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Sample records for achieving clinically significant

  1. Randomization in clinical trials in orthodontics: its significance in research design and methods to achieve it.

    PubMed

    Pandis, Nikolaos; Polychronopoulou, Argy; Eliades, Theodore

    2011-12-01

    Randomization is a key step in reducing selection bias during the treatment allocation phase in randomized clinical trials. The process of randomization follows specific steps, which include generation of the randomization list, allocation concealment, and implementation of randomization. The phenomenon in the dental and orthodontic literature of characterizing treatment allocation as random is frequent; however, often the randomization procedures followed are not appropriate. Randomization methods assign, at random, treatment to the trial arms without foreknowledge of allocation by either the participants or the investigators thus reducing selection bias. Randomization entails generation of random allocation, allocation concealment, and the actual methodology of implementing treatment allocation randomly and unpredictably. Most popular randomization methods include some form of restricted and/or stratified randomization. This article introduces the reasons, which make randomization an integral part of solid clinical trial methodology, and presents the main randomization schemes applicable to clinical trials in orthodontics.

  2. [Hypertriglyceridemia: concept and clinical significance].

    PubMed

    Hirano, Tsutomu

    2013-09-01

    Hypertriglyceridemia is a common lipid disorder as well as hypercholesterolemia. However clinical significance of hypertriglyceridemia is not fully understood because of its heterogeneous lipoprotein phenotypes and complex etiology. Severe hypertriglyceridemia increases the risk for pancreatitis, whereas mild or moderate hypertriglyceridemia may be a risk factor for cardiovascular disease. Patients with hypertriglyceridemia are usually accompanied by other cardiovascular related disorders, such as central obesity, type 2 diabetes, and liver steatosis. Ectopic fat accumulation is often seen in hypertriglyceridemic subjects and various organ injuries are developed by the lipotoxicity. Hypertriglyceridemia is strongly associated with remnant lipoprotein accumulation, increased small dense LDL, and low HDL-cholesterol. All these lipid abnormalities are recognized as cardiovascular risk factors. The pathophysiology of lipoprotein metabolism related to the hypertriglyceridemia is summarized in this brief review.

  3. 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

  4. Achieving quality assurance through clinical audit.

    PubMed

    Patel, Seraphim

    2010-06-01

    Audit is a crucial component of improvements to the quality of patient care. Clinical audits are undertaken to help ensure that patients can be given safe, reliable and dignified care, and to encourage them to self-direct their recovery. Such audits are undertaken also to help reduce lengths of patient stay in hospital, readmission rates and delays in discharge. This article describes the stages of clinical audit and the support required to achieve organisational core values.

  5. 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.

  6. Statistical significance testing and clinical trials.

    PubMed

    Krause, Merton S

    2011-09-01

    The efficacy of treatments is better expressed for clinical purposes in terms of these treatments' outcome distributions and their overlapping rather than in terms of the statistical significance of these distributions' mean differences, because clinical practice is primarily concerned with the outcome of each individual client rather than with the mean of the variety of outcomes in any group of clients. Reports of the obtained outcome distributions for the comparison groups of all competently designed and executed randomized clinical trials should be publicly available no matter what the statistical significance of the mean differences among these groups, because all of these studies' outcome distributions provide clinically useful information about the efficacy of the treatments compared.

  7. 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.

  8. 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.

  9. 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…

  10. Clinically significant drug interactions with atypical antipsychotics.

    PubMed

    Kennedy, William Klugh; Jann, Michael W; Kutscher, Eric C

    2013-12-01

    Atypical antipsychotics [also known as second-generation antipsychotics (SGAs)] have become a mainstay therapeutic treatment intervention for patients with schizophrenia, bipolar disorders and other psychotic conditions. These agents are commonly used with other medications--most notably, antidepressants and antiepileptic drugs. Drug interactions can take place by various pharmacokinetic, pharmacodynamic and pharmaceutical mechanisms. The pharmacokinetic profile of each SGA, especially with phase I and phase II metabolism, can allow for potentially significant drug interactions. Pharmacodynamic interactions arise when agents have comparable receptor site activity, which can lead to additive or competitive effects without alterations in measured plasma drug concentrations. Additionally, the role of drug transporters in drug interactions continues to evolve and may effect both pharmacokinetic and pharmacodynamic interactions. Pharmaceutical interactions occur when physical incompatibilities take place between agents prior to drug absorption. Approximate therapeutic plasma concentration ranges have been suggested for a number of SGAs. Drug interactions that markedly increase or decrease the concentrations of these agents beyond their ranges can lead to adverse events or diminished clinical efficacy. Most clinically significant drug interactions with SGAs occur via the cytochrome P450 (CYP) system. Many but not all drug interactions with SGAs are identified during drug discovery and pre-clinical development by employing a series of standardized in vitro and in vivo studies with known CYP inducers and inhibitors. Later therapeutic drug monitoring programmes, clinical studies and case reports offer methods to identify additional clinically significant drug interactions. Some commonly co-administered drugs with a significant potential for drug-drug interactions with selected SGAs include some SSRIs. Antiepileptic mood stabilizers such as carbamazepine and valproate, as

  11. Dementia Caregiver Intervention Research: In Search of Clinical Significance

    PubMed Central

    Schulz, Richard; O’Brien, Alison; Czaja, Sara; Ory, Marcia; Norris, Rachel; Martire, Lynn M.; Belle, Steven H.; Burgio, Lou; Gitlin, Laura; Coon, David; Burns, Robert; Gallagher-Thompson, Dolores; Stevens, Alan

    2008-01-01

    Purpose We reviewed intervention studies that reported dementia caregiver outcomes published since 1996, including psychosocial interventions for caregivers and environmental and pharmacological interventions for care recipients. Our goal was to focus on issues of clinical significance in caregiver intervention research in order to move the field toward a greater emphasis on achieving reliable and clinically meaningful outcomes. Design and Methods MEDLINE, PsycINFO, and Cumulative Index to Nursing & Allied Health databases from 1996 through 2001 were searched to identify articles and book chapters mapping to two medical subject headings: caregivers and either dementia or Alzheimer’s disease. Articles were evaluated on two dimensions, outcomes in four domains thought to be important to the individual or society and the magnitude of reported effects for these outcomes in order to determine if they were large enough to be clinically meaningful. Results Although many studies have reported small to moderate statistically significant effects on a broad range of outcomes, only a small proportion of these studies achieved clinically meaningful outcomes. Nevertheless, caregiving intervention studies have increasingly shown promise of affecting important public health outcomes in areas such as service utilization, including delayed institutionalization; psychiatric symptomatology, including the successful treatment of major and minor depression; and providing services that are highly valued by caregivers. Implications Assessment of clinical significance in addition to statistical significance is needed in this research area. Specific recommendations on design, measurement, and conceptual issues are made to enhance the clinical significance of future research. PMID:12351794

  12. 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…

  13. Barnacle geese achieve significant energetic savings by changing posture.

    PubMed

    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.

  14. 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.

  15. Quantifying the Clinical Significance of Cannabis Withdrawal

    PubMed Central

    Allsop, David J.; Copeland, Jan; Norberg, Melissa M.; Fu, Shanlin; Molnar, Anna; Lewis, John; Budney, Alan J.

    2012-01-01

    Background and Aims Questions over the clinical significance of cannabis withdrawal have hindered its inclusion as a discrete cannabis induced psychiatric condition in the Diagnostic and Statistical Manual of Mental Disorders (DSM IV). This study aims to quantify functional impairment to normal daily activities from cannabis withdrawal, and looks at the factors predicting functional impairment. In addition the study tests the influence of functional impairment from cannabis withdrawal on cannabis use during and after an abstinence attempt. Methods and Results A volunteer sample of 49 non-treatment seeking cannabis users who met DSM-IV criteria for dependence provided daily withdrawal-related functional impairment scores during a one-week baseline phase and two weeks of monitored abstinence from cannabis with a one month follow up. Functional impairment from withdrawal symptoms was strongly associated with symptom severity (p = 0.0001). Participants with more severe cannabis dependence before the abstinence attempt reported greater functional impairment from cannabis withdrawal (p = 0.03). Relapse to cannabis use during the abstinence period was associated with greater functional impairment from a subset of withdrawal symptoms in high dependence users. Higher levels of functional impairment during the abstinence attempt predicted higher levels of cannabis use at one month follow up (p = 0.001). Conclusions Cannabis withdrawal is clinically significant because it is associated with functional impairment to normal daily activities, as well as relapse to cannabis use. Sample size in the relapse group was small and the use of a non-treatment seeking population requires findings to be replicated in clinical samples. Tailoring treatments to target withdrawal symptoms contributing to functional impairment during a quit attempt may improve treatment outcomes. PMID:23049760

  16. Clinical trials in Russia: achieving excellence

    NASA Astrophysics Data System (ADS)

    Reznik, Robert S.; Ichim, Thomas E.; Petrov, Vladimir; Reznik, Boris N.

    2005-06-01

    The Russian population offers a unique opportunity for conducting clinical trials in general, and specifically in the area of Medical Devices. Although the regulatory framework for approval of clinical trials and eventual marketing registration is based on an American-style format, details of operating in the Russian framework are very different. Understanding and leveraging the unique characteristics of the Russian system on the patient side, the investigator side, and the regulatory side is important in extracting optimum value out of clinical trials in Russia. Having performed Medical Device research and clinical trials in Russia, the authors overview the present system and describe various strategies for working in this growing but still under-utilized clinical trials arena.

  17. 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

  18. 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

  19. Clinical Significance and Pathogenesis of Osteoporosis*

    PubMed Central

    Nordin, B. E. C.

    1971-01-01

    The development of osteoporosis with advancing age in man is a widespread if not a universal phenomenon. The average loss between youth and old age amounts to about 15% of the skeleton but involves a much larger proportion of trabecular than of cortical bone. The principal clinical manifestation of osteoporosis is fracture, and three osteoporotic fracture syndromes can be defined: the lower forearm fracture, which predominantly affects women between the ages of 50 and 65; the fracture of the proximal femur, which affects both sexes over the age of 70; and the relatively rare vertebral crush fracture syndrome, which may present at any age but is most common in elderly women. The lower forearm fracture rate is inversely related to the mean normal lower forearm x-ray “density” of the wrist, which falls by about 30% in the 15 years following the menopause. This process, which is associated with corresponding trabecular bone loss elsewhere in the skeleton, is associated with a corresponding rise in the fasting urinary calcium excretion. Some degree of negative calcium balance, and consequent bone resorption, probably occurs in everyone during the later part of the night because calcium absorption is completed within about three to five hours of a meal. In postmenopausal women, however, the sensitivity of the bone to parathyroid hormone appears to be increased, and their nocturnal negative calcium balance therefore comes to exceed the positive balance which can be achieved during the waking hours. Femoral neck fractures in old people reflect the further progression of osteoporosis with advancing age since the fracture rate is inversely correlated with the mean thickness of the metacarpal cortex in the normal population. This progressive osteoporosis is associated with and could well result from a steady decline in calcium absorption which is at least partially attributable to vitamin-D deficiency and reversible on vitamin-D treatment. The vertebral crush fracture

  20. AEG-1/MTDH/LYRIC: Clinical Significance

    PubMed Central

    Sarkar, Devanand; Fisher, Paul B.

    2014-01-01

    “Gain-of-function” and “loss-of-function” studies in human cancer cells and analysis of a transgenic mouse model have convincingly established that AEG-1/MTDH/LYRIC performs a seminal role in regulating proliferation, invasion, angiogenesis, metastasis, and chemoresistance, the salient defining hallmarks of cancer. These observations are strongly buttressed by clinicopathologic correlations of AEG-1/MTDH/LYRIC expression in a diverse array of cancers distinguishing AEG-1/MTDH/LYRIC as an independent biomarker for highly aggressive metastatic disease with poor prognosis. AEG-1/MTDH/LYRIC has been shown to be a marker predicting response to chemotherapy, and serum anti-AEG-1/MTDH/LYRIC antibody titer also serves as a predictor of advanced stages of aggressive cancer. However, inconsistent findings have been reported regarding the localization of AEG-1/MTDH/LYRIC protein in the nucleus or cytoplasm of cancer cells and the utility of nuclear or cytoplasmic AEG-1/MTDH/LYRIC to predict the course and prognosis of disease. This chapter provides a comprehensive analysis of the existing literature to emphasize the common and conflicting findings relative to the clinical significance of AEG-1/MTDH/LYRIC in cancer. PMID:23889987

  1. 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

  2. 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.

  3. Clinical significance of autoantibodies in autoimmune hepatitis.

    PubMed

    Liberal, Rodrigo; Mieli-Vergani, Giorgina; Vergani, Diego

    2013-10-01

    The accurate diagnosis and classification of autoimmune hepatitis (AIH) rely upon the detection of characteristic autoantibodies. Positivity for anti-nuclear (ANA) and/or anti-smooth muscle (SMA) autoantibodies defines AIH type 1 (AIH-1), whereas anti-liver kidney microsomal type 1 (anti-LKM1) and/or anti-liver cytosol type 1 (anti-LC1) define AIH type 2 (AIH-2). ANA and SMA, and less commonly anti-LKM1, have also been detected in de-novo autoimmune hepatitis developing after liver transplantation, a condition that may affect patients transplanted for non-autoimmune liver disease. The diagnostic autoantibodies associated with AIH-1 are also detected in the paediatric AIH/sclerosing cholangitis overlap syndrome, referred to as autoimmune sclerosing cholangitis (ASC). ASC, like adult primary sclerosing cholangitis, is often associated with atypical perinuclear anti-neutrophil cytoplasmic autoantibodies (p-ANCA), although p-ANCA are also detected in other autoimmune liver diseases. These associations highlight the necessity for simple and prompt diagnostic autoantibody testing, and the requirement for the accurate interpretation of the results of the tests in the clinical context. Fine-mapping of antigenic autoantibody targets has facilitated the development of rapid molecular assays that have the potential to revolutionise the field if properly standardised and when used in combination with classical immunofluorescence. Despite their diagnostic significance, the pathogenic role of the various autoantibodies and the mechanisms by which they can potentially inflict damage onto the liver cell remain a topic for further research.

