue infections (n = 3) osteomyelitis (n = 2), infected joint prosthesis (n = 2), and peritonitis (n = 2) being the most common, thus expanding the spectrum of disease associated with S. tigurinus. PMID:26354809

  20. Clinical Significance and Characterization of Streptococcus tigurinus Isolates in an Adult Population

    PubMed Central

    Bourassa, Lori

    2015-01-01

    Streptococcus tigurinus is a newly described member of the Streptococcus mitis group. Due to the difficulty in distinguishing viridans group streptococci (VGS) by phenotype, analysis of 16S rRNA sequences is necessary for the accurate identification of most species. Through a laboratory policy of analyzing all clinically significant isolates from the VGS group by16S rRNA gene sequencing, we identified 14 S. tigurinus isolates from 11 patients. The Vitek 2 system most commonly gave an excellent rating to an incorrect identification (e.g., Streptococcus mitis), as did matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) (e.g., Streptococcus oralis). S. tigurinus strains were recovered from numerous body sites, including the blood, peritoneal fluid, bone, synovial fluid, a perianal abscess, and an arm wound. Retrospective chart review indicated that most isolates were clinically significant, with bacteremia (n = 5), soft tissue infections (n = 3) osteomyelitis (n = 2), infected joint prosthesis (n = 2), and peritonitis (n = 2) being the most common, thus expanding the spectrum of disease associated with S. tigurinus. PMID:26354809

  1. Expression of endothelin-1 in laryngocarcinoma tissues and its clinical significance

    PubMed Central

    WANG, SHAOZHONG; WU, JIAN; SONG, YISA; ZHONG, HUILING

    2016-01-01

    In recent years, the incidence of laryngeal carcinoma has been on the increase. The aim of the present study was to examine the expression level of endothelin-1 (ET-1) in laryngeal carcinoma tissues and to establish its clinical significance. A total of 82 cases of laryngeal carcinoma tissues were examined, of which 27 cases were stage I, 34 were stage II, and 21 were stage III. The normal mucosal tissues beyond the surgical incision margin in the 82 laryngeal carcinoma patients were used as the normal control. An additional 80 tissue specimens collected from laryngeal carcinoma outpatients were used as benign lesions. ET-1 expression levels in different tissues were determined using streptavidin-peroxidase (SP) immunohistochemistry. The results showed that the ET-1 expression level was highest in laryngeal carcinoma tissues and was significantly higher than that in the other two groups (P<0.05). The ET-1 expression level was higher in stage III compared to that in stage I and II (P<0.05) and higher than that of the normal control (P<0.05). The ET-1 expression level was higher in stage II compared to that in stage I (P<0.05). In conclusion, ET-1 was strongly expressed in laryngeal carcinoma tissues and may play an important role in the pathogenesis and development of laryngeal carcinoma tissues. ET-1 expression in laryngeal carcinoma tissues was associated with the clinical staging of laryngeal carcinoma. PMID:27123118

  2. Classical and Novel Prognostic Markers for Breast Cancer and their Clinical Significance

    PubMed Central

    Taneja, Pankaj; Maglic, Dejan; Kai, Fumitake; Zhu, Sinan; Kendig, Robert D.; Fry, Elizabeth A.; Inoue, Kazushi

    2010-01-01

    The use of biomarkers ensures breast cancer patients receive optimal treatment. Established biomarkers such as estrogen receptor (ER) and progesterone receptor (PR) have been playing significant roles in the selection and management of patients for endocrine therapy. HER2 is a strong predictor of response to trastuzumab. Recently, the roles of ER as a negative and HER2 as a positive indicator for chemotherapy have been established. Ki67 has traditionally been recognized as a poor prognostic factor, but recent studies suggest that measurement of Ki67-positive cells during treatment will more effectively predict treatment efficacy for both anti-hormonal and chemotherapy. p53 mutations are found in 20–35% of human breast cancers and are associated with aggressive disease with poor clinical outcome when the DNA-binding domain is mutated. The utility of cyclin D1 as a predictor of breast cancer prognosis is controversial, but cyclin D1b overexpression is associated with poor prognosis. Likewise, overexpression of the low molecular weight form of cyclin E1 protein predicts poor prognosis. Breast cancers from BRCA1/2 carriers often show high nuclear grades, negativity to ER/PR/HER2, and p53 mutations, and thus, are associated with poor prognosis. The prognostic values of other molecular markers, such as p14ARF, TBX2/3, VEGF in breast cancer are also discussed. Careful evaluation of these biomarkers with current treatment modality is required to determine whether their measurement or monitoring offer significant clinical benefits. PMID:20567632

  3. Statistical controversies in clinical research: statistical significance-too much of a good thing ….

    PubMed

    Buyse, M; Hurvitz, S A; Andre, F; Jiang, Z; Burris, H A; Toi, M; Eiermann, W; Lindsay, M-A; Slamon, D

    2016-05-01

    The use and interpretation of P values is a matter of debate in applied research. We argue that P values are useful as a pragmatic guide to interpret the results of a clinical trial, not as a strict binary boundary that separates real treatment effects from lack thereof. We illustrate our point using the result of BOLERO-1, a randomized, double-blind trial evaluating the efficacy and safety of adding everolimus to trastuzumab and paclitaxel as first-line therapy for HER2+ advanced breast cancer. In this trial, the benefit of everolimus was seen only in the predefined subset of patients with hormone receptor-negative breast cancer at baseline (progression-free survival hazard ratio = 0.66, P = 0.0049). A strict interpretation of this finding, based on complex 'alpha splitting' rules to assess statistical significance, led to the conclusion that the benefit of everolimus was not statistically significant either overall or in the subset. We contend that this interpretation does not do justice to the data, and we argue that the benefit of everolimus in hormone receptor-negative breast cancer is both statistically compelling and clinically relevant. PMID:26861602

  4. Clinical Significance of Asthma Clusters by Longitudinal Analysis in Korean Asthma Cohort

    PubMed Central

    Kim, Sujeong; Yoon, Sun-young; Kwon, Hyouk-Soo; Chang, Yoon-Seok; Cho, You Sook; Jang, An-Soo; Park, Jung Won; Nahm, Dong-Ho; Yoon, Ho-Joo; Cho, Sang-Heon; Cho, Young-Joo; Choi, ByoungWhui; Moon, Hee-Bom; Kim, Tae-Bum

    2013-01-01

    Background We have previously identified four distinct groups of asthma patients in Korean cohorts using cluster analysis: (A) smoking asthma, (B) severe obstructive asthma, (C) early-onset atopic asthma, and (D) late-onset mild asthma. Methods and Results A longitudinal analysis of each cluster in a Korean adult asthma cohort was performed to investigate the clinical significance of asthma clusters over 12 months. Cluster A showed relatively high asthma control test (ACT) scores but relatively low FEV1 scores, despite a high percentage of systemic corticosteroid use. Cluster B had the lowest mean FEV1, ACT, and the quality of life questionnaire for adult Korean asthmatics (QLQAKA) scores throughout the year, even though the percentage of systemic corticosteroid use was the highest among the four clusters. Cluster C was ranked second in terms of FEV1, with the second lowest percentage of systemic corticosteroid use, and showed a marked improvement in subjective symptoms over time. Cluster D consistently showed the highest FEV1, the lowest systemic corticosteroid use, and had high ACT and QLQAKA scores. Conclusion Our asthma clusters had clinical significance with consistency among clusters over 12 months. These distinctive phenotypes may be useful in classifying asthma in real practice. PMID:24391784

  5. Expression of AQP5 and AQP8 in human colorectal carcinoma and their clinical significance

    PubMed Central

    2012-01-01

    Background The aquaporins (AQPs) are a family of small membrane transport proteins whose overexpression has been implicated in tumorigenesis. However, the expression of AQP5 and AQP8 in colorectal cancer and the clinical significance remain unexplored. This study aimed to detect the expression of AQP5 and AQP8 in clinical samples of colorectal cancer and analyze the correlations of their expression with the clinicopathological features of colorectal cancer. Methods Forty pairs of colorectal cancer tissue and paraneoplastic normal tissue were obtained at the time of surgery from patients with colorectal cancer. The expression of AQP5 and AQP8 was detected by immunohistochemical staining and reverse transcriptase polymerase chain reaction. Results AQP5 was mainly expressed in colorectal carcinoma cells and barely expressed in paraneoplastic normal tissues. By contrast, AQP8 was mainly expressed in paraneoplastic normal tissues and barely expressed in colorectal carcinoma cells. AQP5 expression was not significantly associated with the sex or age of the patient with colorectal cancer (P>0.05), but was closely associated with the differentiation, tumor-nodes-metastasis stage and distant lymph node metastasis of colorectal carcinoma (P<0.05). Conclusions AQP5 might be a novel prognostic biomarker for patients with colorectal cancer. PMID:23148732

  6. Incidence and clinical significance of ESR1 mutations in heavily pretreated metastatic breast cancer patients

    PubMed Central

    Niu, Jiaxin; Andres, Grant; Kramer, Kim; Kundranda, Madappa N; Alvarez, Ricardo H; Klimant, Eiko; Parikh, Ankur R; Tan, Bradford; Staren, Edgar D; Markman, Maurie

    2015-01-01

    Background ESR1 mutation has recently emerged as one of the important mechanisms involved in endocrine resistance. The incidence and clinical implication of ESR1 mutation has not been well evaluated in heavily pretreated breast cancer patients. Methods We conducted a retrospective review of advanced breast cancer patients with tumors who underwent next-generation sequencing genomic profiling using Foundation One test at Cancer Treatment Centers of America® regional hospitals between November 2012 and November 2014. Results We identified a total of 341 patients including 217 (59%) estrogen receptor (ER)+, 177 (48%) progesterone receptor (PR)+, 30 (8%) hormone receptor+/HER2 positive, and 119 (32%) triple negative patients. ESR1 mutation was noted in 27/222 (12.1%) ER+ or PR+ breast cancer patients. All ER+ patients received at least one line of an aromatase inhibitor. All 28 patients were found to harbor ESR1 mutations affecting ligand-binding domain with the most common mutations affecting Y537 (17/28, 60.7%) and D538 (9/28, 32.1%). In this cohort, 19 (67.9%) patients carried three or more, seven (25%) patients had one or two additional genomic alterations and one (3.6%) patient had an ESR1 mutation only. Of 28 patients, three patients were treated with fulvestrant immediately before and two patients were treated after next-generation sequencing testing; only one patient achieved stable disease for 8 months and the other four patients had progression of disease. In all, 3/3 (100%) patients before testing and 2/4 (50%) after testing treated with exemestane and everolimus achieved stable disease for at least 6 months. Conclusion ESR1 mutation was found in 12.1% of a large cohort of advanced breast cancer patients. Exemestane in combination with everolimus might be a reasonable option. Prospective studies are warranted to validate these findings. PMID:26648736

  7. Clinical significance of Gremlin 1 in cervical cancer and its effects on cancer stem cell maintenance.

    PubMed

    Sato, Masakazu; Kawana, Kei; Fujimoto, Asaha; Yoshida, Mitsuyo; Nakamura, Hiroe; Nishida, Haruka; Inoue, Tomoko; Taguchi, Ayumi; Takahashi, Juri; Adachi, Katsuyuki; Nagasaka, Kazunori; Matsumoto, Yoko; Wada-Hiraike, Osamu; Oda, Katsutoshi; Osuga, Yutaka; Fujii, Tomoyuki

    2016-01-01

    Gremlin 1 is one of the bone morphogenetic protein (BMP) antagonists and is also related to differentiation in combination with BMPs and is associated with various types of diseases. Gremlin 1 is overexpressed in various types of human cancers and has been reported to play a role in cervical cancer oncogenesis. However, there is no report concerning the relationship between Gremlin 1 and cervical cancer stem cells (CSCs). The objective of the present study was to identify the clinical significance of Gremlin 1 in cervical cancer and its effects on CSC-like properties in vitro. Clinical samples were obtained. Gremlin 1 mRNA expression levels in the cervical cancer tissues were measured by RT-qPCR and assessed for correlation with their clinical prognosis [overall survival (OS), progression-free survival (PFS)] and with other prognostic factors. In vitro, cervical cancer, CaSki cells, exposed to Gremlin 1 (1,000 ng/ml) for 24 h were evaluated for expression of undifferentiated-cell markers (Nanog, Oct3/4, Sox2) by RT-qPCR, the population of ALDH-positive cells by flow cytometry and sphere-forming ability on a ultra-low attachment culture dish. Cervical cancer tissues from 104 patients were collected. A high mRNA expression level of Gremlin 1 was an independent poor prognostic factor of PFS but not of OS. A high mRNA expression level of Gremlin 1 was correlated with bulky (>4 cm) tumors. The Nanog mRNA expression level was significantly increased in the CaSki cells exposed to Gremlin 1 (P=0.0008) but not Oct3/4 and Sox2 mRNA expression levels. The population of ALDH-positive cells in the Gremlin 1-exposed cells was 1.41-fold higher compared with the control (P=0.0184). Sphere-forming ability was increased when 1,000 Gremlin 1-exposed cells were seeded (P=0.0379). In cervical cancer, it is suggested that Gremlin 1 may have a role in clinical recurrence and maintaining CSC-like properties. PMID:26530461

  8. Frequency, Types, and Potential Clinical Significance of Medication-Dispensing Errors

    PubMed Central

    Bohand, Xavier; Simon, Laurent; Perrier, Eric; Mullot, Hélène; Lefeuvre, Leslie; Plotton, Christian

    2009-01-01

    INTRODUCTION AND OBJECTIVES: Many dispensing errors occur in the hospital, and these can endanger patients. The purpose of this study was to assess the rate of dispensing errors by a unit dose drug dispensing system, to categorize the most frequent types of errors, and to evaluate their potential clinical significance. METHODS: A prospective study using a direct observation method to detect medication-dispensing errors was used. From March 2007 to April 2007, “errors detected by pharmacists” and “errors detected by nurses” were recorded under six categories: unauthorized drug, incorrect form of drug, improper dose, omission, incorrect time, and deteriorated drug errors. The potential clinical significance of the “errors detected by nurses” was evaluated. RESULTS: Among the 734 filled medication cassettes, 179 errors were detected corresponding to a total of 7249 correctly fulfilled and omitted unit doses. An overall error rate of 2.5% was found. Errors detected by pharmacists and nurses represented 155 (86.6%) and 24 (13.4%) of the 179 errors, respectively. The most frequent types of errors were improper dose (n = 57, 31.8%) and omission (n = 54, 30.2%). Nearly 45% of the 24 errors detected by nurses had the potential to cause a significant (n = 7, 29.2%) or serious (n = 4, 16.6%) adverse drug event. CONCLUSIONS: Even if none of the errors reached the patients in this study, a 2.5% error rate indicates the need for improving the unit dose drug-dispensing system. Furthermore, it is almost certain that this study failed to detect some medication errors, further arguing for strategies to prevent their recurrence. PMID:19142545

  9. Meta-Analysis of Prognostic and Clinical Significance of CD44v6 in Esophageal Cancer.

    PubMed

    Hu, Bangli; Luo, Wei; Hu, Rui-Ting; Zhou, You; Qin, Shan-Yu; Jiang, Hai-Xing

    2015-08-01

    CD44v6 is a cell adhesion molecule that plays an important role in the development and progression of esophageal cancer. However, the prognostic value and clinical significance of CD44v6 in esophageal cancer remains controversial. In the present study, we aimed to clarify these relationships through a meta-analysis.We performed a comprehensive search of studies from PubMed, EMBASE, Ovid library database, Google scholar, and Chinese National Knowledge Infrastructure databases that were published before June 2015. The odds ratio (OR) and pooled hazard ratio (HR) with the 95% confidence intervals (CI) were used to estimate the effects.Twenty-one studies including 1504 patients with esophageal cancer were selected to assess the prognostic value and clinical significance of CD44v6 in these patients. The results showed that the expression of CD44v6 was higher in esophageal cancer tissue than in normal colorectal tissue (OR=9.19, 95% CI=6.30-13.42). Moreover, expression of CD44v6 was higher in patients with lymphoid nodal metastasis, compared to those without (OR=6.91, 95% CI=4.81-9.93). The pooled results showed that CD44v6 was associated with survival in patients with esophageal cancer (HR = 2.47, 95% CI = 1.56-3.92). No significant difference in CD44v6 expression was found in patients with different histological types and tumor stages (both P>0.05). Moreover, no publication bias was found among the studies (all P > 0.05).This meta-analysis demonstrates that CD44v6 is associated with the metastasis of esophageal cancer and a poor prognosis, but is not associated with the histological types and tumor stages. PMID:26252284

  10. Clinical significance of serum cytokine levels and thrombopoietic markers in childhood idiopathic thrombocytopenic purpura

    PubMed Central

    Del Vecchio, Giovanni Carlo; Giordano, Paola; Tesse, Riccardina; Piacente, Laura; Altomare, Maria; De Mattia, Domenico

    2012-01-01

    Background Biological markers useful for defining children with newly diagnosed immune thrombocytopenic purpura (ITP) who are likely to develop the chronic form of the disease are partially lacking. The purpose of this study was to assess the clinical role of both immunological and thrombopoietic markers in children with ITP and correlate their levels with different disease stages. Materials and methods We enrolled 28 children with ITP at the onset of their disease, who were followed-up for a whole year and divided according to whether their disease resolved within the 12 months (n=13) or became chronic (n=15), 11 subjects with chronic ITP off therapy for at least 1 month at the time of enrolment, and 30 healthy matched controls. Serum levels of T helper type 1 and 2 and T regulatory-associated cytokines, such as interferon γ, tumour necrosis factor α, interleukin (IL) 2, IL6, IL10, and thrombopoietin were measured in all children using quantitative immunoenzymatic assays, while reticulated platelets were evaluated by flow cytometric analysis. Results Serum IL10 levels were significantly higher in patients with an acute evolution of ITP than in either healthy controls (p<0.001) or patients with chronic progression of ITP (p<0.05). Reticulated platelet count and thrombopoietin levels were significantly higher in ITP patients at the onset of their disease, whether with acute resolution or chronic progression, than in healthy subjects (p<0.01; p<0.001), but did not differ between the groups of patients. Conclusion IL-10 seems to predict the clinical course of ITP, as it is significantly higher at the onset of disease in patients who obtain disease remission in less than 1 year. PMID:22153687

  11. Clinical significance of thymidine kinase in Egyptian children with acute lymphoblastic leukemia

    PubMed Central

    Hagag, Adel A.; Saad, Mohamed A.; Mohamed, Sohair A.

    2015-01-01

    Background: Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy, representing one-third of pediatric cancers. Thymidine kinase-1 (TK-1) is expressed in proliferating cells so elevated TK-1 indicates active tumor growth. Objective: To study the clinical significance of TK-1 in children with ALL. Patients and Methods: This study was carried out on 40 children with newly diagnosed ALL who were admitted to Oncology Unit, Pediatric department, Tanta University (26 males and 14 females) with their ages ranged from 4 to 10 years and 30 healthy children of matched age and sex as a control group. For all patients the following were done: Complete blood picture, bone marrow examination, immunophenotyping and TK-1 serum levels. Results: Mean TK-1 level was significantly higher in patients at diagnosis than controls and significantly higher in patients with unfavorable outcome than patients with favorable outcome. Mean TK-1 level was significantly higher in patients in relapse than patients in remission and controls. No significant differences in mean TK-1 level between patients in remission and controls. There were statistically significant differences in disease free survival and overall survival between patients with favorable and unfavorable outcome. Conclusion: From this study we concluded that TK is a helpful marker in diagnosis and follow-up of patients with ALL. Recommendations: Thymidine kinase-1 should be routinely assessed at diagnosis and during follow-up in ALL patients for better diagnostic and prognostic assessment and should be taken in consideration in designing future therapeutic strategies based on patients-specific risk factors. PMID:25992345

  12. The clinical significance of γ-catenin in acute myeloid leukemia

    PubMed Central

    Xu, Jiadai; Wu, Wei; Shen, Wenyi; Liu, Peng

    2016-01-01

    Dysregulation of γ-catenin may function as an oncogenic factor in various malignancies. We investigated γ-catenin expression in acute myeloid leukemia (AML) and explored its role in the pathogenesis of AML. γ-Catenin was significantly overexpressed in AML patients compared to healthy donors. The γ-catenin expression in AML patients with lower white blood cells (<30×109/L) was significantly higher than those with higher white blood cells (≥30×109/L). The expression levels of γ-catenin in AML patients with mutated CEBPα were significantly higher than those with unmutated CEBPα. AML patients with lower γ-catenin levels were more likely to achieve complete remission compared with patients who have higher γ-catenin levels. In K562 cells, γ-catenin knockdown suppressed cellular proliferation, while the cellular migration was greatly enhanced. Moreover, knocking down of γ-catenin enhanced the cytotoxicity of decitabine in K562 cells. Our investigation has indicated a potential role of γ-catenin in the pathogenesis of AML. PMID:27390526

  13. Measuring Academic Achievement of Students with Significant Cognitive Disabilities: Building Understanding of Alternate Assessment Scoring Criteria. Synthesis Report.

    ERIC Educational Resources Information Center

    Quenemoen, Rachel; Thompson, Sandra; Thurlow, Martha

    This report compares the assumptions and values embedded in scoring criteria used in five states (Arkansas, Kentucky, Louisiana, Oregon, and Vermont) for alternate assessments of students with significant cognitive disabilities. The five states use different alternate assessment approaches, including portfolio assessment, performance assessment,…

  14. Subspecies Identification and Significance of 257 Clinical Strains of Mycobacterium avium

    PubMed Central

    Tran, Quynh T.

    2014-01-01

    Mycobacterium avium is abundant in the environment. It has four subspecies of three types: the human or porcine type, M. avium subsp. hominissuis; the bird type, including M. avium subsp. avium serotype 1 and serotype 2, 3 (also M. avium subsp. silvaticum); and the ruminant type, M. avium subsp. paratuberculosis. We determined the subspecies of 257 M. avium strains isolated from patients at the M.D. Anderson Cancer Center from 2001 to 2010 and assessed their clinical significance. An assay of multiplex PCR was used for the typing. Results showed M. avium subsp. hominissuis to be most common (n = 238, 92.6%), followed by M. avium subsp. avium serotype 1 (n = 12, 4.7%) and serotype 2, 3 (n = 7, 2.7%). No strains of M. avium subsp. paratuberculosis were found. Of the 238 patients with M. avium subsp. hominissuis, 65 (27.3%) showed evidence of definite or probable infections, mostly in the respiratory tract, whereas the rest had weak evidence of infection. The bird-type subspecies, despite being infrequently isolated, caused relatively more definite and probable infections (10 of 19 strains, 52.6%). Overall, women of 50 years of age or older were more prone to M. avium infection than younger women or men of all ages were. We therefore conclude that M. avium subsp. hominissuis is the dominant M. avium subspecies clinically, that the two bird-type subspecies do cause human infections, and that M. avium infects mainly postmenopausal women. The lack of human clinical isolation of the ruminant type subspecies may need further investigation. PMID:24501026

  15. Clinically significant pharmacokinetic drug interactions of antiepileptic drugs with new antidepressants and new antipsychotics.

    PubMed

    Spina, Edoardo; Pisani, Francesco; de Leon, Jose

    2016-04-01

    Antiepileptic drugs (AEDs) are frequently co-prescribed with new antidepressants (ADs) or new antipsychotics (APs). A PubMed search with no time limit was used to update the review of the clinically significant pharmacokinetic (PK) drug interactions DIs (DIs) between AEDs with new ADs and APs. Our best interpretation of what to expect regarding dosing changes in the average patient after combining AEDs with new ADs or new APs is summarized on updated tables that integrate the information on in vitro metabolism studies, therapeutic drug monitoring (TDM) studies, case report/series and prospective studies. There will be a need to periodically update these dose correction factors as new knowledge becomes available. These tables will provide some orientation to clinicians with no TDM access and may also encourage clinicians to further study TDM. The clinical relevance of the inductive properties of carbamazepine, phenytoin, phenobarbital and primidone on new ADs and new APs and the inhibitory properties of valproic acid and some new ADs, are relatively well understood. On the other hand, PK DI studies combining new AEDs with weak inductive properties (particularly oxcarbazepine doses≥1200mg/day), topiramate doses≥400mg/day, clobazam, eslicarbazepine, and rufinamide), with new ADs and new APs are needed. Valproic acid may be 1) an inhibitor and/or inducer of clozapine and olanzapine with potential for clinically relevant DIs, 2) an inhibitor of paliperidone, and 3) a weak inducer of aripiprazole. Fluoxetine and fluvoxamine are relevant inhibitors of phenytoin and valproic acid and possibly of clobazam, lacosamide, phenobarbital, or primidone. PMID:26896788

  16. Clinical significance of late gadolinium enhancement in patients<20 years of age with hypertrophic cardiomyopathy.

    PubMed

    Smith, Brandon M; Dorfman, Adam L; Yu, Sunkyung; Russell, Mark W; Agarwal, Prachi P; Mahani, Maryam Ghadimi; Lu, Jimmy C

    2014-04-01

    Late gadolinium enhancement (LGE) on cardiovascular magnetic resonance imaging is associated with adverse events in adults with hypertrophic cardiomyopathy (HC). However, limited data exist on the extent and clinical significance of LGE in the pediatric population. In 30 patients (aged 14.1±3.2 years) with clinically diagnosed HC who underwent cardiovascular magnetic resonance imaging from 2007 to 2012, segments with hypertrophy and LGE were identified by 2 experienced readers blinded to outcome. Radial, circumferential, and longitudinal strains were evaluated using feature tracking software. The composite outcome was defined as cardiac death, nonsustained ventricular tachycardia, ventricular fibrillation, or appropriate implantable cardioverter-defibrillator discharge. LGE was present in 17 of 30 patients (57%), all in a midmyocardial pattern, with median 3 segments per patient (interquartile range [IQR] 2 to 5). No LGE was detected in patients without phenotypic hypertrophy. Segments with LGE had decreased radial (basal segments 20.7% vs 70.9%, p=0.01), circumferential (basal segments -23.2% vs -29.3%, p=0.04), and longitudinal strains (basal segments -13.8% vs -20.9%, p=0.04). After median follow-up of 26.9 months (IQR 7.5 to 34.3), 7 patients who had an adverse outcome (5 ventricular tachycardia, 1 appropriate implantable cardioverter-defibrillator discharge, and 1 death) had more segments of LGE (median 4, IQR 2 to 7 vs 0, IQR 0 to 2, p=0.01). One patient without LGE had ventricular tachycardia on exercise test. In conclusion, LGE occurs in a similar pattern in pediatric patients with HC as in adults, associated with hypertrophy, decreased myocardial strain, and adverse clinical outcomes. Further longitudinal studies are necessary to evaluate the rate of development of LGE and relation to outcomes in a larger cohort. PMID:24513464

  17. Routine Testing for Anaerobic Bacteria in Cerebrospinal Fluid Cultures Improves Recovery of Clinically Significant Pathogens

    PubMed Central

    Pittman, Meredith E.; Thomas, Benjamin S.; Wallace, Meghan A.; Weber, Carol J.

    2014-01-01

    In North America, the widespread use of vaccines targeting Haemophilus influenzae type b and Streptococcus pneumoniae have dramatically altered the epidemiology of bacterial meningitis, while the methodology for culturing cerebrospinal fluid (CSF) specimens has remained largely unchanged. The aims of this study were 2-fold: to document the current epidemiology of bacterial meningitis at a tertiary care medical center and to assess the clinical utility of routinely querying for anaerobes in CSF cultures. To that end, we assessed CSF cultures submitted over a 2-year period. A brucella blood agar (BBA) plate, incubated anaerobically for 5 days, was included in the culture procedure for all CSF specimens during the second year of evaluation. In the pre- and postimplementation years, 2,353 and 2,302 CSF specimens were cultured, with 49 and 99 patients having positive culture results, respectively. The clinical and laboratory data for patients with positive cultures were reviewed. Anaerobic bacteria were isolated in the CSF samples from 33 patients post-BBA compared to two patients pre-BBA (P = 0.01). The anaerobic isolates included Bacteroides thetaiotaomicron (n = 1), Propionibacterium species (n = 15), and Propionibacterium acnes (n = 19) isolates; all of these isolates were recovered on the BBA. Eight of the 35 patients from whom anaerobic organisms were isolated received antimicrobial therapy. Although six of these patients had central nervous system hardware, two patients did not have a history of a neurosurgical procedure and had community-acquired anaerobic bacterial meningitis. This study demonstrates that the simple addition of an anaerobically incubated BBA to the culture of CSF specimens enhances the recovery of clinically significant anaerobic pathogens. PMID:24622102

  18. Adalimumab induction and maintenance therapy achieve clinical remission and response in Chinese patients with Crohn's disease

    PubMed Central

    Ran, Zhi Hua; Gao, Xiang; Chen, Minhu; Zhong, Jie; Sheng, Jian-Qiu; Kamm, Michael A; Travis, Simon; Wallace, Kori; Mostafa, Nael M; Shapiro, Marisa; Li, Yao; Thakkar, Roopal B; Robinson, Anne M

    2016-01-01

    Background/Aims This was a Phase 2 study (NCT02015793) to evaluate the pharmacokinetics, safety, and efficacy of adalimumab in Chinese patients with Crohn's disease (CD). Methods Thirty, adult Chinese patients with CD (CD Activity Index [CDAI] 220–450; high-sensitivity [hs]-C-reactive protein [CRP] ≥3 mg/L) received double-blind adalimumab 160/80 mg or 80/40 mg at weeks 0/2, followed by 40 mg at weeks 4 and 6. An open-label extension period occurred from weeks 8–26; patients received 40 mg adalimumab every other week. Serum adalimumab concentration and change from baseline in fecal calprotectin (FC) were measured during the double-blind period. Clinical remission (CDAI <150), response (decrease in CDAI ≥70 points from baseline), and change from baseline in hs-CRP were assessed through week 26. Nonresponder imputation was used for missing categorical data and last observation carried forward for missing hs-CRP/FC values. No formal hypothesis was tested. Adverse events were monitored. Results Mean adalimumab serum concentrations during the induction phase were 13.9–18.1 µg/mL (160/80 mg group) and 7.5−9.5 µg/mL (80/40 mg group). During the double-blind period, higher remission/response rates and greater reductions from baseline in hs-CRP and FC were observed with adalimumab 160/80 mg compared to that with 80/40 mg. Adverse event rates were similar among all treatment groups. Conclusions Adalimumab serum concentrations in Chinese patients with CD were comparable to those observed previously in Western and Japanese patients. Clinically meaningful remission rates and improvement in inflammatory markers were achieved with both dosing regimens; changes occurred rapidly with adalimumab 160/80 mg induction therapy. No new safety signals were reported. PMID:27175116

  19. Clinical significance of up-regulated ID1 expression in Chinese de novo acute myeloid leukemia

    PubMed Central

    Zhou, Jing-Dong; Yang, Lei; Zhu, Xiao-Wen; Wen, Xiang-Mei; Yang, Jing; Guo, Hong; Chen, Qin; Yao, Dong-Ming; Ma, Ji-Chun; Lin, Jiang; Qian, Jun

    2015-01-01

    To investigate the clinical significance of ID1 expression in Chinese de novo AML patients. Real-time quantitative PCR was carried out to detect the status of ID1 expression in 102 de novo AML patients and 28 controls. ID1 transcript level was significantly increased in AML compared to normal controls (p=0.029). The age in the patients with high ID1 expression is significantly older than in those with low ID1 expression (p=0.044). ID1 overexpression occurred with the highest frequency in the patients with poor karyotype (7/7, 100%), lower frequency in the patients with intermediate karyotype (28/60, 47%), and the lowest frequency in the patients with favorable karyotype (12/31, 39%). Both whole AML and non-M3 patients with high ID1 expression had significantly lower rate of complete remission than those with low ID1 expression (p=0.007 and 0.038). ID1 high-expressed patients showed significantly shorter overall survival (OS) than ID1 low-expressed patients in both whole AML and non-M3 according to Kaplan-Meier analysis (p=0.007 and 0.040). However, multivariate analysis indicated that ID1 overexpression was not an independent risk factor in both whole AML and non-M3 patients. However, the adverse impact of ID1 overexpression on outcome was revealed by both Kaplan-Meier analysis and multivariate analysis in the non-M3 patients less than 60 years old. Our study reveals that ID1 overexpression may be associated with higher risk karyotype classification and act as an independent risk factor in young non-M3 patients. PMID:26191235

  20. Clinical significance of serum laminin and type-IV collagen levels in cutaneous melanoma patients

    PubMed Central

    TAS, FARUK; BILGIN, ELIF; KARABULUT, SENEM; DURANYILDIZ, DERYA

    2016-01-01

    Laminin and type-IV collagen constitute a significant portion of the extracellular matrix. The objective of the present study was to evaluate whether the serum concentrations of laminin and type-IV collagen may serve as biomarkers for cutaneous melanoma. Sixty pathologically confirmed melanoma patients were enrolled in the study. Serum laminin and type-IV collagen levels were assessed using an ELISA. Thirty healthy controls were also examined. No significant differences in the baseline serum levels of laminin were identified between melanoma patients and healthy controls (P=0.45). However, the baseline serum levels of type-IV collagen were significantly elevated in melanoma patients compared with those in the control group (P<0.001). Clinical parameters, including patient age, gender, localization of lesion, histopathology, stage of disease, serum lactate dehydrogenase concentrations and responsiveness to chemotherapy were found not to be associated with the serum levels of laminin and type-IV collagen (P>0.05). Furthermore, the serum levels of laminin and type-IV collagen had no prognostic value regarding the outcome for melanoma patients (P=0.36 and P=0.26, respectively). While laminin levels showed no diagnostic value, the serum concentrations of type-IV collagen were indicated to serve as a diagnostic marker in patients with cutaneous melanoma. In conclusion, type-IV collagen levels may be used as a diagnostic marker for cutaneous melanoma, while being void of any prognostic value. PMID:27330797

  1. Factors influencing the magnitude and clinical significance of drug interactions between azole antifungals and select immunosuppressants.

    PubMed

    Saad, Aline H; DePestel, Daryl D; Carver, Peggy L

    2006-12-01

    The magnitude of drug interactions between azole antifungals and immunosuppressants is drug and patient specific and depends on the potency of the azole inhibitor involved, the resulting plasma concentrations of each drug, the drug formulation, and interpatient variability. Many factors contribute to variability in the magnitude and clinical significance of drug interactions between an immunosuppressant such as cyclosporine, tacrolimus, or sirolimus and an antifungal agent such as ketoconazole, fluconazole, itraconazole, voriconazole, or posaconazole. By bringing similarities and differences among these agents and their potential interactions to clinicians' attention, they can appreciate and apply these findings in a individualized patient approach rather than follow only the one-size-fits-all dosing recommendations suggested in many tertiary references. Differences in metabolism and in the inhibitory potency of cytochrome P450 3A4 and P-glycoprotein influence the onset, magnitude, and resolution of drug interactions and their potential effect on clinical outcomes. Important issues are the route of administration and the decision to preemptively adjust dosages versus intensive monitoring with subsequent dosage adjustments. We provide recommendations for the concomitant use of these agents, including suggestions regarding contraindicated combinations, those best avoided, and those requiring close monitoring of drug dosages and plasma concentrations. PMID:17125435

  2. Clinical significance and management of Barrett's esophagus with epithelial changes indefinite for dysplasia.

    PubMed

    Thota, Prashanthi N; Kistangari, Gaurav; Esnakula, Ashwini K; Gonzalo, David Hernandez; Liu, Xiu-Li

    2016-08-01

    Barrett's esophagus (BE) is defined as the extension of salmon-colored mucosa into the tubular esophagus ≥ 1 cm proximal to the gastroesophageal junction with biopsy confirmation of intestinal metaplasia. Patients with BE are at increased risk of esophageal adenocarcinoma (EAC), and undergo endoscopic surveillance biopsies to detect dysplasia or early EAC. Dysplasia in BE is classified as no dysplasia, indefinite for dysplasia (IND), low grade dysplasia (LGD) or high grade dysplasia (HGD). Biopsies are diagnosed as IND when the epithelial abnormalities are not sufficient to diagnose dysplasia or the nature of the epithelial abnormalities is uncertain due to inflammation or technical issues. Specific diagnostic criteria for IND are not well established and its clinical significance and management has not been well studied. Previous studies have focused on HGD in BE and led to changes and improvement in the management of BE with HGD and early EAC. Only recently, IND and LGD in BE have become focus of intense study. This review summarizes the definition, neoplastic risk and clinical management of BE IND. PMID:27602241

  3. Clinical significance of sleep bruxism on several occlusal and functional parameters.

    PubMed

    Ommerborn, Michelle A; Giraki, Maria; Schneider, Christine; Fuck, Lars Michael; Zimmer, Stefan; Franz, Matthias; Raab, Wolfgang Hans-michael; Schaefer, Ralf

    2010-10-01

    The aim of this study was to evaluate the association between various functional and occlusal parameters and sleep bruxism. Thirty-nine (39) sleep bruxism patients and 30 controls participated in this investigation. The assessment of sleep bruxism was performed using the Bruxcore Bruxism-Monitoring Device (BBMD) combined with a new computer-based analyzing method. Sixteen functional and/or occlusal parameters were recorded. With a mean slide of 0.95 mm in the sleep bruxism group and a mean slide of 0.42 mm in the control group (Mann Whitney U test; p<0.003), results solely demonstrated a significant group difference regarding the length of a slide from centric occlusion to maximum intercuspation. The results suggest that the slightly pronounced slide could be of clinical importance in the development of increased wear facets in patients with current sleep bruxism activity. Following further evaluation including polysomnographic recordings, the BBMD combined with this new analyzing technique seems to be a clinically feasible instrument that allows the practitioner to quantify abrasion over a short period. PMID:21032978

  4. What is the clinical significance of pulmonary hypertension in acute respiratory distress syndrome? A review

    PubMed Central

    Lai, Peggy S.; Mita, Carol; Thompson, B. Taylor

    2014-01-01

    Elevated pulmonary arterial pressures appear to be a prominent feature of the acute respiratory distress syndrome (ARDS). Current clinical guidelines for the management of ARDS do not specifically address treatment of pulmonary hypertension or associated right ventricular dysfunction because the clinical significance of this entity remains unclear. Interpretation of elevated pulmonary arterial pressures, pulmonary vascular resistance, and transpulmonary gradient as well as signs of right ventricular dysfunction is confounded by the effects of positive pressure ventilation. There does not appear to be a consistent relationship between the diagnosis of pulmonary hypertension or right ventricular failure and mortality in patients with ARDS, but it is unclear if right ventricular failure contributes to the mortality risk per se or if the underlying cause of pulmonary hypertension, including intravascular micro and macro thrombosis, are simply markers for systemic dysregulation of coagulation and fibrinolysis that may lead to multiorgan failure in ARDS. While studies of pulmonary vasodilator therapies have not shown a mortality benefit in ARDS, such trials have targeted improved oxygenation rather than improved pulmonary hemodynamics so that the possible contribution of improved right ventricular function to better outcomes has not been directly tested in large trials. Future studies are needed to determine if treatment of pulmonary hypertension and associated right ventricular dysfunction will affect mortality in patients with ARDS. PMID:24193181

  5. Clinical significance and management of Barrett’s esophagus with epithelial changes indefinite for dysplasia

    PubMed Central

    Thota, Prashanthi N; Kistangari, Gaurav; Esnakula, Ashwini K; Gonzalo, David Hernandez; Liu, Xiu-Li

    2016-01-01

    Barrett’s esophagus (BE) is defined as the extension of salmon-colored mucosa into the tubular esophagus ≥ 1 cm proximal to the gastroesophageal junction with biopsy confirmation of intestinal metaplasia. Patients with BE are at increased risk of esophageal adenocarcinoma (EAC), and undergo endoscopic surveillance biopsies to detect dysplasia or early EAC. Dysplasia in BE is classified as no dysplasia, indefinite for dysplasia (IND), low grade dysplasia (LGD) or high grade dysplasia (HGD). Biopsies are diagnosed as IND when the epithelial abnormalities are not sufficient to diagnose dysplasia or the nature of the epithelial abnormalities is uncertain due to inflammation or technical issues. Specific diagnostic criteria for IND are not well established and its clinical significance and management has not been well studied. Previous studies have focused on HGD in BE and led to changes and improvement in the management of BE with HGD and early EAC. Only recently, IND and LGD in BE have become focus of intense study. This review summarizes the definition, neoplastic risk and clinical management of BE IND. PMID:27602241

  6. Assessment of clinical significance of anti-Ge in an untransfused man

    SciTech Connect

    Pearson, H.A.; Richards, V.L.; Wylie, B.R.; Bruce, D.; Watt, J.M.; Wilkie, D.; Kronenberg, H. )

    1991-03-01

    A 19-year-old, untransfused Melanesian man from Papua New Guinea was admitted to the hospital for repair of an atrial septal defect. His serum contained an alloantibody that reacted strongly on the indirect antiglobulin test and was identified as anti-Ge. Gerbich-negative blood was transfused following urgent surgery. A 51Cr red cell survival study performed 2 weeks after surgery yielded zero survival of Gerbich-positive cells after 24 hours. A monocyte-driven, antibody-dependent, cell-mediated cytotoxicity assay performed on both pretransfusion and posttransfusion serum samples and on concentrated serum showed less than 1 percent specific lysis of Gerbich-positive cells. This did not correlate with the indication of clinical significance predicted by the 51Cr study. Red cell adherence and phagocytosis, not evident in a monocyte monolayer assay using native serum, were demonstrable in 16 percent of monocytes by the use of concentrated serum.

  7. Perspectives on the clinical significance of functional pain syndromes in children

    PubMed Central

    Basch, Molly C; Chow, Erika T; Logan, Deirdre E; Schechter, Neil L; Simons, Laura E

    2015-01-01

    Functional pain syndromes (FPS) characterize a subset of individuals who experience pain and related symptoms and disability without clear structural or disease etiology. In the pediatric population, FPS hold high clinical importance due to significant prevalence rates and potential to persist into adulthood. Although extensive research has been executed to disambiguate FPS, the syndromes that fall within its spectrum remain conceptually complex and sometimes ill-defined. This paper provides an overview of available research on the classification and multifaceted etiology of FPS in youth and their effects on interpersonal, psychological, and familial function. Vital aspects of a successful multidisciplinary approach to treating this population are described; however, it is evident that future research requires more longitudinal studies. PMID:26504406

  8. Ultrasonography-Based Thyroidal and Perithyroidal Anatomy and Its Clinical Significance.

    PubMed

    Ha, Eun Ju; Baek, Jung Hwan; Lee, Jeong Hyun

    2015-01-01

    Ultrasonography (US)-guided procedures such as ethanol ablation, radiofrequency ablation, laser ablation, selective nerve block, and core needle biopsy have been widely applied in the diagnosis and management of thyroid and neck lesions. For a safe and effective US-guided procedure, knowledge of neck anatomy, particularly that of the nerves, vessels, and other critical structures, is essential. However, most previous reports evaluated neck anatomy based on cadavers, computed tomography, or magnetic resonance imaging rather than US. Therefore, the aim of this article was to elucidate US-based thyroidal and perithyroidal anatomy, as well as its clinical significance in the use of prevention techniques for complications during the US-guided procedures. Knowledge of these areas may be helpful for maximizing the efficacy and minimizing the complications of US-guided procedures for the thyroid and other neck lesions. PMID:26175574

  9. A Mutation-Sensitive Switch Assay to Detect Five Clinically Significant Epidermal Growth Factor Receptor Mutations

    PubMed Central

    Liu, Bin; Zhou, Lin; Wang, Qian

    2015-01-01

    Epidermal growth factor receptor (EGFR) mutations can affect the therapeutic efficacy of drugs used to treat nonsmall-cell lung cancer (NSCLC). We aimed to develop methods to detect five common EGFR somatic mutations in tumor tissues from NSCLC patients by using a nanoscale mutation-sensitive switch consisting of a high-fidelity polymerase and phosphorothioate-modified allele-specific primers. The five clinically significant EGFR mutations examined here are S768I, T790M, L858R, and 15- and 18-bp deletion mutations in exon 19. Our assays showed sensitivities of 100 copies and specificities of more than three log scales for matched templates relative to mismatched templates by routine polymerase chain reaction (PCR), real-time PCR, and multiplex PCR. This assay would be superior to DNA sequencing in situations where mutant DNA is not abundant. PMID:25918867

  10. Clinical significance of elevated serum and urine amylase levels in patients with appendicitis.

    PubMed

    Swensson, E E; Maull, K I

    1981-12-01

    During the 45 month period beginning January 1977, 251 patients with a pathologically confirmed diagnosis of acute appendicitis underwent celiotomy at the Medical College of Virginia Hospital. A preoperative serum or urine amylase determination was recorded in 155 of the patients (62 percent). Of this group, 15 patients (10 percent) had elevation of serum amylase or 2 hour urine amylase. Hyperamylasemia or hyperamylasuria directly led to misdiagnosis or treatment delay in 5 of the 15 patients. Appendiceal rupture occurred in three patients, two of whom had prolonged (greater than 1 month) hospitalizations directly attributable to the misdiagnosis. As a result of this study, we conclude that (1) acute appendicitis and elevated amylase levels may occur concurrently, (2) hyperamylasemia or hyperamylasuria should not dissuade the surgeon from early operation if other clinical features suggest appendicitis, and (3) abdominal pain and elevation of amylase level define significant intraabdominal disease, not specifically pancreatic disease. PMID:6172043

  11. Ultrasonography-Based Thyroidal and Perithyroidal Anatomy and Its Clinical Significance

    PubMed Central

    Ha, Eun Ju; Lee, Jeong Hyun

    2015-01-01

    Ultrasonography (US)-guided procedures such as ethanol ablation, radiofrequency ablation, laser ablation, selective nerve block, and core needle biopsy have been widely applied in the diagnosis and management of thyroid and neck lesions. For a safe and effective US-guided procedure, knowledge of neck anatomy, particularly that of the nerves, vessels, and other critical structures, is essential. However, most previous reports evaluated neck anatomy based on cadavers, computed tomography, or magnetic resonance imaging rather than US. Therefore, the aim of this article was to elucidate US-based thyroidal and perithyroidal anatomy, as well as its clinical significance in the use of prevention techniques for complications during the US-guided procedures. Knowledge of these areas may be helpful for maximizing the efficacy and minimizing the complications of US-guided procedures for the thyroid and other neck lesions. PMID:26175574

  12. Clinical significance of serum claudin-1 and claudin-7 levels in patients with colorectal cancer

    PubMed Central

    KARABULUT, MEHMET; ALIS, HALIL; BAS, KORAY; KARABULUT, SENEM; AFSAR, CIGDEM USUL; OGUZ, HILAL; GUNALDI, MERAL; AKARSU, CEVHER; KONES, OSMAN; AYKAN, NURI FARUK

    2015-01-01

    The present study aimed to investigate the serum levels and clinical relevance of claudin (CLDN) 1 and CLDN7 in patients with colorectal cancer (CRC). A total of 140 patients with a pathologically confirmed diagnosis of CRC were enrolled in this study. The serum levels of CLDN1 and CLDN7 were determined using the solid-phase sandwich ELISA method. A total of 40 healthy age- and gender-matched controls were included in the analysis. The median age of the patients was 60 years (range, 24–84 years). The localization of the tumor in the majority of the patients was the colon (n=81, 58%). Of the 55 metastatic patients who received palliative chemotheraphy, 31% were chemotherapy-responsive. The baseline median serum CLDN1 and CLDN7 levels were significantly lower in non-metastatic and metastatic patients compared with those in healthy controls (CLND1, P=0.008 and 0.002; and CLND7, P=0.002 and 0.002, respectively). Moreover, known clinical variables, including poor performance status and high carcinoembryonic antigen (CEA) levels were found to be associated with lower serum CLDN1 concentrations for all patients (P=0.03 and P=0.03, respectively). High T stage and high CEA levels were found to be correlated with lower serum CLDN7 concentrations for all patients (P=0.04 and 0.03, respectively). A correlation was identified between CLDN1 and CLDN7 levels in non-metastatic and metastatic CRC patients (both P-values <0.001). Our study results did not reveal any statistical significance for serum CLDN1 or CLND7 concentrations regarding progression-free and overall survival rate. Therefore, reduced serum levels of CLDN1 and CLND7 may be useful markers in the differential diagnosis of CRC. PMID:26807230

  13. The clinical significance of small copy number variants in neurodevelopmental disorders

    PubMed Central

    Asadollahi, Reza; Oneda, Beatrice; Joset, Pascal; Azzarello-Burri, Silvia; Bartholdi, Deborah; Steindl, Katharina; Vincent, Marie; Cobilanschi, Joana; Sticht, Heinrich; Baldinger, Rosa; Reissmann, Regina; Sudholt, Irene; Thiel, Christian T; Ekici, Arif B; Reis, André; Bijlsma, Emilia K; Andrieux, Joris; Dieux, Anne; FitzPatrick, David; Ritter, Susanne; Baumer, Alessandra; Latal, Beatrice; Plecko, Barbara; Jenni, Oskar G; Rauch, Anita

    2014-01-01

    Background Despite abundant evidence for pathogenicity of large copy number variants (CNVs) in neurodevelopmental disorders (NDDs), the individual significance of genome-wide rare CNVs <500 kb has not been well elucidated in a clinical context. Methods By high-resolution chromosomal microarray analysis, we investigated the clinical significance of all rare non-polymorphic exonic CNVs sizing 1–500 kb in a cohort of 714 patients with undiagnosed NDDs. Results We detected 96 rare CNVs <500 kb affecting coding regions, of which 58 (60.4%) were confirmed. 6 of 14 confirmed de novo, one of two homozygous and four heterozygous inherited CNVs affected the known microdeletion regions 17q21.31, 16p11.2 and 2p21 or OMIM morbid genes (CASK, CREBBP, PAFAH1B1, SATB2; AUTS2, NRXN3, GRM8). Two further de novo CNVs affecting single genes (MED13L, CTNND2) were instrumental in delineating novel recurrent conditions. For the first time, we here report exonic deletions of CTNND2 causing low normal IQ with learning difficulties with or without autism spectrum disorder. Additionally, we discovered a homozygous out-of-frame deletion of ACOT7 associated with features comparable to the published mouse model. In total, 24.1% of the confirmed small CNVs were categorised as pathogenic or likely pathogenic (median size 130 kb), 17.2% as likely benign, 3.4% represented incidental findings and 55.2% remained unclear. Conclusions These results verify the diagnostic relevance of genome-wide rare CNVs <500 kb, which were found pathogenic in ∼2% (14/714) of cases (1.1% de novo, 0.3% homozygous, 0.6% inherited) and highlight their inherent potential for discovery of new conditions. PMID:25106414

  14. Clinical significance of COX-2, GLUT-1 and VEGF expressions in endometrial cancer tissues

    PubMed Central

    Ma, Xiaoping; Hui, Yuzuo; Lin, Li; Wu, Yu; Zhang, Xian; Liu, Peishu

    2015-01-01

    Objective: To analyze the clinical significance of COX-2, GLUT-1 and VEGF expressions in endometrial cancer tissues. Methods: One hundred and eight tissue samples from the patients with endometrial cancer enrolled in our hospital from August 2011 to July 2014 were selected, including 60 normal tissue samples (normal group), 60 neoplastic tissue samples (neoplastic group) and 60 cancer tissue samples (cancer group). All the samples were subjected to immunohistochemical assay to detect the expressions of COX-2, GLUT-1 and VEGF. The clinical data were also investigated for correlation analysis. Results: The positive rates of COX-2 in normal group, neoplastic group and cancer groups were 3.3%, 21.7% and 55.0% respectively. The positive rates of GLUT-1 in normal group, neoplastic group and cancer groups were 3.3%, 25.0% and 70.0% respectively. The positive rates of VEGF in normal group, neoplastic group and cancer groups were 1.7%, 23.3% and 63.3% respectively. With increasing stage of such cancer, decreasing degree of differentiation and lymphatic metastasis, the positive expression rates of COX-2, GLUT-1 and VEGF proteins were raised significantly (P<0.05). Spearman’s correlation analysis showed that the expressions of COX-2 and GLUT-1 (r=0.207, P<0.05), COX-2 and VEGF (r=0.243, P<0.05), as well as GLUT-1 and VEGF (r=0.758, P<0.05) were positively correlated. Conclusion: COX-2, GLUT-1 and VEGF were highly prominent in endometrial cancer, especially in the patients with low degree of differentiation, late stage and metastasis. They functioned synergistically in the onset and progression of this cancer. PMID:26101475

  15. Clinical significance of accurate identification of lymph node status in distant metastatic gastric cancer

    PubMed Central

    Zhang, Jingwen; Wang, Hongqiang; Su, Yuqi; Huang, Na; Shi, Min; Bin, Jianping; Liao, Yulin; Liao, Wangjun

    2016-01-01

    PURPOSE The clinical consequences of accurately identifying lymph node (LN) status in distant metastatic gastric cancer (DMGC) are unclear. We aimed to determine the prognostic significance of N stage, positive LN (PLN) count, and the positive LN ratio (LNR). We also retrospectively compared survival outcomes of DMGC patients stratified by LN dissection (LND). RESULTS LND was performed in 1593 patients. The CSS was significantly different between groups divided according to N stage, PLN, and LNR in DMGC patients who underwent LND. Lower LNR was an independent predictor of longer survival in all kinds of patients cohorts, whereas PLN was not such a predictor. PLN count correlated with LND number and LNR. No correlation existed between LNR and LND number. Undergoing LND and having a higher number of dissected LNs were associated with superior CSS. MATERIALS AND METHODS Data from 1889 DMGC patients treated between 2004 and 2009, and documented in the Surveillance, Epidemiology, and End Results (SEER) registry, were reviewed. Pearson's correlation coefficient and the Chi-square test were used to study the relationships between LND number, PLN count, N stage, and the LNR. Cancer-specific survival (CSS) was evaluated using Kaplan-Meier analysis, with the log-rank test performed for univariate analysis (UVA) and the Cox proportional hazards model employed for multivariate analysis (MVA). CONCLUSION LN metastatic variables play important roles in the prognostic evaluation and treatment decisions of DMGC patients. Accurate identification of LN status in DMGC patients is critical. LND performance is associated with increased survival and has clinical practicability. PMID:26556854

  16. Biological and clinical significance of PARP1 protein expression in breast cancer.

    PubMed

    Green, Andrew R; Caracappa, Daniela; Benhasouna, Ahmed A; Alshareeda, Alaa; Nolan, Christopher C; Macmillan, R Douglas; Madhusudan, Srinivasan; Ellis, Ian O; Rakha, Emad A

    2015-01-01

    Poly(ADP-ribose) polymerase-1 (PARP1) is a key facilitator of DNA repair. PARP inhibitors have gained recent attention as promising therapeutic agents for the treatment of solid tumours including breast cancer (BC). However, the biological and clinical significance of PARP1 expression in BC and its role in DNA-damage response (DDR) remain to be defined. We investigated the expression of PARP1 expression, cleaved (PARP1c) and non-cleaved (PAR1nc) forms, in a large and well-characterised cohort of clinically annotated stage I-III operable BCs (n = 1,269) and 43 BRCA1-mutated BCs using immunohistochemistry. PARP1 expression was correlated to clinicopathological variables, outcome and expression of other key DNA repair proteins (BRCA1, RAD51, Ku70/80, PIASγ and CHK1). Expression of PARP1 was exclusively nuclear. 49 and 85 % of sporadic BC showed expression PARP1nc and PARP1c, respectively. In BRCA1-mutated tumours, PARP1nc/PARP1c was highly expressed (95 and 79 %, respectively). PARP1nc expression was positively associated with premenopausal younger age patients, larger size and higher tumour grade. PARP1 was positively associated with DDR-proteins; RAD51, BRCA1, CHK1 and PIASγ (p < 0.001). Negative association was found between PARP1nc and Ki67. PARP1c was associated with ER (p < 0.001). Different associations between PARP1 and DDR-proteins were observed when stratified based on ER/BRCA1 status. PARP1 was not an independent predictor of outcome in sporadic or BRCA1-mutated BC. Our results demonstrate a potential biological role for PARP1c and PARP1nc in DNA repair in BC based on the significant association with other key DNA damage repair proteins. These associations were not restricted to ER-negative or triple-negative subgroup. PMID:25528020

  17. AB029. The clinical significance of RigiScan plus detection

    PubMed Central

    Gao, Bing; Mu, Hongtao; Zhang, Zhichao; Yuan, Yiming; Peng, Jing; Xin, Zhongcheng; Guo, Yinglu

    2016-01-01

    Erectile dysfunction (ED) is a common disease in male outpatient service, the penis hardness testing of ED in the clinical diagnosis has important significance, past some detection methods, such as nocturnal penile tumescence monitoring (NPT) due to time-consuming is not easy in outpatient service and a vasodilator agent intervention tests such as color Doppler detection due to the injection of drugs in the penis is difficult for patients to accept. In 1965 night rapid eye movement sleep phase 3–5 times of penile erection phenomenon was first reported by Fisher, in 1970 the night monitoring instrument of penis erectile hardness is used for evaluation of male erectile function. In 1985 researchers reported the RigiScan plus software was used to record of nocturnal erection, 1994 this method was gradually improved and used in clinical application by Levine. Sol reported that after taking sildenafil the patient was given audio-visual stimulation to induce the penis erects, then the RigiScan plus was used to record erection hardness in 2006. Due to the complexity of the etiology of ED, for the evaluation of penile erectile function should also be in many ways any single check has its limitations, the drug combined with audio-visual sense stimulation induced penile erection hardness monitoring (AVSS + RigiScan plus) in newly diagnosed patients with erectile function has a certain significance. Compared with AVSS + RigiScan examination, NPT is more expensive, time-consuming, and cumbersome, and patients feel unwell. And AVSS + RigiScan is simple, effective, easy, cheap, and the diagnostic accuracy rate matching to NPT, it is suitable for routine examination of patients with newly diagnosed ED.

  18. Clinically achievable plasma deferoxamine concentrations are therapeutic in a rat model of Pneumocystis carinii pneumonia.

    PubMed Central

    Merali, S; Chin, K; Del Angel, L; Grady, R W; Armstrong, M; Clarkson, A B

    1995-01-01

    The iron-chelating drug deferoxamine (DFO) has been shown to be active in animal models of Pneumocystis carinii pneumonia (PCP), with effective daily intraperitoneal bolus dosages being 400 and 1,000 mg of DFO mesylate kg of body weight-1 in mouse and rat models, respectively. Continuous infusion produced a moderately improved response in a rat model. The data reported here demonstrate that the response achieved by continuous infusion of 195 and 335 mg of DFO mesylate kg-1 day-1 in the rat model is associated with mean concentrations in plasma of 1.3 and 2.5 micrograms of DFO ml-1 and mean concentrations in lung tissue of 4.9 and 6.0 micrograms of DFO g of lung tissue-1, respectively. Since current clinical use of DFO mesylate for the treatment of iron overload produces higher concentrations in the plasma of patients, DFO may prove to be a useful anti-PCP treatment. The 2.4- to 3.8-fold higher DFO concentration observed in lung tissue compared with that observed in plasma may be important in the response of PCP to DFO. PMID:8540710

  19. Expression and clinical significance of the proliferation marker minichromosome maintenance protein 2 (Mcm2) in diffuse astrocytomas WHO grade II

    PubMed Central

    2013-01-01

    Background The WHO classification system for astrocytomas is not considered optimal, mainly because of the subjective assessment of the histopathological features. Few prognostic variables have been found that stratify the risk of clinical progression in patients with grade II astrocytoma. For that reason there is a continuous search for biomarkers that can improve the histopathological diagnosis and prognostication of these tumours. Aim This study was designed to investigate the prognostic significance of the proliferative marker Mcm2 (minichromosome maintenance protein 2) in diffuse astrocytomas WHO grade II and correlate the findings with histopathology, mitoses, and Ki67/MIB-1 immunostaining. Method 61 patients with histologically verified grade II astrocytoma (WHO 2007) were investigated. Paraffin sections were immunostained with anti-Mcm2, and the Mcm2 proliferative index (PI) was determined as the percentage of immunoreactive tumour cell nuclei. Results Mcm2 PI was not associated with any histopathological features but correlated significantly with mitotic count and Ki67/MIB-1 PI (p<0.05). In the survival analyses Mcm2 showed trends to poorer survival, however, statistical significance was not achieved in the univariate analyses (p>0.05). Conclusions In our hands Mcm2 immunostaining has no advantage over Ki67/MIB-1 in the evaluation of grade II astrocytomas. Larger studies are needed to fully clarify the prognostic role of this biomarker. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1715002791944037 PMID:23618321

  20. The Clinical Significance of Interleukin–1 Receptor Antagonist +2018 Polymorphism in Rheumatoid Arthritis

    PubMed Central

    Ismail, Endom; Nofal, Omimah Khaled Jaber; Sakthiswary, Rajalingham; Shaharir, Syahrul Sazliyana; Sridharan, Radhika

    2016-01-01

    Objective Interleukin-1 receptor antagonist (IL-1Ra) acts as an inhibitor of IL-1; which is one of the culprit cytokines in rheumatoid arthritis (RA). Although +2018 polymorphism of IL-1Ra has been implicated in the pathogenesis of RA, its importance remains poorly understood. Hence, the purpose of this study was to determine the clinical significance of interleukin-1 receptor antagonist (IL-1Ra) +2018 polymorphism in RA. Methods Polymerase chain reaction (PCR) and sequencing were used to determine the genotypes of the IL-1Ra +2018 for 77 RA patients and 18 healthy controls. All RA patients were assessed for the disease activity score that includes 28 joints (DAS28) and radiographic disease damage based on Modified Sharp Score (MSS). Results The frequency of the T/T and C/T genotypes did not differ significantly (p = 0.893) between the RA patients and the controls. The C/T genotype had significantly higher mean disease activity (DAS 28) and disease damage (MSS) scores with p values of 0.017 and 0.004, respectively. Additionally, the ESR (erythrocyte sedimentation rate), CRP (C-reactive protein), the number of swollen and tender joints were higher for the C/T individuals. On multivariate analysis the CRP, swollen joint count and MSS remained significant with the following p values i.e. 0.045, 0.046 and less than 0.05. Conclusions C/T genotype of IL-1Ra +2018 prognosticates more aggressive disease in RA. PMID:27105431

  1. The significance of the determination of lymphocytes with clinical manifestation of ophthalmic zoster sine herpete

    PubMed Central

    Marumoto, Tatsuya; Hiratsuka, Yoshimune; Murakami, Akira

    2010-01-01

    Objective: To examine the significance of VZV-IgG (IgG) enzyme immunoassay (EIA) and the determination of peripheral blood lymphocyte counts in the diagnosis of ophthalmic zoster sine herpete (ophthalmic ZSH). Method: Clinical case-control study with a sample of 65 patients with ophthalmic ZSH (16 males and 49 females; mean age 56 ± 18 years) in whom pressure elicited pain in tender points of Valleix (tender points of sites at which the trigeminal nerve appears subcutaneously). A total of 41 healthy controls (17 males and 24 females, mean age 48 ± 21 years) were also recruited. In each group, IgG and lymphocyte count were determined upon receiving the consent of patients. Multiple logistic regression analysis was used to evaluate the factors associated with diagnosis of ophthalmic ZSH. Odds ratios and 95% confidence intervals (CI) were determined for each variable. Results: Lymphocyte count in the patients with ophthalmic ZSH was significantly low, though there were no significant differences in age, gender, and IgG between the two groups. Multiple logistic regression analysis revealed that lymphocytes pose a significant prognostic factor, and in case of 1,800 lymphocytes/μl or more, the odds ratio to less than1,800 lymphocytes/μl was 0.29 (95% CI: 0.12–0.72). Conclusion: Patients with orbital pain should be suspected as having ophthalmic ZSH as this allows for the determination of lymphocyte counts after tender points were confirmed. The swift diagnosis of ophthalmic ZSH and the administration of antiviral drugs from an early stage improve the subjective symptoms of the patient and is regarded as necessary to reduce the risk of severe complications. PMID:20689799

  2. Clinical Significance of Positive Pelvic Washings in Uterine Papillary Serous Carcinoma Confined to an Endometrial Polyp.

    PubMed

    Hanley, Krisztina Z; Fadare, Oluwole; Fisher, Kevin E; Atkins, Kristen A; Mosunjac, Marina B

    2016-05-01

    Uterine papillary serous carcinoma (UPSC) represents 10% of endometrial carcinomas. Significant number of patients initially present with extrauterine disease. The role of adjuvant treatment in low stage, especially polyp-confined UPSC is controversial. This multi-institutional study evaluated the significance of positive pelvic washing (PW) and adjuvant treatment on disease recurrence in a setting of endometrial polyp-confined UPSC. Surgical pathology files from 3 institutions were searched for cases of endometrial polyp-confined UPSC. Following histologic review, cases were clinically staged as Stage I, without myoinvasion or lymphovascular invasion. Clinicopathologic characteristics, results of PW, and type of adjuvant therapy were recorded. Statistical analysis using the Kaplan-Meier method for survival and Fisher exact test were performed. Thirty-three patients were included in the study. All patients were diagnosed with polyp-confined UPSC. The size of the polyp ranged from 0.3 to 4.3 cm. PW was positive for tumor cells in 8/33 (24%) patients. Twenty-two patients (66.6%) received some type of adjuvant treatment. Six patients (18%) developed recurrent disease. There was no significant difference in disease-free survival in the patients receiving adjuvant treatment versus not (P=0.375). However, there was significant association (P=0.0013) between positive PW and disease recurrence. Data are conflicting whether positive PW affects prognosis in low-stage endometrial carcinomas. Our study showed that in UPSC, malignant cells can be present in PW without lymphovascular invasion or myoinvasion and may have negative prognostic implication. Our data also reflect the controversies in the role of adjuvant treatment in endometrium-confined UPSC. PMID:26535985

  3. Expression of O6-methylguanine DNA methyltransferase (MGMT) and its clinical significance in gastroenteropancreatic neuroendocrine neoplasm

    PubMed Central

    Yang, Qiu-Chen; Wang, Yu-Hong; Lin, Yuan; Xue, Ling; Chen, Yuan-Jia; Chen, Min-Hu; Chen, Jie

    2014-01-01

    O6-methylguanine-DNA methyltransferase (MGMT) is a widespread DNA repair enzyme defending against mutation caused by guanine O6-alkylating agents. Until now, we know only little about the expression of MGMT in gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN). To study the expression of MGMT and its clinical significance in GEP-NEN, 174 specimens of GEP-NEN were examined, of which 152 specimens came from The First Affiliated Hospital, Sun Yat-sen University during October 1995 to November 2013, 22 specimens came from Peking Union Medical College Hospital during September 2004 to April 2010. MGMT protein was detected with EnVision immunohistochemical staining method. Clinicopathological factors were also collected and analyzed. We observed that the overall expression rate of MGMT was 83.9%. Over expression of MGMT protein was not associated with sex, age, functional status, primary tumor location, grading, classification, TNM stage and metastasis (P > 0.05). Kaplan-Meier analysis revealed that there was no significant difference in survival between MGMT-positive and MGMT-negative tumors of GEP-NEN patients (χ2 = 0.887, P = 0.346). In multivariate analyses carried out by Cox proportional hazards regression model, MGMT expression was also not an independent predictors of survival. These results demonstrated that MGMT protein was highly expressed in GEP-NEN. MGMT deficiency rate was similar in pancreatic NEN and in gastrointestinal NEN. MGMT expression was not correlated with prognosis of GEP-NEN. PMID:25120800

  4. The clinical significance of the neutrophil-to-lymphocyte ratio in multiple sclerosis.

    PubMed

    Demirci, Seden; Demirci, Serpil; Kutluhan, Suleyman; Koyuncuoglu, Hasan Rifat; Yurekli, Vedat Ali

    2016-08-01

    Multiple sclerosis (MS) is one of the main chronic inflammatory diseases of the central nervous system that causes functional disability in young people. The aim of this study was to investigate the neutrophil-to-lymphocyte ratio (NLR) in patients with MS and the relationship between the NLR and the severity of the disease. One hundred and two MS patients (31 patients were in relapse; 71 patients were in remission) and 56 healthy controls were included. Complete blood counts as well as demographic and clinical data from MS patients were evaluated retrospectively. The NLRs were calculated for all participants and were compared; the cut-off value was also determined for the NLR and Expanded Disability Status Scale (EDSS). MS patients had a significantly higher NLR (p < 0.001) than the control group. The NLR levels were significantly higher in patients who were in relapse than patients in remission (p = 0.039). The cut-off value for the NLR to predict an MS diagnosis and activity were determined to be 2.04 and 3.90, respectively. The NLRs were directly correlated with erythrocyte sedimentation rate levels (r = 0.795, p < 0.001). Logistic regression analysis with dichotomous EDSS score showed that a high NLR was an independent predictor of the progression of disability. The NLR may be a biomarker that has simple, quick, inexpensive and reproducible properties in MS to predict patient's prognosis. PMID:26000934

  5. Potential clinical significance of ERβ ON promoter methylation in sporadic breast cancer.

    PubMed

    Božović, Ana; Markićević, Milan; Dimitrijević, Bogomir; Jovanović Ćupić, Snežana; Krajnović, Milena; Lukić, Silvana; Mandušić, Vesna

    2013-01-01

    The aim of the study was to assess how hypermethylation of the ON promoter of the estrogen receptor beta (ERβ) gene affects its expression (at the mRNA and protein level) and to correlate these with some clinical and histopathological parameters. A total of 131 samples of frozen breast cancer tissue was analyzed. A custom-designed, two-step PCR method was used to measure the methylation index of the ERβ gene ON promoter region. Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was performed to quantify mRNA of the ERβ1 isoform, while ERβ1 protein was determined using the Western blot method. There was a significant difference in the methylation index of the ERβ gene ON promoter between the groups of patients with negative and positive axillary lymph node status (P = 0.03). In addition, the methylation index of the ON promoter was positively correlated with estrogen receptor alfa (ERα) protein levels (ρ = 0.31, P = 0.02). There was a significant difference in the methylation index of the ON promoter between the progesterone receptor (PR)-negative and PR-positive groups of patients (P = 0.01). ERβ1 protein levels were negatively correlated with ERα protein (ρ = -0.27, P < 0.01). The methylation index of the ON promoter could be a more reliable additional parameter for prediction and/or prognosis in breast cancer than ERβ1-mRNA and/or protein levels. PMID:23794253

  6. Relationship between ultrasound elastography and myofibroblast distribution in breast cancer and its clinical significance.

    PubMed

    Hao, Yi; Guo, Xia; Ma, Binlin; Zhu, Lin; Liu, Lisha

    2016-01-01

    The study investigated the relationship between ultrasound elastography (USE) scoring and myofibroblast distribution with expression features of α-SMA +/CD34- in patients of Uyghur and Han ethnicities with breast masses in Xinjiang, China. The data was used to evaluate its clinical significance in the early diagnosis of breast cancer. A total of 300 patients with breast masses were included in the study, which involved conventional sonography and USE, with histopathologic diagnosis as the reference standard. Myofibroblast distribution was investigated by detecting the expression levels of α-SMA and CD34 in lesions using immunohistochemistry and real-time PCR. Out of 300 lesions, 185 were histologically malignant and 115 benign. The mean elasticity score for malignant lesions was significantly higher than for benign lesions. The expression level of α-SMA was elevated while the expression level of CD34 was lower in malignancies, compared with benign lesions. The expression of α-SMA was positively associated with the USE scores, while a negative relationship was observed between CD34 expression and USE scoring. The combination of USE and molecular diagnosis provides a promising modality for the early diagnosis and evaluation of the risks in particular types of breast cancer. PMID:26846996

  7. Biological and clinical significance of epigenetic silencing of MARVELD1 gene in lung cancer

    PubMed Central

    Shi, Ming; Wang, Shan; Yao, Yuanfei; Li, Yiqun; Zhang, Hao; Han, Fang; Nie, Huan; Su, Jie; Wang, Zeyu; Yue, Lei; Cao, Jingyan; Li, Yu

    2014-01-01

    Epigenetic silence in cancer frequently altered signal-transduction pathways during the early stages of tumor development. Recent progress in the field of cancer epigenetics has led to new opportunities for diagnosis and treatment of cancer. We previously demonstrated that novel identified nuclear factor MARVELD1 was widely expressed in human tissues, but down-regulated by promoter methylation in multiple cancers. This study was carried out to determine the biological and clinical significance of MARVELD1 gene silencing in lung cancer. Here, we found the reduced MARVELD1 expression significantly correlated with diagnostic histopathology and malignant degree of lung cancers. DNA hypermethylation and histone deacetylation synergistically inactivated MARVELD1 gene in lung cancer cells. Moreover, MARVELD1 modulated the efficiency of nonsense-mediated mRNA decay (NMD) through interaction with NMD core factor SMG1. The decreased MARVELD1 level in lung cancer reduces NMD efficiency through diminishing the association between NMD complex component UPF1/SMG1 and premature termination codons containing mRNA (PTC-mRNA). The results suggested that MARVELD1 silencing is an appealing diagnostic biomarker for lung cancer and epigenetic silencing of MARVELD1 gene links with the regulatory mechanism of NMD pathway in lung cancer, which may be required for tumorigenesis. PMID:25520033

  8. Relationship between ultrasound elastography and myofibroblast distribution in breast cancer and its clinical significance

    PubMed Central

    Hao, Yi; Guo, Xia; Ma, Binlin; Zhu, Lin; Liu, Lisha

    2016-01-01

    The study investigated the relationship between ultrasound elastography (USE) scoring and myofibroblast distribution with expression features of α-SMA + /CD34− in patients of Uyghur and Han ethnicities with breast masses in Xinjiang, China. The data was used to evaluate its clinical significance in the early diagnosis of breast cancer. A total of 300 patients with breast masses were included in the study, which involved conventional sonography and USE, with histopathologic diagnosis as the reference standard. Myofibroblast distribution was investigated by detecting the expression levels of α-SMA and CD34 in lesions using immunohistochemistry and real-time PCR. Out of 300 lesions, 185 were histologically malignant and 115 benign. The mean elasticity score for malignant lesions was significantly higher than for benign lesions. The expression level of α-SMA was elevated while the expression level of CD34 was lower in malignancies, compared with benign lesions. The expression of α-SMA was positively associated with the USE scores, while a negative relationship was observed between CD34 expression and USE scoring. The combination of USE and molecular diagnosis provides a promising modality for the early diagnosis and evaluation of the risks in particular types of breast cancer. PMID:26846996

  9. Immunohistochemical Expression and Clinical Significance of Suggested Stem Cell Markers in Hepatocellular Carcinoma

    PubMed Central

    Sung, Jong Jin; Noh, Sang Jae; Bae, Jun Sang; Park, Ho Sung; Jang, Kyu Yun; Chung, Myoung Ja; Moon, Woo Sung

    2016-01-01

    Background: Increasing evidence has shown that tumor initiation and growth are nourished by a small subpopulation of cancer stem cells (CSCs) within the tumor mass. CSCs are posited to be responsible for tumor maintenance, growth, distant metastasis, and relapse after curative operation. We examined the expression of CSC markers in paraffin-embedded tissue sections of hepatocellular carcinoma (HCC) and correlated the results with clinicopathologic characteristics. Methods: Immunohistochemical staining for the markers believed to be expressed in the CSCs, including epithelial cell adhesion molecule (EpCAM), keratin 19 (K19), CD133, and CD56, was performed in 82 HCC specimens. Results: EpCAM expression was observed in 56% of the HCCs (46/82) and K19 in 6% (5/82). EpCAM expression in HCC significantly correlated with elevated α-fetoprotein level, microvessel invasion of tumor cells, and high histologic grade. In addition, EpCAM expression significantly correlated with K19 expression. The overall survival and relapsefree survival rates in patients with EpCAM-expressing HCC were relatively lower than those in patients with EpCAM-negative HCC. All but two of the 82 HCCs were negative for CD133 and CD56, respectively. Conclusions: Our results suggest that HCCs expressing EpCAM are associated with unfavorable prognostic factors and have a more aggressive clinical course than those not expressing EpCAM. Further, the expression of either CD133 or CD56 in paraffin-embedded HCC tissues appears to be rare. PMID:26581206

  10. Clinical significance of topoisomerase 2A expression and gene change in operable invasive breast cancer.

    PubMed

    Qiao, Jiang-Hua; Jiao, De-Chuang; Lu, Zhen-Duo; Yang, Sen; Liu, Zhen-Zhen

    2015-09-01

    This study aims to investigate clinical significance of topoisomerase 2A (TOP2A) expression and TOP2A gene change in operable invasive breast cancer. This is a retrospective analysis, which includes 256 patients diagnosed as operable invasive breast cancer. All postoperational waxed specimens were subjected to resectioning for staining. Estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2), KI-67, TOP2A expression, and TOP2A gene changes were detected by immunohistochemistry (IHC) and fluorescent in situ hybridization technique (FISH), respectively. Correlation between TOP2A expression and clinicopathological characteristics was also investigated. Effects of TOP2A protein or gene changes on survival rate were detected. Results indicated that 165 were TOP2A positive (64.5 %), and 31 were gene amplification positive (12.1 %). Positive rate of TOP2A expression showed significant correlations with ER, KI-67, and HER-2. The difference of 5-year overall survival (OS) between TOP2A-positive and TOP2A-negative groups did not reach statistical significance (OS: P = 0.321, 85.9 vs. 79.6 %; disease-free survival [DFS]: P = 0.247, 83.3 vs. 75.3 %). Five-year OS in TOP2A amplification group was 68.8 %, which is lower than deficiency and control group (P > 0.05). Subgroup analysis showed no significant differences of OS and DFS either between TOP2A-positive and TOP2A-negative groups or between TOP2A amplification and control group in population of patients with HER-2 amplification, triple negative breast cancer, or hormone-positive breast cancer. In conclusion, positive rate of TOP2A expression correlates significantly with ER, KI-67, and HER-2. However, prognostic significance of either TOP2A expression or TOP2A gene changes in breast cancer and its various subtypes is limited. PMID:25846735

  11. Clinical significance of vascular endothelial growth factor in hepatitis C related hepatocellular carcinoma in Egyptian patients

    PubMed Central

    Atta, Mohamed Magdi El-Sadek Ali; Atta, Hazem Mahmoud; Gad, Magdy Abdel-Mawgoud; Rashed, Laila Ahmad; Said, Ebada M; Hassanien, Sharaf El-Sayed Ali; Kaseb, Ahmed O

    2016-01-01

    Background and aims Several angiogenic factors are involved in the development and progression of hepatocellular carcinoma (HCC), a hypervascular tumor. Vascular endothelial growth factor (VEGF) is a primary driving force for angiogenesis, and its overexpression has been reported in HCC. However, the significance of plasma and tissue VEGF levels in HCC in Egyptian patients with chronic hepatitis C (CHC) infection is understudied. The aim of this study was to evaluate the role of VEGF (measured in plasma and liver tissue) in patients with hepatitis C virus-related HCC and to assess its significance in the diagnosis and prognosis of HCC. Materials and methods A total of 90 subjects were studied. Among 90 subjects, 60 with CHC were examined and were subdivided into two groups: 30 patients with CHC-related HCC (HCC group) and 30 patients with CHC without HCC (non-HCC group). Thirty apparently healthy subjects served as the control group. VEGF was estimated in plasma by enzyme-linked immunosorbent assay and its expression in liver tissue was evaluated by real-time polymerase chain reaction. VEGF expression level and its relationship to tumor parameters, patients’ liver function profile, and patients’ clinical parameters were also investigated. Results Plasma VEGF levels in the HCC group were significantly higher than those of the non-HCC group, and both groups had significantly higher plasma VEGF levels than did the control group. Liver tissue VEGF expression was significantly higher in the HCC group than in the non-HCC group and positively correlated with plasma VEGF in the HCC group. The plasma VEGF levels were positively correlated with patients’ age, aspartate aminotransferase levels, serum alpha-fetoprotein levels, the presence of portal vein thrombosis, and the number of hepatic focal lesions in the HCC group. However, plasma VEGF levels were not significantly correlated with the Child-Pugh score, alanine aminotransferase levels, the size of focal lesions

  12. Polymorphism of human cytochrome P450 2D6 and its clinical significance: part II.

    PubMed

    Zhou, Shu-Feng

    2009-01-01

    Part I of this article discussed the potential functional importance of genetic mutations and alleles of the human cytochrome P450 2D6 (CYP2D6) gene. The impact of CYP2D6 polymorphisms on the clearance of and response to a series of cardiovascular drugs was addressed. Since CYP2D6 plays a major role in the metabolism of a large number of other drugs, Part II of the article highlights the impact of CYP2D6 polymorphisms on the response to other groups of clinically used drugs. Although clinical studies have observed a gene-dose effect for some tricyclic antidepressants, it is difficult to establish clear relationships of their pharmacokinetics and pharmacodynamic parameters to genetic variations of CYP2D6; therefore, dosage adjustment based on the CYP2D6 phenotype cannot be recommended at present. There is initial evidence for a gene-dose effect on commonly used selective serotonin reuptake inhibitors (SSRIs), but data on the effect of the CYP2D6 genotype/phenotype on the response to SSRIs and their adverse effects are scanty. Therefore, recommendations for dose adjustment of prescribed SSRIs based on the CYP2D6 genotype/phenotype may be premature. A number of clinical studies have indicated that there are significant relationships between the CYP2D6 genotype and steady-state concentrations of perphenazine, zuclopenthixol, risperidone and haloperidol. However, findings on the relationships between the CYP2D6 genotype and parkinsonism or tardive dyskinesia treatment with traditional antipsychotics are conflicting, probably because of small sample size, inclusion of antipsychotics with variable CYP2D6 metabolism, and co-medication. CYP2D6 phenotyping and genotyping appear to be useful in predicting steady-state concentrations of some classical antipsychotic drugs, but their usefulness in predicting clinical effects must be explored. Therapeutic drug monitoring has been strongly recommended for many antipsychotics, including haloperidol, chlorpromazine, fluphenazine

  13. The clinical significance of 8q24/MYC rearrangement in chronic lymphocytic leukemia.

    PubMed

    Li, Yan; Hu, Shimin; Wang, Sa A; Li, Shaoying; Huh, Yang O; Tang, Zhenya; Medeiros, L Jeffrey; Tang, Guilin

    2016-05-01

    Chromosome 8q24/MYC rearrangement is associated with Burkitt lymphoma and some aggressive B-cell lymphomas, but is rare in chronic lymphocytic leukemia. We here report a cohort of 20 chronic lymphocytic leukemia patients with 8q24/MYC rearrangement, 3 detected at time of initial diagnosis and 17 acquired after a median interval of 48 months. At the time when 8q24/MYC arrangement was detected, 18 patients had B-symptoms, 17 had lymphadenopathy, and 17 had splenomegaly. Histologically, typical chronic lymphocytic leukemia morphology was seen in six patients, increased prolymphocytes in nine and Richter's transformation in five patients. Eighteen patients had karyotypic information available that showed t(8;v) in a complex karyotype in 12 patients and in a non-complex karyotype in 6 patients. Fluorescence in situ hybridization confirmed MYC rearrangement in 17/17 patients. All patients required therapy after 8q24/MYC rearrangement was detected. At last follow-up, five of six patients with a non-complex karyotype were alive after a median of 74 months (10~143 months) from the detection of 8q24/MYC rearrangement. In contrast, 10 of 12 patients with a complex karyotype died with a median survival of 5.5 months. We conclude that 8q24/MYC rearrangement in chronic lymphocytic leukemia is rare and often acquired during the course of disease. If it is presented in a complex karyotype, it is often associated with Richter's transformation, refractory to therapy and an aggressive clinical course; on the other hand, if it is present in a non-complex karyotype, patients often respond to risk-adapted therapies and achieve remission. PMID:26916070

  14. Clinical significance of glycoprotein nonmetastatic B and its association with HER2 in breast cancer

    PubMed Central

    Kanematsu, Masako; Futamura, Manabu; Takata, Masafumi; Gaowa, Siqin; Yamada, Atsuko; Morimitsu, Kasumi; Morikawa, Akemi; Mori, Ryutaro; Hara, Hideaki; Yoshida, Kazuhiro

    2015-01-01

    Glycoprotein nonmetastatic B (GPNMB) is a potential oncogene that is particularly expressed in melanoma and breast cancer (BC). To clarify its clinical significance in BC, we measured serum GPNMB in vivo and investigated its cross talk with human epidermal growth factor 2 (HER2). GPNMB was expressed in four of six breast cell lines (SK-BR-3, BT-474, MDA-MD-231, and MDA-MD-157), two of six colorectal cell lines, and two of four gastric cancer (GC) cell lines. We established a GPNMB quantification system using enzyme-linked immunosorbent assay (ELISA) for these cell lines. We measured serum GPNMB in vivo in 162 consecutive BC patients and in 88 controls (50 colorectal cancer [CC] and 38 GC patients). The GPNMB concentration in BC, CC and GC was 8.163, 5.751 and 6.55 ng/mL, respectively. The GPNMB level was significantly higher in BC patients than in CC patients (P = 0.021). The HER2-rich subtype of BC patients had significantly higher GPNMB levels than other subtypes (vs. Luminal; P = 0.038; vs. DCIS; P = 0.0195). These high GPNMB levels decreased after treatment (surgery/chemotherapy). Next, we examined the relationship between GPNMB and HER2 in vitro using SK-BR3 and BT-474 (HER2-positive/GPNMB-positive) cells. GPNMB depletion by small interfering RNA (siRNA) increased both HER2 expression and phosphorylation. Trastuzumab (Tra) in combination with docetaxel promoted cell growth inhibition, and treatment with Tra or an Extracellular signal-related kinase (ERK) inhibitor enhanced GPNMB expression. These results indicate that GPNMB might be a surrogate marker for BC and may cross talk with the HER2 signal pathway. GPNMB may therefore emerge as an important player in anti-HER2 therapy. PMID:26077887

  15. The clinical significance of forkhead box protein A1 and its role in colorectal cancer

    PubMed Central

    Ma, Wenqi; Jiang, Jue; Li, Miao; Wang, Hua; Zhang, Hongli; He, Xin; Huang, Lili; Zhou, Qi

    2016-01-01

    Forkhead box protein A1 (FOXA1) is a transcription factor; recent studies have reported that FOXA1 has an oncogenic or tumor suppressive role in human malignancies, and its expression is associated with the prognosis of patients with cancer. However, further studies are required to determine the clinical significance of FOXA1 and its role in colorectal cancer (CRC). In the present study, FOXA1 expression was detected in 90 samples of CRC tissues and matched noncancerous tissues using immunohistochemistry. In these cases, FOXA1 expression was detected in 57.8% (52/90) of the CRC samples, whereas only 37.8% (34/90) of the noncancerous specimens exhibited a positive FOXA1 signal. In addition, the present study demonstrated that the mRNA expression levels of FOXA1 were significantly increased in CRC tissues compared with in matched tumor-adjacent tissues. Furthermore, the positive expression of FOXA1 was associated with poor clinicopathological characteristics of CRC, including poor tumor differentiation, large tumor size, lymph node metastases and advanced tumor-node-metastasis tumor stage. Notably, patients with CRC with positive FOXA1 expression exhibited a significantly reduced 5-year survival rate compared with those with negative FOXA1 expression. Multivariate Cox regression analysis revealed that FOXA1 expression was an independent prognostic indicator for patients with CRC. In addition, FOXA1 knockdown evidently inhibited cell proliferation and induced apoptosis in SW480 and HCT116 CRC cells. Notably, FOXA1 knockdown also prominently reduced the expression of yes-associated protein (YAP) in SW480 and HCT116 cells. In conclusion, the results of the present study indicated that FOXA1 may be considered a potential prognostic marker, and may promote tumor growth of CRC by upregulating YAP expression. PMID:27484093

  16. Clinical and epidemiological significance of enterococci intrinsically resistant to vancomycin (possessing the vanC genotype)

    PubMed Central

    Toye, B; Shymanski, J; Bobrowska, M; Woods, W; Ramotar, K

    1997-01-01

    Constitutive low-level vancomycin resistance is found intrinsically in certain enterococcal species and is encoded by vanC ligase genes. These intrinsically vancomycin-resistant enterococci (VRE) will be referred to as VANC VRE. A prospective study to determine the clinical and epidemiologic significance of VANC VRE was conducted. VANC VRE were recovered from the stools of 34 of 601 (5.7%) patients, a rate similar to that obtained for the stools of 100 outpatients in the community (5%). VANC VRE were also isolated from the nonstool specimens of 9 of 538 patients (1.7%), including two patients with bacteremia. No VRE of the vanA or vanB genotypes were detected in nonstool specimens. Eighty-two hospital contacts of the first 23 patients found to be colonized or infected with VANC VRE were screened, and 6 contacts were found to be gastrointestinal carriers of VANC VRE. However, typing of isolates from these 6 contacts by pulsed-field gel electrophoresis with SmaI showed the isolates to be unique and different from those recovered from the index patients. In fact, all VANC VRE isolates from different patients in this study were unique. A case-control study with patients who were negative when screened for VANC VRE as controls failed to identify any risk factor associated with colonization or infection with this organism. VANC VRE were infrequently recovered from clinical specimens but were occasionally found as part of the normal stool flora. Since no transmission between patients was documented, additional isolation procedures may not be necessary for patients colonized or infected with VANC VRE. PMID:9399514

  17. Identification of major rice allergen and their clinical significance in children

    PubMed Central

    Jeon, You Hoon; Oh, Se Jo; Yang, Hyeon Jong; Lee, Soo Young

    2011-01-01

    Purpose Recently, an increase in the number of patients sensitized to rice allergen with or without clinical symptoms has been reported. This study was designed to determine the major allergens in rice and their clinical significance. Methods Twenty-four children (15 boys and 9 girls; mean age, 16.3 months) with allergic disease, who were sensitized to rice antigen (by UniCAP) in the Pediatric Allergy Respiratory Center at Soonchunhyang University Hospital, were enrolled in this study. The allergenicity of various types of rice (raw, cooked, and heat-treated, simulated gastric fluid [SGF], and simulated intestinal fluid [SIF]) was investigated using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoglobulin E (IgE) immunoblots. The patients' medical records, including laboratory data and allergy symptoms after ingestion of rice were reviewed. Results Patients were sensitized to an average of 13.5 food antigens and their mean total IgE was 6,888.7 kU/L. In SDS-PAGE, more than 16 protein bands were observed in the raw rice, whereas only 14-16 kDa and 31-35 kDa protein bands were observed in cooked rice. The common SDS-PAGE protein bands observed in SGF-, SIF-, and heat-treated rice were 9, 14, and 31 kDa. In a heated-rice IgE immunoblot, protein bands of 9, 14, and 31-33 kDa were found in 27.8%, 38.9%, and 38.9% of all sera, respectively, and in 50%, 50%, and 75%, of ser a from the 4 symptomatic patients, respectively. Conclusion The 9-, 14-, and 31-kDa protein bands appeared to be the major allergens responsible for rice allergy symptoms. PMID:22232624

  18. Proteasome inhibition rescues clinically significant unstable variants of the mismatch repair protein Msh2

    PubMed Central

    Arlow, Tim; Scott, Kristan; Wagenseller, Aubrey; Gammie, Alison

    2013-01-01

    MSH2 is required for DNA mismatch repair recognition in eukaryotes. Deleterious mutations in human MSH2 account for approximately half of the alleles associated with a common hereditary cancer syndrome. Previously, we characterized clinically identified MSH2 missense mutations, using yeast as a model system, and found that the most common cause of defective DNA mismatch repair was low levels of the variant Msh2 proteins. Here, we show that increased protein turnover is responsible for the reduced cellular levels. Increasing gene dosage of more than half of the missense alleles fully restored function. A titration experiment revealed that raising the expression level of one variant to less than wild-type levels restored mismatch repair, suggesting that overexpression is not always required to regain function. We found that the ubiquitin-mediated proteasome degradation pathway is the major mechanism for increased turnover of the Msh2 variants and identified the primary ubiquitin ligase as San1. Deletion of San1 restored protein levels for all but one variant, but did not elevate wild-type Msh2 levels. The unstable variants interacted with San1, whereas wild-type Msh2 did not. Additionally, san1Δ suppressed the mismatch repair defect of unstable variants. Of medical significance, the clinically approved drug Bortezomib partially restored protein levels and mismatch repair function for low-level variants and reversed the resistance to cisplatin, a common chemotherapeutic. Our results provide the foundation for an innovative therapeutic regime for certain mismatch-repair-defective cancers that are refractory to conventional chemotherapies. PMID:23248292

  19. Incidence Rates of Clinically Significant Tinnitus: 10-Year Trend From a Cohort Study in England

    PubMed Central

    Wallenhorst, Christopher; McFerran, Don; Hall, Deborah A.