  4. 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.

  5. [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.

  6. The clinical significance of pancreatic steatosis.

    PubMed

    Smits, Mark M; van Geenen, Erwin J M

    2011-03-01

    More research is now focused on pancreatic steatosis. Multiple definitions, clinical associations and synonyms for pancreatic steatosis are described in the literature and can be confusing. The integration and comparison of several studies concerning this topic is therefore challenging. In the past, pancreatic steatosis was considered an innocuous condition, a bystander of many underlying diseases (such as congenital syndromes, hemochromatosis and viral infection). However, evidence that pancreatic steatosis (strongly associated with obesity and the metabolic syndrome) has a role in type 2 diabetes mellitus, pancreatic exocrine dysfunction, acute pancreatitis, pancreatic cancer and the formation of pancreatic fistula after pancreatic surgery is emerging. This Review focuses on the different etiological factors and the clinical consequences of pancreatic steatosis.

  7. [Neuroplasticity: main mechanisms and their clinical significance].

    PubMed

    Damulin, I V

    2009-01-01

    Common mechanisms of neuroplasticity and their manifestations in different neurological diseases are reviewed. The ambiguity of physiological and clinical changes caused by neuroplasticity is emphasized. Special attention is drawn to the functional post-stroke rehabilitation. The author emphasizes the importance of "cerebral reserve" in normal ageing and Alzheimer's disease. Possibilities of neuroplasticity activation are reviewed. The efficacy of cerebrolysin in the treatment of dementia and stroke is mentioned.

  8. Clinical significance of feline heartworm disease.

    PubMed

    Dillon, R

    1998-11-01

    The clinical signs and diagnostic approach are different in the cat as compared with the dog, which has impaired the veterinarian's ability to detect this parasite in the cat. New techniques and methodologies have enabled the cat owner and veterinarian to recognize this potentially severe disease. Although much is now known about the pathophysiology and biology of this parasite in the cat, the practical application and rapid development of this information to daily practice has led to confusion.

  9. [Coat color in dogs. 2: Clinical significance].

    PubMed

    Laukner, A

    1998-04-01

    The meaning of the coat colour of the dog reaches further than only to the field of breeding for beauty. Besides aspects of destination (hunting dogs, herding dogs) the clinical meaning is of particular interest. Some colours can show certain defects. Diseases of allowed colours are the colour dilution alopecia (CDA) in diluted (mostly "blue") pigmentation with its subtype of Black hair follicular dysplasia (BHFD) in black pigmentation and congenital deafness in extreme piebalds. Not allowed coat colours, which are connected with defects, are the extreme dapple of the Merle-syndrome and the "grey" Collie with cyclic hematopoesis.

  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. The clinical significance of occult HBV infection

    PubMed Central

    Squadrito, Giovanni; Spinella, Rosaria; Raimondo, Giovanni

    2014-01-01

    The presence of hepatitis B virus (HBV) DNA in HBV surface antigen (HBsAg)-negative individuals is defined as occult HBV infection (OBI). OBI is related in some cases to infection with variant viruses (S-escape mutants) undetectable by HBsAg commercial kits. More frequently, however, it is due to infection with wild-type viruses that are strongly suppressed in their replication activity. OBI may be involved in different clinical contexts, including the transmission of the infection by blood transfusion or liver transplantation and its acute reactivation when an immunosuppressive status occurs. Moreover, much evidence suggests that it may contribute to the development of cirrhosis and may have an important role in hepatocarcinogenesis. PMID:24714731

  12. The clinical significance of command hallucinations.

    PubMed

    Hellerstein, D; Frosch, W; Koenigsberg, H W

    1987-02-01

    Patients with command hallucinations (voices ordering particular acts, often violent or destructive ones) are commonly assumed to be at high risk for dangerous behavior. The authors reviewed 789 consecutive inpatient admissions. Of 151 patients with auditory hallucinations, 58 (38.4%) heard commands. The presence of auditory hallucinations was significantly associated with diagnosis, demographic variables, and use of maximal observation and seclusion. However, patients with command hallucinations were not significantly different from patients without commands on demographic and behavioral variables, including suicidal ideation or behavior and assaultiveness. These findings suggest that command hallucinations alone may not imply greater risk for acute, life-threatening behavior.

  13. [Base excess. Parameter with exceptional clinical significance].

    PubMed

    Schaffartzik, W

    2007-05-01

    The base excess of blood (BE) plays an important role in the description of the acid-base status of a patient and is gaining in clinical interest. Apart from the Quick test, the age, the injury severity score and the Glasgow coma scale, the BE is becoming more and more important to identify, e. g. the risk of mortality for patients with multiple injuries. According to Zander the BE is calculated using the pH, pCO(2), haemoglobin concentration and the oxygen saturation of haemoglobin (sO(2)). The use of sO(2 )allows the blood gas analyser to determine only one value of BE, independent of the type of blood sample analyzed: arterial, mixed venous or venous. The BE and measurement of the lactate concentration (cLac) play an important role in diagnosing critically ill patients. In general, the change in BE corresponds to the change in cLac. If DeltaBE is smaller than DeltacLac the reason could be therapy with HCO(3)(-) but also with infusion solutions containing lactate. Physician are very familiar with the term BE, therefore, knowledge about an alkalizing or acidifying effect of an infusion solution would be very helpful in the treatment of patients, especially critically ill patients. Unfortunately, at present the description of an infusion solution with respect to BE has not yet been accepted by the manufacturers.

  14. 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.…

  15. Achieving Core Indicators for HIV Clinical Care Among New Patients at an Urban HIV Clinic.

    PubMed

    Greer, Gillian A; Tamhane, Ashutosh; Malhotra, Rakhi; Burkholder, Greer A; Mugavero, Michael J; Raper, James L; Zinski, Anne

    2015-09-01

    Following the release of the 2010 National HIV/AIDS Strategy for the United States, the Institute of Medicine (IOM) issued core clinical indicators for measuring health outcomes in HIV-positive persons. As early retention in HIV primary care is associated with improved long-term health outcomes, we employed IOM indicators as a guide to examine a cohort of persons initiating HIV outpatient medical care at a university-affiliated HIV clinic in the Southern United States (January 2007-July 2012). Using indicators for visit attendance, CD4 and viral load laboratory testing frequency, and antiretroviral therapy initiation, we evaluated factors associated with achieving IOM core indicators among care- and treatment-naïve patients during the first year of HIV care. Of 448 patients (mean age = 35 years, 35.7% white, 79.0% male, 58.4% education beyond high school, 35.9% monthly income > $1,000 US, 47.3% uninsured), 84.6% achieved at least four of five IOM indicators. In multivariable analyses, persons with monthly income > $1,000 (ORadj. = 3.71; 95% CI: 1.68-8.19; p = 0.001) and depressive symptoms (ORadj. = 2.13; 95% CI: 1.02-4.45; p = 0.04) were significantly more likely to achieve at least four of the five core indicators, while patients with anxiety symptoms were significantly less likely to achieve these indicators (ORadj. = 0.50; 95% CI: 0.26-0.97; p = 0.04). Age, sex, race, education, insurance status, transportation barriers, alcohol use, and HIV status disclosure to family were not associated with achieving core indicators. Evaluating and addressing financial barriers and anxiety symptoms during the first year of HIV outpatient care may improve individual health outcomes and subsequent achievement of the National HIV/AIDS Strategy.

  16. Girl Friends as Significant-Others: Their Influence on Young Men's Career Aspirations and Achievements

    ERIC Educational Resources Information Center

    Otto, Luther B.

    1977-01-01

    Girl friends are significant-others who influence young men's career aspirations and achievements. Girl friends and same sex peers evaluate a youth's educational potential using broader criteria than do parents. (Author/MV)

  17. 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

  18. Clinical Mass Spectrometry: Achieving Prominence in Laboratory Medicine

    SciTech Connect

    Annesley, Thomas M.; Cooks, Robert G.; Herold, David A.; Hoofnagle, Andrew N.

    2016-01-04

    Each year the journal Clinical Chemistry publishes a January special issue on a topic that is relevant to the laboratory medicine community. In January 2016 the topic is mass spectrometry, and the issue is entitled “Clinical Mass Spectrometry: Achieving Prominence in Laboratory Medicine”. One popular feature in our issues is a Q&A on a topic, clearly in this case mass spectrometry. The journal is assembling a panel of 5-6 experts from various areas of mass spectrometry ranging from instrument manufacturing to practicing clinical chemists. Dick Smith is one of the scientist requested to participate in this special issue Q&A on Mass Spectrometry. The Q&A Transcript is attached

  19. Clinical significance of Bacillus species isolated from blood cultures.

    PubMed

    Weber, D J; Saviteer, S M; Rutala, W A; Thomann, C A

    1989-06-01

    To determine the clinical significance of blood isolates of Bacillus, we reviewed all blood cultures obtained at North Carolina Memorial Hospital between 1981 and 1985. Over the five-year study period the number of patients (incidence per 10,000 hospital admissions) from whom Bacillus was isolated increased from 4.97 in 1981 to 12.5 in 1985. The incidence per 1,000 blood cultures also increased from 1.12 in 1981 to 2.33 in 1985. Review of the medical records of 78 of the 95 patients (82%) with positive cultures allowed retrospective classification of five isolates (6.4%) as clinically significant, 33 isolates (42.3%) as possibly significant, and 40 isolates (51.3%) as nonsignificant. Underlying diseases in patients with clinically significant Bacillus bacteremia included burn trauma in two, leukemia in one, carcinoma in one, and gastrointestinal hemorrhage in one. All isolates judged to be clinically significant and the majority of possibly significant isolates were B cereus. We conclude that the isolation of Bacillus species from blood cultures is clinically significant in 5% to 10% of cases, that the incidence of Bacillus bacteremia is increasing, and that burn trauma should be added to the list of conditions known to predispose to clinically significant Bacillus bacteremia.

  20. Children of Divorce: The Question of Clinically Significant Problems.

    ERIC Educational Resources Information Center

    Warren, Nancy J.; And Others

    1986-01-01

    Reports results of a study of a non-clinical sample of children (N=112) from families (N=86) after divorce filing using criteria to assess clinically significant levels of problems in children aged 7-12. Results suggest children may adapt better to divorce than some studies suggest. Children with behavior problems were less likely to have regular…

  1. Update on clinically significant drug interactions in dermatology.

    PubMed

    Barranco, Vincent P

    2006-04-01

    Although there are thousands of drug interactions (DIs) listed in computers and manuals, only about 10% are clinically significant. Equally disturbing is these systems fail to detect up to one third of all dangerous DIs. This update on clinically significant DIs is current through September 2005 and discusses systemic drugs important to dermatologists. In addition, 4 aspects of DIs are discussed that are helpful in replacing rote memory with a step-by-step, logical approach based on scientific evidence.

  2. Mass Spectrometric Immunoassays in Characterization of Clinically Significant Proteoforms

    PubMed Central

    Trenchevska, Olgica; Nelson, Randall W.; Nedelkov, Dobrin

    2016-01-01

    Proteins can exist as multiple proteoforms in vivo, as a result of alternative splicing and single-nucleotide polymorphisms (SNPs), as well as posttranslational processing. To address their clinical significance in a context of diagnostic information, proteoforms require a more in-depth analysis. Mass spectrometric immunoassays (MSIA) have been devised for studying structural diversity in human proteins. MSIA enables protein profiling in a simple and high-throughput manner, by combining the selectivity of targeted immunoassays, with the specificity of mass spectrometric detection. MSIA has been used for qualitative and quantitative analysis of single and multiple proteoforms, distinguishing between normal fluctuations and changes related to clinical conditions. This mini review offers an overview of the development and application of mass spectrometric immunoassays for clinical and population proteomics studies. Provided are examples of some recent developments, and also discussed are the trends and challenges in mass spectrometry-based immunoassays for the next-phase of clinical applications. PMID:28248223

  3. Potentially significant versus clinically significant drug interactions: pomegranate juice as a case in point.

    PubMed

    Andrade, Chittaranjan

    2014-04-01

    In vitro and in vivo laboratory data show that pomegranate juice consistently inhibits intestinal CYP2C9 and CYP3A4 enzymes. Pomegranate juice may therefore increase the bioavailability of drugs that are metabolized by these enzymes. However, studies in humans find that pomegranate juice does not increase exposure to either CYP2C9 or CYP3A4 substrates. These contradictory findings suggest that potential drug interactions identified in the laboratory may not necessarily translate into clinically significant drug interactions in humans, and hence that laboratory data are insufficient grounds upon which clinical decisions may be based.

  4. Cognitive Impairment in Individuals with Insomnia: Clinical Significance and Correlates

    PubMed Central

    Fortier-Brochu, Émilie; Morin, Charles M.