    2015-01-01

    Objective: To investigate the incidence of tinnitus that burdens the health service in England. Design: This was an observational study of 4.7 million residents of England under 85 years of age who were at risk for developing clinically significant tinnitus (sigT). SigT was defined by a discharge from hospital with a primary diagnosis of tinnitus, or a primary care recording of tinnitus with subsequent related medical follow-up within 28 days. The database used was the Clinical Practice Research Datalink and individual records were linked to additional data from the Hospital Episode Statistics. The observational period was from January 1, 2002 to December 31, 2011. Age-, gender-, and calendar year-specific incidence rates for and cumulative incidences of sigT were estimated and a projection of new cases of sigT between 2012 and 2021 was performed. Results: There were 14,303 incident cases of sigT identified among 26.5 million person-years of observation. The incidence rate was 5.4 new cases of sigT per 10,000 person-years (95% confidence interval: 5.3 to 5.5). The incidence rate did not depend on gender but increased with age, peaking at 11.4 per 10,000 in the age group 60 to 69 years. The annual incidence rate of sigT increased from 4.5 per 10,000 person-years in 2002 to 6.6 per 10,000 person-years in 2011. The 10-year cumulative incidence of sigT was 58.4 cases (95% confidence interval: 57.4 to 59.4) per 10,000 residents. Nearly 324,000 new cases of sigT are expected to occur in England between 2012 and 2021. Conclusions: Tinnitus presents a burden to the health care system that has been rising in recent years. Population-based studies provide crucial underpinning evidence; highlighting the need for further research to address issues around effective diagnosis and clinical management of this heterogeneous condition. PMID:25470370

  20. Trends in Clinically Significant Pain Prevalence Among Hospitalized Cancer Patients at an Academic Hospital in Taiwan

    PubMed Central

    Wang, Wei-Yun; Ho, Shung-Tai; Wu, Shang-Liang; Chu, Chi-Ming; Sung, Chun-Sung; Wang, Kwua-Yun; Liang, Chun-Yu

    2016-01-01

    Abstract Clinically significant pain (CSP) is one of the most common complaints among cancer patients during repeated hospitalizations, and the prevalence ranges from 24% to 86%. This study aimed to characterize the trends in CSP among cancer patients and examine the differences in the prevalence of CSP across repeated hospitalizations. A hospital-based, retrospective cohort study was conducted at an academic hospital. Patient-reported pain intensity was assessed and recorded in a nursing information system. We examined the differences in the prevalence of worst pain intensity (WPI) and last evaluated pain intensity (LPI) of ≥4 or ≥7 points among cancer inpatients from the 1st to the 18th hospitalization. Linear mixed models were used to determine the significant difference in the WPI and LPI (≥4 or ≥7 points) at each hospitalization. We examined 88,133 pain scores from the 1st to the 18th hospitalization among cancer patients. The prevalence of the 4 CSP types showed a trend toward a reduction from the 1st to the 18th hospitalization. There was a robust reduction in the CSP prevalence from the 1st to the 5th hospitalization, except in the case of LPI ≥ 7 points. The prevalence of a WPI ≥ 4 points was significantly higher (0.240-fold increase) during the 1st hospitalization than during the 5th hospitalization. For the 2nd, 3rd, and 4th hospitalizations, there was a significantly higher prevalence of a WPI ≥ 4 points compared with the 5th hospitalization. We also observed significant reductions in the prevalence of a WPI ≥ 7 points during the 1st to the 4th hospitalizations, an LPI ≥ 4 points during the 1st to the 3rd hospitalizations, and an LPI ≥ 7 points during the 1st to the 2nd hospitalization. Although the prevalence of the 4 CSP types decreased gradually, it is impossible to state the causative factors on the basis of this observational and descriptive study. The next step will examine the factors that determine the CSP prevalence among

  1. Correlating MDCT Liver Injury Grade and Clinical Outcome in Patients Without Significant Extra-hepatic Injury.

    PubMed

    Kumar, Ravi; Kumar, Atin; Baliyan, Vinit; Gamanagatti, Shivanand; Bhalla, Ashu Seith; Sharma, Raju; Gupta, Amit; Kumar, Subodh; Misra, M C

    2016-08-01

    The aim of the study was to correlate multi-detector computed tomography (MDCT) grading with clinical severity and outcome in liver trauma patients without significant extrahepatic injury. Over a period of 2 years (2011-2013), all patients showing evidence of liver injury on contrast-enhanced CT (CECT) abdomen and without significant extrahepatic trauma were prospectively included in the study. Correlation between the CT injury grade and outcome in terms of mortality, duration of ICU/hospital stay, fluid and blood requirements, need for intervention and complications were assessed. The significance of the difference in mortality, duration of ICU/hospital stay, fluid requirement and blood requirements among the patients with various injury grades was assessed by Kruskal-Wallis test. The significance of the difference in need for intervention and complications among the patients with various injury grades was assessed by Fisher's exact test. A total of 198 patients were found to have evidence of hepatic injury on CECT. Out of 198 patients, 117 had insignificant extrahepatic trauma. The overall mean age for these 117 patients was 25.74 ± 15.53 (age range 2-84 years). Death rates according to AAST grades were 0 % in grades II and III, 6.89 % in grade IV and 9.09 % in grade V (p = 0.053). The mean ICU and total hospital stay for grade II was 1.32 and 5.91 days, for grade III was 1.76 and 8.48, for grade IV was 2.86 and 10.31 days and for grade V was 6.54 and 12 days, respectively (p = 0.0001 for ICU, p = 0.0003 for total stay). Mean input and fluid deficit according to various grades were 8634/2607 ml for grade II, 9535/2555 ml for grade III, 15,549/6242 ml for grade IV and 19,958/8280 ml for grade V (p value input-0.0016, output-input (fluid deficit)-0.0001). Average unit of RBC and sum of the blood products transfused were 1.73 and 2.26 for grade II, 2.18 and 2.72 for grade III, 3.03 and 6.27 for grade IV, 6.85 and 38.12 for grade V

  2. Clinical significance of bax/bcl-2 ratio in chronic lymphocytic leukemia.

    PubMed

    Del Principe, Maria Ilaria; Dal Bo, Michele; Bittolo, Tamara; Buccisano, Francesco; Rossi, Francesca Maria; Zucchetto, Antonella; Rossi, Davide; Bomben, Riccardo; Maurillo, Luca; Cefalo, Mariagiovanna; De Santis, Giovanna; Venditti, Adriano; Gaidano, Gianluca; Amadori, Sergio; de Fabritiis, Paolo; Gattei, Valter; Del Poeta, Giovanni

    2016-01-01

    In chronic lymphocytic leukemia the balance between the pro-apoptotic and anti-apoptotic members of the bcl-2 family is involved in the pathogenesis, chemorefractoriness and clinical outcome. Moreover, the recently proposed anti-bcl-2 molecules, such as ABT-199, have emphasized the potential role of of bcl-2 family proteins in the context of target therapies. We investigated bax/bcl-2 ratio by flow cytometry in 502 patients and identified a cut off of 1.50 to correlate bax/bcl-2 ratio with well-established clinical and biological prognosticators. Bax/bcl-2 was 1.50 or over in 263 patients (52%) with chronic lymphocytic leukemia. Higher bax/bcl-2 was associated with low Rai stage, lymphocyte doubling time over 12 months, beta-2 microglobulin less than 2.2 mg/dL, soluble CD23 less than 70 U/mL and a low risk cytogenetic profile (P<0.0001). On the other hand, lower bax/bcl-2 was correlated with unmutated IGHV (P<0.0001), mutated NOTCH1 (P<0.0001) and mutated TP53 (P=0.00007). Significant shorter progression-free survival and overall survival were observed in patients with lower bax/bcl-2 (P<0.0001). Moreover, within IGHV unmutated (168 patients) and TP53 mutated (37 patients) subgroups, higher bax/bcl-2 identified cases with significant longer PFS (P=0.00002 and P=0.039). In multivariate analysis of progression-free survival and overall survival, bax/bcl-2 was an independent prognostic factor (P=0.0002 and P=0.002). In conclusion, we defined the prognostic power of bax/bcl-2 ratio, as determined by a flow cytometric approach, and highlighted a correlation with chemoresistance and outcome in chronic lymphocytic leukemia. Finally, the recently proposed new therapies employing bcl-2 inhibitors prompted the potential use of bax/bcl-2 ratio to identify patients putatively resistant to these molecules. PMID:26565002

  3. Clinical significance of bax/bcl-2 ratio in chronic lymphocytic leukemia

    PubMed Central

    Del Principe, Maria Ilaria; Bo, Michele Dal; Bittolo, Tamara; Buccisano, Francesco; Rossi, Francesca Maria; Zucchetto, Antonella; Rossi, Davide; Bomben, Riccardo; Maurillo, Luca; Cefalo, Mariagiovanna; De Santis, Giovanna; Venditti, Adriano; Gaidano, Gianluca; Amadori, Sergio; de Fabritiis, Paolo; Gattei, Valter; Del Poeta, Giovanni

    2016-01-01

    In chronic lymphocytic leukemia the balance between the pro-apoptotic and anti-apoptotic members of the bcl-2 family is involved in the pathogenesis, chemorefractoriness and clinical outcome. Moreover, the recently proposed anti-bcl-2 molecules, such as ABT-199, have emphasized the potential role of of bcl-2 family proteins in the context of target therapies. We investigated bax/bcl-2 ratio by flow cytometry in 502 patients and identified a cut off of 1.50 to correlate bax/bcl-2 ratio with well-established clinical and biological prognosticators. Bax/bcl-2 was 1.50 or over in 263 patients (52%) with chronic lymphocytic leukemia. Higher bax/bcl-2 was associated with low Rai stage, lymphocyte doubling time over 12 months, beta-2 microglobulin less than 2.2 mg/dL, soluble CD23 less than 70 U/mL and a low risk cytogenetic profile (P<0.0001). On the other hand, lower bax/bcl-2 was correlated with unmutated IGHV (P<0.0001), mutated NOTCH1 (P<0.0001) and mutated TP53 (P=0.00007). Significant shorter progression-free survival and overall survival were observed in patients with lower bax/bcl-2 (P<0.0001). Moreover, within IGHV unmutated (168 patients) and TP53 mutated (37 patients) subgroups, higher bax/bcl-2 identified cases with significant longer PFS (P=0.00002 and P=0.039). In multivariate analysis of progression-free survival and overall survival, bax/bcl-2 was an independent prognostic factor (P=0.0002 and P=0.002). In conclusion, we defined the prognostic power of bax/bcl-2 ratio, as determined by a flow cytometric approach, and highlighted a correlation with chemoresistance and outcome in chronic lymphocytic leukemia. Finally, the recently proposed new therapies employing bcl-2 inhibitors prompted the potential use of bax/bcl-2 ratio to identify patients putatively resistant to these molecules. PMID:26565002

  4. Clinical Significance and Epidemiologic Analyses of Mycobacterium avium and Mycobacterium intracellulare among Patients without AIDS

    PubMed Central

    Han, Xiang Y.; Tarrand, Jeffrey J.; Infante, Rosa; Jacobson, Kalen L.; Truong, Mylene

    2005-01-01

    The clinical significance and prevalence of Mycobacterium avium and Mycobacterium intracellulare were analyzed in a cohort of 7,472 patients who, from 1999 to 2003, sought care at the University of Texas M.D. Anderson Cancer Center, Houston, and had cultures performed for mycobacteria. Patients were stratified for age, sex, and underlying diseases, and bacteria were identified by 16S rRNA gene sequencing. M. avium was isolated in 62 (0.83%) of 7,472 patients and M. intracellulare in 65 (0.87%). Clinically, only 10 of the 62 (16.2%) patients with M. avium had probable to definite evidence of infection, whereas the majority (83.8%) had weak evidence of infection. Sex and age did not affect the isolation or infection of M. avium. Hematological tumors predisposed to M. avium colonization but not infection. In contrast, 41 of the 65 (63.1%) patients with M. intracellulare had probable to definite infection, a level much higher than those with M. avium (P < 0.001). M. intracellulare was more prevalent in women (1.33% of 3,311) than in men (0.50% of 4,161) (P < 0.001), and underlying diseases had no effect in women. Men with lung cancer had a higher prevalence (1.37%) than men without (0.34%) (4.0-fold; P < 0.001), but it was similar to that in women. A marked age trend for the isolation of M. intracellulare among women was noted: 0.27% (1-fold) for ages of <50 years, 0.85% (3.1-fold) for ages 50 to 59 years, 1.50% (5.6-fold) for ages 60 to 69 years, and 3.74% (13.9-fold) for ages ≥70 years (trend, P < 0.001). The combined rate for women ≥50 was 1.86% (95% confidence interval [1.30 to 2.42%]) (6.9-fold). Together, these results suggest that, among non-AIDS patients, M. intracellulare is more pathogenic and tends to infect women increasingly beyond menopause (age ≥50 years) regardless of underlying disease. The prevalence rate of 1.86% in postmenopausal women suggests the need to further investigate the public health significance of M. intracellulare. PMID:16145084

  5. Clinical significance of cyclooxygenase-2 expression in extranodal natural killer (NK)/T-cell lymphoma, nasal type

    SciTech Connect

    Shim, Su Jung; Yang, Woo-Ick; Shin, Eunah; Koom, Woong Sub; Kim, Yong Bae; Cho, Jae Ho; Suh, Chang Ok; Kim, Joo Hang; Kim, Gwi Eon . E-mail: gekim@yumc.yonsei.ac.kr

    2007-01-01

    Purpose: To determine whether there are any differences in therapeutic response, patterns of systemic recurrence, and prognosis of patients with extranodal natural killer (NK)/T-cell lymphoma, nasal type, by the cyclooxygenase-2 (COX-2) expression. Patients and Methods: Thirty-four patients with Ann Arbor Stage I and II extranodal NK/T-cell lymphoma who underwent chemotherapy or radiotherapy, or both, were retrospectively reviewed. These patients were divided into two groups according to their immunohistochemical staining for COX-2 expressions: a COX-2-negative group (n = 10 patients) and a COX-2-positive group (n = 24 patients). The treatment response, patterns of treatment failure, and survival data for the patients were compared between the COX-2-positive and negative groups. Results: There was no significant difference in the clinical profiles between the COX-2-negative and COX-2-positive groups. All patients (100%) in the COX-2-negative group achieved complete response after initial treatment, whereas only 14 patients (58%) in the COX-2-positive group achieved complete response (p = 0.03). Compared with the patients in the COX-2-negative group, those in the COX-2-positive group had a significantly lower 2-year systemic recurrence-free survival rate (100% for the COX-2-negative group vs. 54% for the COX-2-positive group) (p = 0.02) and a decreased 5-year overall survival rate (70% for the COX-2-negative group vs. 32% for the COX-2-positive group) (p = 0.06). Conclusion: Cyclooxygenase-2 expression can serve as a predictive factor for poor treatment response, higher systemic recurrence, and unfavorable prognosis in patients with extranodal NK/T-cell lymphoma, nasal type.

  6. Clinical significance of the integrin α6β4 in human malignancies

    PubMed Central

    Stewart, Rachel L.; O’Connor, Kathleen L.

    2015-01-01

    Integrin α6β4 is a cellular adhesion molecule that binds to laminins in the extracellular matrix and nucleates the formation of hemidesmosomes. During carcinoma progression, integrin α6β4 is released from hemidesmosomes, where it can then signal to facilitate multiple aspects of tumor progression including sustaining proliferative signaling, tumor invasion and metastasis, evasion of apoptosis, and stimulation of angiogenesis. The integrin achieves these ends by cooperating with growth factor receptors including EGFR, ErbB-2, and c-Met to amplify downstream pathways such as PI3K, AKT, MAPK and the Rho family small GTPases. Furthermore, it dramatically alters the transcriptome toward a more invasive phenotype by controlling promoter DNA demethylation of invasion and metastasis-associated proteins, such as S100A4 and autotaxin, and upregulates and activates key tumor promoting transcription factors such as the NFATs and NFkB. Expression of integrin α6β4 has been studied in many human malignancies where its overexpression is associated with aggressive behavior and a poor prognosis. This review provides an assessment of integrin α6β4 expression patterns and their prognostic significance in human malignancies, and describes key signaling functions of integrin α6β4 that contribute to tumor progression. PMID:26121317

  7. Clinically Significant Depressive Symptoms as a Risk Factor for HIV Infection Among Black MSM in Massachusetts

    PubMed Central

    Reisner, Sari L.; Skeer, Margie; Bright, Donna; Cranston, Kevin; Isenberg, Deborah; Bland, Sean; Barker, Thomas A.; Mayer, Kenneth H.

    2013-01-01

    High rates of depression have been observed among men who have sex with men (MSM) relative to the general adult male population; however, a dearth of research has explored depression among Black MSM. Black MSM (n = 197) recruited via modified respondent-driven sampling between January and July 2008 completed an interviewer-administered quantitative assessment and voluntary HIV counseling and testing. Bivariate and multivariable logistic regression procedures examined the associations of demographics, behavioral HIV risk factors, and psychosocial variables with depressive symptoms by severity, using the 20-item Center for Epidemiologic Studies Depression Scale (CES-D). Adjusting for demographic and behavioral variables, significant factors associated with (1) clinically significant depressive symptoms (33%; CES-D score ≥ 16): being publicly insured by Medicaid, having serodiscordant anal sex with a casual male partner, and being diagnosed with an STD in the prior 12 months; (2) moderate depressive symptoms (19%; CES-D score 16–26): having serodiscordant unprotected anal sex with a casual male partner and being diagnosed with an STD in the prior 12 months; (3) severe depressive symptoms (14%; CES-D score 27+): being publicly insured by Medicaid and reporting difficulty accessing healthcare in the past 12 months. Moderately depressed Black MSM may be more likely to engage in behaviors that place them at increased risk for HIV and other STDs. HIV prevention interventions for Black MSM may benefit from incorporating screening and/or treatment for depression, allowing MSM who are depressed to respond more effectively to behavioral change approaches. PMID:19462228

  8. Clinical significance of subepithelial growth patterns in non-muscle invasive bladder cancer

    PubMed Central

    2011-01-01

    Background We evaluated the clinical significance and prognostic value of histopathological features of bladder cancer, such as subepithelial growth patterns and tumor growth pattern at the invasion front. Methods In total, 130 patients newly diagnosed with non-muscle invasive bladder cancer and underwent transurethral resection between 1998 and 2009 were enrolled. Subepithelial growth patterns consisting of endophytic growth pattern (EGP) and von Brunn's nest involvement (VBNI) were investigated using hematoxylin and eosin-stained slides, and their frequency of occurrence, prognostic value, and correlation with other clinicopathological features was evaluated. Results EGP and VBNI were found in 40 (30.8%) and 5 (3.9%) of the 130 cases, respectively. Of the 26 pT1 tumors, the growth pattern at the invasion front was trabecular in 17 (65.4%) and infiltrative in 9 (34.6%). Although 8 (47.1%) of 17 trabecular tumors coexisted with EGP, no cases with infiltrative tumors had EGP (p = 0.023). VBNI correlated with high tumor grades (p = 0.006) and lymphovascular involvement (p = 0.026). The multivariate Cox proportional hazards analysis revealed that tumor diameter less than 3 cm (p = 0.04) and intravesical bacillus Calmette-Guérin therapy (p = 0.004) were independent favorable prognostic factors for recurrence-free survival, whereas tumor stage was an independent poor prognostic factor for disease progression (p = 0.006). Conclusions Subepithelial growth patterns were not a significant prognostic factor in this study. Additionally, no tumors with an infiltrative growth pattern coexisted with EGP, suggesting that determining the presence of EGP might be helpful for managing non-muscle invasive bladder cancers. PMID:21816111

  9. PCDH8 is Frequently Inactivated by Promoter Hypermethylation in Liver Cancer: Diagnostic and Clinical Significance

    PubMed Central

    Zhang, Cheng; Peng, Yunfei; Yang, Fan; Qin, Ruixi; Liu, Wenjun; Zhang, Cuijuan

    2016-01-01

    AIM: Protocadherin-8 (PCDH8) plays an important role in signaling pathways of cell adhesin, proliferation, and migration. It has been reported that PCDH8 is mutated or methylated in several human cancers. However, little is known about PCDH8 in liver cancer. The aim of this study was to investigate the protein expression and promoter methylation status of PCDH8 in liver cancer and evaluate the association between PCDH8 methylation and the clinicopathological features. METHODS: The methylation status of PCDH8 in 42 hepatocellular carcinoma (HCC), 8 Cholangiocarcinoma (CC) and 50 normal liver tissues were examined using methylation-specific PCR (MSP) and the protein expression of PCDH8 was detected by immunohistochemistry. The relationships between PCDH8 methylation and clinicopathological features as well as overall survival of patients were evaluated. RESULTS: The PCDH8 methylation was more frequent in liver cancer tissues than that in the normal liver tissues (88% vs. 32%, P < 0.001), and is significantly associated with loss of its protein expression (P = 0.004). Moreover, there is a significant correlation between PCDH8 methylation and the alpha-fetoprotein (AFP) level (P = 0.008). Kaplan-Meier survival analysis revealed that patients with PCDH8 methylation have shorter OS and PFS than those without PCDH8 methylation (P = 0.041 and P = 0.028, respectively). CONCLUSION: PCDH8 is often inactivated by promoter methylation in liver cancer. PCDH8 methylation can serve as a valuable diagnostic biomarker for early detection of liver cancer and might be useful to predict an unfavorable clinical feature. PMID:26918058

  10. Assigning site of origin in metastatic neuroendocrine neoplasms: a clinically significant application of diagnostic immunohistochemistry.

    PubMed

    Bellizzi, Andrew M

    2013-09-01

    The neuroendocrine epithelial neoplasms (NENs) include well-differentiated neuroendocrine tumors (WDNETs) and poorly differentiated neuroendocrine carcinomas (PDNECs). Whereas PDNECs are highly lethal, with localized Merkel cell carcinoma somewhat of an exception, WDNETs exhibit a range of "indolent" biologic potentials-from benign to widely metastatic and eventually fatal. Within each of these 2 groups there is substantial morphologic overlap. In the metastatic setting, the site of origin of a WDNET has significant prognostic and therapeutic implications. In the skin, Merkel cell carcinoma must be distinguished from spread of a visceral PDNEC. This review intends to prove the thesis that determining the site of origin of a NEN is clinically vital and that diagnostic immunohistochemistry is well suited to the task. It will begin by reviewing current World Health Organization terminology for the NENs, as well as an embryologic and histologic pattern-based classification. It will present population-based data on the relative frequency and biology of WDNETs arising at various anatomic sites, including the frequency of metastases of unknown primary, and comment on limitations of contemporary imaging techniques, as a means of defining the scope of the problem. It will go on to discuss the therapeutic significance of site of origin. The heart of this review is a synthesis of data compiled from >100 manuscripts on the expression of individual markers in WDNETs and PDNECs, as regards site of origin. These include proteins that are considered "key markers" and others that are either useful "secondary markers," potentially very useful markers that need to be further vetted, or ones that are widely applied despite a lack of efficacy. It will conclude with my approach to the metastatic NEN of unknown origin. PMID:23939147

  11. Look what else we found - clinically significant abnormalities detected during routine ROP screening

    PubMed Central

    Jayadev, Chaitra; Vinekar, Anand; Bauer, Noel; Mangalesh, Shwetha; Mahendradas, Padmamalini; Kemmanu, Vasudha; Mallipatna, Ashwin; Shetty, Bhujang

    2015-01-01

    Purpose: The purpose of this study was to report the spectrum of anterior and posterior segment diagnoses in Asian Indian premature infants detected serendipitously during routine retinopathy of prematurity (ROP) screening during a 1 year period. Methods: A retrospective review of all Retcam (Clarity MSI, USA) imaging sessions during the year 2011 performed on infants born either <2001 g at birth and/or <34.1 weeks of gestation recruited for ROP screening was performed. All infants had a minimum of seven images at each session, which included the dilated anterior segment, disc, and macula center and the four quadrants using the 130° lens. Results: Of the 8954 imaging sessions of 1450 new infants recruited in 2011, there were 111 (7.66%) with a diagnosis other than ROP. Anterior segment diagnoses seen in 31 (27.9%) cases included clinically significant cataract, lid abnormalities, anophthalmos, microphthalmos, and corneal diseases. Posterior segment diagnoses in 80 (72.1%) cases included retinal hemorrhages, cherry red spots, and neonatal uveitis of infective etiologies. Of the 111 cases, 15 (13.5%) underwent surgical procedures and 24 (21.6%) underwent medical procedures; importantly, two eyes with retinoblastoma were detected which were managed timely. Conclusions: This study emphasizes the importance of ocular digital imaging in premature infants. Visually significant, potentially life-threatening, and even treatable conditions were detected serendipitously during routine ROP screening that may be missed or detected late otherwise. This pilot data may be used to advocate for a possible universal infant eye screening program using digital imaging. PMID:26139795

  12. Clinical significance of the muscle-retracting sign during colorectal endoscopic submucosal dissection

    PubMed Central

    Toyonaga, Takashi; Tanaka, Shinwa; Man-I, Mariko; East, James; Ono, Wataru; Nishino, Eisei; Ishida, Tsukasa; Hoshi, Namiko; Morita, Yoshinori; Azuma, Takeshi

    2015-01-01

    Background and study aims: During colorectal endoscopic submucosal dissection (ESD), the feature of a muscle layer being pulled toward a neoplastic tumor is sometimes detected. We call this feature the muscle-retracting sign (MR sign). The aim of this study was to evaluate whether the MR sign is associated with particular types of neoplastic lesions and whether it has any clinical significance for ESD sessions. Patients and methods: A total of 329 patients underwent ESD for 357 colorectal neoplasms. The frequency of positivity for the MR sign was evaluated in different morphologic and histopathologic types of neoplasm. The success rate of complete resection and the incidence of complications were also evaluated according to whether lesions were positive or negative for the MR sign. Results: The rates of positivity for the MR sign in the various lesion types were as follows: laterally spreading tumor – granular nodular mixed type (LST-G-M), 9.6 %; laterally spreading tumor – granular homogeneous type (LST-G-H) and laterally spreading tumor – nongranular type (LST-NG), 0 %; sessile type, 41.2 %. The resection rate was 100 % (329 /329) in lesions negative for the MR sign; however, it was 64.3 % (18 /28) in lesions positive for the MR sign, which was significantly lower (P < 0.001). Conclusions: The MR sign was present only in some protruding lesions, and more importantly, it was associated with a high risk of incomplete tumor removal by ESD. Our data indicate that lesions positive for the MR sign lesions should be dissected with great caution; alternatively, based on the features of the individual case, a switch to surgery should be considered for the benefit of the patient. PMID:26171438

  13. Chemokine receptor CXCR4 and its ligand CXCL12 expressions and clinical significance in bladder cancer.

    PubMed

    Yang, D L; Xin, M M; Wang, J S; Xu, H Y; Huo, Q; Tang, Z R; Wang, H F

    2015-01-01

    It is well known that chemokine receptors and their ligands play important roles in mediating the invasion and metastasis of malignant tumors. This aim of this study was to investigate the expression and clinical significance of chemokine receptor CXCR4 and its ligand CXCL12 in bladder tumor tissues. Cancerous and adjacent normal bladder tissues were collected from 42 patients. The expressions of CXCR4 and CXCL12 proteins were then detected by immunohistochemistry, and the expressions of CXCR4 and CXCL12 mRNAs were detected by RT-PCR. Bladder cancer tissues showed higher positive expressions of CXCR4 and CXCL12 than those in normal bladder mucosal tissues (z = 7.332, 6.758, P < 0.001). Positive expressions of CXCR4 and CXCL12 were related to the differentiation degree and invasive depth of cancer tissues (z = 2.598-4.594, P < 0.05), but not to patient gender or age (z = 0.273-0.554, P > 0.05). The expression of CXCR4 was positively correlated to CXCL12 expression in bladder cancer tissues (r = 0.661, P < 0.05). RT-PCR revealed that CXCR4 and CXCL12 mRNAs were not expressed in normal tissues. Moreover, with increased depth of invasion, CXCR4 and CXCL12 mRNA expressions gradually increased in bladder cancer tissues and showed significant intergroup differences (F = 56.642, 67.928, P < 0.01). Taken together, these results indicate that the chemokine receptor CXCR4 and its ligand CXCL12 play important roles in the occurrence and development of bladder cancer. PMID:26782415

  14. Clinical significance, antimicrobial susceptibility and molecular identification of Nocardia species isolated from children with cystic fibrosis.

    PubMed

    Betrán, Ana; Villuendas, M Cruz; Rezusta, Antonio; Pereira, Javier; Revillo, M José; Rodríguez-Nava, Verónica

    2016-01-01

    Nocardia is an opportunistic pathogen that causes respiratory infections in immunocompromised patients. The aim of this study was to analyze the epidemiology, clinical significance and antimicrobial susceptibility of Nocardia species isolated from eight children with cystic fibrosis. The isolated species were identified as Nocardia farcinica, Nocardia transvalensis, Nocardia pneumoniae, Nocardia veterana and Nocardia wallacei. N. farcinica was isolated in three patients and all of them presented lung affectation with a chronic colonization and pneumonia. N. farcinica showed resistance against gentamicin, tobramycin, cefotaxime, but was susceptible to trimethoprim-sulfamethoxazole and amikacin. N. transvalensis, which was isolated from two patients, showed an association with chronic colonization. N. transvalensis was resistant to tobramycin and amikacin, but susceptible to ciprofloxacin, trimethoprim-sulfamethoxazole and cefotaxime. N. veterana, N. pneumoniae and N. wallacei were isolated from three different patients and appeared in transitory lung colonization. N. veterana and N. pneumoniae were susceptible to imipenem, trimethoprim-sulfamethoxazole, amikacin, tobramycin, and cefotaxime. N. wallacei was resistant to amikacin, tobramycin, imipenem, and trimethoprim-sulfamethoxazole and susceptible to ciprofloxacin and cefotaxime. All the isolates were identified up to species level by 16S rRNA gene sequencing. The presence of Nocardia in the sputum of patients with cystic fibrosis is not always an indication of an active infection; therefore, the need for a treatment should be evaluated on an individual basis. The detection of multidrug-resistant species needs molecular identification and susceptibility testing, and should be performed for all Nocardia infections. PMID:27155949

  15. The biological significance and clinical applications of exosomes in ovarian cancer.

    PubMed

    Dorayappan, Kalpana Deepa Priya; Wallbillich, John J; Cohn, David E; Selvendiran, Karuppaiyah

    2016-07-01

    Exosomes are nano-sized (20-100nm) vesicles released by a variety of cells and are generated within the endosomal system or at the plasma membrane. There is emerging evidence that exosomes play a key role in intercellular communication in ovarian and other cancers. The protein and microRNA content of exosomes has been implicated in various intracellular processes that mediate oncogenesis, tumor spread, and drug resistance. Exosomes may prime distant tissue sites for reception of future metastases and their release can be mediated by the tumor microenvironment (e.g., hypoxia). Ovarian cancer-derived exosomes have unique features that could be leveraged for use as biomarkers to facilitate improved detection and treatment of the disease. Further, exosomes have the potential to serve as targets and/or drug delivery vehicles in the treatment of ovarian cancer. In this review we discuss the biological and clinical significance of exosomes relevant to the progression, detection, and treatment of ovarian cancer. PMID:27058839

  16. The Vital Capacity Is Vital: Epidemiology and Clinical Significance of the Restrictive Spirometry Pattern.

    PubMed

    Godfrey, Mark S; Jankowich, Matthew D

    2016-01-01

    Epidemiologic research has revealed a substantial portion of the general population with abnormal spirometry results that are characterized by decreased FEV1 and FVC but a preserved FEV1/FVC ratio. This restrictive spirometry pattern (RSP) is inconsistently defined in the literature and not well addressed by current guidelines; there is an accumulating body of evidence, however, that RSP is prevalent to a similar degree as airflow obstruction. Genetic and other risk factors for RSP, such as inhalational injuries and early life exposures, continue to be actively described. Although it seems that RSP is closely associated with the metabolic syndrome, diabetes, and systemic inflammation, it is not a simple marker of obesity. RSP is associated with adverse cardiovascular outcomes, as well as mortality, and it may be an underappreciated cause of functional impairments and respiratory symptoms. Improvement in outcomes in this population will require that clinicians have an appreciation for the significance of this spirometry pattern; additional research into the clinical and radiologic phenotype of these subjects is also needed. This article provides an overview of the recent developments in our understanding of this prevalent and highly morbid spirometry pattern. PMID:26356330

  17. Clinical significance of automatic warning function of cardiac remote monitoring systems in preventing acute cardiac episodes

    PubMed Central

    Chen, Shou-Qiang; Xing, Shan-Shan; Gao, Hai-Qing

    2014-01-01

    Objective: In addition to ambulatory Holter electrocardiographic recording and transtelephonic electrocardiographic monitoring (TTM), a cardiac remote monitoring system can provide an automatic warning function through the general packet radio service (GPRS) network, enabling earlier diagnosis, treatment and improved outcome of cardiac diseases. The purpose of this study was to estimate its clinical significance in preventing acute cardiac episodes. Methods: Using 2 leads (V1 and V5 leads) and the automatic warning mode, 7160 patients were tested with a cardiac remote monitoring system from October 2004 to September 2007. If malignant arrhythmias or obvious ST-T changes appeared in the electrocardiogram records was automatically transferred to the monitoring center, the patient and his family members were informed, and the corresponding precautionary or therapeutic measures were implemented immediately. Results: In our study, 274 cases of malignant arrhythmia, including sinus standstill and ventricular tachycardia, and 43 cases of obvious ST-segment elevation were detected and treated. Because of early detection, there was no death or deformity. Conclusions: A cardiac remote monitoring system providing an automatic warning function can play an important role in preventing acute cardiac episodes. PMID:25674124

  18. Clinical significance of regulatory B cells in the peripheral blood of patients with oesophageal cancer

    PubMed Central

    Qian, Li; Bian, Guang-Rong; Wang, Yan; Hu, Juan; Liu, Xia; Xu, Yan

    2015-01-01

    B cell subsets have been found to exhibit a negative regulatory function, like Tregs. The present study investigates the effects of CD5+CD19+ interleukin (IL)-10 (B10) on the occurrence and development of oesophageal carcinoma by analysing B10 levels in the peripheral blood of patients with oesophageal carcinoma. Peripheral blood of 120 oesophageal cancer patients and 120 healthy controls were collected, and regulatory B cell counts were determined by flow cytometry. The level of B10 cells in the peripheral blood of patients with oesophageal carcinoma was significantly higher than that in healthy controls (p < 0.05). In addition, B10 levels in stage III-IV patients (3.5 ±0.7%) were higher than those in stage I-II patients (2.5 ±0.6%), which were in turn higher than those in the healthy controls (1.3 ±0.3%). The level of B10 increased with clinical progression of oesophageal cancer, suggesting that B10 cells may influence the development or progression of oesophageal cancer. PMID:26557042

  19. Clinical significance of preoperative thrombocytosis in patients who underwent radical nephrectomy for nonmetastatic renal cell carcinoma

    PubMed Central

    Choi, Jae Young; Ko, Young Hwii

    2016-01-01

    Purpose The aim of this study was to examine the association of preoperative thrombocytosis with the prognosis of patients with nonmetastatic renal cell carcinoma (RCC). Materials and Methods We conducted a retrospective analysis of 187 patients who underwent a radical nephrectomy for nonmetastatic RCC between July 1997 and June 2009. Thrombocytosis was defined as a platelet count≥400,000 µL, and patients were divided into 2 groups according to presence of preoperative thrombocytosis, and the cancer-specific survival rates and overall survival rates of the 2 groups after radical nephrectomy were compared. Results The mean age of the patients was 56.0±11.7 years and the mean follow-up period was 59.3±42.1 months; there were 20 patients with preoperative thrombocytosis. Thirty patients developed metastases and 9 patients died during the follow-up period. In Kaplan-Meier analysis using a univariate log-rank test, both cancer-specific survival rate (p=0.013) and overall survival rate (p=0.012) showed significant association with preoperative thrombocytosis. Controlling for pathological TNM stage, Fuhrman grade and tumor diameter, the Cox proportional hazards model for cancer-specific survival rates showed that preoperative thrombocytosis was an independent prognostic factor (p=0.025). Conclusions Preoperative thrombocytosis was associated with poorer prognosis in patients with nonmetastatic RCC. Thus, preoperative platelet count may be clinically useful for risk stratification of patients undergoing surgery for nonmetastatic RCC.

  20. Endocannabinoid system as a regulator of tumor cell malignancy – biological pathways and clinical significance

    PubMed Central

    Pyszniak, Maria; Tabarkiewicz, Jacek; Łuszczki, Jarogniew J

    2016-01-01

    The endocannabinoid system (ECS) comprises cannabinoid receptors (CBs), endogenous cannabinoids, and enzymes responsible for their synthesis, transport, and degradation of (endo)cannabinoids. To date, two CBs, CB1 and CB2, have been characterized; however, orphan G-protein-coupled receptor GPR55 has been suggested to be the third putative CB. Several different types of cancer present abnormal expression of CBs, as well as other components of ECS, and this has been shown to correlate with the clinical outcome. Although most effects of (endo)cannabinoids are mediated through stimulation of classical CBs, they also interact with several molecules, either prosurvival or proapoptotic molecules. It should be noted that the mode of action of exogenous cannabinoids differs significantly from that of endocannabinoid and results from the studies on their activity both in vivo and in vitro could not be easily compared. This review highlights the main signaling pathways involved in the antitumor activity of cannabinoids and the influence of their activation on cancer cell biology. We also discuss changes in the expression pattern of the ECS in various cancer types that have an impact on disease progression and patient survival. A growing amount of experimental data imply possible exploitation of cannabinoids in cancer therapy. PMID:27486335

  1. [Measurement of the reserve function of inspiratory muscle and its clinical significance].