    2014-01-01

    Study Objectives: The aims of this study were to (1) investigate the nature of cognitive impairment in individuals with insomnia, (2) document their clinical significance, (3) examine their correlates, and (4) explore differences among individuals with insomnia with and without cognitive complaints. Design: Participants underwent 3 consecutive nights of polysomnography. On the morning following the third night, they completed a battery of questionnaires and neuropsychological tests. Participants: The sample included 25 adults with primary insomnia (mean age: 44.4 ± 11.5 y, 56% women) and 16 controls (mean age: 42.8 ± 12.9 y, 50% women) matched for sex, age, and education. Intervention: N/A. Measurement and Results: Participants completed neuropsychological tests covering attention, memory, working memory, and executive functions, as well as questionnaires assessing the subjective perception of performance, depression, anxiety, fatigue, sleepiness, and hyperarousal. There were significant group differences for the attention and episodic memory domains. Clinically significant deficits were more frequent in the insomnia group. Within the insomnia group, individuals with cognitive complaints exhibited significantly poorer performance on a larger number of neuropsychological variables. All impaired aspects of performance were significantly associated with either subjective or objective sleep continuity, and some were also independently related to sleep microstructure (i.e., relative power for alpha frequencies) or selected psychological variables (i.e., beliefs or arousal). Conclusions: These findings suggest clinically significant alterations in attention and episodic memory in individuals with insomnia. Objective deficits were more pronounced and involved more aspects of performance in a subgroup of individuals with cognitive complaints. These deficits appear associated with sleep continuity, and may also be related to sleep microstructure and dysfunctional beliefs

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

    PubMed

    Pérez, J L

    1997-09-01

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

  6. 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. PMID:27630804

  7. Accurate coding in sepsis: clinical significance and financial implications.

    PubMed

    Chin, Y T; Scattergood, N; Thornber, M; Thomas, S

    2016-09-01

    Sepsis is a major healthcare problem and leading cause of death worldwide. UK hospital mortality statistics and payments for patient episodes of care are calculated on clinical coding data. The accuracy of these data depends on the quality of coding. This study aimed to investigate whether patients with significant bacteraemia are coded for sepsis and to estimate the financial costs of miscoding. Of 54 patients over a one-month period with a significant bacteraemia, only 19% had been coded for sepsis. This is likely to lead to falsely high calculated hospital mortality. Furthermore, this resulted in an underpayment of £21,000 for one month alone.

  8. Investigation of Clinically Significant Change by Severity Level in College Counseling Center Clients

    ERIC Educational Resources Information Center

    Wolgast, Brad M.; Rader, Jill; Roche, Deborah; Thompson, C. Patricia; von Zuben, F. Christian; Goldberg, Allan

    2005-01-01

    The authors investigated the number of sessions necessary for college counseling center clients of different levels of severity of distress at intake to achieve clinically significant change (CS) in therapy. The Outcome Questionnaire-45 (M. J. Lambert, N. B. Hansen, et al., 1996) was used to categorize 914 clients by severity of distress. Analyses…

  9. 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.

  10. 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

  11. Worksite stress management training: moderated effects and clinical significance.

    PubMed

    Flaxman, Paul E; Bond, Frank W

    2010-10-01

    Psychologically healthy participants may dilute the observed effects of worksite stress management training (SMT) programs, therefore hiding the true effectiveness of these interventions for more distressed workers. To examine this issue, 311 local government employees were randomly assigned to SMT based on acceptance and commitment therapy (SMT, n = 177) or to a waitlist control group (n = 134). The SMT program consisted of three half-day training sessions, and imparted a mixture of mindfulness and values-based action skills. Across a 6-month assessment period, SMT resulted in a significant reduction in employee distress. As predicted, the impact of SMT was significantly moderated by baseline distress, such that meaningful effects were found only among a subgroup of initially distressed workers. Furthermore, a majority (69%) of these initially distressed SMT participants improved to a clinically significant degree. The study highlights the importance of accounting for sample heterogeneity when evaluating and classifying worksite SMT programs.

  12. [Circular RNA in human disease and their potential clinic significance].

    PubMed

    Chen, Yonghua; Li, Cheng; Tan, Chunlu; Mai, Gang; Liu, Xubao

    2017-02-10

    Circular RNAs (circ RNAs) are a novel type of RNA that, unlike linear RNAs, form a covalently closed continuous loop and are highly represented in the eukaryotic transcriptome. They share a stable structure, high expression and often exhibit tissue/developmental-stage-specific expression. Emerging evidence indicates that circRNAs might play important roles in human disease, such as cancer, neurological disorders and atherosclerotic vascular disease risk. The huge potentials of circRNAs are recently being discovered from the laboratory to the clinic. CircRNAs might be developed as a potential novel and stable biomarker and potential drugs used in disease diagnosis and treatment. Here, we review the current understanding of the roles of circRNAs in human disease and their potential clinic significance in disease.

  13. Teardrop shadow of the pelvis: anatomy and clinical significance

    SciTech Connect

    Bowerman, J.W.; Sena, J.M.; Chang, R.

    1982-06-01

    The teardrop shadow of the pelvis is poorly understood and as a result its clinical significance is not appreciated. The structure responsible for this shadow was pinpointed by removing sections from the hemipelvis of an anatomic specimen with an electric saw. This structure is located in the anteroinferior portion of the acetabular fossa at the acetabular notch and consists of cortical and medullary bone contributed primarily from the ischium with a much smaller contribution from the superior pubic ramus. The normal and abnormal appearances of the teardrop shadow of the acetabulum of three patients were demonstrated on both plain radiographs and computed tomographic (CT) scans.

  14. [The significance of mammographic symptoms in clinically occult findings].

    PubMed

    de Waal, J C; Steil, B; Baltzer, J; Vaillant, W; Zander, J

    1987-10-01

    The significance of various radiographic signs in 183 patients with clinically occult breast disease is described. 30.6% had a carcinoma of the breast or a carcinoma in situ. The radiological features have varying predictive values and there is variation in the incidence of lymph node metastases. It is considered useful to classify the radiological appearances under the headings of round foci, star-shaped opacities, diffuse opacities, opacities with calcification and groups of micro-calcification. Despite the early diagnosis, 24% of patients already had lymph node metastases.

  15. Mechanism and clinical significance of prostaglandin-induced iris pigmentation.

    PubMed

    Stjernschantz, Johan W; Albert, Daniel M; Hu, Dan-Ning; Drago, Filippo; Wistrand, Per J

    2002-08-01

    The new glaucoma drugs latanoprost, isopropyl unoprostone, travoprost, and bimatoprost cause increased pigmentation of the iris in some patients. The purpose of the present article is to survey the available preclinical and clinical data on prostaglandin-induced iris pigmentation and to assess the phenomenon from a clinical perspective. Most of the data have been obtained with latanoprost, and it appears that there is a predisposition to latanoprost-induced iris pigmentation in individuals with hazel or heterochromic eye color. As latanoprost and travoprost are selective agonists for the prostaglandin F(2alpha) receptor, it is likely that the phenomenon is mediated by this receptor. Several studies indicate that latanoprost stimulates melanogenesis in iridial melanocytes, and transcription of the tyrosinase gene is upregulated. The safety aspects of latanoprost-induced iris pigmentation have been addressed in histopathologic studies, and no evidence of harmful consequences of the side effect has been found. Although a final assessment of the clinical significance of prostaglandin-induced iris pigmentation currently is impossible to make, it appears that the only clear-cut disadvantage is a potential heterochromia between the eyes in unilaterally treated patients because the heterochromia is likely to be permanent, or very slowly reversible.

  16. 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

  17. [Genomics of lung adenocarcinoma: pathogenetic significance and clinical applications.

    PubMed

    Palmirotta, Raffaele; Acquafredda, Silvana; Argentiero, Antonella; Carella, Claudia; Lanotte, Laura; Pappagallo, Nicla; Quaresmini, Davide; Silvestris, Franco

    2016-12-01

    Diagnostic and therapeutic approaches to non small cell lung cancer (NSCLC), especially adenocarcinoma, have recently undergone dramatic evolution according to the tremendous amount of molecular data collected on this cancer. In fact, the application of oncogenomics has identified novel molecular subtypes of NSCLC and led the way to diagnostic criteria based on the expression of specific genetic alterations that can provide prognostic and specific indications to the molecular targeted therapies. In NSCLC, several genes show "driver" molecular alterations that confer oncogenic potential to progenitor cells through the enrollment of metabolic pathways critical for cell proliferation and tumor development. On the other hand, clinical management of NSCLC with small molecules has undoubtedly provided optimistic results with both a significant increase in overall survival and reduction in therapy-related toxicity including relative complications. Thus, pharmacogenomics, as the newest tool for using the targeted therapy represents the most innovative approach for treatment of this cancer once the molecular aberrations are identified. In particular, the relative mutational status of several driver genes including EGFR, ALK, ROS1 and others, is directly correlated to a better response to thyrosin-kinase inhibitors. Furthermore, other therapeutic strategies with inhibitors of angiogenic receptors, PARP, histone-deacetylase, PI3K and HSP90, are intensively studied in pre-clinical models as well as in clinical trials for a potential adoption in clinical practice. The introduction of more advanced techniques for molecular profiling also allows to identify pathogenic variants of many other genes involved in the progression of lung adenocarcinoma with the aim to develop novel molecular targets for pharmacological research. In this review, we will revisit the current applications of oncogenomics in the diagnosis and treatment of this tumor.

  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. The clinical significance of keratinized gingiva around dental implants.

    PubMed

    Greenstein, Gary; Cavallaro, John

    2011-10-01

    Whether or not keratinized tissue is needed around dental implants to maintain peri-implant health is a controversial subject. To clarify this issue a search was conducted for clinical trials that appraised the significance ofkeratinized gingiva (KG) around teeth and dental implants. A critical assessment of the data revealed that the literature is replete with studies that contradict one another with respect to the need for KG as it relates to survivability of implants, gingival response to plaque, inflammation, probing depths, recession, and loss of bone. When groups of patients with and without KG were compared with respect to various clinical parameters, a statistically significant better result in the presence of KG could be interpreted to indicate that having KG is advantageous. However, quantitative differences between groups with and without KG were usually very small. Overall, the data was interpreted to indicate that some patients may need augmentation of keratinized tissue to maintain peri-implant health. Ultimately, the decision to augment KG is a judgment call that needs to be made by the treating clinician, because there are not enough data to facilitate development of definitive guidelines relevant to this subject. Apparently, the need for KG is patient specific, and at present there is no method to reliably predict who would benefit from tissue augmentation.

  20. Additional branches of celiac trunk and its clinical significance.

    PubMed

    Nayak, S R; Prabhu, Latha V; Krishnamurthy, A; Ganesh Kumar, C; Ramanathan, Lakshmi A; Acharya, Abhijith; Prasad Sinha, Abhishek

    2008-01-01

    The anatomical variations of the abdominal arteries are important due to its clinical significance. Various types of vascular anomalies are frequently found in human abdominal viscera, during cadaveric dissection and diagnostic radiological imaging. The present report describes a variation in the celiac trunk as found during routine dissection in a 59-year-old male cadaver. The celiac trunk (CT) was unusually lengthy and took origin from the left antero-lateral surface of the abdominal aorta. Altogether, there were five branches, including three classic branches of CT. The left phrenic artery (LPA) was the first branch of the CT. The remaining four branches were left gastric artery (LGA), splenic artery (SA), common hepatic artery (CHA) and gastroduodenal artery (GDA). There was an arterial loop between the posterior branches of the superior pancreatico-duodenal artery (SPDA), arising from the GDA, and the posterior branch of the inferior pancreatico-duodenal artery (IPDA), arising from the superior mesenteric artery (SMA). The arterial loop formed by the above arteries, supplied the head of the pancreas and duodeno-jejunal flexure. The embryological and clinical significance of above variations has been described.

  1. Clinical and Biological Significance of Tissue Transglutaminase in Ovarian Carcinoma

    PubMed Central

    Hwang, Jee Young; Mangala, Lingegowda S.; Fok, Jansina Y.; Lin, Yvonne G.; Merritt, William M.; Spannuth, Whitney A.; Nick, Alpa M.; Fiterman, Derek J.; Vivas-Mejia, Pablo E.; Deavers, Michael T.; Coleman, Robert L.; Lopez-Berestein, Gabriel; Mehta, Kapil; Sood, Anil K.

    2008-01-01

    Tissue type transglutaminase (TG2) is a unique multifunctional protein that plays a role in many steps in the cancer metastatic cascade. Here, we examined the clinical (n = 93 epithelial ovarian cancers) and biological (in vitro adhesion, invasion, and survival and in vivo therapeutic targeting) significance of TG2 in ovarian cancer. The overexpression of TG2 was associated with significantly worse overall patient survival in both univariate and multivariate analyses. Transfection of TG2 into the SKOV3ip1 cells promoted attachment and spreading on fibronectin-coated surfaces and increased the in vitro invasive potential of these cells. Conversely, TG2 silencing with siRNA of HeyA8 cells significantly decreased the invasive potential of the cells, and also increased docetaxel-induced cell death. In vivo therapy experiments using chemotherapy-sensitive (HeyA8) and resistant (HeyA8-MDR, RMG2) models demonstrated significant anti-tumor activity both with TG2 siRNA-DOPC alone and in combination with docetaxel chemotherapy. This anti-tumor activity was related to decreased proliferation, angiogenesis and increased tumor cell apoptosis in vivo. Taken together, these findings indicate that TG2 overexpression is an adverse prognostic factor in ovarian carcinoma and TG2 targeting may be an attractive therapeutic approach. PMID:18632639

  2. The questioned p value: clinical, practical and statistical significance.

    PubMed

    Jiménez-Paneque, Rosa

    2016-09-09

    The use of p-value and statistical significance have been questioned since the early 80s in the last century until today. Much has been discussed about it in the field of statistics and its applications, especially in Epidemiology and Public Health. As a matter of fact, the p-value and its equivalent, statistical significance, are difficult concepts to grasp for the many health professionals some way involved in research applied to their work areas. However, its meaning should be clear in intuitive terms although it is based on theoretical concepts of the field of Statistics. This paper attempts to present the p-value as a concept that applies to everyday life and therefore intuitively simple but whose proper use cannot be separated from theoretical and methodological elements of inherent complexity. The reasons behind the criticism received by the p-value and its isolated use are intuitively explained, mainly the need to demarcate statistical significance from clinical significance and some of the recommended remedies for these problems are approached as well. It finally refers to the current trend to vindicate the p-value appealing to the convenience of its use in certain situations and the recent statement of the American Statistical Association in this regard.

  3. HMGA2 Expression in Renal Carcinoma and its Clinical Significance

    PubMed Central

    Liu, Ying; Fu, Qi-Zhong; Pu, Lin; Meng, Qing-Guo; Liu, Xian-Feng; Dong, Sheng-Fang; Yang, Jian-Xun; Lv, Guang-Yao

    2015-01-01

    Summary Background The objective of this study is to detect HMGA2 expression in renal carcinoma to explore its relationship with clinicopathology and its significance in prognosis. Methods Expressions of HMGA2 mRNA and protein were detected in 50 renal carcinoma specimens, 50 corresponding adjacent normal kidney tissue samples and 40 renal benign tumour specimens via reverse transcription polymerase chain reaction and immunohistochemical assay. Expression analysis was performed along with clinical data analysis. Results The relative expression levels of HMGA2 mRNA in renal carcinoma, renal benign tumour tissues and adjacent normal renal tissues were 0.84±0.23, 0.19±0.06 and 0.08±0.04, respectively. HMGA2 protein positive rates were 68.0%, 7.5% and 2.0%, with a significant difference (P<0.05). HMGA2 expression was not significantly correlated with gender, age, tumour size and histological type (P>0.05), but was significantly correlated with TNM stages and lymph node metastasis (P<0.05). Conclusions The expressions of HMGA2 gene and protein in renal carcinoma were closely correlated with tumour formation, progression and metastasis. HMGA2 may become a powerful new pathological marker and prognostic factor for renal carcinoma. PMID:28356845

  4. 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.

  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.

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

    PubMed Central

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

    2015-01-01

    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

  7. Clinical significance of plasma metastin level in pancreatic cancer patients.

    PubMed

    Katagiri, Fumihiko; Nagai, Kazuyuki; Kida, Atsushi; Tomita, Kenji; Oishi, Shinya; Takeyama, Masaharu; Doi, Ryuichiro; Fujii, Nobutaka

    2009-03-01

    Metastin, which is a 54-residue peptide coded by KiSS-1 gene, is an endogenous ligand to a G-protein-coupled receptor GPR54. Metastin suppresses a malignant tumor to metastasize and regulates secretion of gonadotropine releasing hormone. Physiological action of metastin has been focused on in oncology. It is reported that less KiSS-1 gene and more hOT7T175 gene which codes GPR54 are expressed in pancreatic cancers than in normal pancreatic tissues; however, there is no study that investigates the relationship between clinicopathological characteristics and plasma metastin concentration in pancreatic cancer patients. The purpose of this study was to investigate the relationship between plasma metastin-like immunoreactive substance (LI) levels and clinical characteristics in pancreatic cancer patients. Thirty-three patients with pathologically confirmed pancreatic cancer before or just after treatments and 24 healthy volunteers were included in the study. Patients were grouped according to the International Union Against Cancer TNM classification. Plasma metastin-LI was measured by enzyme immunoassay. The plasma metastin-LI levels of cancer patients were significantly higher when compared with healthy volunteers. Significant relationship was not found between the plasma metastin-LI levels and the clinicopathological factors such as tumor size, invasion, lymph node metastasis and distant metastasis. The plasma metastin levels may be a significant biomarker to predict the presence of pancreatic cancer and could be used in pancreatic cancer screening.

  8. 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

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

    PubMed

    Moyer, N P

    1987-11-01

    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.

  10. Biomarkers of Metabolic Syndrome: Biochemical Background and Clinical Significance.

    PubMed

    Robberecht, Harry; Hermans, Nina

    2016-03-01

    Biomarkers of the metabolic syndrome are divided into four subgroups. Although dividing them in groups has some limitations, it can be used to draw some conclusions. In a first part, the dyslipidemias and markers of oxidative stress are discussed, while inflammatory markers and cardiometabolic biomarkers are reviewed in a second part. For most of them, the biochemical background and clinical significance are discussed, although here also a well-cut separation cannot always be made. Altered levels cannot always be claimed as the cause, risk, or consequence of the syndrome. Several factors are interrelated to each other and act in a concerted, antagonistic, synergistic, or modulating way. Most important conclusions are summarized at the end of every reviewed subgroup. Genetic biomarkers or influences of various food components on concentration levels are not included in this review article.

  11. Evaluating clinical significance: incorporating robust statistics with normative comparison tests.

    PubMed

    van Wieringen, Katrina; Cribbie, Robert A

    2014-05-01

    The purpose of this study was to evaluate a modified test of equivalence for conducting normative comparisons when distribution shapes are non-normal and variances are unequal. A Monte Carlo study was used to compare the empirical Type I error rates and power of the proposed Schuirmann-Yuen test of equivalence, which utilizes trimmed means, with that of the previously recommended Schuirmann and Schuirmann-Welch tests of equivalence when the assumptions of normality and variance homogeneity are satisfied, as well as when they are not satisfied. The empirical Type I error rates of the Schuirmann-Yuen were much closer to the nominal α level than those of the Schuirmann or Schuirmann-Welch tests, and the power of the Schuirmann-Yuen was substantially greater than that of the Schuirmann or Schuirmann-Welch tests when distributions were skewed or outliers were present. The Schuirmann-Yuen test is recommended for assessing clinical significance with normative comparisons.

  12. 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

  13. 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.

  14. 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

  15. Using nursing clinical decision support systems to achieve meaningful use.

    PubMed

    Harrison, Roberta L; Lyerla, Frank

    2012-07-01

    The Health Information Technology and Clinical Health Act (one component of the American Recovery and Reinvestment Act) is responsible for providing incentive payments to hospitals and eligible providers in an effort to support the adoption of electronic health records. Future penalties are planned for electronic health record noncompliance. In order to receive incentives and avoid penalties, hospitals and eligible providers must demonstrate "meaningful use" of their electronic health records. One of the meaningful-use objectives established by the Centers for Medicare & Medicaid Services involves the use of a clinical decision support rule that addresses a hospital-defined, high-priority condition. This article describes the Plan-Do-Study-Act process for creating and implementing a nursing clinical decision support system designed to improve guideline adherence for hypoglycemia management. This project identifies hypoglycemia management as the high-priority area. However, other facilities with different high-priority conditions may find the process presented in this article useful for implementing additional clinical decision support rules geared toward improving outcomes and meeting federal mandates.

  16. 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.

  17. Cytochrome P450 structure, function and clinical significance: A review.

    PubMed

    Palrasu, Manikandan; Nagini, Siddavaram

    2017-01-25

    The cytochrome P450 (CYP) enzymes are membrane-bound hemoproteins that play a pivotal role in the detoxification of xenobiotics, cellular metabolism and homeostasis. Induction or inhibition of CYP enzymes is a major mechanism that underlies drug-drug interactions. CYP enzymes can be transcriptionally activated by various xenobiotics and endogenous substrates through receptor-dependent mechanisms. CYP enzyme inhibition is a principal mechanism for metabolism-based drug-drug interactions. Many chemotherapeutic drugs can cause drug interactions due to their ability to either inhibit or induce the CYP enzyme system. Predictions based on in silico analyses followed by validation have identified several microRNAs that regulate CYPs. Genetic polymorphisms and epigenetic changes in CYP genes may be responsible for inter-individual and inter-ethnic variations in disease susceptibility and the therapeutic efficacy of drugs. Knowledge about the substrates, inducers, inhibitors of CYP isoforms, and the polymorphisms of CYP enzymes may be used as an aid by clinicians to determine therapeutic strategy, and treatment doses for drugs that are metabolized by CYP gene products. The present review is a comprehensive compilation of cytochrome P450 structure, function, pharmacogenetics, and pharmacoepigenetics and clinical significance.

  18. 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

  19. Clinical Application of Preconditioning and Postconditioning to Achieve Neuroprotection

    PubMed Central

    Dezfulian, Cameron; Garrett, Matthew; Gonzalez, Nestor R.

    2012-01-01

    Ischemic conditioning is a form of endogenous protection induced by transient, subcritical ischemia in a tissue. Organs with high sensitivity to ischemia, such as the heart, the brain, and spinal cord represent the most critical and potentially promising targets for potential therapeutic applications of ischemic conditioning. Numerous preclinical investigations have systematically studied the molecular pathways and potential benefits of both pre- and post-conditioning with promising results. The purpose of this review is to summarize the present knowledge on cerebral pre-and post-conditioning, with an emphasis in the clinical application of these forms of neuroprotection. Methods A systematic Medline search for the terms preconditioning and postconditioning was performed. Publications related to the nervous system and to human applications were selected and analyzed. Findings Pre-and post-conditioning appear to provide similar levels of neuroprotection. The preconditioning window of benefit can be subdivided into early and late effects, depending on whether the effect appears immediately after the sublethal stress or with a delay of days. In general early effects have been associated post-translational modification of critical proteins (membrane receptors, mitochondrial respiratory chain) while late effects are the result of gene up-or down-regulation. Transient ischemic attacks appear to represent a form of clinically relevant preconditioning by inducing ischemic tolerance in the brain and reducing the severity of subsequent strokes. Remote forms of ischemic pre- and post-conditioning have been more commonly used in clinical studies, as the remote application reduces the risk of injuring the target tissue for which protection is pursued. Limb transient ischemia is the preferred method of induction of remote conditioning with evidence supporting its safety. Clinical studies in a variety of populations at risk of central nervous damage including carotid disease

  20. 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.

  1. Acute Chorioamnionitis and Funisitis: Definition, Pathologic Features, and Clinical Significance

    PubMed Central

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

    2015-01-01

    ; however, in fetuses, it is a risk factor for short- and long-term complications (i.e. 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 pathology. Illustrations of the lesions and diagrams of the mechanisms of disease are provided. PMID:26428501

  2. 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

  3. 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.

  4. 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.

  5. A novel approach to achieving significant reverberation control in performance halls

    NASA Astrophysics Data System (ADS)

    Conant, David A.; Chu, William

    2005-09-01

    Conventional methods for achieving broadband, variable sound absorption in large halls normally include heavy application of sound-absorptive drapery and/or thick fibrous panels, applied near available surfaces below, at, and in volumes above the catwalk plane. Occasionally, direct adjustments to room air volume are also provided to effect double-sloped decays. The novel method described here combines carefully located, broad scattering and absorption in singular architectural elements and was applied to a new, 1200-seat concert hall. A change of 0.70 s RT60 in midfrequency is achieved in a visually dramatic manner while neither materially changing room volume nor introducing often-maligned drapery. The aggregate of reverberation control methodologies employed reduces the unoccupied RT60 at midfrequencies from about 3.2 to 1.7 s in this space programed principally for music, including pipe organ. Results of MLS measurements including binaural measurements and binaural recordings of anechoic material and CATT-acoustic modeling and auralizations are discussed.

  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. 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

  8. Clinical Significance of Symptoms in Smokers with Preserved Pulmonary Function

    PubMed Central

    Woodruff, Prescott G.; Barr, R. Graham; Bleecker, Eugene; Christenson, Stephanie A.; Couper, David; Curtis, Jeffrey L.; Gouskova, Natalia A.; Hansel, Nadia N.; Hoffman, Eric A.; Kanner, Richard E.; Kleerup, Eric; Lazarus, Stephen C.; Martinez, Fernando J.; Paine, Robert; Rennard, Stephen; Tashkin, Donald P.; Han, MeiLan K.

    2016-01-01

    BACKGROUND Currently, the diagnosis of chronic obstructive pulmonary disease (COPD) requires a ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) of less than 0.70 as assessed by spirometry after bronchodilator use. However, many smokers who do not meet this definition have respiratory symptoms. METHODS We conducted an observational study involving 2736 current or former smokers and controls who had never smoked and measured their respiratory symptoms using the COPD Assessment Test (CAT; scores range from 0 to 40, with higher scores indicating greater severity of symptoms). We examined whether current or former smokers who had preserved pulmonary function as assessed by spirometry (FEV1:FVC ≥0.70 and an FVC above the lower limit of the normal range after bronchodilator use) and had symptoms (CAT score, ≥10) had a higher risk of respiratory exacerbations than current or former smokers with preserved pulmonary function who were asymptomatic (CAT score, <10) and whether those with symptoms had different findings from the asymptomatic group with respect to the 6-minute walk distance, lung function, or high-resolution computed tomographic (HRCT) scan of the chest. RESULTS Respiratory symptoms were present in 50% of current or former smokers with preserved pulmonary function. The mean (±SD) rate of respiratory exacerbations among symptomatic current or former smokers was significantly higher than the rates among asymptomatic current or former smokers and among controls who never smoked (0.27± 0.67 vs. 0.08±0.31 and 0.03±0.21 events, respectively, per year; P<0.001 for both comparisons). Symptomatic current or former smokers, regardless of history of asthma, also had greater limitation of activity, slightly lower FEV1, FVC, and inspiratory capacity, and greater airway-wall thickening without emphysema according to HRCT than did asymptomatic current or former smokers. Among symptomatic current or former smokers, 42% used

  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 recent inversion of the nipple: a reappraisal.

    PubMed Central

    Neville, E M; Freeman, A H; Adiseshiah, M

    1982-01-01

    In a retrospective survey of 63 cases of inverted nipple, unaccompanied by a palpable mass, 3 histologically confirmed carcinomas were found on combined clinical and mammographic examination - an incidence of 5%. No carcinoma was found in those patients under 50 years of age. The problem of the false negative mammogram is discussed. PMID:7069669

  11. [Acute life threatening catatonia--clinical significance and therapeutic possibilities].

    PubMed

    Bridler, R; Hell, D

    1997-09-13

    Malignant catatonia, associated with different somatic and psychiatric disorders, is a rare, life-threatening syndrome. Immediate recognition and adequate treatment are essential and may be life-saving. We describe a case of malignant catatonia and discuss the clinical implications. Additionally, we review the recent literature regarding epidemiology, nosology, current pathophysiological concepts, differential diagnosis, and treatment recommendations.