    PubMed

    Xiao, X; Luo, Y; Chen, W; Yuan, Y; He, T; Zeng, J

    1995-06-01

    The principles of measuring inspiratory muscle tension-time index (TTim) and the ratio of the works of inspiration over the maximal works of inspiration (Wi/Wi(max)) were investigated and their formulae were deduced, i.e. TTim = (Pi x Ti)/(MIP x Ttot) and Wi/Wi(max) = (Pi x VT)/(MIP x IC). The importance of the inspiratory pressure and the maximal inspiratory pressure (MIP) measured at function residual capacity (FRC) level was emphasized. Both TTim and Wi/Wi(max) were measured in 35 normal subjects and 89 patients with chronic obstructive pulmonary disease (COPD). The results showed that normal value of TTim was 0.0253 +/- 0.0055 which corresponds to the normal value of the diaphragm tension-time index (TTdi = 0.02-0.03) reported by Bellemare. Patients with COPD had a mean TTim much higher than that of normals (P < 0.01). The works of inspiration (Wi) in patients with COPD increased, while the maximal works of inspiration (Wi(max)) declined, so Wi/Wi(max) became significantly greater than that of normals (P < 0.01). The results also showed that there was a linear relationship between Pi/Pimax and TTim or Wi/Wimax (r = 0.7891, 0.9738, 0.6459, 0.9327, P < 0.01). Therefore, we suggest that both TTim and Wi/Wimax can be used as clinical indices to reflect the reserve function of inspiratory muscles. PMID:7490035

  2. Endocannabinoid system as a regulator of tumor cell malignancy - biological pathways and clinical significance.

    PubMed

    Pyszniak, Maria; Tabarkiewicz, Jacek; Łuszczki, Jarogniew J

    2016-01-01

    The endocannabinoid system (ECS) comprises cannabinoid receptors (CBs), endogenous cannabinoids, and enzymes responsible for their synthesis, transport, and degradation of (endo)cannabinoids. To date, two CBs, CB1 and CB2, have been characterized; however, orphan G-protein-coupled receptor GPR55 has been suggested to be the third putative CB. Several different types of cancer present abnormal expression of CBs, as well as other components of ECS, and this has been shown to correlate with the clinical outcome. Although most effects of (endo)cannabinoids are mediated through stimulation of classical CBs, they also interact with several molecules, either prosurvival or proapoptotic molecules. It should be noted that the mode of action of exogenous cannabinoids differs significantly from that of endocannabinoid and results from the studies on their activity both in vivo and in vitro could not be easily compared. This review highlights the main signaling pathways involved in the antitumor activity of cannabinoids and the influence of their activation on cancer cell biology. We also discuss changes in the expression pattern of the ECS in various cancer types that have an impact on disease progression and patient survival. A growing amount of experimental data imply possible exploitation of cannabinoids in cancer therapy. PMID:27486335

  3. 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

  4. Expression and clinical significance of glucose transporter-1 in pancreatic cancer

    PubMed Central

    LU, KAI; YANG, JIAN; LI, DE-CHUN; HE, SONG-BING; ZHU, DONG-MING; ZHANG, LI-FENG; ZHANG, XU; CHEN, XIAO-CHEN; ZHANG, BING; ZHOU, JIAN

    2016-01-01

    Increasing evidence has demonstrated that malignant cells exhibit increased glucose uptake, which facilitates survival and growth in a hypoxic environment. The glucose transporter-1 (GLUT-1) is overexpressed in a variety of malignant tumors. However, the association between GLUT-1 expression and clinicopathological factors, 18F-fluorodeoxyglucose uptake and tumor proliferation in pancreatic cancer has not been investigated to date. In the present study, the expression of GLUT-1 in 53 pancreatic cancer tissues was analyzed, which revealed that GLUT-1 was overexpressed in pancreatic tissue and correlated with poor prognosis and clinicopathological characteristics, including increased tumor size, clinical stage and lymph node metastasis, maximum standardized uptake value (SUVmax) and Ki-67 expression. The receiver operating characteristic curve analysis indicated that a cut-off SUVmax value of 4.830 was associated with optimal sensitivity (88%) and specificity (71.4%) for the detection of strong positive GLUT-1 expression. In addition, as the expression of GLUT-1 was found to correlate with Ki-67 expression, GLUT-1 may exhibit a significant effect on cell proliferation in pancreatic cancer. Overall, these findings indicate that GLUT-1 may represent a prognostic indicator, and a potential therapeutic target for pancreatic cancer. PMID:27347132

  5. Simplified ultrasound protocol for the exclusion of clinically significant carotid artery stenosis

    PubMed Central

    Högberg, Dominika; Dellagrammaticas, Demosthenes; Kragsterman, Björn; Björck, Martin; Wanhainen, Anders

    2016-01-01

    Objectives To evaluate a simplified ultrasound protocol for the exclusion of clinically significant carotid artery stenosis for screening purposes. Material and methods A total of 9,493 carotid arteries in 4,748 persons underwent carotid ultrasound examination. Most subjects were 65-year-old men attending screening for abdominal aortic aneurysm. The presence of a stenosis on B-mode and/or a mosaic pattern in post-stenotic areas on colour Doppler and maximum peak systolic velocity (PSV) in the internal carotid artery (ICA) were recorded. A carotid stenosis was defined as The North American Symptomatic Carotid Endarterectomy Trial (NASCET) >20% and a significant stenosis as NASCET >50%. The kappa (κ) statistic was used to assess agreement between methods. Sensitivity, specificity, positive predictive (PPV), and negative predictive (NPV) values were calculated for the greyscale/mosaic method compared to conventional assessment by means of PSV measurement. Results An ICA stenosis was found in 121 (1.3%) arteries; 82 (0.9%) were graded 20%–49%, 16 (0.2%) were 50%–69%, and 23 (0.2%) were 70%–99%. Eighteen (0.2%) arteries were occluded. Overall, the greyscale/mosaic protocol showed a moderate agreement with ICA PSV measurements for the detection of carotid artery stenosis, κ = 0.455. The sensitivity, specificity, PPV, and NPV for detection of >20% ICA stenosis were 91% (95% CI 0.84–0.95), 97% (0.97–0.98), 31% (0.26–0.36), and 97% (0.97–0.97), respectively. The corresponding figures for >50% stenosis were 90% (0.83–0.95), 97% (0.97–0.98), 11% (0.08–0.15), and 100% (0.99–1.00). Conclusion Compared with PSV measurements, the simplified greyscale/mosaic protocol had a high negative predictive value for detection of >50% carotid stenosis, suggesting that it may be suitable as a screening method to exclude significant disease. PMID:27379448

  6. Fostering Dental Students' Academic Achievements and Reflection Skills Through Clinical Peer Assessment and Feedback.

    PubMed

    Tricio, Jorge A; Woolford, Mark J; Escudier, Michael P

    2016-08-01

    Peer assessment is increasingly being encouraged to enhance dental students' learning. The aim of this study was to evaluate the educational impact in terms of academic achievements and reflective thinking of a formative prospective peer assessment and feedback protocol. Volunteer final-year dental students at King's College London Dental Institute, UK, received training on peer assessment, peer feedback, and self-reflection. At the beginning (baseline) and end (resultant) of the 2012-13 academic year, 86 students (55% of the year group) completed a reflection questionnaire (RQ). Sixty-eight of those students used a modified Direct Observation of Procedural Skills (DOPS) as a framework for peer assessment and peer feedback during a complete academic year. End-of-year, high-stakes examination grades and RQ scores from the participants and nonparticipants were statistically compared. The participants completed 576 peer DOPS. Those 22 students who peer assessed each other ≥10 times exhibited highly statistically significant differences and powerful positive effect sizes in their high-stakes exam grades (p=0.0001, d=0.74) and critical reflection skills (p=0.005, d=1.41) when compared to those who did not assess one another. Furthermore, only the same 22 students showed a statistically significant increase and positive effect size in their critical reflection skills from baseline to resultant (p=0.003, d=1.04). The results of this study suggest that the protocol used has the potential to impact dental students' academic and reflection skills, provided it is practiced in ten or more peer encounters and ensuring peer feedback is provided followed by self-reflection. PMID:27480702

  7. Significant Discrepancies between the Wechsler Adult Intelligence Scale--Revised and the Woodcock-Johnson Psycho-Educational Battery, Part II: Tests of Achievement with a College Population.

    ERIC Educational Resources Information Center

    Salvia, Shawn Amig; Salvia, John

    1986-01-01

    Significant differences were found between college freshmen science (N=50) and nonscience (N=50) majors who were administered the Wechsler Adult Intelligence Scale--Revised (WAIS-R) and the Woodcock-Johnson Psycho-Educational Battery, Part II: Tests of Achievement. (Author/CB)

  8. [Neurotrophic keratopathy--studies on substance P and the clinical significance of corneal sensation].

    PubMed

    Nishida, T; Nakamura, M; Konma, T; Ofuji, K; Nagano, K; Tanaka, T; Enoki, M; Reid, T W; Brown, S M; Murphy, C J; Mannis, M J

    1997-12-01

    Neurotrophic keratopathy, which often follows damage to the trigeminal nerve, is clinically characterized by various types of epithelial disorders and melting of corneal stroma. To understand both the pathology of neurotrophic keratopathy and the physiological significance of corneal sensation, we investigated both the cellular and molecular functions of a sensory neurotransmitter, substance P, in corneal epithelial cells. Our findings prompted us to try a new mode of treatment for neurotrophic keratopathy. Substance P, a member of the tachykinin family, is an 11-amino-acid peptide. In an organ culture system using rabbit corneas, substance P alone had no effect on corneal epithelial migration. In the presence of insulin-like growth factor-1 (IGF-1), however, substance P synergistically facilitated corneal epithelial migration in proportion to the concentration of substance P or of IGF-1. Other neurotransmitters (acetylcholine, norepinephrine, serotonin etc.) or tachykinins (neurokinin A, eledoisin etc.) did not show this synergistic effect with IGF-1. Among receptors for the tachykinin family (NK-1, NK-2, or NK-3) only the NK-1 receptor system was involved in the synergistic effect of substance P and IGF-1 on corneal epithelial migration. IGF-1 affected neither the binding constant nor the number of sites of substance P receptors in corneal epithelial cells, suggesting that the synergistic effect was not regulated at the receptor level. Various extracellular signals activate the intracellular signal transduction system, thus amplifying specific biological functions. We found that the addition of inhibitors of protein kinase C or tyrosine kinase clearly inhibited the synergistic effect of substance P and IGF-1 on corneal epithelial migration, demonstrating that protein kinase C and tyrosine kinase are involved in the synergistic effect. During corneal epithelial wound healing, epithelial cells must attach to a provisional, extracellular fibronectin matrix. We

  9. Transfusion of murine RBCs expressing the human KEL glycoprotein induces clinically significant alloantibodies

    PubMed Central

    Stowell, Sean R.; Girard-Pierce, Kathryn R.; Smith, Nicole H.; Henry, Kate L.; Arthur, C. Maridith; Zimring, James C.; Hendrickson, Jeanne E.

    2013-01-01

    Background Red blood cell (RBC) alloantibodies to non-self antigens may develop following transfusion or pregnancy, leading to morbidity and mortality in the form of hemolytic transfusion reactions or hemolytic disease of the newborn. A better understanding of the mechanisms of RBC alloantibody induction, or strategies to mitigate the consequences of such antibodies, may ultimately improve transfusion safety. However, such studies are inherently difficult in humans. Study Design and Methods We recently generated transgenic mice with RBC specific expression of the human KEL glycoprotein, with the KEL2 or KEL1 antigens. Herein, we investigate recipient alloimmune responses to transfused RBCs in this system. Results Transfusion of RBCs from KEL2 donors into wild type recipients (lacking the human KEL protein but expressing the murine KEL orthologue) resulted in dose dependent anti-KEL glycoprotein IgM and IgG antibody responses, enhanced by recipient inflammation with poly (I:C). Boostable responses were evident upon repeat transfusion, with morbid appearing alloimmunized recipients experiencing rapid clearance of transfused KEL2 but not control RBCs. Although KEL1 RBCs were also immunogenic following transfusion into wild type recipients, transfusion of KEL1 RBCs into KEL2 recipients or vice versa failed to lead to detectable anti-KEL1 or anti-KEL2 responses. Conclusions This murine model, with reproducible and clinically significant KEL glycoprotein alloantibody responses, provides a platform for future mechanistic studies of RBC alloantibody induction and consequences. Long term translational goals of these studies include improving transfusion safety for at risk patients. PMID:23621760

  10. Clinical significance of systematic retroperitoneal lymphadenectomy during interval debulking surgery in advanced ovarian cancer patients

    PubMed Central

    Takada, Toshio; Iitsuka, Chiaki; Nomura, Hidetaka; Abe, Akiko; Taniguchi, Tomoko; Takizawa, Ken

    2015-01-01

    Objective To investigate the clinical significance of systematic retroperitoneal lymphadenectomy during interval debulking surgery (IDS) in advanced epithelial ovarian cancer (EOC) patients. Methods We retrospectively reviewed the medical records of 124 advanced EOC patients and analyzed the details of neoadjuvant chemotherapy (NACT), IDS, postoperative treatment, and prognoses. Results Following IDS, 98 patients had no gross residual disease (NGRD), 15 had residual disease sized <1 cm (optimal), and 11 had residual disease sized ≥1 cm (suboptimal). Two-year overall survival (OS) and progression-free survival (PFS) rates were 88.8% and 39.8% in the NGRD group, 40.0% and 13.3% in the optimal group (p<0.001 vs. NGRD for both), and 36.3% and 0% in the suboptimal group, respectively. Five-year OS and 2-year PFS rates were 62% and 56.1% in the lymph node-negative (LN-) group and 26.2% and 24.5% in the lymph node-positive (LN+) group (p=0.0033 and p=0.0024 vs. LN-, respectively). Furthermore, survival in the LN+ group, despite surgical removal of positive nodes, was the same as that in the unknown LN status group, in which lymphadenectomy was not performed (p=0.616 and p=0.895, respectively). Multivariate analysis identified gross residual tumor during IDS (hazard ratio, 3.68; 95% confidence interval, 1.31 to 10.33 vs. NGRD) as the only independent predictor of poor OS. Conclusion NGRD after IDS improved prognosis in advanced EOC patients treated with NACT-IDS. However, while systematic retroperitoneal lymphadenectomy during IDS may predict outcome, it does not confer therapeutic benefits. PMID:26197771

  11. Clinical and prognostic significance of lung thallium uptake on rest imaging in acute myocardial infarction

    SciTech Connect

    Jain, D.; Lahiri, A.; Raftery, E.B. )

    1990-01-15

    Exercise-induced pulmonary uptake of thallium-201 in patients with ischemic heart disease is probably due to transient pulmonary edema and left ventricular failure induced by exercise. The significance of increased lung uptake of thallium-201 at rest after acute myocardial infarction (AMI) has not been described. Ninety-six patients admitted with chest pain for suspected AMI or unstable angina underwent thallium-201 imaging at rest. Using conventional diagnostic criteria, 62 had AMI, 12 had unstable angina and 22 had neither. Increased lung uptake of thallium-201 was present in 24 of the total 96 (25%) patients, 20 of the 62 (32%) patients with AMI and 4 of 34 (13%) patients with no evidence of infarction. In the AMI group, those with increased lung thallium-201 uptake had a higher mean +/- standard deviation segmental thallium-201 defect score (22 +/- 7 vs 12 +/- 8, p less than 0.0001), lower ejection fraction (35 +/- 14 vs 49 +/- 14%, p less than 0.002), higher peak creatine kinase levels (2,410 +/- 1,247 vs 1,496 +/- 1,228 IU/liter, p less than 0.01), higher wall motion abnormality score (25 +/- 13 vs 13 +/- 12, p less than 0.0001), increased incidence of clinical in-hospital heart failure (15 of 20 vs 7 of 42, p less than 0.0001) and higher short-term mortality (4 of 20 vs 1 of 42, p less than 0.02) compared to those without increased lung thallium-201 uptake.

  12. Selection of human p75NTR tag SNPs and its biological significance for clinical association studies.

    PubMed

    Wang, Yong-Tang; Lu, Xiu-Min; Shu, Ya-Hai; Xiao, Lan; Chen, Kai-Ting

    2014-01-01

    To select tag single nucleotide polymorphisms (SNPs) within and around human p75 neurotrophin receptor (p75NTR) gene in Chinese Han population, the sequence involving p75NTR gene as well as the upstream and downstream of the gene was identified according to the data from National Center for Biotechnology Information (NCBI) GenBank database, and the SNP genotype data involving 63 SNPs in the regions were obtained from Chinese Han Beijing (CHB) population of HapMap database. Then, Haploview (version 4.2) was used to calculate linkage disequilibrium (LD) statistics for the selected 32 common SNPs with a minor allele frequence (MAF) more than 0.05. Haplotype blocks were constructed throughout the p75NTR gene according to the upper and the lower 95% confidence bound of D' value, and the tag SNPs were selected based on the r2 and LOD values between SNPs as well as the results of bioinformatics analysis. The results indicated that five haplotype blocks were constructed within and around p75NTR gene and 12 tag SNPs including rs2537710, rs603769, rs614455, rs2537706, rs534561, rs2072445, rs2072446, rs7219709, rs734194, rs741071, rs741073 and rs2671641 were selected to represent the other 51 SNPs in p75NTR gene. Therefore, the 12 selected SNPs may act as tag SNPs for the entire p75NTR gene in Chinese Han population, which will provide an effective way to select tag SNPs in a whole gene, and its biological significance is to further guide the clinical association studies between the candidate gene and disease susceptibility. PMID:25227100

  13. A clinical algorithm for triaging patients with significant lymphadenopathy in primary health care settings in Sudan

    PubMed Central

    El Hag, Imad A.; Elsiddig, Kamal E.; Elsafi, Mohamed E.M.O; Elfaki, Mona E.E.; Musa, Ahmed M.; Musa, Brima Y.; Elhassan, Ahmed M.

    2013-01-01

    Abstract Background Tuberculosis is a major health problem in developing countries. The distinction between tuberculous lymphadenitis, non-specific lymphadenitis and malignant lymph node enlargement has to be made at primary health care levels using easy, simple and cheap methods. Objective To develop a reliable clinical algorithm for primary care settings to triage cases of non-specific, tuberculous and malignant lymphadenopathies. Methods Calculation of the odd ratios (OR) of the chosen predictor variables was carried out using logistic regression. The numerical score values of the predictor variables were weighed against their respective OR. The performance of the score was evaluated by the ROC (Receiver Operator Characteristic) curve. Results Four predictor variables; Mantoux reading, erythrocytes sedimentation rate (ESR), nocturnal fever and discharging sinuses correlated significantly with TB diagnosis and were included in the reduced model to establish score A. For score B, the reduced model included Mantoux reading, ESR, lymph-node size and lymph-node number as predictor variables for malignant lymph nodes. Score A ranged 0 to 12 and a cut-off point of 6 gave a best sensitivity and specificity of 91% and 90% respectively, whilst score B ranged -3 to 8 and a cut-off point of 3 gave a best sensitivity and specificity of 83% and 76% respectively. The calculated area under the ROC curve was 0.964 (95% CI, 0.949 – 0.980) and -0.856 (95% CI, 0.787 - 0.925) for scores A and B respectively, indicating good performance. Conclusion The developed algorithm can efficiently triage cases with tuberculous and malignant lymphadenopathies for treatment or referral to specialised centres for further work-up.

  14. Clinical significance of changes in the corrected QT interval in stress-induced cardiomyopathy

    PubMed Central

    Lee, Jung-Hee; Uhm, Jae-Sun; Shin, Dong Geum; Joung, Boyoung; Pak, Hui-Nam; Ko, Young-Guk; Hong, Geu-Ru; Lee, Moon-Hyoung

    2016-01-01

    Background/Aims: Although transient changes in the electrocardiogram (ECG) of patients with stress-induced cardiomyopathy (SCMP) are common, there are little data about ECG changes in patients with SCMP and the clinical implications of these variations. Methods: We investigated a total of 128 patients (age, 63.2 ± 15.4 years; female, 60.9%) diagnosed with SCMP. We compared the ECGs taken after SCMP diagnosis and during the recovery phase to those taken before SCMP diagnosis under baseline conditions. All patients were divided into two groups according to corrected QT (QTc) interval changes: recovered QTc group (QTc in SCMP > QTc in recovery phase, n = 77) and nonrecovered QTc group (QTc in SCMP ≤ QTc in recovery phase, n = 51). Results: In comparison of baseline, SCMP, and recovery phase, we found the mean heart rate (81.5 ± 18.7, 96.8 ± 25.3, and 83.0 ± 19.4/min, respectively; p < 0.001), frequencies of ST segment elevation (0.0%, 8.6%, and 1.6%, p = 0.004), ST segment depression (0.0%, 6.3%, and 1.6%, p = 0.007), T wave inversion (4.4 %, 43.8%, and 61.7%, p < 0.001), and QTc (447.4 ± 35.3, 488.9 ± 67.1, and 468.0 ± 49.5, p < 0.001) showed significant changes. In-hospital mortality (9.1% vs. 25.5%, p = 0.012) and critical care (54.5% vs. 72.5%, p = 0.040) occurred more frequently in the nonrecovered QTc group than in recovered QTc group. Conclusions: The QTc can be prolonged in patients with SCMP. Short-term mortality was increased in patients where the QTc did not recover. PMID:27052264

  15. Influencing factors and clinical significance of the metastatic lymph nodes ratio in gastric adenocarcinoma

    PubMed Central

    Yu, Ji-wei; Wu, Ju-gang; Zheng, Lin-hai; Zhang, Biao; Ni, Xiao-chun; Li, Xiao-qiang; Jiang, Bo-jian

    2009-01-01

    Background To investigate influencing factors of the metastatic lymph nodes ratio (MLR) and whether it is related to survival in patients with gastric adenocarcinoma. Methods We retrospectively evaluated the clinical features of 121 patients with gastric adenocarcinoma enrolled in our hospital between 2000 and 2007. The receiver operating characteristic (ROC) curve was used to determine the cutoff of the MLR, and CK20 immunohistochemical staining was used to detect micrometastasis of the lymph nodes. Results The areas under the ROC curve of MLR used to predict the death of 3-year and 5-year postoperative patients were 0.826 ± 0.053 and 0.896 ± 0.046. Thus MLR = 30.95% and MLR = 3.15% were designated as cutoffs. The MLR was then classified into three groups: MLR1 (MLR<3.15%); MLR2(3.15% ≤ MLR ≤ 30.95%); and MLR3 (MLR>30.95%). We found that patients with a higher MLR demonstrated a much poorer survival period after radical operation than those patients with a lower MLR (P = 0.000). The COX model showed that MLR was an independent prognostic factor (P = 0.000). The MLR could also discriminate between subsets of patients with different 5-year survival periods within the same N stage (P < 0.05). The MLR has been shown to be 34.7% (242/697) by HE staining and 43.5% (303/697) by CK staining (P = 0.001). The clinicopathological characteristics of lymph vessel invasion and the depth of invasion could significantly affect the MLR. Conclusion MLR is an independent prognostic factor in gastric cancer. The combined ROC curve with MLR is an effective strategy to produce a curve to predict the 3-year and 5-year survival rates. PMID:19393100

  16. Decreased expression of hsa_circ_001988 in colorectal cancer and its clinical significances

    PubMed Central

    Wang, Xuning; Zhang, Yue; Huang, Liang; Zhang, Jiajin; Pan, Fei; Li, Bing; Yan, Yongfeng; Jia, Baoqing; Liu, Hongyi; Li, Shiyou; Zheng, Wei

    2015-01-01

    Circular RNA (circRNA) is a type of RNAs which, unlike the better known linear RNA, forms a covalently closed continuous loop. They have emerged recently as a new player in governing fundamental biological processes. However it remains elusive about the correlation of hsa_circ_001988 abundance with colorectal cancer. To investigate the circular RNA expression in colorectal cancer, the targeted hsa_circ_001988 was selected from next generation sequence data base generated in house and then designed divergent primers to amplify hsa_circ_001988 and sequenced it for validation. The expression of hsa_circ_001988 in 31 matched colorectal cancer tissue and normal colon mucosa was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). We used ΔCt method and investigated the differences between tumor tissues and normal colon mucosa by paired t-test. One-way analysis of variance was conducted to analyze the relationship between hsa_circ_001988 expression level and clinic pathological factors of patients. Receiver operating characteristic (ROC) curve was built by SPSS to evaluate the diagnostic values. The expression of hsa_circ_001988 was significantly correlated with differentiation (P<0.05) and perineural invasion (P<0.05). The area under ROC curve of hsa_circ_001988 was 0.788 (P<0.05). Those results indicate that hsa_circ_001988 may become a novel potential biomarker in the diagnosis of colorectal cancer and a potential novel target for the treatment of colorectal cancer. PMID:26884878

  17. Clinical Significance of a Point Mutation in DNA Polymerase Beta (POLB) Gene in Gastric Cancer

    PubMed Central

    Tan, Xiaohui; Wang, Hongyi; Luo, Guangbin; Ren, Shuyang; Li, Wenmei; Cui, Jiantao; Gill, Harindarpal S.; Fu, Sidney W.; Lu, Youyong

    2015-01-01

    Gastric cancer (GC) is a major cause of global cancer mortality. Genetic variations in DNA repair genes can modulate DNA repair capability and, consequently, have been associated with risk of developing cancer. We have previously identified a T to C point mutation at nucleotide 889 (T889C) in DNA polymerase beta (POLB) gene, a key enzyme involved in base excision repair in primary GCs. The purpose of this study was to evaluate the mutation and expression of POLB in a larger cohort and to identify possible prognostic roles of the POLB alterations in GC. Primary GC specimens and their matched normal adjacent tissues were collected at the time of surgery. DNA, RNA and protein samples were isolated from GC specimens and cell lines. Mutations were detected by PCR-RFLP/DHPLC and sequencing analysis. POLB gene expression was examined by RT-PCR, tissue microarray, Western blotting and immunofluorescence assays. The function of the mutation was evaluated by chemosensitivity, MTT, Transwell matrigel invasion and host cell reactivation assays. The T889C mutation was detected in 18 (10.17%) of 177 GC patients. And the T889C mutation was associated with POLB overexpression, lymph nodes metastases and poor tumor differentiation. In addition, patients with- the mutation had significantly shorter survival time than those without-, following postoperative chemotherapy. Furthermore, cell lines with T889C mutation in POLB gene were more resistant to the treatment of 5-fluorouracil, cisplatin and epirubicin than those with wild type POLB. Forced expression of POLB gene with T889C mutation resulted in enhanced cell proliferation, invasion and resistance to anticancer drugs, along with increased DNA repair capability. These results suggest that POLB gene with T889C mutation in surgically resected primary gastric tissues may be clinically useful for predicting responsiveness to chemotherapy in patients with GC. The POLB gene alteration may serve as a prognostic biomarker for GC. PMID

  18. Expression and clinical significance of SALL4 and β-catenin in colorectal cancer.

    PubMed

    Hao, Liliang; Zhao, Yan; Wang, Zhen; Yin, Hongzhuan; Zhang, Xin; He, Tao; Song, Shanshan; Sun, Shaolong; Wang, Baosheng; Li, Zhijie; Su, Qi

    2016-04-01

    Previous studies on the expression of Sal-like 4 (SALL4), a zinc finger transcription factor, had conflicting results in colorectal cancer (CRC). The main aim of this study was to investigate the expression of SALL4 and its relationship with β-catenin in CRC. Immunohistochemistry was performed to examine the expression of SALL4 and β-catenin in a cohort of 149 patients with CRC, 12 with atypical hyperplasia, 25 with benign tumor and 38 with normal tissue. Expression patterns of SALL4 and β-catenin and correlation with clinicopathological features were investigated. The relationship between SALL4 and β-catenin was examined by immunofluorescence and co-immunoprecipitation using CRC cell lines, SW480, SW620, HCT116 and HT29. Immunohistochemical analysis revealed significantly lower expression of SALL4 in CRC (46.3 %) than atypical hyperplasia (68.0 %, p < 0.05) and normal tissue (78.9 %, p < 0.01). Well-differentiated CRC seemed to express more SALL4 (47.6 %) than moderately (45.8 %) and poorly-differentiated cancers (18.8 %) (p < 0.05). However, SALL4 expression positively correlated with lymph node metastasis and tumor-node-metastasis (TNM) and Dukes stages (all p < 0.05) suggesting a new mechanism involved in the function of SALL4 in CRC. β-catenin was expressed significantly higher in CRC (69.1 %) than normal tissue (21.1 %, p < 0.01), and positively correlated with CA19-9 level in serum (p < 0.05). SALL4 and β-catenin were positively correlated in CRC (Spearman correlation coefficient R = 0.536, p < 0.01). The group of co-expression of the two molecules showed advanced lymph node metastasis, TNM stage and Dukes stage (all p < 0.05). Double-labeling immunofluorescence and co-immunoprecipitation indicated that SALL4 and β-catenin co-localized in the nucleus and cytoplasm and interacted. Taken together, our results revealed that SALL4 and β-catenin were positively correlated in CRC. In CRC cells, SALL4 and β-catenin co-localized and interacted. The function

  19. Clinical significance of SPRR1A expression in progesterone receptor-positive breast cancer.

    PubMed

    Chen, Guanglei; Li, Gang; Luo, Minna; Wei, Xiaofei; Wang, Dan; Zhang, Hao; Zhao, Xinhan; Chen, Bo; Liu, Caigang

    2015-04-01

    Small proline-rich repeat protein 1A (SPRR1A) is a marker for terminal squamous cell differentiation. Previous studies showed that SPRR1A expression increases in squamous cell carcinoma of the skin, but decreases in esophageal squamous cell carcinoma. This study focuses on the expression of SPRR1A protein in breast cancers (BCs) in China. A total of 111 patients with histologically confirmed BC, who underwent radical surgery between January 2006 and September 2007 in China Medical University, were enrolled. The relationship between SPRR1A expression and clinicopathological factors as well as BC prognoses was also determined. Overall, SPRR1A expression was detected in more than half of the BC specimens by immunohistochemistry (56/111, 53.8%), but there was no significant difference between age groups (≥50 vs. <50 years) in terms of SPRR1A expression (P = 0.915), as well as no differences between SPRR1A expression and the clinical stage (0-I vs. II-III) or nodal status (P = 0.234 and 0.632, respectively). Moreover, human epidermal growth factor receptor 2 overexpression was not correlated with SPRR1A expression, whereas Ki67 was associated with SPRR1A expression (P = 0.155 and 0.028, respectively). Interestingly, SPRR1A expression was significantly associated with progesterone receptor-positive (P = 0.010) rather than estrogen receptor-positive (0.778) BCs. The 5-year survival rate in patients did not differ with the presence or absence of SPRR1A expression (P = 0.753), whereas the combination of SPRR1A expression, progesterone receptor status, and menopausal status allowed identification of a subgroup of BC patients with a good long-term prognosis. Thus, the SPRR1A status might play an important role in the prognosis of postmenopausal breast carcinoma patients, especially that of progesterone receptor-positive subgroups. PMID:25424702

  20. Failure of Ivermectin per Rectum to Achieve Clinically Meaningful Serum Levels in Two Cases of Strongyloides Hyperinfection

    PubMed Central

    Bogoch, Isaac I.; Khan, Kamran; Abrams, Howard; Nott, Caroline; Leung, Elizabeth; Fleckenstein, Lawrence; Keystone, Jay S.

    2015-01-01

    Two cases of Strongyloides hyperinfection are presented. Ivermectin was initially administered orally and per rectum pending the availability of subcutaneous (SC) preparations. In neither case did rectal suppositories of ivermectin achieve clinically meaningful serum values. Clinicians should use SC preparations of ivermectin as early as possible in Strongyloides hyperinfection and dissemination. PMID:25918215

  1. De Garengeot's hernia in an 82-year-old man: a case report and clinical significance.

    PubMed

    Leite, Túlio F; Chagas, Carlos A A; Pires, Lucas A S; Cisne, Rafael; Babinski, Márcio A

    2016-01-01

    The presence of the appendix within a femoral hernia (FH) sac is known as Garengeot's hernia (GH). We report on current study a rare case of an elderly man with a combined inguinal and Garengeot's hernia and discuss the clinical aspects. An 82-year-old man clinically stable, presented history of pain at the right inguinal region for over a week, without vomit, nausea, fever or any alteration of intestinal or urinary eliminations. Clinical examination revealed a FH and the ultrasonography confirmed the hernia sac. During the surgery, the appendix was recognized within the sac, and then, the patient underwent appendectomy and hernia repair. In conclusion, the presence of the vermiform appendix in a FH sac is rare, thus, requiring knowledge of the surgeon regarding this clinical entity. Prompt diagnosis and appropriate surgical treatment is the key to avoid complications. PMID:27381019

  2. [Clarifying some concepts and clinical significance of refractory or recurrent neovascular age-related macular degeneration].

    PubMed

    Zhao, Jingke; Sun, Xiaodong

    2015-11-01

    Anti-VEGF therapy is currently one of the main treatments for neovascular age-related macular degeneration (nAMD). Clinically, patients under standardized anti-VEGF therapy showed different responses, of which recurrences or even insensitivity were found in some patients. However, the specific definitions of these various clinical responses are still unclarified. Therefore, to consolidate and define these concepts are of great importance regarding to future efficacy comparison, treatment response clarification and novel drug switching therapies. PMID:26850580

  3. Clinical conditions and patient factors significantly influence diagnostic utility of D-dimer in venous thromboembolism.

    PubMed

    Qasim, Asghar; Duggan, Mary; O'Connell, Niamh; O'Driscoll, Anne

    2009-06-01

    Determining D-dimer levels remains important in the diagnostic algorithms for venous thromboembolism (VTE). The present study aimed to identify factors influencing D-dimer utility in diagnosing VTE. Consecutive symptomatic medical patients, who attended our emergency department from 1 November 2006 to 31 December 2006, had D-dimer levels measured as fibrinogen equivalent units (FEU), following clinical risk assessment. Diagnosis of VTE was established by venous compression ultrasonography and computed tomographic pulmonary angiography. VTE-negative patients were followed for 2 months to detect future occurrence of thromboembolism. Impact of various factors on D-dimer levels was analyzed. Four thousand and twenty-six patients attended our emergency department, and 525 patients (median age 52 years) had D-dimer assessed. Final diagnosis of VTE was established in 25 (4.7%) patients on radiological investigations. Median D-dimer levels for VTE-negative patients less than 60 years old, with normal renal function and chest radiology were 0.38 microgFEU/ml (range 0.19-2.3), 0.39 microgFEU/ml (range 0.17-3.5) and 0.39 microgFEU/ml (range 0.1-4.3), respectively. Similar figures for those at least 60 years, with renal impairment and abnormal chest radiology, were 0.75 microgFEU/ml (range 0.22-4.3), 0.52 microgFEU/ml (range 0.17-4.4) and 0.92 microgFEU/ml (range 0.26-5.6), respectively. Factors including patient age, renal function and chest radiology had significant influence on D-dimer levels (P < 0.01). A triad of patient age at least 60 years, renal impairment (modification of diet in renal disease stage 2-5) and abnormal chest radiology had a false positive D-dimer in 96% of patients (n = 72). Use of D-dimer in patients with a triad of advanced age, renal impairment and abnormal chest radiology has no practical diagnostic value in VTE. PMID:19276796

  4. No Clinically Significant Association Between CFH and ARMS2 Genotypes and Response to Nutritional Supplements

    PubMed Central

    Chew, Emily Y.; Klein, Michael L.; Clemons, Traci E.; Agrón, Elvira; Ratnapriya, Rinki; Edwards, Albert O.; Fritsche, Lars G.; Swaroop, Anand; Abecasis, Gonçalo R.

    2014-01-01

    Objective To determine whether genotypes at two major loci associated with late age-related macular degeneration (AMD), complement factor H (CFH) and Age-Related Maculopathy Susceptibility 2 (ARMS2), influenced the relative benefits of Age-Related Eye Disease Study (AREDS) supplements. Design Unplanned retrospective evaluation of a prospective, randomized, placebo-controlled clinical trial of vitamins and minerals for the treatment of AMD. Subjects AREDS participants (mean age of 69 years) who were at risk for developing late AMD and who were randomized to the 4 arms of the AREDS supplements. Methods Analyses were performed using the Cox proportional hazards model to predict progression to late AMD (neovascular or central geographic atrophy). Statistical models, adjusted for age, gender, smoking status and baseline AMD severity, were used to examine the influence of genotypes on the response to therapy with 4 randomly assigned arms of AREDS supplement components: placebo, antioxidants (vitamins C, E, beta-carotene), zinc with copper, or the combination. Main Outcome Measures The influence of the genotype on the relative treatment response to the randomized components of the AREDS supplement, measured as progression to late AMD. Results Of the 1237 genotyped AREDS participants of Caucasian ethnicity, 385 (31.1%) developed late AMD during the mean follow-up period of 6.6 years. As previously demonstrated, both CFH genotype (p=0.005), ARMS2 (<0.0001) and supplement were each individually associated with progression to late AMD. An interaction analysis found no evidence that the relative benefits of AREDS supplementation varied by genotype. Analysis of (1) CFH rs1061170 and rs1410996 combined with ARMS2 rs10490924, with the 4 randomly assigned arms of AREDS supplement and (2) analysis of the combination of CFH rs412852 and rs3766405 with ARMS2 c.372_815del443ins54 with the AREDS components resulted in no interaction (p=0.06 and p=0.45, respectively, before multiplicity

  5. Integrated genomic and transcriptomic analysis of human brain metastases identifies alterations of potential clinical significance.

    PubMed

    Saunus, Jodi M; Quinn, Michael C J; Patch, Ann-Marie; Pearson, John V; Bailey, Peter J; Nones, Katia; McCart Reed, Amy E; Miller, David; Wilson, Peter J; Al-Ejeh, Fares; Mariasegaram, Mythily; Lau, Queenie; Withers, Teresa; Jeffree, Rosalind L; Reid, Lynne E; Da Silva, Leonard; Matsika, Admire; Niland, Colleen M; Cummings, Margaret C; Bruxner, Timothy J C; Christ, Angelika N; Harliwong, Ivon; Idrisoglu, Senel; Manning, Suzanne; Nourse, Craig; Nourbakhsh, Ehsan; Wani, Shivangi; Anderson, Matthew J; Fink, J Lynn; Holmes, Oliver; Kazakoff, Stephen; Leonard, Conrad; Newell, Felicity; Taylor, Darrin; Waddell, Nick; Wood, Scott; Xu, Qinying; Kassahn, Karin S; Narayanan, Vairavan; Taib, Nur Aishah; Teo, Soo-Hwang; Chow, Yock Ping; kConFab; Jat, Parmjit S; Brandner, Sebastian; Flanagan, Adrienne M; Khanna, Kum Kum; Chenevix-Trench, Georgia; Grimmond, Sean M; Simpson, Peter T; Waddell, Nicola; Lakhani, Sunil R

    2015-11-01

    Treatment options for patients with brain metastases (BMs) have limited efficacy and the mortality rate is virtually 100%. Targeted therapy is critically under-utilized, and our understanding of mechanisms underpinning metastatic outgrowth in the brain is limited. To address these deficiencies, we investigated the genomic and transcriptomic landscapes of 36 BMs from breast, lung, melanoma and oesophageal cancers, using DNA copy-number analysis and exome- and RNA-sequencing. The key findings were as follows. (a) Identification of novel candidates with possible roles in BM development, including the significantly mutated genes DSC2, ST7, PIK3R1 and SMC5, and the DNA repair, ERBB-HER signalling, axon guidance and protein kinase-A signalling pathways. (b) Mutational signature analysis was applied to successfully identify the primary cancer type for two BMs with unknown origins. (c) Actionable genomic alterations were identified in 31/36 BMs (86%); in one case we retrospectively identified ERBB2 amplification representing apparent HER2 status conversion, then confirmed progressive enrichment for HER2-positivity across four consecutive metastatic deposits by IHC and SISH, resulting in the deployment of HER2-targeted therapy for the patient. (d) In the ERBB/HER pathway, ERBB2 expression correlated with ERBB3 (r(2)  = 0.496; p < 0.0001) and HER3 and HER4 were frequently activated in an independent cohort of 167 archival BM from seven primary cancer types: 57.6% and 52.6% of cases were phospho-HER3(Y1222) or phospho-HER4(Y1162) membrane-positive, respectively. The HER3 ligands NRG1/2 were barely detectable by RNAseq, with NRG1 (8p12) genomic loss in 63.6% breast cancer-BMs, suggesting a microenvironmental source of ligand. In summary, this is the first study to characterize the genomic landscapes of BM. The data revealed novel candidates, potential clinical applications for genomic profiling of resectable BMs, and highlighted the possibility of therapeutically targeting

  6. The clinical significance of radionuclide bone and gallium scanning in osteomyelitis of the head and neck

    SciTech Connect

    Noyek, A.M.; Kirsh, J.C.; Greyson, N.D.; Wortzman, G.; Jazrawy, H.; Freeman, J.L.; Blair, R.L.; Chapnik, J.S.

    1984-05-01

    Osteomyelitis of the head and neck remains a difficult clinical problem both in diagnosis and treatment evaluation. The purpose of this manuscript is to review our clinical experience with 25 cases of osteomyelitis distributed evenly among the temporal bone and skull base, the paranasal sinuses, and the mandible. Radionuclide bone and gallium scan images accurately depicted the biologic activity of the disease process and permitted accurate treatment evaluation and patient monitoring. This work demonstrates the potentials and limitations of radionuclide imaging with bone and gallium scan agents and attempts to define a role for their contemporary use in the management of osteomyelitis of the head and neck.

  7. Statistical, Practical, Clinical, and Personal Significance: Definitions and Applications in Speech-Language Pathology

    ERIC Educational Resources Information Center

    Bothe, Anne K.; Richardson, Jessica D.

    2011-01-01

    Purpose: To discuss constructs and methods related to assessing the magnitude and the meaning of clinical outcomes, with a focus on applications in speech-language pathology. Method: Professionals in medicine, allied health, psychology, education, and many other fields have long been concerned with issues referred to variously as practical…

  8. Significant roadblocks exist in developing sputum sample libraries for clinical validation of novel in vitro diagnostics

    PubMed Central

    Dollow, Joshua M; Green, Justin A

    2014-01-01

    With the continuing rise of multiresistant pathogens, reliable, cost-effective, and novel diagnostics are urgently required by clinicians and clinical trialists to diagnose conditions such as respiratory tract infections to enable rational antimicrobial choice and enhance clinical outcomes. However, during product development, validation of these in vitro diagnostic devices, a key regulatory hurdle, requires sputum samples in large numbers. The Rapid Point-of-Care test Platform for Infectious Diseases (RAPP-ID) consortium is tasked with producing point of care test (POCT) platforms for rapid diagnosis of lower respiratory tract infections, including tuberculosis and blood stream infections. Validation of diagnostic platforms would ideally use well-characterized samples in a sputum library taken from a range of clinical settings to allow for a wide panel of pathogens to be assessed. These samples would be stored in specific stable conditions (monitored temperature, specific medium) until required for validation. Therefore we reviewed the current literature for details of storage conditions of sputum samples and for previous validation studies of other diagnostic tests using this methodology. However, we conclude that little data exists, and thus the acquisition and successful storage of good quality clinical samples are major roadblocks in the validation of novel POCT platforms, and that while not without limitations, spiked sputum samples appear the best solution until sputum library laboratory techniques allowing careful preservation of pathogens are improved. PMID:24489460

  9. The geyser sign and torn rotator cuff: clinical significance and pathomechanics.

    PubMed

    Craig, E V

    1984-12-01

    The geyser radiographic sign on shoulder arthrogram is characterized by leakage of dye from the glenohumeral joint into the subdeltoid bursa. The dye outlines the acromioclavicular joint. It is usually an indication of a full-thickness cuff tear of long duration. The clinical occurrence and pathomechanics of this finding indicate that repair is generally difficult. PMID:6499313

  10. Face-to-Face vs. Real-Time Clinical Education: No Significant Difference

    ERIC Educational Resources Information Center

    Mohammed, Y. Q.; Waddington, G.; Donnan, P.

    2007-01-01

    The main objective of this pilot research project was to determine whether the use of an internet broadband link to stream physiotherapy clinical education workshop proceedings in "real-time" is of equivalent educational value to the traditional face-to-face experience. This project looked at the benefits of using the above technology as…

  11. Enhanced loading regimen of teicoplanin is necessary to achieve therapeutic pharmacokinetics levels for the improvement of clinical outcomes in patients with renal dysfunction.