  12. Clinical significance of occult hepatitis B virus infection.

    PubMed

    Romero, Miriam; Madejón, Antonio; Fernández-Rodríguez, Conrado; García-Samaniego, Javier

    2011-03-28

    Occult hepatitis B virus (HBV) infection (OBI) is defined as the presence of HBV DNA in the liver (with or without detectable HBV DNA in serum) for individuals testing HBV surface antigen negative. Until recently, the clinical effect of OBI was unclear on the progression of liver disease; on the development of hepatocellular carcinoma; and on the risk for reactivation or transmission of HBV infection. Several studies suggest a high prevalence of OBI among patients with cryptogenic chronic liver disease, but its role in the progression to cirrhosis remains unclear. Although OBI has been well documented in human immunodeficiency virus (HIV)-positive patients, especially among those coinfected with hepatitis C virus, further studies are needed to determine its current clinical impact in HIV setting.

  13. 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

  14. 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.

  15. 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

  16. 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

  17. Significant increase in ecosystem C can be achieved with sustainable forest management in subtropical plantation forests.

    PubMed

    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 products

  18. Airway hyperresponsiveness in asthma: mechanisms, clinical significance, and treatment.

    PubMed

    Brannan, John D; Lougheed, M Diane

    2012-01-01

    Airway hyperresponsiveness (AHR) and airway inflammation are key pathophysiological features of asthma. Bronchial provocation tests (BPTs) are objective tests for AHR that are clinically useful to aid in the diagnosis of asthma in both adults and children. BPTs can be either "direct" or "indirect," referring to the mechanism by which a stimulus mediates bronchoconstriction. Direct BPTs refer to the administration of pharmacological agonist (e.g., methacholine or histamine) that act on specific receptors on the airway smooth muscle. Airway inflammation and/or airway remodeling may be key determinants of the response to direct stimuli. Indirect BPTs are those in which the stimulus causes the release of mediators of bronchoconstriction from inflammatory cells (e.g., exercise, allergen, mannitol). Airway sensitivity to indirect stimuli is dependent upon the presence of inflammation (e.g., mast cells, eosinophils), which responds to treatment with inhaled corticosteroids (ICS). Thus, there is a stronger relationship between indices of steroid-sensitive inflammation (e.g., sputum eosinophils, fraction of exhaled nitric oxide) and airway sensitivity to indirect compared to direct stimuli. Regular treatment with ICS does not result in the complete inhibition of responsiveness to direct stimuli. AHR to indirect stimuli identifies individuals that are highly likely to have a clinical improvement with ICS therapy in association with an inhibition of airway sensitivity following weeks to months of treatment with ICS. To comprehend the clinical utility of direct or indirect stimuli in either diagnosis of asthma or monitoring of therapeutic intervention requires an understanding of the underlying pathophysiology of AHR and mechanisms of action of both stimuli.

  19. [Etiology, pathophysiology and clinical significance of hereditary fructose intolerance].

    PubMed

    Fauth, U; Halmágyi, M

    1991-10-01

    Due to repeatedly described incidents in patients with undiscovered hereditary fructose intolerance, the application of fructose and sorbit-containing parenteral solutions is a topic vehemently discussed. This paper presents a survey of the literature dealing with the inborn defect of fructose-1-phosphate aldolase. The physiology and pathophysiology of fructose metabolism are described as well as the clinical appearance and diagnostic possibilities. The acute course of a fructose incompatibility is determined by a threatening decrease in the blood glucose level, which is attributed to the inhibition of several enzymes of glycolysis and gluconeogenesis by an intracellular accumulation of fructose-1-phosphate. Within hours a global functional breakdown of organs, which normally have the enzyme, occurs. The impairment of the liver function finds expression in a severe coagulopathy, the damage of the kidney leads to anuria. In chronic oral fructose supply, damage of the liver and small intestinal mucosa with corresponding gastrointestinal symptoms determine the clinical course. Concerning diagnosis, contrary to the liver biopsy and the fructose tolerance test, the mucosal biopsy with determination of fructose-1-phosphate aldolase activity has the advantage of greater specificity and is better tolerated by the patient. A total abstinence to fructose and sorbitol-containing solutions is not considered to be necessary when the rarity of the illness is taken into account and certain precautions are taken. These include a specific anamnesis of nutrition as well as a total abstinence from fructose and sorbitol in infants and in the unconscious patient. For clinical routine a simple fructose tolerance test is suggested.

  20. 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

  1. Clinically significant drug interactions with antacids: an update.

    PubMed

    Ogawa, Ryuichi; Echizen, Hirotoshi

    2011-10-01

    One may consider that drug-drug interactions (DDIs) associated with antacids is an obsolete topic because they are prescribed less frequently by medical professionals due to the advent of drugs that more effectively suppress gastric acidity (i.e. histamine H(2)-receptor antagonists [H2RAs] and proton pump inhibitors [PPIs]). Nevertheless, the use of antacids by ambulant patients may be ever increasing, because they are freely available as over-the-counter (OTC) drugs. Antacids consisting of weak basic substances coupled with polyvalent cations may alter the rate and/or the extent of absorption of concomitantly administered drugs via different mechanisms. Polyvalent cations in antacid formulations may form insoluble chelate complexes with drugs and substantially reduce their bioavailability. Clinical studies demonstrated that two classes of antibacterials (tetracyclines and fluoroquinolones) are susceptible to clinically relevant DDIs with antacids through this mechanism. Countermeasures against this type of DDI include spacing out the dosing interval - taking antacid either 4 hours before or 2 hours after administration of these antibacterials. Bisphosphonates may be susceptible to DDIs with antacids by the same mechanism, as described in the prescription information of most bisphosphonates, but no quantitative data about the DDIs are available. For drugs with solubility critically dependent on pH, neutralization of gastric fluid by antacids may alter the dissolution of these drugs and the rate and/or extent of their absorption. However, the magnitude of DDIs elicited by antacids through this mechanism is less than that produced by H2RAs or PPIs; therefore, the clinical relevance of such DDIs is often obscure. Magnesium ions contained in some antacid formulas may increase gastric emptying, thereby accelerating the rate of absorption of some drugs. However, the clinical relevance of this is unclear in most cases because the difference in plasma drug concentration

  2. Molecular Pathology of Hepatic Neoplasms: Classification and Clinical Significance

    PubMed Central

    Walther, Zenta; Jain, Dhanpat

    2011-01-01

    Recent technological advances have enabled investigators to characterize the molecular genetics and genomics of hepatic neoplasia in remarkable detail. From these studies, an increasing number of molecular markers are being identified that correlate with clinically important tumor phenotypes. This paper discusses current knowledge relevant to the molecular classification of epithelial primary hepatic tumors that arise in adults, including focal nodular hyperplasia (FNH), hepatocellular adenoma (HCA), hepatocellular carcinoma (HCC), cholangiocarcinoma (CC), and combined HCC-CC. Genetic analysis has defined molecular subtypes of HCA that are clinicopathologically distinct and can be distinguished through immunohistochemistry. Gene expression studies have identified molecular signatures of progression from dysplastic nodules (DNs) to early HCC in cirrhosis. Analyses of the mutational spectra, chromosomal aberrations and instability, transcriptomics, and microRNA profiles of HCC have revealed the existence of biologically distinct subtypes of this common malignancy, with prognostic implications. Molecular characterization of biliary and hepatic progenitor cell phenotypes in liver cancer has shed new light on the histogenesis of these tumors and has focused attention on novel therapeutic targets. In coming years, the molecular classification of hepatic neoplasms will be increasingly valuable for guiding patient care, as targeted therapies for liver cancer are developed and brought into clinical practice. PMID:21559202

  3. 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

  4. Clinicopathologic correlations and significance of clinically occult mammary lesions.

    PubMed

    Schwartz, G F; Feig, S A; Patchefsky, A S

    1978-03-01

    Experience with 189 clinically occult, i.e., nonpalpable breast lesions is presented. The described technique of localization and excision all but guarantees removal of even the smallest radiographically suspicious findings with an inconspicuous incision and minimal breast deformity. The incidence of carcinoma encountered in these 189 biopsies is 27.5%. Axillary node metastases were present in less than 25% of the invasive nonpalpable cancers, approximately half of what might have been expected if the lesions had been discovered in the usual manner. There were no patients with axillary node metastases among those with in situ ductal or microinvasive ductal carcinomas. This implies a better prognosis and lower death rate from breast cancer in these patients. Screening programs employing mammography, designed to detect breast cancers in this pre-palpable stage, are encountered as a means of uncovering a higher proportion of such cancers at an earlier stage in their natural histories.

  5. [Clinically significant drug-drug interactions between analgesics and psychotopics].

    PubMed

    Strobach, Dorothea

    2012-07-01

    Combining analgesic and psychotropic drugs can lead to pharmacodynamic and pharmacokinetic drug interactions. Under treatment with several serotonergic substances serotonin syndrome can occur, e.g., with certain opioids and antidepressant drugs. Serotonin reuptake inhibitors also affect the serotonin level in platelets, this can raise the risk for gastrointestinal bleeding especially in combination with non-steroidal antirheumatic drugs. Anticholinergic effects and sedation are common side effects of psychotropic but also analgesic drugs with possible additive results. A wide range of interactions between analgesics and psychotropics can occure during metabolism, especially via the cytochrome-P-system. The clinical relevance of warnings on drug interactions from data banks has always to be judged for the individual patient.

  6. Clinical and biochemical significance of toxin production by Aeromonas hydrophila.

    PubMed

    Kindschuh, M; Pickering, L K; Cleary, T G; Ruiz-Palacios, G

    1987-05-01

    Production of cytotoxin and enterotoxin by Aeromonas strains obtained from stools of 50 children in Mexico and Texas and from blood of 9 children with sepsis was determined. Results were correlated with clinical features of infected children as well as with biochemical traits of Aeromonas strains. Cytotoxin was produced by 40 of 42 Aeromonas strains (95%) isolated from stools of children with diarrhea, by all 8 isolates from stools of well children, and by all 9 isolates from children with sepsis. There was no difference in the quantities (amount of cytotoxin per milligram of protein required to kill 50% of the cells) of cytotoxin produced and in clinical manifestations among the groups. None of the isolates produced a toxin that could be neutralized by antiserum raised against Shiga toxin produced by Shigella dysenteriae 1 60R. Heat-labile-like enterotoxin (LT) was produced by 26 of 42 stool isolates (62%), while only 1 of the 42 isolates (2%) produced enterotoxinlike activity in suckling mice; 65% of the cytotoxin-producing strains also produced an LT-like material. All strains from blood produced LT-like material, and 2 of 6 (33%) produced activity in suckling mice. All strains produced hemolysin; 37 of 57 (65%) were Voges-Proskauer positive; 27 of 57 (47%) were lysine decarboxylase positive by API 20E strips, none were positive for lysine decarboxylose production by lysin-iron agar slants at 24 h, but 17 of 54 (31%) were positive at 48 h. There was no correlation between biochemical reactions and enterotoxin or cytotoxin production. There appears to be no correlation between toxin production by Aeromonas spp. and gastroenteritis.

  7. The clinical achievement portfolio: an outcomes-based assessment project in nursing education.

    PubMed

    Tracy, S M; Marino, G J; Richo, K M; Daly, E M

    2000-01-01

    Dynamic healthcare market forces impel educators to search for innovative methods of academic assessment to measure learning outcomes. The clinical achievement portfolio is a creative and systematic tool for documenting continuous improvement of student clinical learning. The authors describe the use of the portfolio as a pilot project aimed at introducing reflective thinking and measuring clinical learning in undergraduate nursing education. Potential benefits of the clinical portfolio and implications for future research are proposed.

  8. Clinical and prognostic significance of coagulation assays in lung cancer.

    PubMed

    Tas, Faruk; Kilic, Leyla; Serilmez, Murat; Keskin, Serkan; Sen, Fatma; Duranyildiz, Derya

    2013-03-01

    Activation of coagulation and fibrinolysis is frequently encountered among cancer patients. Such tumors are supposed to be associated with higher risk of invasion, metastases and eventually worse outcome. The aim of this study is to explore the prognostic value of blood coagulation tests for lung cancer patients. The study comprised 110 lung cancer patients. Pretreatment blood coagulation tests including PT, aPTT, PTA, INR, D-dimer, fibrinogen levels and platelet counts were evaluated. The plasma level of all coagulation tests revealed statistically significant difference between patient and control group (p < 0.001). There was a significant association between D-Dimer levels and histological subtypes of NSCLC, pointing an elevated plasma D-dimer level in squamous cell cancer (p = 0.035). Patients with extensive stage SCLC exhibited evidently higher levels of D-Dimer, INR and PLT (p = 0.037, p = 0.042, p = 0.04, respectively). Prolongation of PT and INR had statistically significant adverse effect on survival (p = 0.05 and p = 0.014, respectively). Although prolonged aPTT and high levels of D-dimer was associated with worse survival, the difference was not statistically significant (p = 0.117, p = 0.104). Multivariate analysis revealed INR as the sole independent prognostic variable among coagulation parameters (p = 0.05). In conclusion, elevation of PT and INR are associated with decreased survival in lung cancer patients.

  9. Equine cyathostomins: a review of biology, clinical significance and therapy

    PubMed Central

    Corning, Susan

    2009-01-01

    The small strongyles of horses, also known as cyathostomins, are considered the most prevalent and pathogenic parasites of horses today. The clinical syndrome of larval cyathostominosis which occurs as a result of mass emergence of inhibited stages has a high fatality rate despite the best standard of care given to affected horses. Management of the challenge level of cyathostomins to prevent the syndrome is preferable. Many different management programmes have been tried over the past two decades, with mixed success. Programmes have relied heavily on repeated use of anthelmintic treatments throughout the life of a horse. The widespread incidence of resistance to certain anthelmintics is reducing these options. An understanding of the biology of cyathostomins, risk factors for infection and appropriate strategic use of still effective anthelmintics is essential for the future management of this parasite group. This review highlights the necessity to use currently available anthelmintics that are appropriately suited to the biology of cyathostomins, and to maintain heir efficacy through an appropriate treatment strategy. PMID:19778462

  10. Platelet-mimicry of cancer cells: epiphenomenon with clinical significance.

    PubMed

    Tímár, József; Tóvári, József; Rásó, Erzsébet; Mészáros, Livia; Bereczky, Bíborka; Lapis, Károly

    2005-01-01

    Stem cell mimicry of cancer cells has been known for a long time and is considered to be responsible for ectopic gene expressions. The stem cell characteristics of tumor cells are shown to be involved in epithelial-mesenchymal transition and in the phenomenon of vascular mimicry. Certain cancer types acquire a geno-phenotype closely resembling the platelets and express several megakaryocytic genes (adhesion receptors alpha IIb beta 3, thrombin receptor and PECAM/CD 31 and/or platelet-type 12-LOX) able to activate the coagulation cascade or the platelets themselves. Here we define these potentials as platelet mimicry of cancer cells typical of pancreatic, breast, prostate, colorectal and urogenital cancers and melanoma. Data all support that platelet mimicry of certain cancer types is an important factor in their hematogenous dissemination and provides an attractive therapeutic target. Besides the long-available preclinical data, clinical trials have only recently provided evidence that targeting platelet mimicry of cancers is an efficient way to prevent tumor progression. The systematic discovery of the markers of platelet mimicry in various cancer types and their molecular targeting may provide new supportive therapeutic modalities for the management of the progressing disease.

  11. Mammalian aquaporins: diverse physiological roles and potential clinical significance

    PubMed Central

    Verkman, A. S.

    2013-01-01

    Aquaporins have multiple distinct roles in mammalian physiology. Phenotype analysis of aquaporin-knockout mice has confirmed the predicted role of aquaporins in osmotically driven transepithelial fluid transport, as occurs in the urinary concentrating mechanism and glandular fluid secretion. Aquaporins also facilitate water movement into and out of the brain in various pathologies such as stroke, tumour, infection and hydrocephalus. A major, unexpected cellular role of aquaporins was revealed by analysis of knockout mice: aquaporins facilitate cell migration, as occurs in angiogenesis, tumour metastasis, wound healing, and glial scar formation. Another unexpected role of aquaporins is in neural function – in sensory signalling and seizure activity. The water-transporting function of aquaporins is likely responsible for these roles. A subset of aquaporins that transport both water and glycerol, the ‘aquaglyceroporins’, regulate glycerol content in epidermal, fat and other tissues. Mice lacking various aquaglyceroporins have several interesting phenotypes, including dry skin, resistance to skin carcinogenesis, impaired cell proliferation, and altered fat metabolism. The various roles of aquaporins might be exploited clinically by development of drugs to alter aquaporin expression or function, which could serve as diuretics, and in the treatment of brain swelling, glaucoma, epilepsy, obesity and cancer. PMID:18482462

  12. [Clinical significance of betadine vaginal suppository treatment in pregnancy].

    PubMed

    Gimes, G; Péter, F

    1997-11-01

    Clinical experience proved the efficacy of Betadine suppository in the treatment of bacterial vaginosis and mycotic infections of the vagina. Vaginal infections, frequently observed in pregnancy, can led to maternal and fetal complications, thus Betadine should be used both for prevention and therapy. One can ask if iodine absorbed from the vagina can influence the fetal thyroid function? 64 pregnant women received 7 day Betadine suppository (200 mg polyvidonum-iodine PVP) treatment for colpitis on 37-40 gestational week with excellent therapeutic result. TSH levels were measured by immunoassay in the serum of newborns 4-5 days after delivery, no signs of hypothyroidism were observed. Authors recommended 7 day Betadine vaginal suppository regimen for the prevention of intrauterine infections, treatment of mixed (bacterial, mycotical) vaginal infections, and restoration of the normal vaginal equilibrium of bacterias, since the risk of hypothyroidism is negligeable in mature newborns. In case of prematurity hypothyroidism is more frequently found also without iodine treatment therefore TSH level control is recommended in each case.

  13. 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

  14. 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

  15. Characterization of two unusual clinically significant Francisella strains.

    PubMed Central

    Clarridge, J E; Raich, T J; Sjösted, A; Sandström, G; Darouiche, R O; Shawar, R M; Georghiou, P R; Osting, C; Vo, L

    1996-01-01

    We have isolated two phenotypically distinct nonfastidious Francisella strains (Fx1 and Fx2) from the blood of compromised patients with pneumonia and compared them with eight other Francisella strains, including Francisella tularensis biovar tularensis, F. tularensis biovar novicida, and F. philomiragia. Our isolates grew well on sheep blood agar, chocolate agar, modified Thayer-Martin agar, and Trypticase soy agar. Fx1 and Fx2 were determined to be within the Francisella genus by cellular fatty acid analysis and by the utilization of glucose, production of H2S and catalase, and lack of motility, oxidase, nitrate reductase, and gelatinase. They were additionally shown to belong to the species F. tularensis by sequencing of two variable regions comprising approximately 500 nucleotides of the 16S rRNA gene. Also, RNA probe hybridization confirmed their belonging to the species F. tularensis. However, the new strains, which are not identical, are distinguished from other F. tularensis strains by growth characteristics, repetitive extragenic palindromic PCR fragment pattern, and some biochemical tests. Key biochemical differences included the findings that Fx1 was positive for beta-galactosidase and arabinose hydrolysis and that both strains were citrulline ureidase positive and glycerol negative. Commercial F. tularensis antiserum agglutinated stock F. tularensis strains but not Fx1, Fx2, F. tularensis biovar novicida, or F. philomiragia; serum from either patient failed to agglutinate or only weakly agglutinated commercial antigen but showed agglutination when tested against each patient's respective isolate. Fx1 and Fx2 produced beta-lactamase. Because of their good growth, negative serology, and biochemical profile, the organisms could be misidentified in the clinical laboratory if standard strategies or commercial identification systems are used. PMID:8818897

  16. Structure, function and clinical significance of transferrin receptors.

    PubMed

    Feelders, R A; Kuiper-Kramer, E P; van Eijk, H G

    1999-01-01

    Iron plays an essential role in a spectrum of metabolic processes. Cellular iron uptake is facilitated by transferrin receptor (TfR)-mediated endocytosis. In recent years more insight has been obtained in TfR physiology and the regulation of cellular iron homeostasis. The synthesis of TfR and the iron storage protein ferritin is regulated reciprocally at the post-transcriptional level according to the cellular iron status. As a result of externalization of TfR during the endocytic cycle, a soluble form of TfR can be detected in serum. The serum TfR (sTfR) level is closely related to erythroid TfR turnover and the prime determinants of the sTfR concentration are cellular iron demands and erythroid proliferation rate. In the absence of a hyperplastic erythropoiesis the sTfR level is a sensitive parameter of early tissue iron deficiency. The entire spectrum of body iron status can be assessed by measurement of serum ferritin and sTfR levels, with ferritin as marker of tissue iron stores and sTfR as index of tissue iron needs. The sTfR may be a promising tool to detect iron deficiency in inflammatory states and in the anaemia of chronic disease as its concentration is, in contrast to ferritin levels, not influenced by the acute phase response. Determination of sTfR levels may also improve assessment of body iron stores during pregnancy and in neonates. Finally, the sTfR may be a useful parameter to monitor erythropoiesis in various clinical settings, for instance in the prediction of the haematological response to erythropoietin treatment. However, standardization of the sTfR assay, with definition of reference and pathological ranges, is necessary for the definitive introduction of the sTfR as major parameter of iron metabolism.

  17. [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.

  18. Evaluation of Clinical Significance of Dermoscopy in Alopecia Areata

    PubMed Central

    Guttikonda, Akhila Sai; Aruna, Chintaginjala; Ramamurthy, D V S B; Sridevi, K; Alagappan, Senthil Kumar L

    2016-01-01

    Background: Alopecia areata (AA) is a common, chronic inflammatory disease characterized by nonscarring hair loss on the scalp or any hair-bearing area of the body. Recently, dermoscopy, a noninvasive diagnostic procedure, has been employed for the diagnosis of AA. Aim: To evaluate various dermoscopic patterns in AA and correlate these patterns with the disease activity and severity. Materials and Methods: Dermoscopy was performed on AA patients using DL1 dermoscope (magnification ×10 was used). The dermoscopic patterns recorded were analyzed to identify any correlation with the disease activity and severity. Results: A total of fifty patients of AA were recruited in the study. Female outnumbered males with the ratio being 1.173:1. Mean age of the patients was 25.06 years. Mean duration of disease was 14 months. The most common site involved was scalp (80%) and type noted was patchy (84%). Various dermoscopic patterns noted were yellow dots (YD) (88%), short vellus hair (66%), black dots (BD) (58%), broken hairs (BHs) (56%), tapering hair (TH) (26%), Coudability hairs (14%), pigtail hair (14%), and Pohl-Pinkus constrictions (2%). Statistically significant correlation was observed between BD, BHs, THs, and disease activity. No significant correlation was found between severity and any of the dermoscopic features. Conclusion: The most common dermoscopic pattern in our study was YD. Presence of BDs, BHs, and THs indicate active disease. Dermoscopic patterns were not affected by severity of the disease. PMID:27904180

  19. Expression and clinical significance of Sirt1 in colorectal cancer.

    PubMed

    Yu, Deng-Feng; Jiang, Su-Juan; Pan, Zhi-Peng; Cheng, Wei-Dong; Zhang, Wen-Jun; Yao, Xiao-Kun; Li, Yu-Cheng; Lun, Yong-Zhi

    2016-02-01

    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.

  20. Clinical and biological significance of circulating tumor cells in cancer.

    PubMed

    Masuda, Takaaki; Hayashi, Naoki; Iguchi, Tomohiro; Ito, Shuhei; Eguchi, Hidetoshi; Mimori, Koshi

    2016-03-01

    accumulated, adding to our body of knowledge on CTCs. In this review, we will summarize recent approaches to detect or capture CTCs. Moreover, we will introduce recent studies of the clinical and biological importance of CTCs and host cells.

  1. 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

  2. The clinical significance of cereblon expression in multiple myeloma.

    PubMed

    Schuster, Steven R; Kortuem, K Martin; Zhu, Yuan Xiao; Braggio, Esteban; Shi, Chang-Xin; Bruins, Laura A; Schmidt, Jessica E; Ahmann, Greg; Kumar, Shaji; Rajkumar, S Vincent; Mikhael, Joseph; Laplant, Betsy; Champion, Mia D; Laumann, Kristina; Barlogie, Bart; Fonseca, Rafael; Bergsagel, P Leif; Lacy, Martha; Stewart, A Keith

    2014-01-01

    Cereblon (CRBN) mediates immunomodulatory drug (IMiD) action in multiple myeloma (MM). We demonstrate here that no patient with very low CRBN expression responded to IMiD plus dexamethasone therapy. In 53 refractory MM patients treated with pomalidomide and dexamethasone, CRBN levels predict for decreased response rates and significant differences in PFS (3.0 vs. 8.9 months, p<0.001) and OS (9.1 vs. 27.2 months, p=0.01) (lowest quartile vs. highest three quartiles). While higher CRBN levels can serve as a surrogate for low risk disease, our study demonstrates that low CRBN expression can predict resistance to IMiD monotherapy and is a predictive biomarker for survival outcomes.

  3. Bone cysts in sarcoidosis: what is their clinical significance?

    PubMed

    Yanardağ, Halil; Pamuk, Omer Nuri

    2004-09-01

    The incidence of bone cysts in sarcoidosis, a multisystemic disease, varies in different series, and these cysts are generally asymptomatic. We evaluated bone cysts in 516 sarcoidosis patients with available hand X-rays and in 200 patients with foot X-rays. Bone cysts were present in 21 cases (19 females, two males). The cysts were localized in phalanges of the hand in all cases, in feet in five cases, and in nasal bone in one. Six patients with bone cysts also had lupus pernio. Among those with cystic bone lesions, females were more frequent; extrapulmonary and skin involvement and lupus pernio were significantly more common. We diagnosed cystic bone lesions in 3.6% of our sarcoidosis patients and conclude that cysts were more frequent in females and in patients with lupus pernio.

  4. 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

  5. Clinical significance of lymphadenectomy in patients with gastric cancer

    PubMed Central

    Tóth, Dezső; Plósz, János; Török, Miklós

    2016-01-01

    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

  6. 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.

  7. Clinical significance of Her2/neu overexpression in urothelial carcinomas.

    PubMed

    Alexa, Aurora; Baderca, Flavia; Zăhoi, Delia Elena; Lighezan, Rodica; Izvernariu, D; Raica, M

    2010-01-01

    HER2/neu is a defective transmembrane tyrosine kinase receptor, homologue to the epidermal growth factor receptor, showing overexpression in a large variety of tumor cells. There are no studies published so far regarding HER2/neu overexpression and sensitivity of the urothelial tumors of the urinary bladder to anti-HER2/neu therapy. There are a relatively high number of articles in the literature referring to HER2/neu expression in urothelial tumors of the urinary bladder, but only two of them had investigated HER2/neu expression in patients with urothelial tumors of the upper urinary tract. We have studied HER2/neu overexpression in 59 patients with urothelial carcinomas of the urinary tract by immunohistochemistry. Normal urothelium and the elements of the neighboring renal parenchyma were negative. Out of the 59 cases of urothelial carcinomas, 38 were negative (0 and +1) and 21 were positive: eight were moderately and 13 were intensely positive (+2 and +3). The percentage of positive cases was 35.59%. The negative cases were mostly well-differentiated, G1 tumors, no matter the T-tumor stage. Most of the cases were diagnosed as papillary or, rarely, infiltrative. There is no correlation between HER2/neu overexpression and the tumor stage. The same was true for the lymph node status. The expression intensity, however, was significantly correlated with the differentiation grade. Overexpression was most likely present in tumors with high differentiation grade (p<0.05).