    PubMed

    Ueda, T; Takesue, Y; Nakajima, K; Ichiki, K; Doita, A; Wada, Y; Tsuchida, T; Takahashi, Y; Ishihara, M; Ikeuchi, H; Uchino, M; Kimura, T

    2016-09-01

    We evaluated the clinical efficacy and safety of teicoplanin according to the pharmacokinetics (PK) therapeutic level achieved in patients with renal dysfunction. Target trough concentration (Cmin) was ≥15-30 μg/ml which has been recommended in patients with normal renal function. Adult patients (estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2)) who were treated by teicoplanin were included in the study. We adopted two types of regimen for the initial 3 days: the conventional regimen, and the enhanced loading regimen (10 mg/kg twice daily on the 1st day, followed by 6.7-10 mg/kg once daily for the 2nd and 3rd days]. Two hundred and eighty-eight patients were evaluated for safety, and 106 patients with methicillin-resistant Staphylococcus aureus (MRSA) infections were evaluated for clinical efficacy. A significantly higher success rate was obtained in patients who achieved the target initial Cmin compared with those that did not (75.0 % vs 50.0 %, p = 0.008). In a multivariate analysis, initial Cmin ≥15 μg/ml was an independent factor for clinical success (adjusted odds ratio: 4.20, 95 % confidence interval: 1.34-13.15). In patients with 15-30 μg/ml of maximal Cmin during therapy, nephrotoxicity occurred in 13.1 %, and hepatotoxicity in 2.6 %, and these incidences were not significantly higher compared with those patients with <15 μg/ml. In conclusion, achievement of Cmin of 15-30 μg/ml without delay was necessary to improve clinical outcomes for the treatment by teicoplanin in patients with renal dysfunction. Further investigation is required regarding the optimal loading regimen to achieve the therapeutic levels in those patients. PMID:27278654

  12. Paving the critical path: how can clinical pharmacology help achieve the vision?

    PubMed

    Lesko, L J

    2007-02-01

    It has been almost 3 years since the launch of the FDA critical path initiative following the publication of the paper "Innovation or Stagnation: Challenges and Opportunities on the Critical Path of New Medical Product Development." The initiative was intended to create an urgency with the drug development enterprise to address the so-called "productivity problem" in modern drug development. Clinical pharmacologists are strategically aligned with solutions designed to reduce late phase clinical trial failures to show adequate efficacy and/or safety. This article reviews some of the ways that clinical pharmacologists can lead and implement change in the drug development process. It includes a discussion of model-based, semi-mechanistic drug development, drug/disease models that facilitate informed clinical trial designs and optimal dosing, the qualification process and criteria for new biomarkers and surrogate endpoints, approaches to streamlining clinical trials and new types of interaction between industry and FDA such as the end-of-phase 2A and voluntary genomic data submission meetings respectively. PMID:17259944

  13. Nursing Students Achieving Community Health Competencies through Undergraduate Clinical Experiences: A Gap Analysis.

    PubMed

    Pijl-Zieber, Em M; Barton, Sylvia; Awosoga, Oluwagbohunmi A; Konkin, Jill

    2015-01-01

    In Canada, it is widely believed that nursing practice and health care will move from acute care into the community. At the same time, increasing numbers of nursing students are engaged in non-traditional clinical experiences for their community health rotation. These clinical experiences occur at agencies not organizationally affiliated with the health care system and typically do not employ registered nurses (RNs). What has yet to be established is the degree to which nursing students are actually being prepared for community health nursing roles through their community health clinical rotations. In this paper we report the findings of a mixed method study that explored the gap between desired and observed levels of competence in community health of senior nursing students and new graduates. The gap was quantified and then the nature of the gap further explored through focus groups. PMID:26461843

  14. Statistical Versus Clinical Significance for Infants with Brain Injury: Reanalysis of Outcome Data from a Randomized Controlled Study

    PubMed Central

    Badr, Lina Kurdahi

    2009-01-01

    By adopting more appropriate statistical methods to appraise data from a previously published randomized controlled trial (RCT), we evaluated the statistical and clinical significance of an intervention on the 18 month neurodevelopmental outcome of infants with suspected brain injury. The intervention group (n =32) received extensive, individualized cognitive/sensorimotor stimulation by public health nurses (PHNs) while the control group (n = 30) received standard follow-up care. At 18 months 43 infants remained in the study (22 = intervention, 21 = control). The results indicate that there was a significant statistical change within groups and a clinical significance whereby more infants in the intervention group improved in mental, motor and neurological functioning at 18 months compared to the control group. The benefits of looking at clinical significance from a meaningful aspect for practitioners are emphasized. PMID:19276403

  15. WISC-III and CAS: Which Correlates Higher with Achievement for a Clinical Sample?

    ERIC Educational Resources Information Center

    Naglieri, Jack A.; De Lauder, Brianna Y.; Goldstein, Sam; Schwebech, Adam

    2006-01-01

    The relationships between Wechsler Intelligence Scale for Children-Third Edition (WISC-III) and the Cognitive Assessment System (CAS) with the Woodcock-Johnson Tests of Achievement (WJ-III) were examined for a sample of 119 children (87 males and 32 females) ages 6 to 16. The sample was comprised of children who were referred to a specialty clinic…

  16. Persistent Left Superior Vena Cava: A Rare Case with Clinical Significance

    PubMed Central

    Kumar, Raj; Yadav, Sankalp; Verma, Deepak

    2016-01-01

    Persistent Left Superior Vena Cava (PLSVC) is a rare congenital vascular anomaly (incidence of 0.3-0.5% of the general population) which being mostly asymptomatic in its presentation, is usually detected incidentally. There are many practical clinical implications associated with it including arrhythmias. We report a rare case of PLSVC with absent Right Superior Vena Cava (RSVC) (isolated PLSVC), in a 55-year-old lady who had complete heart block followed by sepsis and was diagnosed to have this condition during the permanent cardiac pacemaker implantation and central venous catheter insertion showing an abnormal path of the catheter/pacing leads. The authors also give an insight into its clinical relevance. PMID:27437282

  17. Tests of pancreatic exocrine function - clinical significance in pancreatic and non-pancreatic disorders.

    PubMed

    Keller, Jutta; Aghdassi, Ali Alexander; Lerch, Markus M; Mayerle, Julia V; Layer, Peter

    2009-01-01

    The pancreas functions as the main factory for digestive enzymes and therefore enables food utilisation. Pancreatic exocrine insufficiency, partial or complete loss of digestive enzyme synthesis, occurs primarily in disorders directly affecting pancreatic tissue integrity. However, other disorders of the gastrointestinal tract, such as coeliac disease, inflammatory bowel disease, Zollinger-Ellison syndrome or gastric resection can either mimic or cause pancreatic exocrine insufficiency. The overt clinical symptoms of pancreatic exocrine insufficiency are steatorrhoea and maldigestion, which frequently become apparent in advanced stages. Several direct and indirect function tests are available for assessment of pancreatic function but until today diagnosis of excretory insufficiency is difficult as in mild impairment clinically available function tests show limitations of diagnostic accuracy. This review focuses on diagnosis of pancreatic exocrine insufficiency in pancreatic and non-pancreatic disorders. PMID:19505669

  18. Clinical Significance and Pathogenesis of Staphylococcal Small Colony Variants in Persistent Infections.

    PubMed

    Kahl, Barbara C; Becker, Karsten; Löffler, Bettina

    2016-04-01

    Small colony variants (SCVs) were first described more than 100 years ago for Staphylococcus aureus and various coagulase-negative staphylococci. Two decades ago, an association between chronic staphylococcal infections and the presence of SCVs was observed. Since then, many clinical studies and observations have been published which tie recurrent, persistent staphylococcal infections, including device-associated infections, bone and tissue infections, and airway infections of cystic fibrosis patients, to this special phenotype. By their intracellular lifestyle, SCVs exhibit so-called phenotypic (or functional) resistance beyond the classical resistance mechanisms, and they can often be retrieved from therapy-refractory courses of infection. In this review, the various clinical infections where SCVs can be expected and isolated, diagnostic procedures for optimized species confirmation, and the pathogenesis of SCVs, including defined underlying molecular mechanisms and the phenotype switch phenomenon, are presented. Moreover, relevant animal models and suggested treatment regimens, as well as the requirements for future research areas, are highlighted. PMID:26960941

  19. Clinical significance and new detection system of autoantibodies in myositis with interstitial lung disease.

    PubMed

    Nakashima, R; Hosono, Y; Mimori, T

    2016-07-01

    Anti-aminoacyl-tRNA synthetase (ARS) and anti-melanoma differentiation-associated gene 5 (MDA5) antibodies are closely associated with interstitial lung disease in polymyositis and dermatomyositis. Anti-ARS-positive patients develop common clinical characteristics termed anti-synthetase syndrome and share a common clinical course, in which they respond well to initial treatment with glucocorticoids but in which disease tends to recur when glucocorticoids are tapered. Anti-MDA5 antibody is associated with rapidly progressive interstitial lung disease and poor prognosis, particularly in Asia. Therefore, intensive immunosuppressive therapy is required for anti-MDA5-positive patients from the early phase of the disease. New enzyme-linked immunosorbent assays to detect anti-ARS and anti-MDA5 antibodies have recently been established and are suggested to be efficient and useful. These assays are expected to be widely applied in daily practice. PMID:27252271

  20. Clinical Significance of Langerhans Cells in Squamous Cell Carcinoma of the Larynx

    PubMed Central

    Esteban, Francisco; Ruiz-Cabello, Francisco; Gonzalez-Moles, Miguel Angel; Lopez-Gonzalez, Miguel Angel; Funez, Rafael; Redondo, Maximino

    2012-01-01

    Langerhans cells (LCs) may be involved in the immunosurveillance against tumors as antigen-presenting cells. Our objective has been to determine the relevance of LC in progression of larynx squamous cell carcinomas and their relationship with different subpopulations of tumor-infiltrating cells. LCs were investigated by immunohistochemical methods using anti-CD1 antibody. LCs were detected in most of the primary tumors studied (44 out of 50) and also in metastases (6 out of 10) and recurrences (2 out of 3), but we did not find any statistical association between number of LCs and clinical-pathological parameters or survival. However, the number of LCs was increased in patients with evident infiltration of lymphocytes, mainly cytotoxic T cells. We can conclude that although LCs did not show clinical utility as prognostic marker, they may play a role in releasing an active immune response in larynx carcinomas, according to their ability to present antigens to sensitized T cells. PMID:22481933

  1. Current perspectives on the epidemiology and pathogenesis of clinically significant Vibrio spp.

    PubMed Central

    Janda, J M; Powers, C; Bryant, R G; Abbott, S L

    1988-01-01

    Recent taxonomic advances have now implicated several different Vibrio species as human pathogens. While the most common clinical presentation of Vibrio infection continues to be gastroenteritis, an increasing number of extraintestinal infections are being reported, particularly in immunocompromised individuals. Detection of Vibrio infections requires a good clinical history and the use of appropriate isolation and identification procedures by the laboratory to confirm illnesses attributed to Vibrio species. Except for Vibrio cholerae O1 and Vibrio parahaemolyticus, there is little direct evidence linking the production of a myriad of cell-associated or extracellular factors produced by each species with human disease and pathogenesis. Many questions regarding pathogenic Vibrio species remain unanswered, including their frequency and distribution in environmental specimens (water, shellfish), infective doses, virulence potential of individual isolates, and markers associated with such strains. Images PMID:3058295

  2. Electrocardiographic right and left bundle branch block patterns in athletes: prevalence, pathology, and clinical significance.

    PubMed

    Kim, Jonathan H; Baggish, Aaron L

    2015-01-01

    Differentiating benign electrocardiographic (ECG) patterns in athletes from those representative of underlying cardiac pathology is both clinically relevant and challenging. Complete right (RBBB) and left (LBBB) bundle branch block are relatively rare in asymptomatic athletic populations, and current expert consensus guidelines recommend further clinical investigation upon detection of either ECG pattern. However, present data suggest that typical RBBB is not associated with structural cardiac pathology and may alternatively represent an ECG marker of exercise-induced right ventricular remodeling. In accordance with current guidelines, the presence of asymptomatic LBBB in athletes is not associated with normal exercise physiology and more likely indicative of underlying cardiac pathology. While long-term outcomes for asymptomatic athletes with RBBB or LBBB remain unknown, current evidence regarding these ECG patterns should be considered to improve the specificity of future athlete-specific ECG interpretation guidelines. PMID:25836379

  3. Biologic and clinical significance of molecular profiling in Chronic Lymphocytic Leukemia

    PubMed Central

    Tom, Butler; Gribben, J.G.

    2010-01-01

    CLL is extremely heterogeneous in its clinical course, with some patients living decades with no need for treatment whilst others have a rapidly aggressive clinical course. A major focus of research has been to try to identify those biological factors that influence this heterogeneity. The goal of therapy has been to maintain the best quality of life and treat only when patients become symptomatic from their disease. For the majority of patients this means following a “watch and wait” approach to determine the rate of progression of the disease and assess for development of symptoms. Any alteration to this approach will require identification of criteria that define patients sufficiently “high-risk” that they gain benefit by introduction of early therapy. The use of molecular profiling to suggest particular therapies is currently appropriate only in defining the treatment of the minority of patients with 17p deletions or p53 mutations and in all other circumstances remains a clinical trial question. PMID:20398985

  4. The significance of clinical practice guidelines on adult varicocele detection and management

    PubMed Central

    Shridharani, Anand; Owen, Ryan C; Elkelany, Osama O; Kim, Edward D

    2016-01-01

    Varicoceles are the most common correctable etiology of male factor infertility. However, the detection and management of varicoceles have not been standardized. This has led to decades of debate regarding the effect of varicocele on male infertility and subsequently whether repair leads to an improved fertility status. The current body of evidence investigating the role of varicocele and varicocelectomy is weak and conflicting. The stance taken by the AUA and ASRM suggests that there is insufficient outcomes data to support evidenced-based guidelines, citing evidence used to provide current recommendations are generally of a low quality level. On the other hand, the EAU Guidelines give a level 1a of evidence for management of varicoceles that are clinically palpable, associated with subnormal semen analyses and having otherwise unexplained fertility. Besides aiding with clinical varicocele detection and management, clinical practice opinion statements and guidelines aim to direct and strengthen the infrastructure of future studies. We review the current status of opinion statements and guidelines in varicocele and management detection with focus on their application in practice. PMID:26806081

  5. Peripheral neuropathy associated with monoclonal IgG of undetermined significance: clinical, electrophysiologic, pathologic and therapeutic study of 14 cases.

    PubMed

    Hermosilla, E; Lagueny, A; Vital, C; Vital, A; Ferrer, X; Steck, A; Julien, J

    1996-01-01

    Fourteen patients with peripheral neuropathy and monoclonal IgG of undetermined significance are reported with a retrospective study of the clinical features, electrophysiologic and sural nerve biopsy findings. There were two groups. Five patients had a relapsing chronic sensorimotor polyneuropathy with clinical (5/5), electrophysiologic (4/5) and pathologic (5/5) features compatible with chronic inflammatory demyelinating polyneuropathies (CIDP). The nine others had a slowly progressive sensory (5/9) (SPNP) or sensorimotor (4/9) (SMPNP) axonal polyneuropathy. Four patients of the first group were treated with intravenous human immunoglobulin (400 mg/kg/day for five days) with significant clinical improvement. The motor conduction velocities and distal latencies of two of these patients improved following treatment, thus matching the clinical improvement. Our results on peripheral nerve biopsies confirm the differentiation of patients with CIDP from those with SMPNP and SPNP. There was no specific immunologic serologic reactivity in any of the cases. PMID:10975722

  6. Classification, Identification, and Clinical Significance of Haemophilus and Aggregatibacter Species with Host Specificity for Humans

    PubMed Central

    2014-01-01

    SUMMARY The aim of this review is to provide a comprehensive update on the current classification and identification of Haemophilus and Aggregatibacter species with exclusive or predominant host specificity for humans. Haemophilus influenzae and some of the other Haemophilus species are commonly encountered in the clinical microbiology laboratory and demonstrate a wide range of pathogenicity, from life-threatening invasive disease to respiratory infections to a nonpathogenic, commensal lifestyle. New species of Haemophilus have been described (Haemophilus pittmaniae and Haemophilus sputorum), and the new genus Aggregatibacter was created to accommodate some former Haemophilus and Actinobacillus species (Aggregatibacter aphrophilus, Aggregatibacter segnis, and Aggregatibacter actinomycetemcomitans). Aggregatibacter species are now a dominant etiology of infective endocarditis caused by fastidious organisms (HACEK endocarditis), and A. aphrophilus has emerged as an important cause of brain abscesses. Correct identification of Haemophilus and Aggregatibacter species based on phenotypic characterization can be challenging. It has become clear that 15 to 20% of presumptive H. influenzae isolates from the respiratory tracts of healthy individuals do not belong to this species but represent nonhemolytic variants of Haemophilus haemolyticus. Due to the limited pathogenicity of H. haemolyticus, the proportion of misidentified strains may be lower in clinical samples, but even among invasive strains, a misidentification rate of 0.5 to 2% can be found. Several methods have been investigated for differentiation of H. influenzae from its less pathogenic relatives, but a simple method for reliable discrimination is not available. With the implementation of identification by matrix-assisted laser desorption ionization–time of flight mass spectrometry, the more rarely encountered species of Haemophilus and Aggregatibacter will increasingly be identified in clinical microbiology

  7. Clinical significance of brain phenylalanine concentration assessed by in vivo proton magnetic resonance spectroscopy in phenylketonuria.

    PubMed

    Leuzzi, V; Bianchi, M C; Tosetti, M; Carducci, C L; Carducci, C A; Antonozzi, I

    2000-09-01

    Recent studies using in vivo proton magnetic resonance spectroscopy (1H MRS) have suggested that plasma phenylalanine (Phe) may not be a reliable indicator of brain Phe level in subjects with phenylketonuria (PKU). Interindividual variation in cerebral Phe can contribute to the phenotypic variability of the disease. We report the results of the direct assessment of brain Phe by 1H MRS in 10 off-diet PKU patients (aged 15.5-30.5 years), 4 detected and treated early, 6 late. In a single patient, brain Phe was evaluated before and 15 days after diet discontinuation. FLAIR MRI and 1H MRS were performed in the same setting by a 1.5 T clinical MR scanner. MR images were scored according to the extent of the lobar white-matter hyperintensity. Brain 1H MRS Phe signal (resonating at 7.36 ppm) was evaluated as a ratio to the creatine+phosphocreatine signal. Brain Phe was correlated with clinical, biochemical and MRI findings. Results were as follows. (1) An abnormal concentration of brain Phe was detected in all 10 PKU subjects (ranging from 0.030 to 0.074), associated with a wide interindividual variability of concurrent plasma Phe (ranging from 724 to 2800 micromol/L). (2) In late-detected subjects, brain Phe concentration correlated with clinical phenotype better than did plasma Phe. The discrepancy between brain and plasma Phe was relevant from a clinical point of view in two cases: in one, a late-detected patient with normal mental development, a high level of plasma Phe was associated with a relatively low concentration of brain Phe; in the other, a late-detected subject with severe neurological impairment, a very high level of brain Phe was associated with plasma Phe compatible with the diagnosis of mild PKU. (3) White-matter alterations were detected in all patients. FLAIR MRI sequences disclosed an involvement of optic chiasma and tracts in 7 subjects. No correlation was found between white-matter alterations and concurrent brain Phe concentrations. (4) In the only

  8. Nuclear imaging of the breast: Translating achievements in instrumentation into clinical use

    PubMed Central

    Hruska, Carrie B.; O'Connor, Michael K.

    2013-01-01

    Approaches to imaging the breast with nuclear medicine and/or molecular imaging methods have been under investigation since the late 1980s when a technique called scintimammography was first introduced. This review charts the progress of nuclear imaging of the breast over the last 20 years, covering the development of newer techniques such as breast specific gamma imaging, molecular breast imaging, and positron emission mammography. Key issues critical to the adoption of these technologies in the clinical environment are discussed, including the current status of clinical studies, the efforts at reducing the radiation dose from procedures associated with these technologies, and the relevant radiopharmaceuticals that are available or under development. The necessary steps required to move these technologies from bench to bedside are also discussed. PMID:23635248

  9. Nuclear imaging of the breast: Translating achievements in instrumentation into clinical use

    SciTech Connect

    Hruska, Carrie B.; O'Connor, Michael K.

    2013-05-15

    Approaches to imaging the breast with nuclear medicine and/or molecular imaging methods have been under investigation since the late 1980s when a technique called scintimammography was first introduced. This review charts the progress of nuclear imaging of the breast over the last 20 years, covering the development of newer techniques such as breast specific gamma imaging, molecular breast imaging, and positron emission mammography. Key issues critical to the adoption of these technologies in the clinical environment are discussed, including the current status of clinical studies, the efforts at reducing the radiation dose from procedures associated with these technologies, and the relevant radiopharmaceuticals that are available or under development. The necessary steps required to move these technologies from bench to bedside are also discussed.

  10. The clinical significance of classical and new emerging determinants of adenomyosis

    PubMed Central

    Bodur, Serkan; Dundar, Ozgur; Pektas, Mine Kanat; Babayigit, Mustafa Alparslan; Ozden, Okan; Kucukodacı, Zafer

    2015-01-01

    Objective: The present study aims to analyze the diagnostic accuracy of clinical characteristics together with new emerging laboratory markers of adenomyosis. Methods: This study was a retrospective analysis of clinical and laboratory characteristics of 99 women who underwent hysterectomies with (study group) or without (control group) a diagnosis of adenomyosis, 56 and 43 patients in each group, respectively. Results: The women with adenomyosis were more likely to have younger age (OR = 1.14, 0.789-0.971 95% CI, P = 0.010), higher parity (OR = 1.81, 0.308-0.988 95% CI, P = 0.046), higher number of curettage (OR = 1.90, 1.189-3.041 95% CI, P = 0.007), dysmenorrhea (OR = 117.49, 2.715-5084.883 95% CI, P = 0.013) and elevated mean platelet volume (OR = 5.17, 2.054-13.028 95% CI, P = 0.000). After receiver-operating-characteristics curve analysis, using a cut-point of 8.5 fL, the preoperative mean platelet volume predicted adenomyosis with a sensitivity of 56.6% and specificity of 82.6%. Conclusions: Those findings suggest gynecologists to give priority on adenomyosis when premenopausal paraous patient with a history of curettages admitted with a complaint of dysmenorrhea and elevated levels of MPV. PMID:26221354

  11. Clinical significance of de Garengeot's hernia: A case of acute appendicitis and review of the literature

    PubMed Central

    Piperos, Theodoros; Kalles, Vasileios; Al Ahwal, Yousef; Konstantinou, Evangelos; Skarpas, George; Mariolis-Sapsakos, Theodoros

    2011-01-01

    Introduction The presence of the appendix in a femoral hernia sac is known as de Garengeot's hernia. We report a rare case of an elderly woman with femoral hernia appendicitis and discuss the surgical pitfalls and considerations through a literature review. Presentation of case An 83-year-old woman presented with fever and right lower quadrant abdominal pain. Clinical examination revealed a femoral hernia. Ultrasonography confirmed bowel was present in the hernia sac. In the operation room, an acutely inflamed appendix was recognized within the sac. The patient underwent appendectomy and hernia repair with sutures. Discussion Acute appendicitis within a femoral hernia is rare and multiple dilemmas exist regarding its treatment. An incision below the inguinal ligament is a reasonable choice in order to access the hernia sac. A mesh should be placed in non-infectious appendectomy while herniorrhaphy is preferred in cases of appendicitis. Conclusion The presence of the vermiform appendix in a femoral hernia sac is rare but the surgeon should be aware of this clinical entity. Prompt diagnosis and appropriate surgical treatment is the key to avoid complications. PMID:22288062

  12. Clinical significance of microRNAs in chronic and acute human leukemia.

    PubMed

    Yeh, Chien-Hung; Moles, Ramona; Nicot, Christophe

    2016-01-01

    Small non-coding microRNAs (miRNAs) are epigenetic regulators that target specific cellular mRNA to modulate gene expression patterns and cellular signaling pathways. miRNAs are involved in a wide range of biological processes and are frequently deregulated in human cancers. Numerous miRNAs promote tumorigenesis and cancer progression by enhancing tumor growth, angiogenesis, invasion and immune evasion, while others have tumor suppressive effects (Hayes, et al., Trends Mol Med 20(8): 460-9, 2014; Stahlhut and Slack, Genome Med 5 (12): 111, 2013). The expression profile of cancer miRNAs can be used to predict patient prognosis and clinical response to treatment (Bouchie, Nat Biotechnol 31(7): 577, 2013). The majority of miRNAs are intracellular localized, however circulating miRNAs have been detected in various body fluids and represent new biomarkers of solid and hematologic cancers (Fabris and Calin, Mol Oncol 10(3):503-8, 2016; Allegra, et al., Int J Oncol 41(6): 1897-912, 2012). This review describes the clinical relevance of miRNAs, lncRNAs and snoRNAs in the diagnosis, prognosis and treatment response in patients with chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML) and acute adult T-cell leukemia (ATL). PMID:27179712

  13. Clinical significance of the isolation of Candida species from hospitalized patients

    PubMed Central

    Magalhães, Yankee C.; Bomfim, Maria Rosa Q.; Melônio, Luciane C.; Ribeiro, Patrícia C.S.; Cosme, Lécia M.; Rhoden, Cristianne R.; Marques, Sirlei G.

    2015-01-01

    In this study, we isolated and phenotypically identified 108 yeast strains from various clinical specimens collected from 100 hospitalized patients at three tertiary hospitals in São Luís-Maranhão, Brazil, from July to December 2010. The isolates were analyzed for their susceptibility to four of the most widely used antifungal agents in the surveyed hospitals, amphotericin B, fluconazole, 5-flucytosine and voriconazole. The species identified were Candida albicans (41.4%), Candida tropicalis (30.1%), C. glabrata (7.4%), Candida parapsilosis (5.5%), Candida krusei (4.6%), Cryptococcus neoformans (4.6%), Trichosporon spp . (3.7%), Candida norvegensis (0.9%), Rhodotorula glutinis (0.9%) and Pichia farinosa (0.9%). A higher isolation rate was observed in the following clinical specimens: urine (54 isolates; 50%), respiratory tract samples (21 isolates; 19.4%) and blood (20 isolates; 18.6%). Candida albicans isolates were 100% sensitive to all antifungal agents tested, whereas Candida krusei and Crytococcus neoformans displayed intermediate resistance to 5-flucytosine, with Minimal Inhibitory Concentration (MIC) values of 8 mg/mL and 16 mg/mL, respectively. Both strains were also S-DD to fluconazole with an MIC of 16 mg/mL. C. tropicalis was resistant to 5-flucytosine with an MIC of 32 μg/mL. This study demonstrates the importance of identifying the yeast species involved in community and nosocomial infections. PMID:26221096

  14. Clinical significance of the isolation of Candida species from hospitalized patients.

    PubMed

    Magalhães, Yankee C; Bomfim, Maria Rosa Q; Melônio, Luciane C; Ribeiro, Patrícia C S; Cosme, Lécia M; Rhoden, Cristianne R; Marques, Sirlei G

    2015-03-01

    In this study, we isolated and phenotypically identified 108 yeast strains from various clinical specimens collected from 100 hospitalized patients at three tertiary hospitals in São Luís-Maranhão, Brazil, from July to December 2010. The isolates were analyzed for their susceptibility to four of the most widely used antifungal agents in the surveyed hospitals, amphotericin B, fluconazole, 5-flucytosine and voriconazole. The species identified were Candida albicans (41.4%), Candida tropicalis (30.1%), C. glabrata (7.4%), Candida parapsilosis (5.5%), Candida krusei (4.6%), Cryptococcus neoformans (4.6%), Trichosporon spp . (3.7%), Candida norvegensis (0.9%), Rhodotorula glutinis (0.9%) and Pichia farinosa (0.9%). A higher isolation rate was observed in the following clinical specimens: urine (54 isolates; 50%), respiratory tract samples (21 isolates; 19.4%) and blood (20 isolates; 18.6%). Candida albicans isolates were 100% sensitive to all antifungal agents tested, whereas Candida krusei and Crytococcus neoformans displayed intermediate resistance to 5-flucytosine, with Minimal Inhibitory Concentration (MIC) values of 8 mg/mL and 16 mg/mL, respectively. Both strains were also S-DD to fluconazole with an MIC of 16 mg/mL. C. tropicalis was resistant to 5-flucytosine with an MIC of 32 μg/mL. This study demonstrates the importance of identifying the yeast species involved in community and nosocomial infections. PMID:26221096

  15. Immunological and clinical significance of HLA class I antigen processing machinery component defects in malignant cells.

    PubMed

    Concha-Benavente, Fernando; Srivastava, Raghvendra; Ferrone, Soldano; Ferris, Robert L

    2016-07-01

    Experimental as well as clinical studies demonstrate that the immune system plays a major role in controlling generation and progression of tumors. The cancer immunoediting theory supports the notion that tumor cell immunogenicity is dynamically shaped by the immune system, as it eliminates immunogenic tumor cells in the early stage of the disease and then edits their antigenicity. The end result is the generation of a tumor cell population able to escape from immune recognition and elimination by tumor infiltrating lymphocytes. Two major mechanisms, which affect the target cells and the effector phase of the immune response, play a crucial role in the editing process. One is represented by the downregulation of tumor antigen (TA) processing and presentation because of abnormalities in the HLA class I antigen processing machinery (APM). The other one is represented by the anergy of effector immune infiltrates in the tumor microenvironment caused by aberrant inhibitory signals triggered by immune checkpoint receptor (ICR) ligands, such as programmed death ligand-1 (PD-L1). In this review, we will focus on tumor immune escape mechanisms caused by defects in HLA class I APM component expression and/or function in different types of cancer, with emphasis on head and neck cancer (HNC). We will also discuss the immunological implications and clinical relevance of these HLA class I APM abnormalities. Finally, we will describe strategies to counteract defective TA presentation with the expectation that they will enhance tumor recognition and elimination by tumor infiltrating effector T cells. PMID:27264839

  16. Clinically Significant Fatigue: Prevalence and Associated Factors in an International Sample of Adults with Multiple Sclerosis Recruited via the Internet

    PubMed Central

    Weiland, Tracey J.; Jelinek, George A.; Marck, Claudia H.; Hadgkiss, Emily J.; van der Meer, Dania M.; Pereira, Naresh G.; Taylor, Keryn L.

    2015-01-01

    Background Fatigue contributes a significant burden of disease for people with multiple sclerosis (PwMS). Modifiable lifestyle factors have been recognized as having a role in a range of morbidity outcomes in PwMS. There is significant potential to prevent and treat fatigue in PwMS by addressing modifiable risk factors. Objectives To explore the associations between clinically significant fatigue and demographic factors, clinical factors (health-related quality of life, disability and relapse rate) and modifiable lifestyle, disease-modifying drugs (DMD) and supplement use in a large international sample of PwMS. Methods PwMS were recruited to the study via Web 2.0 platforms and completed a comprehensive survey measuring demographic, lifestyle and clinical characteristics, including health-related quality of life, disability, and relapse rate. Results Of 2469 participants with confirmed MS, 2138 (86.6%) completed a validated measure of clinically significant fatigue, the Fatigue Severity Scale. Participants were predominantly female from English speaking countries, with relatively high levels of education, and due to recruitment methods may have been highly pro-active about engaging in lifestyle management and self-help. Approximately two thirds of our sample (1402/2138; 65.6% (95% CI 63.7–67.7)) screened positive for clinically significant fatigue. Bivariate associations were present between clinically significant fatigue and several demographic, clinical, lifestyle, and medication variables. After controlling for level of disability and a range of stable socio-demographic variables, we found increased odds of fatigue associated with obesity, DMD use, poor diet, and reduced odds of fatigue with exercise, fish consumption, moderate alcohol use, and supplementation with vitamin D and flaxseed oil. Conclusion This study supports strong and significant associations between clinically significant fatigue and modifiable lifestyle factors. Longitudinal follow-up of this

  17. Presence of Arteriovenous Communication between Left Testicular Vessels and Its Clinical Significance.

    PubMed

    Kumar, Naveen; Swamy, Ravindra; Patil, Jyothsna; Guru, Anitha; Aithal, Ashwini; Shetty, Prakashchandra

    2014-01-01

    Maintenance of testicular temperature below body temperature is essential for the process of spermatogenesis. This process of thermoregulation is mainly achieved by testicular veins through pampiniform venous plexus of the testis by absorbing the heat conveyed by the testicular arteries. However, this mechanism of thermoregulation may be hampered if an abnormal communication exists between the testicular vessels. We report herewith a rare case of arteriovenous communication between testicular artery and testicular vein on left side. The calibre of the communicating vessel was almost similar to left testicular artery. Such abnormal communication may obstruct the flow of blood in the vein by causing impairment in the perfusion pressure with the eventual high risk of varicocele. PMID:24716087

  18. Cutaneous vasculitis in primary Sjögren syndrome: classification and clinical significance of 52 patients.

    PubMed

    Ramos-Casals, Manuel; Anaya, Juan-Manuel; García-Carrasco, Mario; Rosas, José; Bové, Albert; Claver, Gisela; Diaz, Luis-Aurelio; Herrero, Carmen; Font, Josep

    2004-03-01

    To analyze the different clinical and histologic types of cutaneous vasculitis in patients with primary Sjögren syndrome (SS), we investigated the clinical and immunologic characteristics of 558 consecutive patients with primary SS from our units and selected those with clinical evidence of cutaneous lesions, excluding drug reactions and xeroderma. All patients fulfilled 4 or more of the diagnostic criteria for SS proposed by the European Community Study Group in 1993. A total of 89 (16%) patients presented with cutaneous involvement (88 female patients and 1 male; mean age, 51.8 yr). The main cutaneous involvement was cutaneous vasculitis, present in 52 (58%) patients. There were 51 (98%) female patients and 1 (2%) male, with a mean age at diagnosis of cutaneous vasculitis of 51 years (range, 20-80 yr). Fourteen presented with cryoglobulinemic vasculitis, 11 with urticarial vasculitis, and the remaining 26, with cutaneous purpura not associated with cryoglobulins. A skin biopsy specimen was obtained in 38 patients (73%). Involvement of small-sized vessels was observed in 36 (95%) patients (leukocytoclastic vasculitis), while the remaining 2 (5%) presented with medium-sized vessel vasculitis (necrotizing vasculitis). Patients with cutaneous vasculitis had a higher prevalence of articular involvement (50% vs 29%, p = 0.044), peripheral neuropathy (31% vs 4%, p < 0.001), Raynaud phenomenon (40% vs 15%, p = 0.008), renal involvement (10% vs 0%, p = 0.028), antinuclear antibodies (88% vs 60%, p = 0.002), rheumatoid factor (78% vs 48%, p = 0.004), anti-Ro/SS-A antibodies (70% vs 43%, p = 0.011), and hospitalization (25% vs 4%, p = 0.005) compared with SS patients without vasculitis. Six (12%) patients died, all of whom had multisystemic cryoglobulinemia.In conclusion, cutaneous involvement was detected in 16% of patients with primary SS, with cutaneous vasculitis being the most frequent process. The main characteristics of SS-associated cutaneous vasculitis were the

  19. Clinical Significance of the Glasgow Prognostic Score for Survival after Colorectal Cancer Surgery.

    PubMed

    Eren, Tunc; Burcu, Busra; Tombalak, Ercument; Ozdemir, Tugrul; Leblebici, Metin; Ozemir, Ibrahim Ali; Ziyade, Sedat; Alimoglu, Orhan

    2016-06-01

    Glasgow prognostic score (GPS) has been found to be a useful tool in various cancer types. Our aim was to evaluate the significance of GPS in patients operated on for colorectal cancer (CRC). Patients with CRC who underwent radical resections between April 2010 and January 2015 were retrospectively evaluated. GPS was estimated based on the preoperative measurement of C-reactive protein and serum albumin levels. Data including demographics, laboratory and pathological parameters, surgical outcomes, and late-term follow-up results were analyzed. The study group of 115 patients consisted of 51 (44 %) women and 64 (56 %) men with a median age of 66 (range 32-91) years. The mean follow-up period was 20 (range 7-41) months. Tumor size and wound infection rates were significantly increased in patients with higher GPS (p = 0.019 and p = 0.003, respectively). According to multivariate analyses, CEA and GPS were found to be independent risk factors significantly effecting mortality (p = 0.001 and p = 0.009, respectively). At the end of the late-term follow-up period, it was detected that cancer-specific survival significantly decreased as the GPS increased (p = 0.016). The GPS is a significant prognostic factor in CRC and should be included in the routine preoperative assessment of all surgically treated CRC patients. PMID:26925798

  20. Genetic and Chromosomal Aberrations and Their Clinical Significance in Renal Neoplasms

    PubMed Central

    Yap, Ning Yi; Rajandram, Retnagowri; Ng, Keng Lim; Pailoor, Jayalakshmi; Fadzli, Ahmad; Gobe, Glenda Carolyn

    2015-01-01

    The most common form of malignant renal neoplasms is renal cell carcinoma (RCC), which is classified into several different subtypes based on the histomorphological features. However, overlaps in these characteristics may present difficulties in the accurate diagnosis of these subtypes, which have different clinical outcomes. Genomic and molecular studies have revealed unique genetic aberrations in each subtype. Knowledge of these genetic changes in hereditary and sporadic renal neoplasms has given an insight into the various proteins and signalling pathways involved in tumour formation and progression. In this review, the genetic aberrations characteristic to each renal neoplasm subtype are evaluated along with the associated protein products and affected pathways. The potential applications of these genetic aberrations and proteins as diagnostic tools, prognostic markers, or therapeutic targets are also assessed. PMID:26448938

  1. [Expression and Clinical Significance of Lymphoid Enhancer-Binding Factor 1 in Acute Leukemias].

    PubMed

    Huo, Wan-Ying; Gao, Ju

    2015-06-01

    Lymphoid enhancer-binding factor 1 (LEF1), a key downstream effector of Wnt/β-catenin signal transduction pathway, plays a crucial role in the maintenance, proliferation and differentiation of normal hematopoietic stem/progenitor cells through regulating the transcription of its target genes. Aberrant LEF1 expression has been documented in a variety of leukemias, and implicated in the prediction of prognosis. Nevertheless, discrepancies exist regarding the expression level and clinical implication of LEF1 in different types of leukemias, suggesting LEF1 might exert distinct roles in different types of leukemia. In the present article, recent research advances of the relationship of LEF1 and regulation of hematopoiesis and leukemogenesis are reviewed. PMID:26117056

  2. The Clinical Significance of Phosphorylated Heat Shock Protein 27 (HSPB1) in Pancreatic Cancer

    PubMed Central

    Okuno, Mitsuru; Adachi, Seiji; Kozawa, Osamu; Shimizu, Masahito; Yasuda, Ichiro

    2016-01-01

    Pancreatic cancer is one of most aggressive forms of cancer. After clinical detection it exhibits fast metastatic growth. Heat shock protein 27 (HSP27; HSPB1) has been characterized as a molecular chaperone which modifies the structures and functions of other proteins in cells when they are exposed to various stresses, such as chemotherapy. While the administration of gemcitabine, an anti-tumor drug, has been the standard treatment for patients with advanced pancreatic cancer, accumulating evidence shows that HSP27 plays a key role in the chemosensitivity to gemcitabine. In addition, phosphorylated HSP27 induced by gemcitabine has been associated with the inhibition of pancreatic cancer cell growth. In this review, we summarize the role of phosphorylated HSP27, as well as HSP27, in the regulation of chemosensitivity in pancreatic cancer. PMID:26805817

  3. [Clinical significance of natriuretic peptides in the differential diagnosis of dyspnea].

    PubMed

    Špác, Jiří

    2016-01-01

    Acute dyspnea is one of the most common emergency department symptoms. But early diagnosis and treatment could be e challenging because of multiple potential causes. The gold standard biomarkers in cardiac dyspnea are B-type natriuretic peptide (BNP) and N-terminal pro-B-type (natriuretic peptide NT-pro BNP), which play an important role in the diagnosis, prognosis, and management of acute decompensated heart failure. The purpose of this review is to analyze diagnostic potential of BNP and NT-pro BNP biomarkers use in patients with acute dyspnea. BNP and NT-proBNP are markers of cardiac stress but are not cardiac-specific. They have comparable clinical utility, and both help in excluding acute cardiac dyspnea but they cannot reliably discriminate systolic from diastolic HF.Key word: acute dyspnea - natriuretic peptide - heart failure. PMID:27627091

  4. The Clinical Significance of Phosphorylated Heat Shock Protein 27 (HSPB1) in Pancreatic Cancer.

    PubMed

    Okuno, Mitsuru; Adachi, Seiji; Kozawa, Osamu; Shimizu, Masahito; Yasuda, Ichiro

    2016-01-01

    Pancreatic cancer is one of most aggressive forms of cancer. After clinical detection it exhibits fast metastatic growth. Heat shock protein 27 (HSP27; HSPB1) has been characterized as a molecular chaperone which modifies the structures and functions of other proteins in cells when they are exposed to various stresses, such as chemotherapy. While the administration of gemcitabine, an anti-tumor drug, has been the standard treatment for patients with advanced pancreatic cancer, accumulating evidence shows that HSP27 plays a key role in the chemosensitivity to gemcitabine. In addition, phosphorylated HSP27 induced by gemcitabine has been associated with the inhibition of pancreatic cancer cell growth. In this review, we summarize the role of phosphorylated HSP27, as well as HSP27, in the regulation of chemosensitivity in pancreatic cancer. PMID:26805817

  5. [Corticobasal degeneration. The significance of clinical criteria for establishing the diagnosis].

    PubMed

    Feifel, E; Brenner, M; Teiwes, R; Lücking, C H; Deuschl, G

    1994-10-01

    Neuropathological studies show that about 20% of all patients suffering from an acinetic-rigid syndrome can not be given the diagnosis of idiopathic Parkinson's disease. Among these non-idiopathic Parkinson-syndromes the corticobasal degeneration (CBD) can be regarded as a separate disease entity. The pathological findings of moderate predominantly frontal and parietal cerebral atrophy, cortical Pick-cells and specific corticobasal inclusion bodies are considered valuable features which support the diagnosis. The clinical Characteristics of CBD are demonstrated in 3 patients including an acinetic-rigid syndrome, limb apraxia and "alien limb"-syndrome, as well as reflex myoclonus. Eye movement disorders, dementia and other rare symptoms may also be present. Electrophysiological reflex-testing helps to corroborate diagnosis. These findings and a summary which includes the previously published cases of CBD show that CBD in most cases can be diagnosed intra vitam. PMID:7808563

  6. The roles and clinical significance of microRNAs in cervical cancer.

    PubMed

    Wang, Fenfen; Li, Baohua; Xie, Xing

    2016-02-01

    Cervical carcinogenesis induced by persistent human papillomavirus (HPV) infection represents a stepwise progression from precursors to invasive cervical cancer. Accumulated evidence has shown aberrant expression of microRNAs (miRNAs) in cervical cancer tissues and cells. Further studies reveal that miRNAs play key roles in the initiation and progression of cervical cancer, via specific signaling pathways, including E6-p53, E7-pRb, phosphoinositide-3 kinase (PI3K)-Akt, Notch, Wnt/β-catenin, and Hedgehog pathways. Some studies demonstrate that miRNAs might serve as biomarkers or therapeutic targets, presenting a potential prospect in clinical practice. All results provide new insights into the function of miRNAs and the pathogenesis of cervical cancer induced by viral oncoproteins. New approaches for miRNA-based prevention and management for cervical cancer will be developed in the future. PMID:26356641

  7. Clinical spectrum associated with MOG autoimmunity in adults: significance of sharing rodent MOG epitopes.

    PubMed

    Sepúlveda, Maria; Armangue, Thaís; Martinez-Hernandez, Eugenia; Arrambide, Georgina; Sola-Valls, Nuria; Sabater, Lidia; Téllez, Nieves; Midaglia, Luciana; Ariño, Helena; Peschl, Patrick; Reindl, Markus; Rovira, Alex; Montalban, Xavier; Blanco, Yolanda; Dalmau, Josep; Graus, Francesc; Saiz, Albert

    2016-07-01

    The aim of this study was to report the clinical spectrum associated with antibodies to myelin oligodendrocyte glycoprotein (MOG) in adult patients, and to assess whether phenotypic variants are dependent on recognition of rodent MOG epitopes. We retrospectively analyzed the features, course and outcome of 56 patients whose samples were investigated by brain tissue immunohistochemistry and cell-based assays using human and rodent MOG. The median age at symptom onset was 37 years (range 18-70); 35 patients (63 %) were female. After a median follow-up of 43 months (range 4-554), only 14 patients (25 %) developed a neuromyelitis optica spectrum disorder (NMOSD), 27 patients (47 %) retained the initial diagnosis of isolated optic neuritis, 7 (12 %) of longitudinally extensive transverse myelitis, and 2 (4 %) of acute disseminated encephalomyelitis; 6 patients (11 %) developed atypical demyelinating syndromes (4 had relapsing episodes of short myelitis lesions which in one occurred with optic neuritis; 1 had relapsing brainstem symptoms, and 1 relapsing demyelinating encephalomyelitis). The course was frequently associated with relapses (71 %) and good outcome. Twenty-seven patients (49 %) had antibodies that recognized rodent MOG epitopes, and 9 of them (16 %) showed a myelin staining pattern in rodent tissue. Only the myelin staining pattern was linked to NMOSD (p = 0.005). In conclusion, MOG autoimmunity in adult patients associates with a clinical spectrum wider than the one expected for patients with suspected NMOSD and overall good outcome. Antibodies to rodent MOG epitopes do not associate with any phenotypic variant. PMID:27147513

  8. Clinical and legal significance of fragmentation of bullets in relation to size of wounds: retrospective analysis

    PubMed Central

    Coupland, Robin

    1999-01-01

    Objective To examine the relation between fragmentation of bullets and size of wounds clinically and in the context of the Hague Declaration of 1899. Design Retrospective analysis of prospectively collected data on hospital admissions. Setting Hospitals of the International Committee of the Red Cross. Subjects 5215 people wounded by bullets in armed conflicts (5933 wounds). Main outcome measures Grade of wound computed from the Red Cross wound classification and presence of bullet fragments on radiography. Results Of the 347 wounds with fragmentation of bullets, 251 (72%) were large wounds (grade 2 or 3)—that is, those with a clinically detectable cavity. Of the 5586 wounds without fragmentation of bullets, 2915 (52.1%) were large wounds. Only 7.9% (251/3166) of large wounds were associated with fragmentation of bullets. Conclusions Fragmentation of bullets is associated with large wounds, but most large wounds do not contain bullet fragments. In addition, bullet fragments may occur in wounds that are not defined as large. Fragmentation of bullets is neither a necessary nor sufficient cause of large wounds, and surgeons should not diagnose extensive tissue damage because of the presence of fragments on radiography. Such findings also do not necessarily represent the use of bullets which contravene the law of war. Future legislation should take into account not only the construction of bullets but also their potential to transfer energy to the human body. Key messagesThe use of certain bullets has been prohibited in warWounds from bullets are caused by transfer of kinetic energy from the bullet to the tissuesThe relation between size of wound and fragmentation of bullets can be examined using the Red Cross wound classification system Fragments of bullets seen on radiographs of wounds sustained in wars do not necessarily represent large wounds or the use of illegal bulletsExisting legislation on the construction of bullets should be supplemented by legislation on

  9. Clinical Significance of Tumor-Associated Inflammatory Cells in Metastatic Neuroblastoma

    PubMed Central

    Asgharzadeh, Shahab; Salo, Jill A.; Ji, Lingyun; Oberthuer, André; Fischer, Matthias; Berthold, Frank; Hadjidaniel, Michael; Liu, Cathy Wei-Yao; Metelitsa, Leonid S.; Pique-Regi, Roger; Wakamatsu, Peter; Villablanca, Judith G.; Kreissman, Susan G.; Matthay, Katherine K.; Shimada, Hiroyuki; London, Wendy B.; Sposto, Richard; Seeger, Robert C.