  8. 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

  9. 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

  10. 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.

  11. What is the Clinical Significance of Cerebrospinal Fluid Biomarkers in Parkinson's disease? Is the Significance Diagnostic or Prognostic?

    PubMed

    Kim, Dana; Paik, Jin Hui; Shin, Dong-Woon; Kim, Hak-Su; Park, Chang-Shin; Kang, Ju-Hee

    2014-12-01

    The clinical diagnostic criteria of Parkinson's disease (PD) have limitations in detecting the disease at early stage and in differentiating heterogeneous clinical progression. The lack of reliable biomarker(s) for early diagnosis and prediction of prognosis is a major hurdle to achieve optimal clinical care of patients and efficient design of clinical trials for disease-modifying therapeutics. Numerous efforts to discover PD biomarkers in CSF were conducted. In this review, we describe the molecular pathogenesis of PD and discuss its implication to develop PD biomarkers in CSF. Next, we summarize the clinical utility of CSF biomarkers including alpha-synuclein for early and differential diagnosis, and prediction of PD progression. Given the heterogeneity in the clinical features of PD and none of the CSF biomarkers for an early diagnosis have been developed, research efforts to develop biomarkers to predict heterogeneous disease progression is on-going. Notably, a rapid cognitive decline followed by the development of dementia is a risk factor of poor prognosis in PD. In connection to this, CSF levels of Alzheimer's disease (AD) biomarkers have received considerable attention. However, we still need long-term longitudinal observational studies employing large cohorts to evaluate the clinical utility of CSF biomarkers reflecting Lewy body pathology and AD pathology in the brain. We believe that current research efforts including the Parkinson's Progression Markers Initiative will resolve the current needs of early diagnosis and/or prediction of disease progression using CSF biomarkers, and which will further accelerate the development of disease-modifying therapeutics and optimize the clinical management of PD patients.

  12. What is the Clinical Significance of Cerebrospinal Fluid Biomarkers in Parkinson's disease? Is the Significance Diagnostic or Prognostic?

    PubMed Central

    Kim, Dana; Paik, Jin Hui; Shin, Dong-Woon; Kim, Hak-Su; Park, Chang-Shin

    2014-01-01

    The clinical diagnostic criteria of Parkinson's disease (PD) have limitations in detecting the disease at early stage and in differentiating heterogeneous clinical progression. The lack of reliable biomarker(s) for early diagnosis and prediction of prognosis is a major hurdle to achieve optimal clinical care of patients and efficient design of clinical trials for disease-modifying therapeutics. Numerous efforts to discover PD biomarkers in CSF were conducted. In this review, we describe the molecular pathogenesis of PD and discuss its implication to develop PD biomarkers in CSF. Next, we summarize the clinical utility of CSF biomarkers including alpha-synuclein for early and differential diagnosis, and prediction of PD progression. Given the heterogeneity in the clinical features of PD and none of the CSF biomarkers for an early diagnosis have been developed, research efforts to develop biomarkers to predict heterogeneous disease progression is on-going. Notably, a rapid cognitive decline followed by the development of dementia is a risk factor of poor prognosis in PD. In connection to this, CSF levels of Alzheimer's disease (AD) biomarkers have received considerable attention. However, we still need long-term longitudinal observational studies employing large cohorts to evaluate the clinical utility of CSF biomarkers reflecting Lewy body pathology and AD pathology in the brain. We believe that current research efforts including the Parkinson's Progression Markers Initiative will resolve the current needs of early diagnosis and/or prediction of disease progression using CSF biomarkers, and which will further accelerate the development of disease-modifying therapeutics and optimize the clinical management of PD patients. PMID:25548535

  13. Clinical Outcomes according to the Achievement of Target Low Density Lipoprotein-Cholesterol in Patients with Acute Myocardial Infarction

    PubMed Central

    Ahn, Taehoon; Lee, Kyounghoon; Kang, Woong Chol; Han, Seung Hwan; Ahn, Youngkeun; Jeong, Myung Ho

    2017-01-01

    Background and Objectives The clinical outcome of patient with an acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI), with or without achievement of target low density lipoprotein-cholesterol (LDL-C), has little known information. This study investigated if target LDL-C level (below 70 mg/dL) achievements in patients with AMI showed better clinical outcomes or not. Subjects and Methods Between May 2008 and September 2012, this study enrolled 13473 AMI patients in a large-scale, prospective, multicenter Korean Myocardial Infarction (KorMI) registry. 12720 patients survived and 6746 patients completed a 1-year clinical follow up. Among them 3315 patients received serial lipid profile follow-ups. Propensity score matching was applied to adjust for differences in clinical baseline and angiographic characteristics, producing a total of 1292 patients (646 target LDL-C achievers vs. 646 non-achievers). The primary end point was the composite of a 1-year major adverse cardiac event (MACE) including cardiac death, recurrent myocardial infarction (MI), target lesion revascularization (TLR) and coronary artery bypass grafting. Results After propensity score matching, baseline clinical and angiographic characteristics were similar between the two groups. Clinical outcomes of the propensity score matched patients who showed no significant differences in cardiac death (0.5% vs. 0.5%, p=1.000), recurrent MI (1.1% vs. 0.8%, p=0.562), TLR (5.0% vs. 4.5%, p=0.649), MACEs (6.5% vs. 5.9%, p=0.644) and stent thrombosis (2.5% vs. 1.9%, p=0.560). Conclusion In this propensity-matched comparison, AMI patients undergoing PCI with a target LDL-C (below 70 mg/dL) achievement did not show better clinical outcomes. PMID:28154588

  14. 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.

  15. 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…

  16. 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.…

  17. Use of electronic data and existing screening tools to identify clinically significant obstructive sleep apnea

    PubMed Central

    Severson, Carl A; Pendharkar, Sachin R; Ronksley, Paul E; Tsai, Willis H

    2015-01-01

    OBJECTIVES: To assess the ability of electronic health data and existing screening tools to identify clinically significant obstructive sleep apnea (OSA), as defined by symptomatic or severe OSA. METHODS: The present retrospective cohort study of 1041 patients referred for sleep diagnostic testing was undertaken at a tertiary sleep centre in Calgary, Alberta. A diagnosis of clinically significant OSA or an alternative sleep diagnosis was assigned to each patient through blinded independent chart review by two sleep physicians. Predictive variables were identified from online questionnaire data, and diagnostic algorithms were developed. The performance of electronically derived algorithms for identifying patients with clinically significant OSA was determined. Diagnostic performance of these algorithms was compared with versions of the STOP-Bang questionnaire and adjusted neck circumference score (ANC) derived from electronic data. RESULTS: Electronic questionnaire data were highly sensitive (>95%) at identifying clinically significant OSA, but not specific. Sleep diagnostic testing-determined respiratory disturbance index was very specific (specificity ≥95%) for clinically relevant disease, but not sensitive (<35%). Derived algorithms had similar accuracy to the STOP-Bang or ANC, but required fewer questions and calculations. CONCLUSIONS: These data suggest that a two-step process using a small number of clinical variables (maximizing sensitivity) and objective diagnostic testing (maximizing specificity) is required to identify clinically significant OSA. When used in an online setting, simple algorithms can identify clinically relevant OSA with similar performance to existing decision rules such as the STOP-Bang or ANC. PMID:26083542

  18. Clinical significance of Staphylococcus saprophyticus identified on blood culture in a tertiary care hospital.

    PubMed

    Choi, Sang-Ho; Woo, Jun Hee; Jeong, Jin-Yong; Kim, Nam Joong; Kim, Mi-Na; Kim, Yang Soo; Ryu, Jiso

    2006-11-01

    Staphylococcus saprophyticus is a well-known cause of acute uncomplicated urinary tract infection in young women. However, the clinical significance of this organism isolated from blood culture has not been determined. We assessed the clinical significance and characteristics of S. saprophyticus identified on blood culture. A total of 24 patients were identified, and 7 patients (29.2%) were considered to have clinically significant bacteremia. Of the 7 patients with clinically significant bacteremia, hematologic malignancy was the most common underlying illness (5 patients), and tunneled-central venous catheter was the most common portal of entry (4 patients). In no case did S. saprophyticus bacteremia originate from the urinary tract. One patient died during hospitalization. However, the death was not directly related to bacteremia. In conclusion, our data suggest that bacteremia caused by S. saprophyticus is most commonly associated with tunneled-central venous catheter in patients with hematologic malignancies and may be associated with a lower risk of mortality.

  19. [Significance of clinical laboratory accreditation based on ISO 15189, and recent trend of international clinical laboratory accreditation program].

    PubMed

    Kawai, Tadashi

    2014-06-01

    ISO 15189 was first published in 2003, its second edition in 2007, and its third edition in 2012 by the ISO. Since 2003, through the approval of ILAC, ISO 15189 has been used for the accreditation of clinical/medical laboratories throughout the world, and approximately 5,000 clinical laboratories have now been accredited. In Japan, the JAB, in cooperation with the JCCLS, introduced the clinical laboratory accreditation program based on ISO 15189 in 2005, and 70 labs had been accredited by January 2014. It has been purely voluntary, without any governmental or regulatory involvement so far. However, it has been gradually accepted to be significant for maintaining quality management and for the improvement of clinical laboratory efficiency. The program will expand widely throughout the world in order to accomplish "one-stop testing" among clinical laboratories, at least regarding frequently-used routine laboratory tests.

  20. 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

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

    PubMed

    Lorenz, Laura S; Chilingerian, Jon A

    2011-02-16

    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

  2. THE CLINICAL SIGNIFICANCE OF A POSITIVE AMNISURE TEST™ IN WOMEN WITH TERM LABOR WITH INTACT MEMBRANES

    PubMed Central

    LEE, Seung Mi; LEE, JoonHo; SEONG, Hyo Suk; LEE, Si Eun; PARK, Joong Shin; ROMERO, Roberto; YOON, Bo Hyun

    2009-01-01

    Objective The Amnisure ROM™ test is approved for the diagnosis of rupture of membranes (ROM). Yet, a fraction of patients with a positive test have intact membranes by sterile speculum examination. The objective of this study was to determine the clinical significance of this finding. Methods The study population consisted of 4 groups of nulliparous women at term: 1) not in labor without clinical evidence of ROM (n=125); 2) in labor without clinical ROM with a negative Amnisure test™ (n=56); 3) in labor without clinical ROM with a positive Amnisure test™ (n=25); and 4) in labor with clinical ROM (n=30). The Amnisure test™ was performed in cases without clinical ROM (Groups 1, 2 and 3). Results 1) The Amnisure test™ was positive more frequently in women in labor with intact membranes than in patients not in labor at term without ROM (30.9% (25/81 women) vs. 4.8% (6/125 women); p<0.001); 2) patients in labor without clinical ROM with a positive Amnisure test™ had a significantly shorter admission-to-delivery interval than those in labor without clinical ROM with a negative Amnisure test™ (p<0.05). Conclusion 1) A positive Amnisure test™ is present in about one-third nulliparous women at term presenting in labor with intact membranes; 2) Patients with a positive Amnisure test™ had a shorter admission-to-delivery interval than those with a negative test. PMID:19350444

  3. 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.

  4. 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.

  5. Supporting Low-Achieving EFL Learners: Expectations, Procedure and Significance of Remedial Sessions at a Saudi University

    ERIC Educational Resources Information Center

    Alghamdi, Fatimah M. A.; Siddiqui, Ozma

    2016-01-01

    This study reports on and investigates an institutionalized remedial approach held by an English language institute (ELI) at a Saudi University in order to support foundation year struggling students who often achieve low grades or fail to pass a certain level of the English language program. The study utilizes semi-structured interviews to…

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

    PubMed

    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

    2016-05-17

    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.

  7. Effectiveness of Telemetry Guidelines in Predicting Clinically Significant Arrhythmias in Hospitalized Patients

    PubMed Central

    Dhillon, Sandeep K.; JosephTawil; Goldstein, Baruch; Eslava-Manchego, Dayana; Singh, Jagdeep; Hanon, Sam; Schweitzer, Paul; Bergmann, Steven R.

    2012-01-01

    Background Cardiac rhythm monitoring is widely applied on hospitalized patients. However, its value has not been evaluated systematically. Methods This study considered the utility of our institutional telemetry guidelines in predicting clinically significant arrhythmias. A retrospective analysis was performed of 562 patients admitted to the telemetry unit. A total of 1932 monitoring days were evaluated. Patients were divided into 2 groups based on telemetry guidelines: “telemetry indicated” and “telemetry not indicated”. Results Differences in arrhythmia event rates and pre-defined clinical significance were determined. One hundred and forty-four (34%) vs. 16 (11%) patients had at least one arrhythmic event in the “telemetry indicated” group compared with the “telemetry not indicated” group, respectively (P = 0.001). No patient in the “telemetry not indicated” group had a clinically significant arrhythmia. In contrast, of patients in the “telemetry indicated” group who had at least one arrhythmic event, 36% were considered clinically significant (P < 0.05). Conclusion In conclusion, this study validates and supports the use of our institutional telemetry guidelines to allocate this resource appropriately and predict clinically significant arrhythmias.

  8. 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.

  9. 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

  10. Achieving quality and fiscal outcomes in patient care: the clinical mentor care delivery model.

    PubMed

    Burritt, Joan E; Wallace, Patricia; Steckel, Cynthia; Hunter, Anita

    2007-12-01

    Contemporary patient care requires sophisticated clinical judgment and reasoning in all nurses. However, the level of development regarding these abilities varies within a staff. Traditional care models lack the structure and process to close the expertise gap creating potential patient safety risks. In an innovative model, senior, experienced nurses were relieved of direct patient care assignments to oversee nursing care delivery. Evaluation of the model showed significant impact on quality and fiscal outcomes.