    2012-01-01

    Purpose Children diagnosed at age ≥ 18 months with metastatic MYCN-nonamplified neuroblastoma (NBL-NA) are at high risk for disease relapse, whereas those diagnosed at age < 18 months are nearly always cured. In this study, we investigated the hypothesis that expression of genes related to tumor-associated inflammatory cells correlates with the observed differences in survival by age at diagnosis and contributes to a prognostic signature. Methods Tumor-associated macrophages (TAMs) in localized and metastatic neuroblastomas (n = 71) were assessed by immunohistochemistry. Expression of 44 genes representing tumor and inflammatory cells was quantified in 133 metastatic NBL-NAs to assess age-dependent expression and to develop a logistic regression model to provide low- and high-risk scores for predicting progression-free survival (PFS). Tumors from high-risk patients enrolled onto two additional studies (n = 91) served as independent validation cohorts. Results Metastatic neuroblastomas had higher infiltration of TAMs than locoregional tumors, and metastatic tumors diagnosed in patients at age ≥ 18 months had higher expression of inflammation-related genes than those in patients diagnosed at age < 18 months. Expression of genes representing TAMs (CD33/CD16/IL6R/IL10/FCGR3) contributed to 25% of the accuracy of a novel 14-gene tumor classification score. PFS at 5 years for children diagnosed at age ≥ 18 months with NBL-NA with a low- versus high-risk score was 47% versus 12%, 57% versus 8%, and 50% versus 20% in three independent clinical trials, respectively. Conclusion These data suggest that interactions between tumor and inflammatory cells may contribute to the clinical metastatic neuroblastoma phenotype, improve prognostication, and reveal novel therapeutic targets. PMID:22927533

  10. The significance of Y chromosome microdeletion analysis in subfertile men with clinical variocele

    PubMed Central

    Ersoy, Hamit; Ozok, Ugur; Eraslan, Asir; Yararbas, Kanay; Goktug, Goksel; Tukun, Ajlan

    2010-01-01

    Introduction The aim of study is determining the cost-effectiveness of detection analysis in the presence of exceptional patients who have mild semen disorders, and beware of unnecessary varicocele repairs; and to ascertain whether patients with clinical varicocele should undergo Y chromosome (Yq) microdeletion analysis as a routine procedure. Material and methods Varicocele with reflux was diagnosed in 51 male patients with subfertility symptoms upon physical examination (PE), confirmed by scrotal colour-Doppler ultrasound (CDU). After cytogenetic examination, Yq microdeletion analysis was performed on the peripheral blood samples using Promega Y Chromosome Deletion Detection System Version 2. Varicocele repair was performed under general anaesthesia with optical magnification (3-fold) through a subinguinal approach. Results The mean age of the patients was 27.9. Values of semen concentration ranged from 0 to 72 million/ml, motility from 0 to 65% (A + B) and Kruger from 0% to 18%. The PE revealed normal size and consistency in the bilateral testicles. All patients were cytogenetically normal. However, Yq microdeletion was detected in 2 patients, 1 with mild oligoteratozoospermia and partial AZFb deletion (sY121) and the second patient with severe oligozoospermia and partial AZFc deletion (sY254 and sY255), and they were not subjected to varicocelectomy. Conclusions The routine performance of pre-operative Yq microdeletion analysis in patients with clinical varicocele does not seem to be cost-effective but the omission of patients with mild oligozoospermia would have subjected them to an unnecessary varicocelectomy and/or further ICSI applications and also would have caused the failure of referral for genetic counselling. PMID:22371775

  11. Downregulation of ADAMTS8 by DNA Hypermethylation in Gastric Cancer and Its Clinical Significance

    PubMed Central

    Zhang, Jiakui; Li, Xin; Zhang, Chundong; Zhang, Hongbin; Jin, Junzhe; Dai, Dongqiu

    2016-01-01

    A disintegrin and metallopeptidase with thrombospondin motif type 8 (ADAMTS8), a member of the ADAMTS family, was discovered as a novel angiogenesis inhibitor. We analyzed the expression and methylation of ADAMTS8 in primary gastric tumors and gastric cancer cell lines. We also examined the relationship between ADAMTS8 expression and methylation and clinicopathologic features. The results showed that the significant downregulation of ADAMTS8 mRNA expression was observed in gastric cancer cell lines and tissues, and its expression was related to invasive depth and lymph node metastasis. CpG was hypermethylated in gastric cancer cell lines MKN45, MGC803, and BGC823, as well as primary gastric cancer specimens. ADAMTS8 mRNA expression was significantly lower in methylated primary gastric tumors. A significant association was found between ADAMTS8 methylation status and lymph node metastasis in primary gastric cancer. Moreover, ADAMTS8 expression was upregulated in the gastric cancer cell lines MGC803, BGC823, and MKN45 after treatment with 5-aza-2′-deoxycytidine. Thus, our results demonstrate that expression of ADAMTS8 mRNA is significantly decreased and DNA methylation is frequent in gastric cancer. ADAMTS8 hypermethylation is associated with decreased expression in gastric cancer and may play an important role in the invasion and metastasis of gastric cancer. PMID:27493958

  12. Hematological and plasma biochemical reference ranges of Alaskan seabirds: Their ecological significance and clinical importance

    USGS Publications Warehouse

    Newman, S.H.; Piatt, J.F.; White, J.

    1997-01-01

    Blood was analyzed from 151 pelagic marine birds to establish reference ranges for hematological and plasma biochemical parameters from healthy, wild populations of Pacific seabirds. Of the 13 species examined, 9 were from the Family Alcidae (N = 122 individuals) and the remainder (N = 29) from the Families Phalacrocoracidae, Laridae, and Procellariidae. Three of 8 hematological parameters (total white blood cell count, lymphocyte count and eosinophil count) differed significantly among species, as did 9 of 13 plasma biochemical parameters (alkaline phosphatase, aspartate aminotransferase, creatine kinase, cholesterol, glucose, lactate dehydrogenase, total bilirubin, total protein and field total protein). There were no differences among species for packed cell volume, buffy coat, cell counts of heterophils, monoqtes and basophils, or for concentrations of alanine aminotransferase, triglycerides, uric acid and calcium. Plasma calcium concentration, triglyceride levels and field total protein varied significantly between sexes, with females having higher mean concentrations of all 3 parameters. However, no significant relationships between measures of breeding condition (brood patch size, subcutaneous and mesenteric fat deposits, or ovarian follicle size and ovary weight) and calcium or alkaline phosphatase concentrations in female birds could be identified. Alanine aminotransferase and uric acid were the only analytes which did not differ significantly between species or sexes.

  13. A Visitor's Guide to Effect Sizes--Statistical Significance versus Practical (Clinical) Importance of Research Findings

    ERIC Educational Resources Information Center

    Hojat, Mohammadreza; Xu, Gang

    2004-01-01

    Effect Sizes (ES) are an increasingly important index used to quantify the degree of practical significance of study results. This paper gives an introduction to the computation and interpretation of effect sizes from the perspective of the consumer of the research literature. The key points made are: (1) "ES" is a useful indicator of the…

  14. Expression and clinical significance of Apollon in esophageal squamous cell carcinoma

    PubMed Central

    Li, Rong; Chen, Bo-lin; Zhou, Yan-wu; Guo, Ren-wei; Shuai, Meng-ting; Zeng, Jun-xian; Leng, Ai-min

    2016-01-01

    Apollon, an unusually large member of the inhibitors of apoptosis protein family, may be important for oncogenesis development. The aim of the present study was to assess the association between esophageal squamous cell carcinoma (ESCC) and Apollon expression levels, and to highlight the association between Apollon and the occurrence, development and prognosis of ESCC. Apollon expression was detected by immunohistochemical staining and reverse transcription-quantitative polymerase chain reaction in ESCC tissues, adjacent non-cancerous tissues and paired normal tissues respectively, in order to analyze the association between Apollon expression and the clinicopathological features of ESCC. Survival analysis was used to assess the prognostic significance of Apollon expression. It was determined that the mRNA and protein expression levels of Apollon were significantly higher in the carcinoma tissues compared with the adjacent non-cancerous tissues and normal control tissues (P<0.001). There was a significant difference in lymph node involvement and the tumor, nodes, and metastases stage in patients categorized according to different Apollon expression levels. The prognostic significance of Apollon was also determined using the log-rank method. The overexpression of Apollon was associated with shorter overall survival and disease-free survival rates. The present study indicates that Apollon expression is associated with the biological characteristics of ESCC, and may be a valuable prognostic factor and a novel chemotherapeutic target for ESCC treatment. PMID:27432467

  15. Expression of livin, survivin and caspase-3 in prostatic cancer and their clinical significance

    PubMed Central

    Gu, Junfei; Ren, Lixin; Wang, Xiaolu; Qu, Changbao; Zhang, Yong

    2015-01-01

    To explore the expressions level of Livin, Survivin and Caspase-3 in prostatic cancer and the relationship among the 3 proteins and the clinicopathological features as well as the correlation among them. Totally, 43 paraffin-embedded prostate cancer tissues obtained from patients who were performed with rectal prostate biopsy or excision and 17 paraffin-embedded prostatic hyperplasia tissues were collected. All the specimens were confirmed by pathology. Immunohistochemistry SP method was used to detect the expressions of Livin, Survivin and Caspase-3 in prostatic cancer compared to hyperplasia tissues. The positive expression rates of both Livin and Survivin in prostatic cancer tissue were higher than those in prostatic hyperplasia tissue (93.02% vs. 64.70%, P < 0.05; 83.72% vs. 35.29%, P < 0.01). However, the positive expression rate of Caspase-3 in prostatic cancer tissue was obviously lower than that in prostatic hyperplasia tissue (25.58% vs. 58.82%, P < 0.01). Both Livin and Survivin expressions in prostatic cancer tissue were related to pathological grading (Gleason scores) (X2 = 14.000, P = 0.001), but not related to preoperative PSA, clinical stages and distant metastasis (P > 0.05). Capsase-3 expression in prostatic cancer tissue was related to pathological grading (Gleason scores) (X 2 = 14.000, P = 0.001) and clinical stages (X 2 = 4.896, P = 0.027), but not related to preoperative PSA and distant metastasis (P > 0.05). In prostatic cancer tissue, Livin expression had no correlation with Survivin expression (r = 0.127, P = 0.419 > 0.05), but negatively correlated with Caspase-3 expression (r = -0.497, P = 0.001). Survivin expression was negatively correlated with Caspase-3 expression (r = -0.354, P = 0.020). Livin, Survivin and Caspase-3 are closely related to the occurrence and development of prostatic cancer and which are expected to become new targets for diagnosis and treatment in future. PMID:26823716

  16. Factors influencing the outcome of intrauterine insemination (IUI): age, clinical variables and significant thresholds.

    PubMed

    Speyer, B E; Abramov, B; Saab, W; Doshi, A; Sarna, U; Harper, J C; Serhal, P

    2013-10-01

    The aim was to investigate the influence of various biological factors upon the outcome of intrauterine insemination (IUI). The total IUI history (856 cycles) of 352 couples was studied. Live-birth showed a strong negative correlation with female age but no correlation with male age. Antimüllerian hormone (AMH) and antral follicle count (AFC) correlated negatively with female age, and follicle stimulating hormone (FSH) correlated positively. Significant thresholds were found for all three variables, and also for total motile count (TMC) in the prepared sperm. Calculating pregnancy losses per positive pregnancy showed a strong correlation with increasing female age. This was highly significant for biochemical losses but not for fetal heart miscarriages. Male age had no effect on rate of pregnancy loss. In conclusion, female age, FSH, AMH and TMC are good predictive factors for live-birth and therefore relate to essential in vivo steps in the reproductive process. PMID:24127958

  17. Characterization of clinically significant isolates of Staphylococcus epidermidis from patients with endocarditis.

    PubMed Central

    Etienne, J; Brun, Y; el Solh, N; Delorme, V; Mouren, C; Bes, M; Fleurette, J

    1988-01-01

    Biotyping, slime production, bacteriophage typing, serotyping, antibiograms, and plasmid profiles were used to characterize 19 Staphylococcus epidermidis strains isolated from 12 patients with prosthetic valve endocarditis and from 7 patients with native valve endocarditis. With the API Staph battery, 12 different biocodes with, at the most, three differences were obtained. Slime production was found for 10 strains (53%). Agglutinogens investigated by agglutination with two specific sera were found for 12 strains (63.1%). Three strains were phage typable (15.2%). Against a panel of nine antimicrobial agents, 15 different profiles were found. Multiply antibiotic-resistant strains were isolated from patients with prosthetic valve endocarditis when disease onset occurred less than 18 months after heart surgery and from patients with native valve endocarditis who received antibiotics immediately prior to their illness. All of the strains were available for plasmid analysis, and all the DNA profiles were distinct. On gels run in Tris-borate buffer, 73.7% of the strains had large plasmids of more than 30 megadaltons. A small plasmid of 2.8 megadaltons was found in multiply resistant strains and in strains resistant only to tetracyclines. None of the isolates appeared to be the same strain, and the bacteriological differences between the strains were confirmed mainly by the antibiotic susceptibility profile and the plasmid pattern analysis. These bacteriological results were in agreement with the clinical data. Images PMID:3366858

  18. Clinical and immunological significance of HLA-E in stem cell transplantation and cancer.

    PubMed

    Wieten, L; Mahaweni, N M; Voorter, C E M; Bos, G M J; Tilanus, M G J

    2014-12-01

    Human leukocyte antigen-E (HLA-E) is a nonclassical HLA class I molecule that canonically binds peptides derived from the leader sequence of classical HLA class I. HLA-E can also bind peptides from stress protein [e.g. heat shock protein 60 (Hsp60)] and pathogens, illustrating the importance of HLA-E for anti-viral and anti-tumor immunity. Like classical HLA class I molecules, HLA-E is ubiquitously expressed, however, it is characterized by only a very limited sequence variability and two dominant protein forms have been described (HLA-E*01:01 and HLA-E*01:03). HLA-E influences both the innate and the adaptive arms of the immune system by the engagement of inhibitory (e.g. NKG2A) and activating receptors [e.g. αβ T cell receptor (αβTCR) or NKG2C] on NK cells and CD8 T cells. The effects of HLA-E on the cellular immune response are therefore complex and not completely understood yet. Here, we aim to provide an overview of the immunological and clinical relevance of HLA-E and HLA-E polymorphism in stem cell transplantation and in cancer. We review novel insights in the mechanism via which HLA-E expression levels are controlled and how the cellular immune response in transplantation and cancer is influenced by HLA-E. PMID:25413103

  19. The Significance of Strategic Community Engagement in Recruiting African American Youth & Families for Clinical Research

    PubMed Central

    Bell, Carl C.; Burriss, Antoinette; Poole, H. Kathy

    2011-01-01

    We present baseline data and describe the utility of a community engaged, culturally relevant approach to recruiting African American youth and families for phase I of The AAKOMA Project. The AAKOMA Project is a two phase treatment development study to improve mental health service use among depressed African American youth. We completed capacity building activities using a community engaged framework and Community Based Participatory Research (CBPR) methods. Replicating the (Alvarez et al. in West J Nurs Res 28:541–560, 2006) model of systematic community out-reach enhanced our ability to effectively recruit partners and evaluate outreach efforts as demonstrated by our Recruitment Success Factor (RSF—i.e. ‘an adjusted ratio of eligible participant yield to contacts made’). Using the chi-square goodness-of-fit statistic; we compared the RSFs of the various modes of participant study entry to determine which was most effective. Our target enrollment was 56 persons. We recruited 130 and enrolled 57. Our baseline data is drawn from a gender balanced and socioeconomically diverse sample who participated in youth focus groups and individual interviews and adult focus groups. We identified 3 study participant referral modes (self-referral, provider referral and participant-to-participant referral) with multiple sources per mode and an overall RSF of 0.41. Study findings support the effectiveness of assiduous and systematic community interaction, reflective review of recruitment efforts and the importance of disseminating information on strategic recruitment processes for engaging diverse populations in clinical research. PMID:22984337

  20. TNFRSF14 aberrations in follicular lymphoma increase clinically significant allogeneic T-cell responses

    PubMed Central

    Kotsiou, Eleni; Okosun, Jessica; Besley, Caroline; Iqbal, Sameena; Matthews, Janet; Fitzgibbon, Jude; Gribben, John G.

    2016-01-01

    Donor T-cell immune responses can eradicate lymphomas after allogeneic hematopoietic stem cell transplantation (AHSCT), but can also damage healthy tissues resulting in harmful graft-versus-host disease (GVHD). Next-generation sequencing has recently identified many new genetic lesions in follicular lymphoma (FL). One such gene, tumor necrosis factor receptor superfamily 14 (TNFRSF14), abnormal in 40% of FL patients, encodes the herpes virus entry mediator (HVEM) which limits T-cell activation via ligation of the B- and T-lymphocyte attenuator. As lymphoma B cells can act as antigen-presenting cells, we hypothesized that TNFRSF14 aberrations that reduce HVEM expression could alter the capacity of FL B cells to stimulate allogeneic T-cell responses and impact the outcome of AHSCT. In an in vitro model of alloreactivity, human lymphoma B cells with TNFRSF14 aberrations had reduced HVEM expression and greater alloantigen-presenting capacity than wild-type lymphoma B cells. The increased immune-stimulatory capacity of lymphoma B cells with TNFRSF14 aberrations had clinical relevance, associating with higher incidence of acute GVHD in patients undergoing AHSCT. FL patients with TNFRSF14 aberrations may benefit from more aggressive immunosuppression to reduce harmful GVHD after transplantation. Importantly, this study is the first to demonstrate the impact of an acquired genetic lesion on the capacity of tumor cells to stimulate allogeneic T-cell immune responses which may have wider consequences for adoptive immunotherapy strategies. PMID:27103745

  1. Fate of intravenously injected mesenchymal stem cells and significance for clinical application.

    PubMed

    Wagner, Beate; Henschler, Reinhard

    2013-01-01

    Mesenchymal stromal cells (MSCs) have initially been characterized as a fibroblastlike cell population that can be expanded readily in vitro, and is able to support hematopoiesis in vitro and in vivo. By serendipity it was discovered that MSCs can also be administered into the bloodstream. This mode of application formed a major breakthrough in the clinical use of MSCs, because MSC transplantation was found to cure severe immune hyperactivation states such as graft-versus-host disease after allogeneic bone marrow transplantation, or bacterial sepsis. However, MSCs were found difficult to trace and consensus to date is lacking in the scientific community as to where transplanted MSCs end up in the body and which major principles are responsible for the therapeutic effects of MSCs. This chapter gives an overview of the current knowledge on interactions of freshly transplanted MSCs with the cells in the blood stream and the vessel wall, with major organs such as lung, liver, gut, and spleen, and discusses the limitations of the methodologies used to trace transplanted MSCs. The findings will be put into perspective on how therapeutically applied, culture-expanded MSCs may exert beneficial effects. PMID:23334265

  2. [Clinically significant toxicity and tolerance of the main antibiotics used in lower respiratory tract infections].

    PubMed

    Rouveix, B

    2006-01-01

    The purpose of this article was not to review all reported adverse reactions of antibiotics used in the treatment of lower respiratory tract infections but rather to focus either on those which might have an impact on observance, efficacy, and resistance, or on rare but life-threatening adverse effects such as torsade de pointe. The latter are mostly predictable and prescribers should adhere to precautions and contraindications. For new antibiotics, the number of patients enrolled in phase I to III clinical trials is far to small to detect such rare adverse effects and large post registration tolerance surveys are mandatory. ss-lactams are well tolerated. The risk of anaphylactic reaction is magnified by patient reports and can be reduced by skin testing. Macrolides are well tolerated as well. The risk of cardiac toxicity should be reduced by assessing individual susceptibility and avoiding drug interactions. The tolerance to telithromycin, a new ketolide, is similar to that of macrolides. Serious toxic reactions such as convulsions, tendon rupture, torsade de pointe, and hypoglycemia are associated with the use of fluoroquinolones. Most of these adverse reactions can be often circumvented by avoiding exposure patients at risk. Quinupristin/dalfopristin can induce arthralgia and myalgia and the major adverse effects of linezolid are IMAO like reactions, reversible myelosuppression, and peripheral neuropathy. Most of the adverse antibiotic reactions are reported when precautions of use in susceptible patients are not taken into account. When they are, the safety/risk ratio is good. PMID:16876974

  3. Clinical significance of donor-specific human leukocyte antigen antibodies in liver transplantation

    PubMed Central

    Cuadrado, Antonio; San Segundo, David; López-Hoyos, Marcos; Crespo, Javier; Fábrega, Emilio

    2015-01-01

    Antibody-mediated rejection (AMR) caused by donor-specific anti-human leukocyte antigen antibodies (DSA) is widely accepted to be a risk factor for decreased graft survival after kidney transplantation. This entity also plays a pathogenic role in other solid organ transplants as it appears to be an increasingly common cause of heart graft dysfunction and an emerging issue in lung transplantation. In contrast, the liver appears relatively resistant to DSA-mediated injury. This “immune-tolerance” liver property has been sustained by a low rate of liver graft loss in patients with preformed DSA and by the intrinsic liver characteristics that favor the absorption and elimination of DSA; however, alloantibody-mediated adverse consequences are increasingly being recognized, and several cases of acute AMR after ABO-compatible liver transplant (LT) have been reported. Furthermore, the availability of new solid-phase assays, allowing the detection of low titers of DSA and the refinement of objective diagnostic criteria for AMR in solid organ transplants and particularly in LT, have improved the recognition and management of this entity. A cost-effective strategy of DSA monitoring, avoidance of class II human leukocyte antigen mismatching, judicious immunosuppression attached to a higher level of clinical suspicion of AMR, particularly in cases unresponsive to conventional anti-rejection therapy, can allow a rational approach to this threat. PMID:26494958

  4. TNFRSF14 aberrations in follicular lymphoma increase clinically significant allogeneic T-cell responses.

    PubMed

    Kotsiou, Eleni; Okosun, Jessica; Besley, Caroline; Iqbal, Sameena; Matthews, Janet; Fitzgibbon, Jude; Gribben, John G; Davies, Jeffrey K

    2016-07-01

    Donor T-cell immune responses can eradicate lymphomas after allogeneic hematopoietic stem cell transplantation (AHSCT), but can also damage healthy tissues resulting in harmful graft-versus-host disease (GVHD). Next-generation sequencing has recently identified many new genetic lesions in follicular lymphoma (FL). One such gene, tumor necrosis factor receptor superfamily 14 (TNFRSF14), abnormal in 40% of FL patients, encodes the herpes virus entry mediator (HVEM) which limits T-cell activation via ligation of the B- and T-lymphocyte attenuator. As lymphoma B cells can act as antigen-presenting cells, we hypothesized that TNFRSF14 aberrations that reduce HVEM expression could alter the capacity of FL B cells to stimulate allogeneic T-cell responses and impact the outcome of AHSCT. In an in vitro model of alloreactivity, human lymphoma B cells with TNFRSF14 aberrations had reduced HVEM expression and greater alloantigen-presenting capacity than wild-type lymphoma B cells. The increased immune-stimulatory capacity of lymphoma B cells with TNFRSF14 aberrations had clinical relevance, associating with higher incidence of acute GVHD in patients undergoing AHSCT. FL patients with TNFRSF14 aberrations may benefit from more aggressive immunosuppression to reduce harmful GVHD after transplantation. Importantly, this study is the first to demonstrate the impact of an acquired genetic lesion on the capacity of tumor cells to stimulate allogeneic T-cell immune responses which may have wider consequences for adoptive immunotherapy strategies. PMID:27103745

  5. Clinical and biological significance of HAX-1 overexpression in nasopharyngeal carcinoma

    PubMed Central

    Shao, Xiaoyi; Ni, Haosheng; Shi, Si; Shan, Ying; Gu, Zhifeng; You, Yiwen

    2016-01-01

    HS1-associated protein X-1 (HAX-1) is an important marker in many types of cancers and contributes to cancer progression and metastasis. We examined the expression of HAX-1 in nasopharyngeal carcinoma (NPC) and experimentally manipulated its expression. We observed that HAX-1 expression is elevated in NPC and is correlated with lymph node metastasis, M classification, clinical stage, and poor prognosis. In addition, overexpression of HAX-1 promoted NPC proliferation both in vitro and in vivo. Exosomes are potential carriers of pro-tumorigenic factors that participate in oncogenesis. We found that NPC-derived exosomes are enriched in HAX-1 and accelerate NPC tumor growth and angiogenesis in vitro and in vivo. Furthermore, we demonstrated that oncogenic HAX-1 facilitates the growth of NPC when it is transferred via exosomes to recipient human umbilical vein endothelial cells (HUVECs). Oncogenic HAX-1 also increases the proliferation, migration, and angiogenic activity of HUVECs. Our findings provide unique insight into the pathogenesis of NPC and underscore the need to explore novel therapeutic targets such as HAX-1 to improve NPC treatment. PMID:26871467

  6. [Clinical course and prognostic significance of immunological and functional parameters after severe trauma].

    PubMed

    Lendemans, S; Kreuzfelder, E; Waydhas, C; Nast-Kolb, D; Flohé, S

    2004-03-01

    Generalized severe trauma leads to an increased incidence of SIRS, sepsis, and MOF. The aim of this prospective study was to investigate the immunological parameters in terms of their predictive value for multiple organ failure (MOF).HLA-DR expression on peripheral monocytes was analyzed by flow cytometry, the ex vivo endotoxin-stimulated TNFalpha synthesis of whole blood, and the serum levels of IL-6, IL-10, procalcitonin (PCT), and CRP were analyzed by ELISA in 16 severely injured patients with an ISS >25. Initially after trauma elevated serum levels of IL-6, IL-10, and PCT were found, while TNFalpha-producing capacity and HLA-DR expression on monocytes decreased. In patients with MOF a further decrease of HLA-DR expression on days 3-4 after injury was observed accompanied by elevated levels of IL-10 at this time point. However, the TNFalpha-producing capacity was even enhanced in patients with MOF in the 2nd week after trauma. Later PCT levels were also higher in patients with MOF.Monitoring of immunological parameters after severe injury is useful to identify mediator constellations that are associated with the development and clinical course of MOF even in extremely injured patients. PMID:14999368

  7. Clinical significance of screening for subclinical Cushing's disease in patients with pituitary tumors.

    PubMed

    Tamada, Daisuke; Kitamura, Tetsuhiro; Otsuki, Michio; Oshino, Satoru; Saitoh, Youichi; Shimomura, Iichiro

    2016-01-01

    Cushing's syndrome (CS) is a clinical state caused by chronic excess of glucocorticoid, and results in hypertension, impaired glucose tolerance, and dyslipidemia. Recently, a mild state of pituitary CS without typical Cushingoid appearance (subclinical Cushing's disease; SCD) has been identified. However, the true prevalence of SCD and its effect on metabolic disorders remain obscure. The aim of this prospective study was to determine the prevalence of SCD according to the guideline proposed by the working group of the Japanese Ministry of Health, Welfare and Labor, and to assess the outcome of surgery on metabolic disorders. The prevalence of SCD was investigated in 105 consecutive patients diagnosed with pituitary adenomas by MRI. ACTH-dependent hypercortisolism was diagnosed based on the results of the 0.5 mg dexamethasone suppression test (serum cortisol >3.0 μg/dL) plus one positive finding of the following two tests: midnight serum cortisol level >5.0 μg/dL or ACTH increase >50% after 1-deamino-5-D-arginine vasopressin (DDAVP) challenge. The final diagnosis of SCD was established by positive staining for ACTH in surgically-excised pituitary adenoma. Three patients (4.8%) were diagnosed with SCD among 62 patients with pituitary adenoma. Transsphenoidal adenomectomy partially resulted in improvement of blood pressure and glucose metabolism in SCD patients. Our results emphasize the importance of SCD screening in patients with pituitary tumors, especially in those patients with metabolic disorders. PMID:26536898

  8. Clinical significance of acquired loss of the X chromosome in bone marrow.

    PubMed

    Tang, Zhenya; Li, Yan; Wang, Sa A; Hu, Shimin; Li, Shaoying; Lu, Xinyan; Khoury, Joseph D; Medeiros, L Jeffrey; Tang, Guilin

    2016-08-01

    Acquired loss of the X chromosome (-X) as a sole abnormality is detected rarely in bone marrow (BM) and its clinical importance remains largely unknown. We studied 38 patients with isolated -X in BM. All patients were women, with a median age of 71 years. At the time of -X detection, BM was positive for myeloid neoplasm in 14 patients, lymphoma/myeloma in 10 patients, and was normal in 14 patients. -X was detected as a major clone in 15 patients (11 of them had myeloid neoplasm) and a minor clone in 23 patients. Combined morphologic and FISH analysis was performed in 16 cases, -X was detected in myeloid/erythroid cells in all 16 patients and in lymphocytes in 15 patients. With a median of 23 months follow-up, none of the patients with a negative BM or BM with involvement by lymphoid neoplasms developed a secondary myeloid neoplasm. We conclude that isolated -X is a rare finding in BM. In majority of patients, -X presents as a minor clone and is likely to be an aging effect or a benign finding; whereas when -X presents as a major clone in BM, it is often disease associated. PMID:27299973

  9. Gastric Collision Tumors: An Insight into Their Origin and Clinical Significance

    PubMed Central

    Constantinidou, Anastasia; Kontos, Michael

    2015-01-01

    Collision tumors are rare neoplasms displaying two distinct cell populations developing in juxtaposition to one another without areas of intermingling. They are rare entities with only 63 cases described in English literature. Tumors encountered are gastric adenocarcinomas colliding with lymphomas, gastrointestinal stromal tumors, squamous cell carcinomas, and neuroendocrine tumors. Their cell origin is obsolete by the time of diagnosis. Different tumorigenesis theories have been suggested to explain their behavior, yet none has managed to provide satisfactory explanation for all cases. Clinically they are indistinguishable from the dominant tumor. Lack of data does not allow detailed assessment of their behavior yet they seem aggressive neoplasms with dismal prognosis. The majority of cases have been diagnosed postoperatively during histologic examination of specimens. There are no guidelines or concrete evidence to support best way of adjuvant or other types of treatment. However, these rare neoplasms might help in unlocking secrets of cancer behavior including tumorigenesis, differentiation, and adhesion and thus clinicians should be aware of their existence. PMID:25767509

  10. Clinical significance of knowledge about the structure, function, and impairments of working memory

    PubMed Central

    Brodziak, Andrzej; Brewczyński, Adam; Bajor, Grzegorz

    2013-01-01

    A review of contemporary research on the working memory system (WMS) is important, both due to the need to focus the discussion on further necessary investigations on the structure and function of this key part of the human brain, as well as to share this knowledge with clinicians. In our introduction we try to clarify the actual terminology and provide an intuitively understandable model for 3 basic cognitive operations: perception, recognition, imagery, and manipulation of recalled mental images. We emphasize the importance of knowledge of the structure and function of the WMS for the possibility to demonstrate the links between genetic polymorphisms and the prevalence to some mental disorders. We also review current knowledge of working memory dysfunction in the most common diseases and specific clinical situations such as maturation and aging. Finally, we briefly discuss methods for assessment of WMS capacity. This article establishes a kind of compendium of knowledge for clinicians who are not familiar with the structure and operation of the WMS. PMID:23645218

  11. Clinical Significance of Preoperative Neutrophil – to - Lymphocyte Ratio in Renal Cell Carcinoma

    PubMed Central

    Otunctemur, Alper; Dursun, Murat; Besiroglu, Huseyin; Ozer, Kutan; Horsanali, Ozan; Ozbek, Emin

    2016-01-01

    ABSTRACT Introduction: We investigated the prognostic significance of the neutrophil-to-lymphocyte ratio on tumor stage and Fuhrman nuclear grade in renal cell carcinoma. Methods: The records of 432 patients with RCC who underwent radical or partial nephrectomy between 2005 and 2014 were retrospectively reviewed. Patients were classified as group lower tumor stage(T1 + T2) and higher(T3 + T4). As like tumor stage, Fuhrman nuclear grade were classified lower (G1+G2) and higher(G3+G4) too. The best NLR cut off value was 3.01. Two sample t-test or Mann–Whitney U-test used for the continuous variables and a chi-square test or Fisher's exact test used for the categorical variables. Results: Among the 432 total patients analyzed in our study, there were 275 males (63.7%) and 157 females (36.3%). Mean laboratory values were CRP 2.73 ± 1.93 mg/dL (normal less than 0.3), neutrophil count 4,23 ± 1.46/μL, lymphocyte count 1,61 ± 0,61/μL and NLR 2.64 ± 1.24. According to our data, statistically pretreatment NLR significantly correlated with CRP (p<0.0001). And tumor patologic stage (p=0.08), tumor histologic grade (p<0.001) was significantly associated with NLR. Discussion: We compared the relationship of preoperative NLR and NC parameters with RCC tumor stage and grade. And NLR were found to have statistically significant higher T stage and grade at RCC. Further studies with more patients are needed to confirm our study. PMID:27564277

  12. Clinical Significance of KISS1 Protein Expression for Brain Invasion and Metastasis

    PubMed Central

    Ulasov, Ilya V.; Kaverina, Natalya V.; Pytel, Peter; Thaci, Bart; Liu, FeiFei; Hurst, Douglas R.; Welch, Danny R.; Sattar, Husein A.; Olopade, Olufunmilayo I.; Baryshnikov, Anatoly Y.; Kadagidze, Zaira G.; Lesniak, Maciej S.

    2013-01-01

    BACKGROUND Metastases to the brain represent a feared complication and contribute to the morbidity and mortality of breast cancer. Despite improvements in therapy, prognostic factors for development of metastases are lacking. KISS1 is a metastasis suppressor that demonstrates inhibition of metastases formation in several types of cancer. The purpose of this study was to determine the importance of KISS1 expression in breast cancer progression and the development of intracerebral lesions. METHODS In this study, we performed a comparative analysis of 47 brain metastases and 165 primary breast cancer specimens by using the antihuman KISS1 antibody. To compare KISS1 expression between different groups, we used a 3-tier score and the automated score computer software (ACIS) evaluation. To reveal association between mRNA and protein expression, we used quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis. Significance of immunohistochemistry stainings was correlated with clinicopathological data. RESULTS We identified that KISS1 expression is significantly higher in primary breast cancer compared with brain metastases (P < .05). The mRNA analysis performed on 33 selected ductal carcinoma brain metastatic lesions and 36 primary ductal carcinomas revealed a statistically significant down-regulation of KISS1 protein in metastatic cases (P = .04). Finally, we observed a significant correlation between expression of KISS1 and metastasis-free survival (P = .04) along with progression of breast cancer and expression of KISS1 in primary breast cancer specimens (P = .044). CONCLUSIONS In conclusion, our study shows that breast cancer expresses KISS1. Cytoplasmic expression of KISS1 may be used as a prognostic marker for increased risk of breast cancer progression. PMID:21928364

  13. Carbonic anhydrase IX is a clinically significant tissue and serum biomarker associated with renal cell carcinoma

    PubMed Central

    TAKACOVA, MARTINA; BARTOSOVA, MARIA; SKVARKOVA, LUCIA; ZATOVICOVA, MIRIAM; VIDLICKOVA, IVANA; CSADEROVA, LUCIA; BARATHOVA, MONIKA; BREZA, JAN; BUJDAK, PETER; PASTOREK, JAROMIR; BREZA, JAN; PASTOREKOVA, SILVIA

    2013-01-01

    Carbonic anhydrase IX (CA IX) is regarded as one of the most prominent markers of tumor hypoxia with potential to serve as a diagnostic biomarker, prognostic indicator as well as tumor therapeutic target. The aim of the present study was to perform an in-depth analysis of CA IX expression in blood and tissue samples and to evaluate the significance of CA IX status for different renal cell carcinomas (RCCs). The expression of CA IX was determined in blood and tissue samples from 74 kidney cancer patients using reverse transcription polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), Western blotting (WB) and immunohistochemistry (IHC). The CA IX status was correlated with RCC type and tumor stage. IHC and WB provided evidence for a significantly higher expression of CA IX in clear cell RCC (CCRCC) specimens compared to other RCCs. RT-PCR assay revealed that 32.42% of all RCC patients possess CA9-positive cells in peripheral blood and three-quarters of CA9-positive patients were diagnosed with CCRCC. When the patients were subdivided according to tumor stage, decreased positivity was observed with higher tumor stage (50% in T1 vs. 17% in T3). Serum CA IX levels determined by ELISA were significantly higher in CCRCC patients than in non-CCRCC. A significant association between s-CA IX and CCRCC tumor stage was also determined (T1-87.51 vs. T3-341.98 pg/ml, p=0.046). We demonstrated that the CA IX expression profiles in blood and tissue samples from 74 kidney cancer patients are closely correlated with their histological subtypes. This is the first study reporting CA IX expression in blood and tissue samples from kidney cancer patients determined by four different methods. PMID:23255918

  14. The Clinical Significance of IDH Mutations in Essential Thrombocythemia and Primary Myelofibrosis

    PubMed Central

    Yonal-Hindilerden, Ipek; Daglar-Aday, Aynur; Hindilerden, Fehmi; Akadam-Teker, Basak; Yilmaz, Ceylan; Nalcaci, Meliha; Yavuz, Akif Selim; Sargin, Deniz

    2016-01-01

    Background Limited data exist regarding impact of IDH mutations in Philadelphia-negative myeloproliferative neoplasms (Ph-negative MPNs). Prognostic significance of IDH mutations was asessed in 184 Ph-negative MPN patients - 107 essential thrombocythemia (ET) and 77 primary myelofibrosis (PMF). Methods High-resolution melting (HRM) analysis was used to detect IDH1 and IDH2 mutations. Results PMF and ET patients showed no significant difference for prevalence of IDH mutations. Mutant IDH (IDH1 or IDH2) was documented in five of PMF (6.5%) and two of ET patients (1.9%). IDH mutations in ET patients included one IDH1 R132C and one IDH2 R140Q. Of the five IDH-mutated PMF patients, four (80%) displayed IDH1 (three IDH1 R132C and one IDH1 R132S) and one (20%) carried IDH2 (IDH2 R140Q) mutation. Sixty percent (three in five) of IDH-mutated PMF patients carried JAK2V617F with following allele burdens: 31-50%, 5-12.5% and 31-50%, respectively. Three of 77 PMF patients (3.9%) simultaneously harbored IDH and JAK2V617F mutations. IDH mutations in PMF showed a trend towards higher rate in females (100% and 52.8%, respectively). Bleeding complications were significantly higher in IDH-mutated PMF patients compared to IDH wild-type counterparts. Trend towards a lower prevalance of acetylsalicylic acid (ASA) use was present in IDH mutant PMF patients compared to wild-type counterparts (20% and 63.9%, respectively). Death rate was higher in IDH-mutated PMF patients compared to IDH wild-type PMF patients (60% and 15.3%). In univariate analysis, a significantly shorter leukemia-free survival (LFS) was observed in IDH-mutated PMF patients. Conclusions We conclude that IDH mutations indicate a risk for leukemic transformation in PMF. PMID:26668680

  15. Preemptive antiretroviral therapy modifications for the management of potential clinically significant drug interactions with direct acting hepatitis C therapies.

    PubMed

    Stambough, Megan; Roman, Martha; Blair, Donald C; Sidman, Eric F; Miller, Christopher D

    2016-03-01

    We report a case series of HIV/HCV co-infected patients who underwent preemptive antiretroviral therapy modifications to manage clinically significant drug interactions with HCV therapy. Among the 15 patients reviewed, all changed to a raltegravir-based regimen and none experienced a loss of virologic suppression or increase in HIV-RNA. PMID:25824150

  16. Towards Achieving the Full Clinical Potential of Proton Therapy by Inclusion of LET and RBE Models

    PubMed Central

    Jones, Bleddyn

    2015-01-01

    Despite increasing use of proton therapy (PBT), several systematic literature reviews show limited gains in clinical outcomes, with publications mostly devoted to recent technical developments. The lack of randomised control studies has also hampered progress in the acceptance of PBT by many oncologists and policy makers. There remain two important uncertainties associated with PBT, namely: (1) accuracy and reproducibility of Bragg peak position (BPP); and (2) imprecise knowledge of the relative biological effect (RBE) for different tissues and tumours, and at different doses. Incorrect BPP will change dose, linear energy transfer (LET) and RBE, with risks of reduced tumour control and enhanced toxicity. These interrelationships are discussed qualitatively with respect to the ICRU target volume definitions. The internationally accepted proton RBE of 1.1 was based on assays and dose ranges unlikely to reveal the complete range of RBE in the human body. RBE values are not known for human (or animal) brain, spine, kidney, liver, intestine, etc. A simple efficiency model for estimating proton RBE values is described, based on data of Belli et al. and other authors, which allows linear increases in α and β with LET, with a gradient estimated using a saturation model from the low LET α and β radiosensitivity parameter input values, and decreasing RBE with increasing dose. To improve outcomes, 3-D dose-LET-RBE and bio-effectiveness maps are required. Validation experiments are indicated in relevant tissues. Randomised clinical studies that test the invariant 1.1 RBE allocation against higher values in late reacting tissues, and lower tumour RBE values in the case of radiosensitive tumours, are also indicated. PMID:25790470

  17. Maternal Antibodies: Clinical Significance, Mechanism of Interference with Immune Responses, and Possible Vaccination Strategies

    PubMed Central

    Niewiesk, Stefan

    2014-01-01

    Neonates have an immature immune system, which cannot adequately protect against infectious diseases. Early in life, immune protection is accomplished by maternal antibodies transferred from mother to offspring. However, decaying maternal antibodies inhibit vaccination as is exemplified by the inhibition of seroconversion after measles vaccination. This phenomenon has been described in both human and veterinary medicine and is independent of the type of vaccine being used. This review will discuss the use of animal models for vaccine research. I will review clinical solutions for inhibition of vaccination by maternal antibodies, and the testing and development of potentially effective vaccines. These are based on new mechanistic insight about the inhibitory mechanism of maternal antibodies. Maternal antibodies inhibit the generation of antibodies whereas the T cell response is usually unaffected. B cell inhibition is mediated through a cross-link between B cell receptor (BCR) with the Fcγ-receptor IIB by a vaccine–antibody complex. In animal experiments, this inhibition can be partially overcome by injection of a vaccine-specific monoclonal IgM antibody. IgM stimulates the B cell directly through cross-linking the BCR via complement protein C3d and antigen to the complement receptor 2 (CR2) signaling complex. In addition, it was shown that interferon alpha binds to the CD21 chain of CR2 as well as the interferon receptor and that this dual receptor usage drives B cell responses in the presence of maternal antibodies. In lieu of immunizing the infant, the concept of maternal immunization as a strategy to protect neonates has been proposed. This approach would still not solve the question of how to immunize in the presence of maternal antibodies but would defer the time of infection to an age where infection might not have such a detrimental outcome as in neonates. I will review successful examples and potential challenges of implementing this concept. PMID

  18. Clinical significance of kallikrein-related peptidase-4 in oral cancer.

    PubMed

    Papagerakis, Petros; Pannone, Giuseppe; Zheng, L I; Athanassiou-Papaefthymiou, Maria; Yamakoshi, Yashuo; McGuff, Howard Stan; Shkeir, Omar; Ghirtis, Konstantinos; Papagerakis, Silvana

    2015-04-01

    Kallikrein-related-peptidase-4 (KLK4), a serine protease originally discovered in developing tooth with broad target sequence specificity, serves vital functions in dental enamel formation. KLK4 is involved in degradation of extracellular matrix proteins and it is thought that this proteolytic activity could also promote tumor invasion and metastasis. Recent studies have associated KLK4 expression with tumor progression and clinical outcome, particularly in prostate and ovarian cancer. Very little is known in regard KLK4 involvement in oral squamous cell carcinomas (OSCCs). Our objective was to investigate KLK4 expression in OSCC pathogenesis and disease progression. KLK4 expression was evaluated by immunohistochemistry, western blots and zymograms in OSCC lines. Invasion assays using high versus low/undetectable KLK4-expressing OSCC cell lines were performed jointly with KLK4 siRNA inhibition. A large collection of OSCC specimens was evaluated for KLK4 expression and correlation with patients' characteristics and outcomes were determined. Our data indicate that KLK4 is differentially expressed in oral carcinomas. OSCC cell lines with high invasive and metastatic potential have the highest levels of KLK4 expression. KLK4 mRNA and protein expression correlated with enzyme activity detected by zymograms. Inhibition of KLK4 expression results in diminished invasive potential in OSCC cell lines. Consistently, KLK4 expression is stronger in primary tumors that later either recurred or developed metastases, suggesting that its preferential expression in OSCC might contribute to individual tumor biology. Therefore, this study provides supportive evidence in favor of a prognostic value for KLK4 in OSCC and suggests that KLK4 could serve as a potential therapeutic target in patients with oral cancer. PMID:25862839

  19. Clinical significance of single microscopic focus of adenocarcinoma at prostate biopsy

    PubMed Central

    Çalışkan, Selahattin; Koca, Orhan; Akyüz, Mehmet; Öztürk, Metin; Karaman, Muhammet

    2015-01-01

    Objective Prostate cancer (PC) is one of the most common cancer and an important reason of cancer specific death. The incidence of patients who diagnosed at low stage increased because of widespread using Prostate Specific Antigen (PSA) testing. We evaluated the patients who were diagnosed single microscopic focus of adenocarcinoma and treated radical prostatectomy at final pathology. Methods The patients who underwent transrectal ultrasound guided prostate biopsy between January 2004 and January 2012 were enrolled retrospectively. We extracted the patients who were diagnosed single microscopic focus of adenocarcinoma and treated with RP. Single microscopic adenocarcinoma was defined as one single focus measuring 3 mm or less, well differentiated (Gleason ≤6) adenocarcinoma. 37 patients were included at the study. Clinical data; including age, serum PSA levels, PSA density and prior biopsy and prostatectomy specimen results were recorded. In pathological examination; high molecular weight cytokeratin (HMW-CK), p63, and alpha-methylacyl-CoA racemase (AMACR) were used for differential diagnosis. Results The patients' ages were between 42 and 77 with a mean age of 64.9 ± 7.57 years. Mean PSA levels and prostate volumes were 8.03 ± 5.21 ng/ml and 54 ± 25.51 cc. T0, T2a, T2c and T3a were reported in 2 patients, 17 patients, 17 patients and 1 patient after pathological evaluation. According to the Gleason grading system; 6 patients were 7 (3 + 4), one patient was 7 (4 + 3), one patient was 5 (3 + 2) and 27 patients were 6 (3 + 3). Conclusion Small volume of cancer at prostate biopsy is not necessarily small cancer in radical prostatectomy. The treatment choice may be over or under treatment for some patients, so the patients must be informed when choosing the treatment. PMID:26779460

  20. Clinical and prognostic significance of PD-1 and PD-L1 expression in sarcomas.

    PubMed

    Paydas, Semra; Bagir, Emine Kilic; Deveci, Mehmet Ali; Gonlusen, Gulfiliz

    2016-08-01

    Programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) are new targets in cancer immunotherapy in recent years. The aim of this study is to evaluate the PD-1/PD-L1 expressions in sarcomas and to determine association between PD-1/PD-L1 expressions and clinical/pathological properties in some sarcoma subtypes. Formalin-fixed, paraffin-embedded tissue samples from 65 cases with sarcomas were analyzed. Immunohistochemical staining was performed to detect the PD-1 and PD-L1 expressions in tumor tissue and microenvironment, separately. PD-1 expression in tumor tissue and microenvironment was detected in 11 (17 %) and 8 (12 %) cases, respectively. PD-L1 expression in tumor tissue and microenvironment was detected in 19 (29 %) and 20 cases (30 %), respectively. None of the 5 Ewing sarcomas involving bone showed PD-1/PD-L1 expression, while 2 of 3 cases with Ewing sarcomas involving soft tissue showed PD-1 and PD-L1 expression. Among 5 cases with Kaposi sarcoma, four showed PD-1 and/or PD-L1 expression in tumor or microenvironment. PD-1/PD-L1 expressions were detected 3 of 6 cases with pleomorphic sarcoma, 2 of 4 cases with peripheral nerve sheath tumors and 1 of 4 cases with synovial sarcoma. Interestingly, strongest PD-1/PD-L1 expressions in our study group were detected in 2 sarcoma cases with the history of giant cell tumor. PD-1 and PD-L1 expressions are up to 30 % of the cases with sarcomas. It may be rational to target programmed death pathway in Kaposi sarcoma, pleomorphic sarcoma and peripheral nerve sheath tumors. Strong expression of PD-1/PD-L1 in cases with previous giant cell bone tumor has been found to be interesting and must be studied in giant cell tumor samples. PMID:27421997

  1. Preconditioning Provides Neuroprotection in Models of CNS Disease: Paradigms and Clinical Significance

    PubMed Central

    Stetler, R. Anne; Leak, Rehana K.; Gan, Yu; Li, Peiying; Hu, Xiaoming; Jing, Zheng; Chen, Jun; Zigmond, Michael J.; Gao, Yanqin

    2014-01-01

    Preconditioning is a phenomenon in which brief episodes of a sublethal insult induce robust protection against subsequent lethal injuries. Preconditioning has been observed in multiple organisms and can occur in the brain as well as other tissues. Extensive animal studies suggest that the brain can be preconditioned to resist acute injuries, such as ischemic stroke, neonatal hypoxia/ischemia, trauma, and agents that are used in models of neurodegenerative diseases, such as Parkinson’s disease and Alzheimer’s disease. Effective preconditioning stimuli are numerous and diverse, ranging from transient ischemia, hypoxia, hyperbaric oxygen, hypothermia and hyperthermia, to exposure to neurotoxins and pharmacological agents. The phenomenon of “cross-tolerance,” in which a sublethal stress protects against a different type of injury, suggests that different preconditioning stimuli may confer protection against a wide range of injuries. Research conducted over the past few decades indicates that brain preconditioning is complex, involving multiple effectors such as metabolic inhibition, activation of extra- and intracellular defense mechanisms, a shift in the neuronal excitatory/inhibitory balance, and reduction in inflammatory sequelae. An improved understanding of brain preconditioning should help us identify innovative therapeutic strategies that prevent or at least reduce neuronal damage in susceptible patients. In this review, we focus on the experimental evidence of preconditioning in the brain and systematically survey the models used to develop paradigms for neuroprotection, and then discuss the clinical potential of brain preconditioning. In a subsequent components of this two-part series, we will discuss the cellular and molecular events that are likely to underlie these phenomena. PMID:24389580

  2. High Frequency of Clinically Significant Bacteremia in Adults Hospitalized With Falciparum Malaria.

    PubMed

    Nyein, Phyo Pyae; Aung, Ne Myo; Kyi, Tint Tint; Htet, Zaw Win; Anstey, Nicholas M; Kyi, Mar Mar; Hanson, Josh

    2016-01-01

    Background.  African children with severe falciparum malaria commonly have concomitant Gram-negative bacteremia, but co-infection has been thought to be relatively rare in adult malaria. Methods.  Adults with a diagnosis of falciparum malaria hospitalized at 4 tertiary referral hospitals in Myanmar had blood cultures collected at admission. The frequency of concomitant bacteremia and the clinical characteristics of the patients, with and without bacteremia, were explored. Results.  Of 67 adults hospitalized with falciparum malaria, 9 (13% [95% confidence interval, 5.3%-21.6%]) were also bacteremic on admission, 7 (78%) with Gram-negative enteric organisms (Escherichia coli [n = 3], typhoidal Salmonella species [n = 3], nontyphoidal Salmonella [n = 1]). Bacteremic adults had more severe disease (median Respiratory Coma Acidosis Malaria [RCAM] score 3; interquartile range [IQR], 1-4) than those without bacteremia (median RCAM score 1; IQR, 1-2) and had a higher frequency of acute kidney injury (50% vs 16%, P = .03). Although 35 (52%) were at high risk of death (RCAM score ≥2), all 67 patients in the study survived, 51 (76%) of whom received empirical antibiotics on admission. Conclusions.  Bacteremia was relatively frequent in adults hospitalized with falciparum malaria in Myanmar. Like children in high transmission settings, bacteremic adults in this low transmission setting were sicker than nonbacteremic adults, and were often difficult to identify at presentation. Empirical antibiotics may also be appropriate in adults hospitalized with falciparum malaria in low transmission settings, until bacterial infection is excluded. PMID:26989752

  3. High Frequency of Clinically Significant Bacteremia in Adults Hospitalized With Falciparum Malaria

    PubMed Central

    Nyein, Phyo Pyae; Aung, Ne Myo; Kyi, Tint Tint; Htet, Zaw Win; Anstey, Nicholas M.; Kyi, Mar Mar; Hanson, Josh

    2016-01-01

    Background. African children with severe falciparum malaria commonly have concomitant Gram-negative bacteremia, but co-infection has been thought to be relatively rare in adult malaria. Methods. Adults with a diagnosis of falciparum malaria hospitalized at 4 tertiary referral hospitals in Myanmar had blood cultures collected at admission. The frequency of concomitant bacteremia and the clinical characteristics of the patients, with and without bacteremia, were explored. Results. Of 67 adults hospitalized with falciparum malaria, 9 (13% [95% confidence interval, 5.3%–21.6%]) were also bacteremic on admission, 7 (78%) with Gram-negative enteric organisms (Escherichia coli [n = 3], typhoidal Salmonella species [n = 3], nontyphoidal Salmonella [n = 1]). Bacteremic adults had more severe disease (median Respiratory Coma Acidosis Malaria [RCAM] score 3; interquartile range [IQR], 1–4) than those without bacteremia (median RCAM score 1; IQR, 1–2) and had a higher frequency of acute kidney injury (50% vs 16%, P = .03). Although 35 (52%) were at high risk of death (RCAM score ≥2), all 67 patients in the study survived, 51 (76%) of whom received empirical antibiotics on admission. Conclusions. Bacteremia was relatively frequent in adults hospitalized with falciparum malaria in Myanmar. Like children in high transmission settings, bacteremic adults in this low transmission setting were sicker than nonbacteremic adults, and were often difficult to identify at presentation. Empirical antibiotics may also be appropriate in adults hospitalized with falciparum malaria in low transmission settings, until bacterial infection is excluded. PMID:26989752

  4. Clinical significance of urinary liver-type fatty acid binding protein at various stages of nephropathy.

    PubMed

    Viswanathan, V; Sivakumar, S; Sekar, V; Umapathy, D; Kumpatla, S

    2015-01-01

    This cross-sectional study was to evaluate the levels of urinary liver-type fatty acid binding protein (u-LFABP pg/mg urine creatinine ratio) at different stages of diabetic nephropathy and to see its correlation with other clinical parameters in South Indian patients with type 2 diabetes mellitus (T2DM). A total of 65 (M: F; 42:23) T2DM subjects were divided into three groups, and were compared with 13 (M: F; 3:10) nondiabetic controls. The study groups were as follows: normoalbuminuric (n = 22), microalbuminuric (n = 22) and macroalbuminuric (n = 21). Estimated glomerular filtration rate (eGFR) was calculated using Cockcroft and Gault formula. u-LFABP levels in spot urine samples were measured with a solid phase enzyme linked immunosorbent assay. This study showed that u-LFABP levels were undetectable in healthy controls and was very low in the normoalbuminuric subjects. Elevated levels of u-LFABP are evident from the microalbuminuric stage indicating tubular damage. The levels of u-LFABP increased gradually with declining renal function. Geometric mean (95% confidence interval) for normoalbuminuria was 0.65 (0.47-0.97), microalbuminuria was 0.99 (0.55-1.97) and macroalbuminuria was 5.16 (1.8-14.5), (P = 0.005). In conclusion, u-LFABP levels were elevated in patients with reduced eGFR and showed a positive correlation with systolic blood pressure and protein to creatinine ratio in the total study subjects. PMID:26628791

  5. Clinical significance of urinary liver-type fatty acid binding protein at various stages of nephropathy

    PubMed Central

    Viswanathan, V.; Sivakumar, S.; Sekar, V.; Umapathy, D.; Kumpatla, S.

    2015-01-01

    This cross-sectional study was to evaluate the levels of urinary liver-type fatty acid binding protein (u-LFABP pg/mg urine creatinine ratio) at different stages of diabetic nephropathy and to see its correlation with other clinical parameters in South Indian patients with type 2 diabetes mellitus (T2DM). A total of 65 (M: F; 42:23) T2DM subjects were divided into three groups, and were compared with 13 (M: F; 3:10) nondiabetic controls. The study groups were as follows: normoalbuminuric (n = 22), microalbuminuric (n = 22) and macroalbuminuric (n = 21). Estimated glomerular filtration rate (eGFR) was calculated using Cockcroft and Gault formula. u-LFABP levels in spot urine samples were measured with a solid phase enzyme linked immunosorbent assay. This study showed that u-LFABP levels were undetectable in healthy controls and was very low in the normoalbuminuric subjects. Elevated levels of u-LFABP are evident from the microalbuminuric stage indicating tubular damage. The levels of u-LFABP increased gradually with declining renal function. Geometric mean (95% confidence interval) for normoalbuminuria was 0.65 (0.47–0.97), microalbuminuria was 0.99 (0.55–1.97) and macroalbuminuria was 5.16 (1.8–14.5), (P = 0.005). In conclusion, u-LFABP levels were elevated in patients with reduced eGFR and showed a positive correlation with systolic blood pressure and protein to creatinine ratio in the total study subjects. PMID:26628791

  6. Expression of phosphorylated Akt/mTOR and clinical significance in human ameloblastoma

    PubMed Central

    Li, Ning; Sui, Jianfu; Liu, Hao; Zhong, Ming; Zhang, Min; Wang, Yan; Hao, Fengyu

    2015-01-01

    This study aimed to evaluate the expression of AKT and phosphorylated AKT (p-Akt) in human ameloblastoma (AB). Immunohistochemistry showed human AB was positive for Akt and Akt expression was mainly found in the cytoplasm of epithelial cells. The Akt expression in AB was significantly higher than that in normal oral mucosa (NOM), but still lower than that in oral squamous cell carcinoma (OSCC). NOM was negative for p-Akt, but AB was positive for p-Akt. In some AB tissues, p-Akt expression was found in both cytoplasm and nucleus. Akt expression in AB was significantly different from that in NOM and OSCC. The p-Akt in AB was markedly higher than that in NOM, but lower than that in OSCC. mTOR expressed in cytoplasm in AB, but not in NOM. P-mTOR expressed on cell membrane in NOM, while in cytoplasm and nucleus in Ab. Results of western blot assay showed that Akt expression was found in all the AB tissues, and increased in tissues with malignant transformation. In addition, the p-Akt expression also markedly increased in AB, but was still lower than that in OSCC tissues. Compared to NOM, mTOR and p-mTOR expression significantly increased in AB. BandScan 5.0 software was used to detect the optical density of protein bands. Results showed p-Akt, mTOR and p-mTOR expression in AB was markedly different from that in control group. PMID:26131097

  7. Clinical significance of enlarged lateral pelvic lymph nodes before and after preoperative chemoradiotherapy for rectal cancer

    PubMed Central

    INOUE, YASUHIRO; SAIGUSA, SUSUMU; HIRO, JUNICHIRO; TOIYAMA, YUJI; ARAKI, TOSHIMITSU; TANAKA, KOJI; MOHRI, YAUSHIKO; KUSUNOKI, MASATO

    2016-01-01

    Preoperative chemoradiotherapy (CRT) with total mesorectal excision (TME) is the widely accepted treatment for rectal cancer (RC) in Western countries. However, there remains controversy as to whether preoperative CRT is useful in tumors that extend beyond the mesorectum, including metastasis to the lateral pelvic lymph nodes (LPLN). The aim of this study was to assess the prognostic significance of LPLN enlargement in patients with RC who receive preoperative CRT followed by TME without LPLN dissection. We evaluated the prognostic effect of radiographic LPLN enlargement before and after CRT, as well as the patients' clinicopathological and genetic profiles. Of the 104 patients investigated, pretreatment imaging identified 19 (18%) as LPLN-positive (>7 mm in diameter). Of these 19 patients, 7 (37%) exhibited LPLN downsizing to <7 mm following CRT. The median follow-up period was 52 months. The 5-year cancer-specific survival (CSS) or relapse-free survival (RFS) did not differ significantly between patients who did and those who did not have positive LPLN on pretreatment imaging. However, LPLN that remained positive after CRT were significantly associated with poorer 5-year CSS (73 vs. 84%, respectively; P=0.0052) and RFS (32 vs. 78%, respectively; P=0.0264). None of the patients whose LPLN were downsized to <7 mm following CRT developed recurrence; however, those with positive LPLN after CRT had a 55% higher recurrence rate, characterized by delayed local recurrence, a pattern that may be affected by certain chemokines. In conclusion, changes in initially positive LPLN (>7 mm) may predict the prognosis of patients with RC who receive preoperative CRT-TME. LPLN positivity after CRT was associated with shorter CSS and RFS. Strategies to improve patient survival may include selective LPLN dissection or more aggressive multimodality therapy. PMID:27313860

  8. Clinical significance of interleukin-4 and interleukin-18 levels in aggressive non-Hodgkin's lymphoma patients.

    PubMed

    Soydinc, H O; Guney, N; Basaran, M; Duranyildiz, D; Yasasever, V

    2016-01-01

    Strong evidence indicates that tumor growth can be actively controlled by the immune system, and interleukins (ILs) are known to play an influential role in immune response regulation. Moreover, inflammatory cytokines are significantly involved in lymphoma pathogenesis. We aimed to investigate serum levels of IL-4 and IL-18 in aggressive non-Hodgkin's lymphoma (A-NHL) patients and their relationship with prognostic parameters and therapy outcome. These serum factors were measured by enzyme-linked immunosorbent assay in 46 patients with pathologically verified A-NHL before and after chemotherapy, and in 20 healthy controls. No significant difference in serum IL-4 (P = 0.11) and IL-18 (P = 0.261) levels was observed between the A-NHL and controls groups. None of the prognostic parameters analyzed significantly correlated with serum IL-4 concentration, while only lactate dehydrogenase (LDH) measurements were associated with IL-18 values. Serum IL-18 was elevated in the patients with high LDH levels compared to those exhibiting normal values (P = 0.045). In addition, no correlation was found between the concentrations of serum IL-4 and IL-18 in A-NHL patients (r = 0.188, P = 0.187). While IL-18 values did not change, serum IL-4 levels decreased following chemotherapy, independently from treatment response (P = 0.002). Our study is the first to report the response of serum IL-4 levels to chemotherapy. In conclusion, although IL-4 serum concentration has no diagnostic role, it is sensitivite to standard chemotherapy in A-NHL. However, serum IL-18 measurements have no diagnostic or prognostic role in this disease. PMID:27525895

  9. Clinical significance of NOTCH1 intracellular cytoplasmic domain translocation into the nucleus in gastric cancer

    PubMed Central

    Saito, Shinichiro; Ishiguro, Hideyuki; Kimura, Masahiro; Ogawa, Ryo; Miyai, Hirotaka; Tanaka, Tatsuya; Mizoguchi, Koji; Takeyama, Hiromitsu

    2016-01-01

    Recent studies have shown constitutive activation of the Notch signaling pathway in various types of malignancies. However, it remains unclear whether this signaling pathway is activated in gastric cancer. In the present study, the aim was to investigate the role of Notch signaling in gastric cancer by investigating the subcellular localization of Notch-associated proteins in tissue samples from gastric cancer patients. Samples were obtained from 115 gastric cancer patients who had undergone surgery at the Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Science without pre-operative chemotherapy or radiation. Subsequently the correlation between translocation of NOTCH1 intracellular cytoplasmic domain (NICD) into the nucleus (as measured by immunostaining) and survival in gastric cancer patients after surgery was investigated. The results were analyzed in reference to the patients' clinicopathological characteristics and the effects of these results on patient prognosis were determined. Significant correlations were observed between NICD nuclear localization and clinicopathological characteristics, such as tumor status (T factor), lymph node status (N factor), pathological stage and differentiation status. No significant correlations were observed between NICD nuclear localization and age, gender, tumor location, vein invasion or lymphatic invasion. Patients with >30% of cancer cell nuclei positively stained for NICD (as revealed by immunostaining) were associated with a significantly shorter survival following surgery than patients with <30% NICD-positive cancer cell nuclei (log-rank test, P=0.0194). Univariate analysis revealed that among the clinicopathological factors examined, T factor [risk rate (RR)=10.870; P=0.0016], N factor (RR=41.667; P=0.0003), lymphatic invasion (RR=13.158; P=0.0125), vein invasion (RR=25.000; P= 0.0019) and translocation of NICD to the nucleus (RR=3.937; P=0.0312) were all identified to be

  10. Downregulation of long noncoding RNA NONHSAT037832 in papillary thyroid carcinoma and its clinical significance.

    PubMed

    Lan, Xiabin; Sun, Wei; Zhang, Ping; He, Liang; Dong, Wenwu; Wang, Zhihong; Liu, Siming; Zhang, Hao

    2016-05-01

    Long noncoding RNA (lncRNA) is a kind of RNA that is longer than 200 nucleotides with limited or no protein-coding potential. Studies have proved that lncRNAs play important regulatory roles in gene expression and contribute to oncogenesis and cancer metastasis. However, the expression level of lncRNAs and their clinicopathologic significance in papillary thyroid carcinoma (PTC) have not been well studied. In this study, we investigated the expression level of a novel lncRNA NONHSAT037832 in PTC and paired noncancerous thyroid tissues as well as some cell lines by quantitative real-time polymerase chain reaction. The association between the expression level of NONHSAT037832 and clinicopathologic characteristics of patients with PTC was further analyzed. Three receiver operating characteristic curves (ROCs) were established to evaluate the diagnostic value of NONHSAT037832. The results suggested that the expression level of NONHSAT037832 was significantly decreased in PTC compared with paired noncancerous tissues (P < 0.01). And, NONHSAT037832 was also significantly downregulated in two PTC cell lines (K1 and IHH-4) compared to normal thyroid follicular epithelial cell line Nthy-ori 3-1 (P < 0.01). Downregulated NONHSAT037832 was significantly associated with lymph node metastasis (P = 0.015) and tumor size (P = 0.032). The ROCs revealed that NONHSAT037832 had a high diagnostic value for differentiating between PTC and noncancerous diseases as well as identifying PTC with lymph node metastasis and larger tumors (≥3 cm). The area under curve was up to 0.897 (95%CI = 0.852-0.942, P = 0.000), 0.641 (95%CI = 0.519-0.762, P = 0.033), and 0.702 (95%CI = 0.567-0.827, P = 0.008), respectively. This study indicated that NONHSAT037832 might serve as a potential biomarker of PTC. PMID:26611646

  11. Pulmonary uptake in Indium-111 leukocyte imaging: clinical significance in patients with suspected occult infections

    SciTech Connect

    Cook, P.S.; Datz, F.L.; Disbro, M.A.; Alazraki, N.P.; Taylor, A.T.

    1984-02-01

    A retrospective review was undertaken to evaluate the frequency and significance of pulmonary activity noted on 306 indium-111 leukocyte studies involving 232 patients with suspected occult infections. Forty-eight studies showed pulmonary activity in one of two patterns of uptake, focal or diffuse. Fourteen of 27 studies (52%) with focal uptake and two of 21 studies (10%) with diffuse uptake were associated with infectious processes. Lung uptake of indium-111-labeled leukocytes was a poor predictor of pulmonary infection in patients studied for occult infection, although the focal pattern was more likely than the diffuse pattern to be associated with infection.

  12. [Human atrial natriuretic peptide: a secretory product of the heart and its significance for physiology and clinical practice].

    PubMed

    Vierhapper, H; Waldhäusl, W

    1987-03-01

    This review deals with the physiological and clinical importance of human atrial natriuretic peptide (hANP). This peptide, which is produced by the myocardial cells of the right atrium, induces a diuretic and natriuretic response and has an inhibitory effect on aldosterone secretion. Recent elucidation of the peptide's structure represents the latest achievement in the search for an endogenous, natriuretic and hypotensive substance and has resulted in the publication of much, partly only preliminary data of its role within the homeostatic control of body sodium and water, as well as in various pathological disorders. The extensive literature is reviewed. PMID:2953110

  13. Do we use the right criteria for determining the clinical significance of incidental prostate cancer at radical cystoprostatectomy?

    PubMed

    Gakis, Georgios; Stenzl, Arnulf; Renninger, Markus

    2013-10-01

    Prostate-sparing techniques have been advocated to improved functional outcomes after radical cystoprostatectomy (RCP) for invasive bladder cancer, but this may endanger the oncological outcome. This review addresses the current status of risk factors of prostate cancer (PCa) recurrence in patients with incidental PCa after RCP. The overall 7-year risk of PCa recurrence after RCP is approximately 9%. Increased risk has been suggested in the presence of clinically significant PCa as: ≥ pT3a stage, presence of lymph-node metastasis, positive surgical margins, Gleason pattern ≥ 4, tumour multifocality (three or more foci) and tumour volume >0.5 cm(3). However, the prognostic significance of these parameters has not been evaluated within multivariable analyses so far. Preoperatively elevated prostate-specific antigen (PSA) values correlate weakly with the clinical significance of incidental PCa, while prostate biopsy has a limited accuracy for detecting incidental PCa in the preoperative setting. Genetic markers, e.g. the prostate stem cell antigen (PSCA) gene, have recently been associated with risk of recurrence in patients with incidental PCa. Incidental PCa at RCP is usually clinically insignificant. Yet, clinicopathological parameters for clinical significant cancers have not been investigated independently in the literature so far. Consequently, lifelong PSA surveillance should be conducted in all patients with incidental PCa after RCP. In the presence of clinically significant PCa treatment decisions should be based not only on histological criteria but also on patient-centred parameters (e.g. patient age and comorbidities). Assessment of PSCA expression in RCP specimens may enable improved risk assessment for PCa recurrence after RCP. PMID:23078550

  14. The Welsh study of mothers and babies: protocol for a population-based cohort study to investigate the clinical significance of defined ultrasound findings of uncertain significance

    PubMed Central

    2014-01-01

    Background Improvement in ultrasound imaging has led to the identification of subtle non-structural markers during the 18 – 20 week fetal anomaly scan, such as echogenic bowel, mild cerebral ventriculomegaly, renal pelvicalyceal dilatation, and nuchal thickening. These markers are estimated to occur in between 0.6% and 4.3% of pregnancies. Their clinical significance, for pregnancy outcomes or childhood morbidity, is largely unknown. The aim of this study is to estimate the prevalence of seven markers in the general obstetric population and establish a cohort of children for longer terms follow-up to assess the clinical significance of these markers. Methods/Design All women receiving antenatal care within six of seven Welsh Health Boards who had an 18 to 20 week ultrasound scan in Welsh NHS Trusts between July 2008 and March 2011 were eligible for inclusion. Data were collected on seven markers (echogenic bowel, cerebral ventriculomegaly, renal pelvicalyceal dilatation, nuchal thickening, cardiac echogenic foci, choroid plexus cysts, and short femur) at the time of 18 – 20 week fetal anomaly scan. Ultrasound records were linked to routinely collected data on pregnancy outcomes (work completed during 2012 and 2013). Images were stored and reviewed by an expert panel. The prevalence of each marker (reported and validated) will be estimated. A projected sample size of 23,000 will allow the prevalence of each marker to be estimated with the following precision: a marker with 0.50% prevalence to within 0.10%; a marker with 1.00% prevalence to within 0.13%; and a marker with 4.50% prevalence to within 0.27%. The relative risk of major congenital abnormalities, stillbirths, pre-term birth and small for gestational age, given the presence of a validated marker, will be reported. Discussion This is a large, prospective study designed to estimate the prevalence of markers in a population-based cohort of pregnant women and to investigate associations with adverse

  15. Genetic Polymorphism of CHRM2 in COPD: Clinical Significance and Therapeutic Implications.

    PubMed

    Cherubini, Emanuela; Esposito, Maria Cristina; Scozzi, Davide; Terzo, Fabrizio; Osman, Giorgia Amira; Mariotta, Salvatore; Mancini, Rita; Bruno, Pierdonato; Ricci, Alberto

    2016-08-01

    Chronic Obstructive Pulmonary Disease (COPD) is a common preventable and treatable disease, characterized by persistent airflow limitation not fully reversible. However, a number of patients with COPD respond to bronchodilator agents. Some studies have shown polymorphisms in the b2-adrenergic (ADRb2) and muscarinic M2 and M3 receptors (CHRM) that may participate in the modulation of the receptor responses. This study was designed to investigate the existence and the role of adrenergic and muscarinic receptor polymorphisms and their functional impact in COPD. Eighty-two patients with COPD and 17 healthy smokers were recruited and screened for ADRb2 (T164I and R175R), for CHRM2 (rs1824024) and for CHRM3 (-513C/A and -492C/T). Among the polymorphisms studied our results was not able to demonstrate statistically significant association between the polymorphisms studied and COPD risk. Contrarily, we identified, in our COPD population, a significant association with the CHRM2 (rs1824024) polymorphism and disease severity, with lower lung function test values, frequent exacerbations, and poor response to anti-cholinergic drugs. These results suggest the potential role of receptor polymorphism assessment to discriminate newly COPD phenotypes. J. Cell. Physiol. 231: 1745-1751, 2016. © 2015 Wiley Periodicals, Inc. PMID:26633752

  16. HPLC determination and clinical significance of serum prednisone in patients with nephrotic syndrome

    PubMed Central

    Chen, Chun-Mei; Xia, Yun-Cheng; Zhang, Xu-Guang; Peng, Can-Hui; Liu, Fu-You; Peng, You-Ming; Sun, Lin

    2014-01-01

    Aim: A rapid protocol is necessary to determine the serum concentrations of prednisone. Methods: The HP1100 high-performance liquid chromatographic (HPLC) system was employed. The HP Lichrosphere C8 column (250 mm × 4 mm, i.d., 5 μm particle size) was used. The mobile phase was methanol, tetrahydrofuran and water in the ratio 25:25:50. The flow rate was 1.0 ml/min. The sample was monitored by UV absorbance at 240 nm. Acetanilide was used as the internal standard, and methanol was added into the serum for depositing the protein. Results: The chromatography was effective and was not interfered with by the serum components. Good linearity was observed, within the range of 10-500 μg/L for prednisone, and the detection limit was 5 μg/L. The serum concentrations of prednisone between the nephrotic syndrome (NS) group and the control group were significantly different (P < 0.05), while there was no significant difference between the females and males of the NS group (P > 0.05). The serum ncentration of prednisone in the steroid-resistant group was lower than that in the steroid-sensitive group (P < 0.05). Conclusions: HPLC is a practical and reliable method to determine the serum concentration of prednisone with high accuracy, precision, linearity and repeatability. PMID:25664064

  17. Clinical Significance of TIPE2 Protein Upregulation in Non-Hodgkin's Lymphoma.

    PubMed

    Hao, Chunyan; Zhang, Na; Geng, Minghong; Ren, Qing; Li, Yan; Wang, Yan; Chen, Youhai H; Liu, Suxia

    2016-09-01

    Non-Hodgkin's lymphoma (NHL), which includes diffuse large B-cell lymphoma (DLBCL) and peripheral T-cell lymphoma, is a refractory malignant tumor originated from the lymphatic system. TNFAIP8L2 (TIPE2 or tumor necrosis-alpha-induced protein-8 like 2) is a negative regulator for inflammation and an inhibitor for carcinogenesis. However, whether TIPE2 plays a role in lymphomagenesis is unknown. In this study, we determined TIPE2 expression in NHL by immunohistochemistry and investigated its clinicopathological significance in DLBCL. We found that TIPE2 expression was upregulated in both DLBCL and peripheral T-cell lymphoma. But the expression of TIPE2 in T lymphomas was weaker than that in DLBCL. Interestingly, among DLBCL, TIPE2 expression was significantly stronger in the germinal center B-cell (GCB) type than in the non-GCB type. These results suggest that the expression of TIPE2 protein could be a predictor of better prognosis for DLBCL. PMID:27578327

  18. [Urinary incontinence in castrated bitches. Part 1: Significance, clinical aspects and etiopathogenesis].

    PubMed

    Arnold, S

    1997-01-01

    Acquired urinary incontinence occurs in 20% of spayed dogs and there exists a strong correlation between body weight and the risk of urinary incontinence. Bitches with a body weight of more than 20 kg have a risk of 30% white smaller dogs have a risk of 10%. A particular breed disposition exists in Boxers in which 65% are affected. Other breeds with a more than average disposition for urinary incontinence are Dobermans and Giant Schnauzers. Urinary incontinence due to spaying manifests itself mainly while the dogs are sleeping. The cause is a urethral sphincter incompetence which can be verified by a urethral pressure profile (UPP). The microtransducer method proved to be a suitable method for urodynamic studies. It could be demonstrated that the urethral closure pressure is significantly lower in incontinent bitches (4.6 +/- 2.3 cm H2O) than in continent bitches (18.6 +/- 10.5 cm H2O). In addition, the urethral closure pressure for continent bitches dropped significantly within 12 months after surgery. Histological examination revealed that the functional urethral closure cannot be explained by the extent of discernible structures of the urethral wall as seen by light microscopy. PMID:9411733

  19. Clinical significance of subclinical varicocelectomy in male infertility: systematic review and meta-analysis.

    PubMed

    Kim, H J; Seo, J T; Kim, K J; Ahn, H; Jeong, J Y; Kim, J H; Song, S H; Jung, J H

    2016-08-01

    Recent meta-analysis by the Cochrane collaboration concluded that treatment of varicocele may improve an infertile couple's chance of pregnancy. However, there has been no consensus on the management of subclinical varicocele. Therefore, we determine the impact of varicocele treatment on semen parameters and pregnancy rate in men with subclinical varicocele. The randomised controlled trials that assessed the presence and/or treatment of subclinical varicocele were included for systematic review and meta-analysis. Random effect model was used to calculate the weighted mean difference of semen parameters and odds ratio of pregnancy rates. Seven trials with 548 participants, 276 in subclinical varicocelectomy and 272 in no-treatment or clomiphene citrate subjects, were included. Although there was also no statistically significant difference in pregnancy rate (OR 1.29, 95% CI 0.99-1.67), surgical treatment resulted in statistically significant improvements on forward progressive sperm motility (MD 3.94, 95% CI 1.24-6.65). However, the evidence is not enough to allow final conclusions because the quality of included studies is very low and further research is needed. PMID:26589369

  20. Interactions between synchrotron radiation X-ray and biological tissues — theoretical and clinical significance

    PubMed Central

    Chen, Heyu; He, Xin; Sheng, Caibin; Ma, Yingxin; Nie, Hui; Xia, Weiliang; Ying, Weihai

    2011-01-01

    Synchrotron radiation (SR) X-ray has great potential for its applications in both diagnosis and treatment of diseases, due to its characteristic properties including coherence, collimation, monochromaticity, and exceptional brightness. Great advances have been made regarding potential medical applications of SR X-ray in recent years, particularly with the development of the third generation of SR light sources. However, multiple studies have also suggested damaging effects of SR X-ray on biological samples ranging from protein crystals to cells and biological tissues. It has become increasingly important to conduct comprehensive studies on two closely related topics regarding SR X-ray in medical applications: The safety issues regarding the medical applications of SR X-ray and the fundamental mechanisms underlying the interactions between SR X-ray and biological tissues. In this article, we attempted to provide an overview of the literatures regarding these two increasingly significant topics. We also proposed our hypothesis that there are significant differences between the biological tissue-damaging mechanisms of SR X-ray and those of normal X-ray, due to the characteristic properties of SR X-ray such as high dose rate. Future studies are warranted to test this hypothesis, which may profoundly improve our understanding regarding the fundamental mechanisms underlying the interactions between light and matter. These studies would also constitute an essential basis for establishing the safety standard for the medical applications of SR X-ray. PMID:22162780

  1. Prenatal Diagnosis of Persistent Left Superior Vena Cava and its Clinical Significance

    PubMed Central

    Esmer, Aytül Çorbacıoğlu; Yüksel, Atıl; Çalı, Halime; Özsürmeli, Mehmet; Ömeroğlu, Rukiye Eker; Kalelioğlu, İbrahim; Has, Recep

    2014-01-01

    Background: Persistent left superior vena cava (PLSVC) is a variant of systemic venous return which is observed in 0.3% of autopsies in the general population and in 4–8% of patients with congenital heart disease. Aims: To evaluate associated cardiac, extracardiac and chromosomal anomalies in prenatally diagnosed cases of PLSVC and to review their outcome. Study Design: Retrospective comparative study. Methods: The data of patients with a prenatal diagnosis of PLSVC between May 2008 and January 2013 were reviewed retrospectively. Results: Data of 31 cases were reviewed. Fifteen (48.4%) cases were associated with cardiac defects and 17 (54.8%) cases had associated extracardiac sonographic or postpartum findings. Two fetuses had karyotype anomalies. Outcome was significantly more favorable in cases not associated with cardiac defects in comparison to those associated with cardiac anomalies (84.6% vs. 33.3%, p=0.009). All cases with isolated PLSVC survived, while among the cases associated with extracardiac anomalies, with cardiac anomalies and with both extra-cardiac and cardiac anomalies, the survival rate was 75%, 50% and 22.2%, respectively. The most frequent group of cardiac anomalies associated with PLSVC was septal defects and VSD was the most common heart defect individually, being observed in nine fetuses. Conclusion: Prenatally diagnosed PLSVC is associated with cardiac and extracardiac anomalies in the majority of cases. Outcome is significantly worse if PLSVC is associated with a cardiac defect, and the prognosis is excellent in isolated cases. PMID:25207167

  2. Clinical and Prognostic Significance of Preoperative Plasma Fibrinogen Levels in Patients with Operable Breast Cancer

    PubMed Central

    Lu, Xiaofei; Liu, Haixia; Li, Xiangyi; Ma, Rong

    2016-01-01

    Purpose Elevated plasma fibrinogen levels are associated with tumor progression and poor outcomes in different cancer patients. The objective of this study was to investigate the clinical and prognostic value of preoperative plasma fibrinogen levels in patients with operable breast cancer. Methods Two hundred and twenty-three patients diagnosed with breast cancer were retrospectively evaluated in this study. Plasma fibrinogen levels were examined before treatment and analyzed along with patient clinicopathological parameters, disease-free survival (DFS) and overall survival(OS). Both univariate and multivariate analyses were performed to identify the clinicopathological parameters associated with DFS and OS. Results Elevated preoperative plasma fibrinogen levels were directly associated with age of diagnose (≤47 vs. >47, p<0.001), menopause (yes vs. no, p<0.001), tumor size (T1&T2 vs.T3&T4, p = 0.033), tumor stage (Ⅰvs.Ⅱvs.Ⅲ, p = 0.034) and lymph node involvement (N = 0 vs. 1≤N≤3 vs. N≥4, p<0.001), but not with histological grade, molecular type and other Immunohistochemical parameters(ER, PR, HER2 and Ki-67). In a univariate survival analysis, tumor stage, tumor size, lymph node involvement (p<0.001/ p<0.001)and plasma fibrinogen (p<0.001/ p<0.001) levels were associated with disease-free and overall survival, but just lymph nodes involvement (p<0.001, hazard ratio [HR] = 2.9, 95% confidence interval [CI] = 1.6–5.3/ p = 0.006, HR = 3.2, 95% CI = 1.4–7.3) and plasma fibrinogen levels (p = 0.006, HR = 3.4, 95% CI = 1.4–8.3/ p = 0.002, HR = 10.1, 95% CI = 2.3–44.6) were associated with disease-free and overall survival in a multivariate survival analysis, respectively. Conclusions This study demonstrates that elevated preoperative plasma fibrinogen levels are associated with breast cancer progression and are independently associated with a poor prognosis in patients with operable breast cancer. PMID:26799214

  3. Prognostic Factors Affecting Locally Recurrent Rectal Cancer and Clinical Significance of Hemoglobin

    SciTech Connect

    Rades, Dirk Kuhn, Hildegard; Schultze, Juergen; Homann, Nils; Brandenburg, Bernd; Schulte, Rainer; Krull, Andreas; Schild, Steven E.; Dunst, Juergen

    2008-03-15

    Purpose: To investigate potential prognostic factors, including hemoglobin levels before and during radiotherapy, for associations with survival and local control in patients with unirradiated locally recurrent rectal cancer. Patients and Methods: Ten potential prognostic factors were investigated in 94 patients receiving radiotherapy for recurrent rectal cancer: age ({<=}68 vs. {>=}69 years), gender, Eastern Cooperative Oncology Group performance status (0-1 vs. 2-3), American Joint Committee on Cancer (AJCC) stage ({<=}II vs. III vs. IV), grading (G1-2 vs. G3), surgery, administration of chemotherapy, radiation dose (equivalent dose in 2-Gy fractions: {<=}50 vs. >50 Gy), and hemoglobin levels before (<12 vs. {>=}12 g/dL) and during (majority of levels: <12 vs. {>=}12 g/dL) radiotherapy. Multivariate analyses were performed, including hemoglobin levels, either before or during radiotherapy (not both) because these are confounding variables. Results: Improved survival was associated with better performance status (p < 0.001), lower AJCC stage (p = 0.023), surgery (p = 0.011), chemotherapy (p = 0.003), and hemoglobin levels {>=}12 g/dL both before (p = 0.031) and during (p < 0.001) radiotherapy. On multivariate analyses, performance status, AJCC stage, and hemoglobin levels during radiotherapy maintained significance. Improved local control was associated with better performance status (p = 0.040), lower AJCC stage (p = 0.010), lower grading (p = 0.012), surgery (p < 0.001), chemotherapy (p < 0.001), and hemoglobin levels {>=}12 g/dL before (p < 0.001) and during (p < 0.001) radiotherapy. On multivariate analyses, chemotherapy, grading, and hemoglobin levels before and during radiotherapy remained significant. Subgroup analyses of the patients having surgery demonstrated the extent of resection to be significantly associated with local control (p = 0.011) but not with survival (p = 0.45). Conclusion: Predictors for outcome in patients who received radiotherapy for

  4. Correcting arterial blood gases for temperature: (when) is it clinically significant?

    PubMed

    Bisson, Jamie; Younker, Jackie

    2006-01-01

    Interpreting arterial blood gases (ABGs) is a common practice in intensive care units. The use of the temperature correction facility, however, is not standardized, and the effects of temperature correction on the ABG result may affect the overall management of the patient. The aim of this study was to discuss the significance of temperature correction. Current practice in the UK and Australia is discussed along with a review of physiological principles of oxygenation and acid-base balance. The alpha-stat and pH-stat methods of blood gas analysis are presented, with arguments for and against using the temperature correction facility for blood gas analysis. The study concludes with recommendations for practice. PMID:16983854

  5. Data on clinical significance of GAS2 in colorectal cancer cells.

    PubMed

    Chang, Chun-Chao; Huang, Chi-Cheng; Yang, Shung-Haur; Chien, Chih-Cheng; Lee, Chia-Long; Huang, Chi-Jung

    2016-09-01

    The growth arrest-specific 2 (GAS2) was cloned and found to be upregulated in the feces of recurrent CRC patients. This overexpressed GAS2 induced different patterns of gene expressions in CRC cells. Briefly, one cell proliferation marker, Ki-67 antigen (Ki-67), was upregulated in the cells with overexpressed GAS2, "Correlation between proliferation markers: PCNA, Ki-67, MCM-2 and antiapoptotic protein Bcl-2 in colorectal cancer" [1]. Whereas, the expression of another cell proliferation marker, proliferating cell nuclear antigen (PCNA), changed insignificantly [1]. In addition, the mRNA level of one cyclin involving in both cell cycle G1/S and G2/M transitions was also not affected by GAS2 overexpression, "Cdc20 and Cks direct the spindle checkpoint-independent destruction of cyclin A" [2]. The experimental design and procedures in this article can be helpful for understanding the molecular significance of GAS2 in SW480 and SW620 CRC cells. PMID:27284567

  6. [Clinical significance of telomerase activity in precancerous lesion of the liver (adenomatous hyperplasia)].

    PubMed

    Nishimoto, A; Miura, N; Oshimura, M

    1998-05-01

    To understand the role of telomere dynamics in hepatocellular carcinogenesis, we examined the lengths of terminal restriction fragments (TRFs) in hepatocellular carcinoma (HCC) and surrounding tissues with chronic active hepatitis (CAH), liver cirrhosis (LC) and atypical adenomatous hyperplasia (AAH). The peak TRFs in all HCCs were significantly shorter than those of the surrounding tissues (CAH, LC). TRF in AAH was shortened and similar to that of HCC. Telomerase was examined in CAH, LC, AH, and HCC, and detected in high levels almost exclusively in HCCs. Interestingly, the intensity of telomerase activity in the AH was similar to that of HCC. Thus, the progressive shortening of telomere and the activation of telomerase may be a useful marker for the early detection of malignant progression in liver disease. PMID:9613131

  7. Occipital deep white matter hyperintensity as seen by MRI: 1. Clinical significance.

    PubMed

    Miyazaki, M; Hashimoto, T; Tayama, M; Kuroda, Y

    1992-05-01

    Magnetic resonance imaging was performed in 270 patients with various neurologic complaints (1-15Y) with a 0.5 tesla superconducting imaging system using a field echo T1-weighted sequence and spin echo T2-weighted and PD-weighted sequences. Twenty-seven of them had deep white matter hyperintensity (DWMH) in the occipital lobe on T2-weighted images. The frequency of mild DWMH differed in different age groups, suggesting that mild DWMH may result from delayed myelination in the central nervous system. However, the frequency of severe DWMH, which was revealed as isointense relative to cerebrospinal fluid, did not differ in different age groups and it was significantly more common in severely retarded patients. Classification of DWMH based on the signal intensity is valuable to distinguish white matter abnormalities in the occipital lobe from delayed myelination in the same site. PMID:1514653

  8. The clinical significance and impact of interleukin 15 on keratinocyte cell growth and migration

    PubMed Central

    Jones, A.M.; Griffiths, J.L.; Sanders, A.J.; Owen, S.; Ruge, F.; Harding, K.G.; Jiang, W.G.

    2016-01-01

    Chronic wounds represent a significant burden to health services and are associated with patient morbidity. Novel methods to diagnose and/or treat problematic wounds are needed. Interleukin (IL)-15 is a cytokine involved in a number of biological processes and disease states such as inflammation, healing and cancer progression. The current study explores the expression profile of IL-15 and IL-15 receptor α (IL-15Rα) in chronic wounds and its impact on keratinocytes. IL-15 and IL-15Rα expression were examined in healing and non-healing chronic wounds using qPCR and immunohistochemical analysis. The impact of recombinant IL-15 (rhIL-15) on human adult low calcium temperature (HaCaT) keratinocyte growth and migratory potential was further examined. IL-15 transcript expression was slightly, though non-significantly elevated in healing chronic wounds compared with non-healing chronic wounds. IL-15 protein staining was minimal in both subtypes of chronic wounds. By contrast, IL-15Rα transcript and protein expression were both observed to be enhanced in non-healing chronic wounds compared with healing chronic wounds. The treatment of HaCaT cells with rhIL-15 generally enhanced cell growth and promoted migration. Analysis with small molecule inhibitors suggested that the pro-migratory effect of rhIL-15 may be associated with ERK, AKT, PLCγ and FAK signalling. IL-15 may promote healing traits in keratinocytes and the differential expression of IL-15Rα is observed in chronic wounds. Together, this may imply a complex role for this interleukin in wound healing. PMID:27460304

  9. The clinical significance and impact of interleukin 15 on keratinocyte cell growth and migration.

    PubMed

    Jones, A M; Griffiths, J L; Sanders, A J; Owen, S; Ruge, F; Harding, K G; Jiang, W G

    2016-09-01

    Chronic wounds represent a significant burden to health services and are associated with patient morbidity. Novel methods to diagnose and/or treat problematic wounds are needed. Interleukin (IL)-15 is a cytokine involved in a number of biological processes and disease states such as inflammation, healing and cancer progression. The current study explores the expression profile of IL-15 and IL-15 receptor α (IL-15Rα) in chronic wounds and its impact on keratinocytes. IL-15 and IL-15Rα expression were examined in healing and non-healing chronic wounds using qPCR and immunohistochemical analysis. The impact of recombinant IL-15 (rhIL-15) on human adult low calcium temperature (HaCaT) keratinocyte growth and migratory potential was further examined. IL-15 transcript expression was slightly, though non-significantly elevated in healing chronic wounds compared with non-healing chronic wounds. IL-15 protein staining was minimal in both subtypes of chronic wounds. By contrast, IL-15Rα transcript and protein expression were both observed to be enhanced in non-healing chronic wounds compared with healing chronic wounds. The treatment of HaCaT cells with rhIL-15 generally enhanced cell growth and promoted migration. Analysis with small molecule inhibitors suggested that the pro-migratory effect of rhIL-15 may be associated with ERK, AKT, PLCγ and FAK signalling. IL-15 may promote healing traits in keratinocytes and the differential expression of IL-15Rα is observed in chronic wounds. Together, this may imply a complex role for this interleukin in wound healing. PMID:27460304

  10. Renal adenylate cyclase assay for biologically active parathyroid hormone: clinical utility and physiological significance.

    PubMed

    Auf'mkolk, B; Hesch, R D

    1986-01-01

    The stimulation of cyclic AMP production by human renal cortical membranes in the presence of the GTP analogue 5'-guanylimidodiphosphate and a calcium chelator represents a homologous assay system for the evaluation of biologically active parathyroid hormone (bioPTH) in human serum. Bioactive PTH was raised above normal (normal range: undetectable to 4.6 pmol human PTH(1-34) per 1) in 13/17 (76%) patients with primary hyperparathyroidism, in 5/6 (83%) patients with surgically proven hyperparathyroidism secondary to chronic renal failure, in 4/5 (80%) patients with hyperparathyroidism secondary to hypocalcaemia, in all three patients with pseudohypoparathyroidism, in 5/17 (29%) patients with osteoporosis and in 1/9 (11%) patients with renal stones and/or hypercalciuria. Bioactive PTH correlated positively with immunoreactive PTH (iPTH) measured with a radioimmunoassay predominantly recognizing the middle- and carboxyl-terminal region of the PTH molecule (r = 0.503, P less than 0.001). A positive correlation (r = 0.572, P less than 0.05) was found between values of serum calcium and bioPTH in the group with primary hyperparathyroidism. Immunoreactive PTH did not correlate significantly with calcium in this group. In the other patients except those who had chronic renal failure, a negative correlation between serum calcium and both bioPTH and iPTH was observed (P less than 0.01). When alkaline phosphatase was compared with bioPTH in all patients, the correlation was positive (r = 0.390, P less than 0.01); no significant correlation existed between iPTH and alkaline phosphatase in the patients studied.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3944539

  11. Various ARID1A expression patterns and their clinical significance in gastric cancers.

    PubMed

    Kim, Young-Bae; Ham, In-Hye; Hur, Hoon; Lee, Dakeun

    2016-03-01

    AT-rich interactive domain 1A (ARID1A) is frequently mutated in gastric cancers, and loss of ARID1A expression is considered a poor prognostic factor in various cancers. However, in practice, ARID1A shows various expression patterns, and our understanding of its significance is limited. We performed immunohistochemistry for ARID1A, MLH1, and pS6 using whole tissue blocks of 350 gastric cancers and classified the ARID1A expression as follows: retained (63.7%), reduced (17.7%), complete loss (14.9%), and partial loss (3.7%). Complete/partial loss was more common in poorly differentiated histology (P < .001), and reduced or complete loss of ARID1A was frequent in cases with MLH1 loss (P < .001). The ARID1A-reduced group showed only slightly inferior disease-free survival (DFS; P = .254) and overall survival (OS; P = .377) compared to those of the ARID1A-retained group, whereas the group with complete loss showed significantly worse DFS (hazard ratio [HR], 1.732; P = .015) and OS (HR, 1.751; P = .013). Worse DFS (HR, 2.672; P = .005) and OS (HR, 2.531; P = .002) were also noted in the group with partial loss. High expression of pS6 was observed more frequently in groups showing altered ARID1A expression patterns (P < .001). In conclusion, reduced ARID1A expression is not a major prognostic determinant, although it may lead to AKT pathway activation. Tumor cells lacking ARID1A expression may influence the prognosis even if they constitute only a small proportion of the tumor sample. Our data provide an enhanced roadmap for understanding ARID1A with implications for future research and therapeutics. PMID:26826411

  12. Pulmonary cysts identified on chest CT: Are they part of aging change or of clinical significance?

    PubMed Central

    Araki, Tetsuro; Nishino, Mizuki; Gao, Wei; Dupuis, Josée; Putman, Rachel K.; Washko, George R.; Hunninghake, Gary M.; O'Connor, George T.; Hatabu, Hiroto

    2016-01-01

    Objective To investigate the prevalence and natural course of pulmonary cysts in a population-based cohort and to describe the CT image characteristics in association with participant demographics and pulmonary functions. Materials and Methods Chest CT scans of 2633 participants (mean 59.2 years; 50% female) of the Framingham Heart Study (FHS) were visually evaluated for the presence of pulmonary cysts and their image characteristics. These findings were correlated with participant demographics and results of pulmonary function tests as well as the presence of emphysema independently detected on CT. The interval change was investigated by comparison with previous CT scans (median interval, 6.1 years). Results Pulmonary cysts were seen in 7.6% (95% CI, 6.6-8.7; 200/2633). They were not observed in participants younger than 40 years old, and the prevalence increased with age. Multiple cysts (≥5) were seen in 0.9% of all participants. Participants with pulmonary cysts showed significantly lower BMI (P<0.001). Pulmonary cysts were most likely to appear solitary in the peripheral area of the lower lobes and remain unchanged or slightly increase in size over time. Pulmonary cysts showed no significant influence on pulmonary functions (P=0.07-0.6) except for DLCO (P=0.03) and no association with cigarette smoking (P=0.1-0.9) or emphysema (P=0.7). Conclusions Pulmonary cysts identified on chest CT may be a part of the aging changes of the lungs, occurring in asymptomatic individuals older than 40 years, and are associated with decreased BMI and DLCO. Multiple pulmonary cysts may need to be evaluated for the possibility of cystic lung diseases. PMID:26514407

  13. Clinical significance of circulating blood and endothelial cell microparticles in sickle-cell disease.

    PubMed

    Kasar, Mutlu; Boğa, Can; Yeral, Mahmut; Asma, Suheyl; Kozanoglu, Ilknur; Ozdogu, Hakan

    2014-01-01

    Increased thrombocyte activation leads to a higher likelihood of coagulation in sickle-cell disease. On the other hand, chronic inflammation and endothelial cell activation promote vaso-occlusion. The effect of circulating microparticles derived from erythrocytes, monocytes, thrombocytes, and endothelial cells on the vaso-occlusive process is unclear. This study aims to analyze the relationship between sickle-cell disease and miscellaneous organ complications by defining the circulating microparticles during the steady-state and painful crisis periods in 45 patients with sickle-cell disease. Microparticle analysis was conducted using an eight-parameter flow cytometric method, using CD61 PERCP, CD142PE, CD106 FITC, CD14 APC-H7, CD235a FITC, and Annexin-V APC monoclonal antibodies. Microparticle levels of sickle-cell patients were found to be significantly higher during both painful crisis and steady-state situations compared with the control group (for all, p < 0.001). Among these microparticles, levels of erythrocyte microparticles (eMPs) were significantly higher during crisis than in the steady-state period (eMP steady state vs. painful crisis: 7.59 ± 12.24 vs. 7.59 ± 12.24, respectively; p < 0.01). Microparticles, including eMPs, were not affected by hydroxyurea treatment. Their level did not reflect the high frequency of crisis (>3 times/year). Thrombocyte microparticle levels were found to be higher in patients with nephropathia than in those without (48.05 ± 40.23 vs. 7.67 ± 6.75, respectively; p < 0.049). Circulating microparticles seem to be involved in the pathogenesis of sickle-cell disease. eMPs may help with the management of crisis. Thrombocyte microparticles might predict renal damage induced by vaso-occlusion. PMID:24254379

  14. Upregulation of miR-183 expression and its clinical significance in human brain glioma.

    PubMed

    Ye, Zhennan; Zhang, Zihuan; Wu, Lingyun; Liu, Cegang; Chen, Qiang; Liu, Jingpeng; Wang, Xiaoliang; Zhuang, Zong; Li, Wei; Xu, Shanshui; Hang, Chunhua

    2016-08-01

    Glioma is the most common type of primary malignant tumor in the central nervous system (CNS) with a high incidence and a high mortality rate, as well as an extremely low 5-year survival rate. As a class of small non-coding RNAs, microRNAs (miRNAs) may be closely involved in carcinogenesis and might also be connected with glioma diagnosis and prognosis. In this study, we aimed at investigating the expression level of microRNA-183 (miR-183) in 105 cases of glioma tissues of four World Health Organization (WHO) grades and 10 cases of normal brain tissues and its potential predictive and prognostic values in glioma. We found that the expression levels of miR-183 were significantly higher in glioma tissues than that in normal brain tissues, and also higher in high-grade gliomas (WHO grade III and IV) compared with low-grade gliomas (WHO grade I and II). The miR-183 expression level was classified as low or high according to the median value. High expression of miR-183 was found to significantly correlate with larger tumor size, higher WHO grade, and worse Karnofsky performance score (KPS). Kaplan-Meier survival analysis showed that patients with high miR-183 expression had worse overall survival (OS) and progression-free survival (PFS) than patients with low miR-183 expression. Moreover, univariate and multivariate analyses indicated that miR-183 expression level was an independent prognostic parameter of a patient's OS and PFS. In conclusion, our study indicated that miR-183 was upregulated in glioma, and that it may be used as a potential biomarker of poor prognosis in patients with glioma. PMID:27215622

  15. Clinical significance of serum soluble interleukin-2 receptor in chronic myeloproliferative disorders.

    PubMed

    Kawatani, T; Endo, A; Tajima, F; Ooi, S; Kawasaki, H

    1997-02-01

    Serum soluble interleukin-2 receptor (sIL-2R) levels were determined in patients with chronic myeloproliferative disorders (CMPD): 18 with chronic myelogenous leukemia in chronic phase (CML in CP), seven with CML in accelerated phase (AP) or blastic crisis (BC), six with polycythemia vera (PV), eight with essential thrombocythemia (ET), one with primary myelofibrosis (PMF), and 50 controls. The mean (+/-S.E.M.) levels were higher in CMPD than in controls (CML in AP or BC, 2693 +/- 694 U/ml, P < 0.0001; CML in CP, 792 +/- 63 U/ml, P < 0.0001; PV 553 +/- 89 U/ml, P < 0.05; ET, 449 +/- 56 U/ml; PMF, 628 U/ml vs. controls, 395 +/- 25 U/ml). Patients with CML in CP had significantly higher serum sIL-2R levels than patients with ET (P < 0.005), and levels were markedly elevated in AP and BC (P < 0.001). Serum sIL-2R levels were positively correlated with WBC count and lactic dehydrogenase in CMPD, and in CML in CP. Serum sIL-2R levels in CMPD were negatively correlated with RBC and platelet counts. Serum sIL-2R levels were significantly lower in patients with CML in CP who showed a cytogenetic response after interferon (IFN) therapy than in those who showed no response (P < 0.05). These findings suggest that a high serum sIL-2R level reflects the leukocyte growth in CMPD and is useful both for differentiating CML from other CMPD and for predicting the response to IFN therapy in CML. PMID:9071816

  16. Downregulation of WIF-1 and Wnt5a in patients with colorectal carcinoma: clinical significance.

    PubMed

    Abdelmaksoud-Dammak, Rania; Miladi-Abdennadher, Imen; Saadallah-Kallel, Amena; Khabir, Abdelmajid; Sellami-Boudawara, Tahia; Frikha, Mounir; Daoud, Jamel; Mokdad-Gargouri, Raja

    2014-08-01

    Activation of the wingless-type (Wnt) signaling pathway is common in various human cancers including colorectal cancer (CRC). Wnt inhibitory factor-1 (WIF-1) is a secreted antagonist that can bind Wnt ligands and therefore inhibits the Wnt signaling pathway. In this study, we aimed to analyze the expression of two members of Wnt signaling (WIF-1 and Wnt5a) in Tunisian patients with sporadic CRC. WIF-1 was frequently methylated in tumor tissues (87.95 %) compared to normal mucosa (39.54 %) and correlated with distant metastasis and vascular invasion (P = 0.001 and 0.037, respectively). The unmethylated profile of the WIF-1 promoter conferred a benefit to patients in terms of overall survival (P log rank = 0.024). In addition, in the group of patients with methylated WIF-1 promoter, the overall survival rate was significantly prolonged for those with small tumor size (<5 cm) and absence of distant metastasis (P log rank = 0.007 and 0.036, respectively). Aberrant CpG methylation of the WIF-1 promoter leads to transcriptional silencing of this tumor suppressor gene in tumor tissues (P = 0.001). Furthermore, we showed that the level of Wnt5a mRNA was significantly lower in tumor compared to normal tissues (P = 0.031) and lower still in those showing more aggressive behavior (presence of lymph nodes and advanced TNM stage). Our finding supports that WIF-1 is frequently methylated and that Wnt5a acts as a tumor suppressor gene in CRC. Loss of WIF-1 and Wnt5a functions results in more aggressive behavior of the disease. PMID:24833087

  17. Carotid Artery Stenosis at MSCT: Is there a Threshold in Millimeters that Determines Clinical Significance?

    SciTech Connect

    Saba, Luca; Sanfilippo, Roberto; Montisci, Roberto; Mallarini, Giorgio

    2012-02-15

    Purpose: The purpose of this work was to determine whether it is possible to identify a reliable carotid stenosis threshold-measured in millimeters (mm)-that is associated with cerebrovascular symptoms. Methods: Written, informed consent was obtained for each patient; 149 consecutive patients (98 men; median age, 68 years) were studied for suspected pathology of the carotid arteries by using MDCTA. In each patient, carotid artery stenosis was quantified using the mm-method. Continuous data were described as the mean value {+-} standard deviation (SD), and they were compared by using the Student's t test. A ROC curve was calculated to test the study hypothesis and identify a specific mm-stenosis threshold. Logistic regression analysis was performed to include other MDCTA findings, such as plaque type and ulcerations. A P value < 0.05 was considered to indicate statistical significance. Results: Twenty-six patients were excluded. Of those remaining, 75 patients suffered cerebrovascular symptoms (61%). There was a statistically significant difference (P = 0.0046) in the mm-carotid stenosis between patients with symptoms (1.31 {+-} 0.64 mm SD) and without symptoms (1.68 {+-} 0.79 mm SD). Multiple logistic regression analysis confirmed that symptoms were associated with increased luminal stenosis (P = 0.013) and with the presence of fatty plaques (P = 0.0491). Moreover, the ROC curve (Az = 0.669; {+-}0.051 SD; P = 0.0009) indicated that a threshold of 1.6 mm stenosis was associated with a sensitivity to symptoms of 76%. Conclusions: The results of our study suggest an association between luminal stenosis (measure in mm) and the presence of cerebrovascular symptoms. Luminal stenosis of 1.6 mm is associated, with a sensitivity of 76%, with cerebrovascular symptoms.

  18. Clinically significant chronic liver disease in people with Type 2 diabetes: the Edinburgh Type 2 Diabetes Study

    PubMed Central

    Fallowfield, J.A.; Guha, I.N.; Williamson, R.M.; Ali, M.; Glancy, S.; Strachan, M.W.J.; Price, J.F.

    2016-01-01

    Background: Type 2 diabetes is an independent risk factor for chronic liver disease, however disease burden estimates and knowledge of prognostic indicators are lacking in community populations. Aims: To describe the prevalence and incidence of clinically significant chronic liver disease amongst community-based older people with Type 2 diabetes and to determine risk factors which might assist in discriminating patients with unknown prevalent or incident disease. Design: Prospective cohort study. Methods: Nine hundred and thirty-nine participants in the Edinburgh Type 2 Diabetes Study underwent investigation including liver ultrasound and non-invasive measures of non-alcoholic steatohepatitis (NASH), hepatic fibrosis and systemic inflammation. Over 6-years, cases of cirrhosis and hepatocellular carcinoma were collated from multiple sources. Results: Eight patients had known prevalent disease with 13 further unknown cases identified (prevalence 2.2%) and 15 incident cases (IR 2.9/1000 person-years). Higher levels of systemic inflammation, NASH and hepatic fibrosis markers were associated with both unknown prevalent and incident clinically significant chronic liver disease (all P < 0.001). Conclusions: Our study investigations increased the known prevalence of clinically significant chronic liver disease by over 150%, confirming the suspicion of a large burden of undiagnosed disease. The disease incidence rate was lower than anticipated but still much higher than the general population rate. The ability to identify patients both with and at risk of developing clinically significant chronic liver disease allows for early intervention and clinical monitoring strategies. Ongoing work, with longer follow-up, including analysis of rates of liver function decline, will be used to define optimal risk prediction tools. PMID:26454513

  19. Microbiology, Genomics, and Clinical Significance of the Pseudomonas fluorescens Species Complex, an Unappreciated Colonizer of Humans

    PubMed Central

    Scales, Brittan S.; Dickson, Robert P.; LiPuma, John J.

    2014-01-01

    SUMMARY Pseudomonas fluorescens is not generally considered a bacterial pathogen in humans; however, multiple culture-based and culture-independent studies have identified it at low levels in the indigenous microbiota of various body sites. With recent advances in comparative genomics, many isolates originally identified as the “species” P. fluorescens are now being reclassified as novel Pseudomonas species within the P. fluorescens “species complex.” Although most widely studied for its role in the soil and the rhizosphere, P. fluorescens possesses a number of functional traits that provide it with the capability to grow and thrive in mammalian hosts. While significantly less virulent than P. aeruginosa, P. fluorescens can cause bacteremia in humans, with most reported cases being attributable either to transfusion of contaminated blood products or to use of contaminated equipment associated with intravenous infusions. Although not suspected of being an etiologic agent of pulmonary disease, there are a number of reports identifying it in respiratory samples. There is also an intriguing association between P. fluorescens and human disease, in that approximately 50% of Crohn's disease patients develop serum antibodies to P. fluorescens. Altogether, these reports are beginning to highlight a far more common, intriguing, and potentially complex association between humans and P. fluorescens during health and disease. PMID:25278578

  20. Clinic significance of markedly decreased α-klothoin women with preeclampsia.

    PubMed

    Fan, Cuifang; Wang, Yueqiao; Wang, Jingyi; Lei, Di; Sun, Yanmei; Lei, Sicong; Hu, Min; Tian, Yatao; Li, Rui; Wang, Suqing

    2016-01-01

    Preeclampsia (PE) is a leading cause of maternal and perinatal morbidity and mortality. Klotho is a novel gene and the secret form, α-klotho (α-KL), is related to preeclampsia. We conducted this cross-sectional study in Wuhan, China. We used immunohistochemistry, real-time PCR, western blot, ELISA to measure α-KL expression in placenta and its secretion in maternal and umbilical cord serum, and analyzed correlations between α-KL level and other parameters in normal and preeclampsia pregnancy. We found that both mRNA and protein expression of placental α-KL in women with PE was significantly lower than that in normal pregnancy. Also, expression level of α-KL in both maternal and umbilical cord was markedly decreased in PE patients. Further analyses showed that serum α-KL exhibited positive association with fetal birth weight, and reverse association with oxidative stress and renal function markers. Receiver operating characteristic analysis suggested α-KL might be a potential predictor for preeclampsia. PMID:27347309

  1. Detection of fibronectin receptor in sera: its clinical significance as a parameter of hepatic fibrosis.

    PubMed

    Yamauchi, M; Nakajima, H; Ohata, M; Hirakawa, J; Mizuhara, Y; Nakahara, M; Kimura, K; Fujisawa, K; Kameda, H

    1991-08-01

    Pooled sera collected from cirrhotic patients was fractionated by affinity chromatography with a fibronectin receptor monoclonal antibody against the beta-subunit of fibronectin receptor. Eluates were assayed using Western immunoblotting. The relative mobility of the protein reactive with fibronectin receptor antibody was nearly identical to that of the beta-subunit of fibronectin receptor, confirming that fibronectin receptor is present in human serum. Serum levels of the beta-subunit of fibronectin receptor were analyzed by sandwich enzyme-linked immunosorbent assay in patients with various liver diseases. The serum level of fibronectin receptor (micrograms/ml) was significantly higher in patients with chronic hepatitis (inactive, 2.59 +/- 0.04; active, 3.45 +/- 0.13), cirrhosis (4.77 +/- 0.30), alcoholic liver disease (2.96 +/- 0.16) and hepatocellular carcinoma (4.71 +/- 0.49) than in normal subjects (2.11 +/- 0.08). Strong positive correlation was observed between serum levels of fibronectin receptor and histological findings, particularly in the degree of hepatic fibrosis. Immunohistochemical studies with fibronectin receptor antibody revealed that the beta-subunit of fibronectin receptor was present on the plasma membrane of hepatocytes and sinusoidal lining cells in the normal liver and was increased in fibrotic areas and on the plasma membrane of hepatocytes and sinusoidal lining cells of fibrotic liver. The serum level of fibronectin receptor in patients with chronic liver diseases may therefore be a useful marker of hepatic fibrosis. PMID:1830562

  2. Within-Home Blood Pressure Variability on a Single Occasion Has Clinical Significance

    PubMed Central

    Shibasaki, Seiichi; Hoshide, Satoshi; Kario, Kazuomi

    2016-01-01

    There is growing evidence that diversely defined blood pressure variability (BPV) is an independent predictor of hypertensive target organ damage (TOD) and cardiovascular events. Several mechanisms have been speculated to underlie episodes of increased BPV, including the impairment of autonomic or hormonal regulation, renal dysfunction, and increased arterial stiffness. Within-home BPV, defined as differences in BP values obtained on a single occasion at home, could have prognostic significance for hypertensive TOD. It is typically thought that BP values are decreased with repeated measurements on a single occasion at home, but in the present subanalysis of 4,149 J-HOP (Japan Morning Surge-Home Blood Pressure) study patients, approximately 20% of the patients' home BP values were increased or unchanged by repeated measurements on a single occasion. In addition, those patients were likely to have hypertensive TOD. Thus, home BP measurement should be taken twice or more to detect the increase trend in home BP, which has been defined as within-home BPV. PMID:27493902

  3. [Changes of 2015 WHO Histological Classification of Lung Cancer 
and the Clinical Significance].

    PubMed

    Yang, Xin; Lin, Dongmei

    2016-06-20

    Due in part to remarkable advances over the past decade in our understanding of lung cancer, particularly in area of medical oncology, molecular biology, and radiology, there is a pressing need for a revised classification, based not on pathology alone, but rather on an integrated multidisciplinary approach to classification of lung cancer. The 2015 World Health Organization (WHO) Classification of Tumors of the Lung, Pleura, Thymus and Heart has just been published with numerous important changes from the 2004 WHO classification. The revised classification has been greatly improved in helping advance the field, increasing the impact of research, improving patient care and assisting in predicting outcome. The most significant changes will be summarized in this paper as follows: (1) main changes of lung adenocarcinoma as proposed by the 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) classification, (2) reclassifying squamous cell carcinomas into keratinizing, nonkeratinizing, and basaloid subtypes with the nonkeratinizing tumors requiring immunohistochemistry proof of squamous differentiation, (3) restricting the diagnosis of large cell carcinoma only to resected tumors that lack any clear morphologic or immunohistochemical differentiation with reclassification of the remaining former large cell carcinoma subtypes into different categories, (4) grouping of neuroendocrine tumors together in one category, (5) and the current viewpoint of histologic grading of lung cancer. PMID:27335291

  4. Clinical significance of nerve growth factor and tropomyosin-receptor-kinase signaling pathway in intrahepatic cholangiocarcinoma

    PubMed Central

    Yang, Xiao-Qing; Xu, Yun-Fei; Guo, Sen; Liu, Yi; Ning, Shang-Lei; Lu, Xiao-Fei; Yang, Hui; Chen, Yu-Xin

    2014-01-01

    AIM: To investigate the correlation between nerve growth factor-tropomyosin-receptor-kinase (NGF-TrkA) signaling pathway and prognosis in intrahepatic cholangiocarcinoma (IHCC). METHODS: NGF and TrkA expression in 83 samples of IHCC was assessed by immunohistochemistry. Correlations between NGF-TrkA expression and clinicopathological features were analyzed by χ2 test. Moreover, we evaluated the association between NGF-TrkA and overall survival by univariate and multivariate analysis. With experiments in vitro, we investigated the crucial role of NGF-TrkA on proliferation and invasion of IHCC cells with recombinant NGF-β stimulation. RESULTS: We found that NGF and TrkA expression was significantly related with differentiation (P = 0.024) and intraneural invasion (P = 0.003), respectively. Additionally, double higher expression of NGF and TrkA was identified as an independent prognostic factor in IHCC (P = 0.003). Moreover, we demonstrated that NGF-TrkA signaling pathway can promote IHCC proliferation and invasion. CONCLUSION: NGF-TrkA double higher expression is an independent prognostic factor in IHCC. NGF-TrkA pathway can promote IHCC progression, indicating that NGF-TrkA may become a potential drug target. PMID:24744599

  5. Clinical significance of subcutaneous calcinosis in patients with systemic sclerosis. Does diltiazem induce its regression?

    PubMed Central

    Vayssairat, M; Hidouche, D; Abdoucheli-Baudot, N; Gaitz, J

    1998-01-01

    OBJECTIVE—To establish whether diltiazem reduces subcutaneous calcinosis (SCC) in patients with systemic sclerosis (SSc), and whether this calcinosis is related to other signs or symptoms.
METHODS—47 patients with SSc were evaluated and divided into two groups according to the presence or absence of SCC.
RESULTS—Among the 12 patients with SCC who were treated with diltiazem and had sequential hand radiographs (differential time between the two radiographs: 7.8±4 years), there was a slight radiological improvement in three patients only. More patients with SCC had anticentromere antibodies than patients without (p=0.003), fewer had anti-Scl 70 antibodies (p=0.01), more had telangiectasia and giant capillaries (p=0.04 and 0.048 respectively), and SCC patients had significantly fewer capillaries at the nailfold (p=0.03).
CONCLUSION—These results do not clearly indicate that diltiazem is effective in calcinosis associated with SSc. Among the patients with SSc, those who also had SCC exhibited a distinctive autoimmune profile and more severe cutaneous capillary injury than those without SCC.

 Keywords: systemic sclerosis; scleroderma; calcinosis; diltiazem PMID:9709184

  6. Clinical and therapeutic significance of sirtuin-4 expression in colorectal cancer.

    PubMed

    Huang, Guoyu; Cheng, Jun; Yu, Fudong; Liu, Xisheng; Yuan, Chenwei; Liu, Chenchen; Chen, Xiaolei; Peng, Zhihai

    2016-05-01

    Several members of the sirtuin family (SIRT1-7), which are a highly conserved family of NAD+-dependent enzymes, play an important role in tumor formation. Recent studies indicate that SIRT4 acts as a tumor suppressor by regulating glutamine metabolism. In the present study, we investigated the expression and activity of SIRT4 in colorectal cancer. Using a tissue microarray of 89 colorectal cancer cases, we found that SIRT4 was significantly downregulated in colorectal cancer tissues compared with that noted in the corresponding normal tissue (P<0.001). Lower SIRT4 levels were associated with worse pathological differentiation (P=0.031) and poorer post-operative overall survival rate (P=0.041). We found that SIRT4 overexpression inhibited the proliferation of colorectal cancer cells in vitro and in vivo. SIRT4 inhibited the glutamine metabolism of colorectal cancer cells and synergistically with glycolysis inhibitors induced cell death. SIRT4 also increased the sensitivity of colorectal cancer cells to chemotherapeutic drug 5-fluorouracil by inhibiting the cell cycle. Together, these results highlight the prognostic value of SIRT4 in colorectal cancer and the potential application of SIRT4 in colorectal cancer treatment. PMID:26986234

  7. Clinic significance of markedly decreased α-klothoin women with preeclampsia

    PubMed Central

    Fan, Cuifang; Wang, Yueqiao; Wang, Jingyi; Lei, Di; Sun, Yanmei; Lei, Sicong; Hu, Min; Tian, Yatao; Li, Rui; Wang, Suqing

    2016-01-01

    Preeclampsia (PE) is a leading cause of maternal and perinatal morbidity and mortality. Klotho is a novel gene and the secret form, α-klotho (α-KL), is related to preeclampsia. We conducted this cross-sectional study in Wuhan, China. We used immunohistochemistry, real-time PCR, western blot, ELISA to measure α-KL expression in placenta and its secretion in maternal and umbilical cord serum, and analyzed correlations between α-KL level and other parameters in normal and preeclampsia pregnancy. We found that both mRNA and protein expression of placental α-KL in women with PE was significantly lower than that in normal pregnancy. Also, expression level of α-KL in both maternal and umbilical cord was markedly decreased in PE patients. Further analyses showed that serum α-KL exhibited positive association with fetal birth weight, and reverse association with oxidative stress and renal function markers. Receiver operating characteristic analysis suggested α-KL might be a potential predictor for preeclampsia. PMID:27347309

  8. Expression and clinical significance of A‐kinase anchor protein 4 in lung adenocarcinoma tissue

    PubMed Central

    Guo, Kang; Yu, Xiao‐Yun; Yu, Zhuang; Xu, Ping

    2015-01-01

    Abstract Background The A‐kinase anchor proteins (AKAP) are a growing family of scaffolding proteins involved in the occurrence, proliferation, and metastasis of tumors by controlling intracellular signals. In this study, the expression and significance of AKAP4 were analyzed in patients with lung adenocarcinoma and adjacent non‐cancerous tissues. Methods Using reverse transcriptase‐polymerase chain reaction and Western blot, AKAP4 messenger ribonucleic acid (mRNA) and protein expression levels were measured in 108 cases of lung adenocarcinoma and adjacent non‐cancerous tissues. Results AKAP4 mRNA and protein were expressed in lung adenocarcinoma tissues, but not in adjacent non‐cancerous tissues. The expression of AKAP4 mRNA and protein was closely associated with lymphatic metastasis (P < 0.05), but had no relationship with stage, differentiation degree, gender, age or smoking (P > 0.05). AKAP4 expression had an adverse effect on the overall survival rate (P < 0.05). Conclusion The expression of AKAP4 was high in lung adenocarcinoma tissue, which may be closely related to the lymphatic metastasis of lung adenocarcinoma. AKAP4 may be a novel lung adenocarcinoma molecule marker and a predictor of poor prognosis. PMID:27148411

  9. Clinical significance of visceral adiposity assessed by computed tomography: A Japanese perspective

    PubMed Central

    Ryo, Miwa; Kishida, Ken; Nakamura, Tadashi; Yoshizumi, Tohru; Funahashi, Tohru; Shimomura, Iichiro

    2014-01-01

    Abdominal obesity, rather than total amount of fat, is linked to obesity-related disorders. Visceral adiposity is an important component of obesity-related disorders in Japanese individuals with a mild degree of adiposity compared with Western subjects. In 1983, our group reported techniques for body fat analysis using computed tomography (CT) and established the concept of visceral fat obesity in which intra-abdominal fat accumulation is an important factor in the development of obesity-related complications, such as diabetes, lipid disorders, hypertension and atherosclerosis. Our group also established ideal imaging conditions for determining abdominal fat area at the umbilical level CT scan. Visceral fat area (VFA) measured in a single slice at L4 level correlated significantly with the total abdominal visceral fat volume measured on multislice CT scan. In a large-scale study of a Japanese population, the mean number of obesity-related cardiovascular risk factors (hypertension, low high-density lipoprotein cholesterolemia and/or hypertriglyceridemia, and hyperglycemia) was greater than 1.0 at 100 cm2 of VFA, irrespective of gender, age and body mass index. Our group also demonstrated that reduction of visceral fat accumulation subsequent to voluntary lifestyle modification, “Hokenshido”, correlated with a decrease in the number of obesity-related cardiovascular risk factors. It is important to select the most appropriate subjects from the general population (e.g., non-obese subjects with a cluster of risk factors for the metabolic syndrome) that are most suitable for body weight reduction, with the goal of preventing atherosclerotic cardiovascular diseases. PMID:25071881

  10. Clinical significance of brain white matter hyperintensities in young adults with psychiatric illness.

    PubMed

    Breeze, Janis L; Hesdorffer, Dale C; Hong, Xiaoni; Frazier, Jean A; Renshaw, Perry F

    2003-01-01

    Magnetic resonance imaging (MRI) provides detailed images of brain anatomy, with especially clear definition of gray and white matter structures. Several brain MRI studies have suggested that adults with bipolar disorder (BD) are more likely to have "white matter hyperintensities" (WMH) than adults without BD. The disproportionately greater frequency of these lesions in otherwise physically healthy patients suggests that the illness itself, or treatments used to control the illness, may be risk factors for the development of white matter changes. Similarly, WMH may be an etiological factor for some types of BD. In addition to reviewing the relevant literature, this research study attempted to determine whether lithium treatment is associated with an increased prevalence of WMH in young adults with psychiatric illness. To test this hypothesis, we evaluated over 600 brain MRI scans from inpatients at McLean Hospital, Belmont, Massachusetts. We controlled for possible confounding variables such as age, vascular disease, substance abuse, and markers of illness severity. We found that individuals with BD were no more likely to have WMH than other psychiatric patients. Lithium use was nonsignificantly associated with the presence of WMH. A multivariate regression model for the presence of WMH showed that heart disease, female gender, and multiple psychiatric admissions were significant predictors of WMH. This study does not support previous findings that BD, compared to other psychiatric illnesses, was associated with increased risk of WMH. Lithium use may be subtly associated with WMH. Our results are consistent with previous research that found an association between cardiovascular disease, advanced age, and the presence of WMH, though our analysis appears to be unique in its inclusion of cardiovascular disease as a risk factor in young adults with psychiatric illness. PMID:14555427

  11. Transdermal nicotine patches do not cause clinically significant gastroesophageal reflux or esophageal motor disorders.

    PubMed

    Wright, R A; Goldsmith, L J; Ameen, V; D'Angelo, A; Kirby, S L; Prakash, S

    1999-12-01

    Transdermal nicotine delivery systems are widely used in smoking cessation. The purpose of this study was to determine whether common symptoms of pyrosis and dyspepsia associated with these patches are related to gastroesophageal reflux or esophageal dysmotility. Twenty-seven paid volunteer cigarette smokers (> 15 cigarettes/day) without symptomatic gastroesophageal reflux disease participated in this single-blinded, placebo-controlled study. Twenty subjects completed the study. Subjects underwent three sequential 24-h intraesophageal pH/motor studies (Synectics model T32342084, Shore View, MN). The pH/motility probe was positioned 5 cm above the manometrically determined LES. A placebo patch was applied for the first 24-h study and a 15-mg nicotine patch (Nicotrol) was applied for the initial 16 h (removed for remaining 8 h) of the second 24-h period. A 21-mg nicotine patch (Nicoderm) was applied for another 24-h study period. All subjects consumed an identical, defined diet documented by meal receipts, and refrained from smoking and tobacco use throughout the study periods (CO breath test confirmation). The Wilcoxon, paired t-test, exact McNemar statistical methods were used. The results showed that there were no significant differences in reflux symptoms (pyrosis, chest pain, nausea, dysphagia), supine gastroesophageal reflux (number of episodes, duration, or cumulative acid exposure), or the total number of reflux episodes between placebo and nicotine patch treatment periods. The number of post-prandial upright acid reflux episodes (p = 004) and number of upright acid reflux episodes lasting more than 5 min (p = 0.007) were statistically higher with the placebo patch compared to the active nicotine patches. No differences in intraesophageal pH or motility indices were noted between the two transdermal nicotine patches (Nicotrol, Nicoderm). It was concluded that dyspeptic symptoms in subjects utilizing transdermal nicotine patches are not related to

  12. Brain Iron Homeostasis: From Molecular Mechanisms To Clinical Significance and Therapeutic Opportunities

    PubMed Central

    Haldar, Swati; Tripathi, Ajai K.; Horback, Katharine; Wong, Joseph; Sharma, Deepak; Beserra, Amber; Suda, Srinivas; Anbalagan, Charumathi; Dev, Som; Mukhopadhyay, Chinmay K.; Singh, Ajay

    2014-01-01

    Abstract Iron has emerged as a significant cause of neurotoxicity in several neurodegenerative conditions, including Alzheimer's disease (AD), Parkinson's disease (PD), sporadic Creutzfeldt-Jakob disease (sCJD), and others. In some cases, the underlying cause of iron mis-metabolism is known, while in others, our understanding is, at best, incomplete. Recent evidence implicating key proteins involved in the pathogenesis of AD, PD, and sCJD in cellular iron metabolism suggests that imbalance of brain iron homeostasis associated with these disorders is a direct consequence of disease pathogenesis. A complete understanding of the molecular events leading to this phenotype is lacking partly because of the complex regulation of iron homeostasis within the brain. Since systemic organs and the brain share several iron regulatory mechanisms and iron-modulating proteins, dysfunction of a specific pathway or selective absence of iron-modulating protein(s) in systemic organs has provided important insights into the maintenance of iron homeostasis within the brain. Here, we review recent information on the regulation of iron uptake and utilization in systemic organs and within the complex environment of the brain, with particular emphasis on the underlying mechanisms leading to brain iron mis-metabolism in specific neurodegenerative conditions. Mouse models that have been instrumental in understanding systemic and brain disorders associated with iron mis-metabolism are also described, followed by current therapeutic strategies which are aimed at restoring brain iron homeostasis in different neurodegenerative conditions. We conclude by highlighting important gaps in our understanding of brain iron metabolism and mis-metabolism, particularly in the context of neurodegenerative disorders. Antioxid. Redox Signal. 20, 1324–1363. PMID:23815406

  13. Clinical significance of coagulase-negative staphylococci isolates from nosocomial bloodstream infections.

    PubMed

    Morad Asaad, Ahmed; Ansar Qureshi, Mohamed; Mujeeb Hasan, Syed

    2016-05-01

    Background Identification of coagulase-negative staphylococci (CoNS) as nosocomial pathogens or contaminants is significant for microbiologists and clinicians. This study aimed to determine the frequency of isolation and antimicrobial resistance patterns of CoNS isolates from nosocomial bloodstream infections (BSIs) and to identify risk factors associated with true bacteremia caused by these emerging pathogens in a Saudi tertiary care hospital. Methods All CoNS-positive cultures from inpatients were identified using the standard methods during a 10-month period. Antimicrobial susceptibility testing was done using the reference broth microdilution method. Results A total of 208 isolates were identified; of these 75 (32.2%) were considered infection associated, and 133 (67.8%) were considered contamination. S. epidermidis accounted for 34.7% of bacteremia cases, followed by S. hominis (21.3%), S. haemolyticus (16%), and S. saprophyticus (12%). Central venous catheters (p ≤ 0.0001), prior antibiotic therapy (p ≤ 0.0001), the occurrence of more than one positive blood culture (p ≤ 0.0001), and intensive care unit (ICU) admission (p = 0.007) were all independently associated with CoNS bacteremia. Overall, all isolates were highly resistant to penicillin (94.7%), oxacillin (90.7%), and erythromycin (85.3%). The rates of susceptibility to vancomycin, daptomycin, and teicoplanin were 98.7%, 98.7%, and 93.3%, respectively. Conclusions Our results further highlight that accurate identification and susceptibility testing of CoNS isolates from nosocomial BSIs are crucial to minimize excessive antibiotic use and unnecessary catheter removal. In addition, daptomycin may be an efficient alternative therapeutic option for CoNS resistant to oxacillin and other commonly used antibiotics. PMID:26666168

  14. Clinical significance of nonspecificity of antiphospholipid antibodies in recurrent abortions and unexplained infertility

    PubMed Central

    Malik, Priyanka; Kaur, Maninder; Bedi, Gurdeep Kaur; Kaur, Khushpreet

    2016-01-01

    Background: Antiphospholipid antibodies (APLA) are acquired autoantibodies directed to phospholipids which are associated with slow progressive thrombosis and infarction of placenta. Infertility and recurrent pregnancy loss may occur because of impaired trophoblast function, placental infarction, and abnormal blood clotting. Aim: To evaluate APLA (IgG and IgM) in cases of infertility and recurrent abortions. Materials and Methods: A prospective study comprising 70 subjects was carried out. Fifty cases of unexplained infertility and recurrent abortions (25 each) constituted the study group. Twenty healthy multipara females of same reproductive age group constituted the control group. Venous blood samples were collected, and serum was analyzed for two types of APLA (IgG and IgM) by ELISA method. Results: The mean IgM and IgG levels in recurrent abortions group were 8.10 MPL-U/ml and 6.17 GPL-U/ml, respectively whereas in control group, the levels were 4.67 MPL-U/ml and 4.53 GPL-U/ml, respectively. The difference was statistically nonsignificant. The mean IgM and IgG levels in unexplained infertility group were 7.30 MPL-U/ml and 6.12 GPL-U/ml, respectively whereas in control group, the levels were 4.67 MPL-U/ml and 4.53 GPL-U/ml, respectively. Again the difference was statistically nonsignificant. Conclusions: The present study concludes that there is no