  11. 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.

  12. The Functional Significance of Affect Recognition, Neurocognition, and Clinical Symptoms in Schizophrenia

    PubMed Central

    Hsiao, Sigmund

    2017-01-01

    Objectives The complex relationship and exact extent of the contribution of plausible indictors to social functional outcome in schizophrenia remain unclear. The present study aimed to explore the functional significance of clinical symptoms, neurocognition, and affect recognition simultaneously in schizophrenia. Methods The clinical symptoms, basic neurocognition, facial emotion recognition, and social functioning of 154 subjects, including 74 with schizophrenia and 80 nonclinical comparisons, were assessed. Results We observed that various subdomains of social functioning were extensively related to general intelligence, basic neurocognition, facial emotion recognition, and clinical symptoms, with different association patterns. Multivariate regression analyses revealed that years of education, age, sustained attention, working memory, and facial emotion recognition were significantly associated with global social functioning in schizophrenia. Conclusion Our findings suggest that affect recognition combined with nonsocial neurocognition demonstrated a crucial role in predicting global social function in schizophrenia. PMID:28099444

  13. 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…

  14. 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…

  15. 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…

  16. 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

  17. Clinical significance of GLUT-1 expression in patients with esophageal cancer treated with concurrent chemoradiotherapy.

    PubMed

    Chiba, Itaru; Ogawa, Kazuhiko; Morioka, Takamitsu; Shimoji, Hideaki; Sunagawa, Nao; Iraha, Shiro; Nishimaki, Tadashi; Yoshimi, Naomi; Murayama, Sadayuki

    2011-01-01

    This study aimed to investigate whether glucose transporter-1 (GLUT-1) expression in a pretreatment esophageal cancer biopsy was predictive of clinical outcomes in patients with esophageal cancer undergoing concurrent chemoradiotherapy (CRT). A total of 25 patients with esophageal cancer treated with concurrent CRT were reviewed. Radiotherapy was administered up to total doses of 40-66.6 Gy (median 66.6 Gy) with a single fraction of 1.8-2 Gy. Regarding chemotherapy, cisplatin (80 mg/m(2) on day 1) and 5-fluorouracil (800 mg/m(2) on days 2-6) were used concurrently with radiotherapy, every 3-4 weeks for a total of 1-2 courses. Tissue samples from esophageal carcinoma were obtained from the 25 patients by biopsy prior to concurrent CRT, and a semiquantitative analysis of GLUT-1 expression was performed using immunohistochemical staining. High GLUT-1 expression was observed in 7 of 25 (28%) patients, and GLUT-1 expression was significantly correlated with clinical T stage (p=0.0454), clinical N stage (p=0.0324) and initial response to CRT (p=0.0185). Patients with a high GLUT-1 expression had significantly poorer local control (LC) (5-year LC 28.6%) than those with a low expression (5-year LC 73.4%, p<005). Multivariate analysis revealed that GLUT-1 and the number of chemotherapy courses were independent prognostic factors for LC. Patients with a high GLUT-1 expression had significantly lower recurrence-free survival (RFS) compared to those with a low GLUT-1 expression (p=0.0405). Multivariate analysis revealed that GLUT-1, the number of chemotherapy courses and clinical M stage were independent prognostic factors for RFS. GLUT-1 expression was significantly correlated with clinical T stage, clinical N stage and initial response to concurrent CRT, and was predictive of LC and RFS for patients with esophageal cancer treated with concurrent CRT.

  18. 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.

  19. Osteonectin-expressing cells in human stomach cancer and their possible clinical significance.

    PubMed

    Maeng, Hack-Young; Song, Seok Bean; Choi, Dong-Kug; Kim, Kyoon Eon; Jeong, Hyun Young; Sakaki, Yoshiyuki; Furihata, Chie

    2002-10-08

    The clinical significance of osteonectin in human stomach cancer was examined immunohistochemically and molecular biologically in 31 differentiated and eight undifferentiated stomach adenocarcinomas and 19 non-cancer stomach tissues. Osteonectin-mAb-stained cells were observed in stroma of 90% differentiated and 63% undifferentiated adenocarcinomas, and of 26% non-cancer stomach tissues. Competitive reverse transcriptase polymerase chain reaction results generally coincided with immunohistochemical data. The present results suggest that osteonectin is highly expressed in reactive stroma associated with invasive differentiated adenocarcinomas and that it may serve as a useful clinical diagnostic marker for stomach cancer.

  20. [SIRS (systemic inflammatory response syndrome): clinical entity, definitions, and the significance].

    PubMed

    Kushimoto, S; Yamamoto, Y

    1999-01-01

    The clinical entity, definitions, and the significance of SIRS (systemic inflammatory response syndrome) were reviewed. The term, SIRS was proposed to define sepsis and its sequelae clearly in 1991, in order to make early detection of the disease possible, and to improve the ability to compare innovative potential diagnostic and therapeutic modalities by standardizing terms. Although the criteria of SIRS is not strict and too sensitive, SIRS has been shown to be useful as a warning sign of severe condition in clinical setting. We also discussed about a new concept, CARS (compensatory anti-inflammatory response syndrome), which was characterized as anti-inflammatory mediators-dominant condition, in this issue.

  1. Mechanisms and clinical significance of early recurrences of atrial arrhythmias after catheter ablation for atrial fibrillation

    PubMed Central

    Liang, Jackson J; Dixit, Sanjay; Santangeli, Pasquale

    2016-01-01

    Early recurrence of atrial arrhythmias (ERAA) after ablation is common and strongly predicts late recurrences and ablation failure. However, since arrhythmia may eventually resolve in up to half of patients with ERAA, guidelines do not recommend immediate reintervention for ERAA episodes occurring during a 3-mo post-ablation blanking period. Certain clinical demographic, electrophysiologic, procedural, and ERAA-related characteristics may predict a higher likelihood of long-term ablation failure. In this review, we aim to discuss potential mechanisms of ERAA, and to summarize the clinical significance, prognostic implications, and treatment options for ERAA. PMID:27957250

  2. Covering all clinically significant areas of the colon surface in virtual colonoscopy

    NASA Astrophysics Data System (ADS)

    Kreeger, Kevin; Dachille, Frank; Wax, Mark R.; Kaufman, Arie E.

    2002-04-01

    We have developed a method that automatically displays, places in sized order and allows viewing of the areas of the colon surface not visualized during initial endoscopic navigational viewing. While complete surface visualization is possible, we demonstrate that all of these missed patches do not have to be reviewed to detect clinically significant colon polyps. CT scans are performed on 147 patients and volunteers after bowel preparation and colon distention with CO2. After automatic segmentation and electronic cleansing of the colon lumen, the medial axis (centerline) is extracted. Volume rendering fly-through along the centerline is performed and visualized surfaces are marked. To simulate optical colonoscopy, the virtual camera is passed in the antegrade direction. For virtual colonoscopy, the camera is passed both antegrade and retrograde, and the combined visible surface voxel count is recorded. After both fly-throughs, the total visualized surface is recorded and all 'patches' of connected surface area not yet seen are identified, measured, sorted by size, and counted. Clinically significant patches, defined as smallest diameter being > 5mm, are sequentially visualized by stepping through the sorted list until reaching the patch diameter of 5 mm.. for each. By enabling endoscopic navigation in both antegrade and retrograde directions, virtual colonoscopy is able to evaluate behind haustral folds and around sharp bends, thereby visualizing significantly more surface area than optical colonoscopy. Furthermore, automatic marking of the visualized surface area and identifying and viewing unseen patches allows examination of all clinically significant surfaces of the colon.

  3. 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

  4. Identifying risk factors for clinically significant diabetic macula edema in patients with type 2 diabetes mellitus.

    PubMed

    Kamoi, Kyuzi; Takeda, Keiji; Hashimoto, Kaoru; Tanaka, Reiko; Okuyama, Shinya

    2013-05-01

    It is known that clinic blood pressure (BP), gender, cigarette smoking, dyslipidemia, anemia and thiazolidenediones (TZD) treatment are predictors for clinically significant diabetic macula edema (CSDME). We examined a most risky factor for CSDME in Japanese patients with type 2 diabetes mellitus (T2DM) and diabetic retinopathy (DR) confirmed using optical coherence tomography by multiple regression analysis (MRA). As the risk factors, wakening-up BP was added to such factors. Seven diabetic Japanese patients with CSDME (group 1) and 124 subjects without CSDME (group 2) assonated with DR using optical coherence tomography were studied. The durations of T2DM in groups 1 and 2 were 15±10 years and 20±15 years, respectively. There was no statistically difference in means of gender, duration, age, body mass index (BMI), HbA1c, TC, LDL and TC/HDL, serum creatinine, urinary albumin excretion rate, and clinic BP between two groups. Morning systolic home BP (MSHBP), cigarette smoking and foveal thickness were significantly (p<0.001) higher in group 1 than group 2, whereas visual acuity was significantly (p<0.00?) lower in group 1 than in group 2. The patients in both groups had received various kinds of drugs for hyperglycemia, hypertension and others. There were no significant differences in the variables in both groups. MRA revealed that MSHBP, cigarette smoking and pioglitazone as TZD treatment were significantly positive predictors for CSDME, while BMI had a significantly negative predictor. Other variables were not significantly correlated to CSDME. The review summarizes a multiple regression analysis revealed that MSHBP makes an addition to predictive factors for CSDME among risk factors reported previously in patient with T2DM.

  5. Expression and clinical significance of Kelch-like epichlorohydrin-associated protein 1 in breast cancer.

    PubMed

    Zhang, L; Yang, W P; Wu, L Y; Zhu, X; Wei, C Y

    2016-05-12

    Our objective was to explore the expression and clinical significance of Kelch-like epichlorohydrin-associated protein 1 (Keap1) in breast cancer tissue. Eighty-one breast cancer patients having undergone surgical treatment in our hospital between March 2002 and December 2008 were enrolled in this study. Normal tissue adjacent to tumors was used for the control samples. Diagnoses for all patients were confirmed by postoperative pathological examination. Immunohistochemical assays were used to measure the expression of Keap1 protein in breast cancer tissue and adjacent normal tissue, and its clinical significance was explored. We observed that 24.6% breast cancer tissue samples were positive for Keap1, a significantly lower proportion than that seen with adjacent normal tissue specimens (80.2%; P < 0.05). The presence of Keap1 expression did not correlate with age, tumor size, pathological classification, or degree of differentiation. However, it was found to be significantly associated with tumor-node-metastasis stage and the presence of lymphatic metastasis. Kaplan-Meier survival analysis showed a remarkably higher five-year survival rate among patients with positive Keap1 expression than in those lacking detectable levels of the protein (P = 0.032). Keap1 expression is significantly decreased in breast cancer tissue; therefore, the early detection of its expression might have great significance in determining prognosis for breast cancer patients.

  6. Significance of frailty for predicting adverse clinical outcomes in different patient groups with specific medical conditions.

    PubMed

    Ritt, Martin; Gaßmann, Karl-Günter; Sieber, Cornel Christian

    2016-10-01

    Frailty is a major health burden in an aging society. It constitutes a clinical state of reduced physiological reserves that is associated with a diminished ability to withstand internal and external stressors. Frail patients have an increased risk for adverse clinical outcomes, such as mortality, readmission to hospital, institutionalization and falls. Of further clinical interest, frailty might be at least in part reversible in some patients and subject to preventive strategies. In daily clinical practice older patients with a complex health status, who are mostly frail or at least at risk of developing frailty, are frequently cared for by geriatricians. Recently, clinicians and scientists from other medical disciplines, such as cardiology, pulmonology, gastroenterology, nephrology, endocrinology, rheumatology, surgery and critical care medicine also discovered frailty to be an interesting instrument for risk stratification of patients, including younger patients. In this review we highlight the results of recent studies that demonstrated the significance of frailty to predict adverse clinical outcomes in patients with specific medical conditions, such as cardiac, lung, liver and kidney diseases as well as diabetes mellitus, osteoarthritis, trauma patients, patients undergoing surgery and critically ill patients. Multiple studies in patients with the aforementioned specific medical conditions could be identified demonstrating a predictive role of frailty for several adverse clinical outcomes. The association between frailty and adverse clinical outcomes reported in these studies was in part independent of several major potential confounder factors, such as age, sex, race, comorbidities and disabilities and were also detected in younger patients.

  7. Clinical Significance of Nontuberculous Mycobacteria Isolated From Respiratory Specimens in a Chinese Tuberculosis Tertiary Care Center

    PubMed Central

    Duan, Hongfei; Han, Xiqin; Wang, Qingfeng; Wang, Jing; Wang, Jun; Chu, Naihui; Huang, Hairong

    2016-01-01

    The clinical relevance of non-tuberculous mycobacteria (NTM) has been reported to be different dramatically by species or by regions, however, no such evaluation has been performed in China.A retrospective study was performed in Beijing Chest Hospital. All the NTM strains isolated from respiratory specimens in the past 5 years, and patients’ clinical records (symptoms and radiographic information etc.) were investigated. The clinical relevance was evaluated according to the criteria recommended by the American Thoracic society. Totally 232 NTM strains were recruited, among them, M. intracellulare was the dominant species (40.5%), followed by M. abscessus (28.4%). 109 patients, with 185 total isolates, had full clinical records available for review. 84.4% (38/45), 85.7% (24/28%) and 63.6% (7/11) of patients with isolation of M. intracellulare, M. abscessus and M. kansasii, respectively, were categorized as definite NTM disease. Whereas all the 10 patients with isolation of M. gordonae were defined as unlikely NTM disease. The majority of NTMs isolates yielded from respiratory specimens in Beijing Chest Hospital were clinically significant, and M. intracellulare and M. abscessus was the dominated species of NTM lung disease. NTM lung infections demonstrated some specific chest radiograph characteristics. PMID:27808247

  8. Clinical significance of occult metastatic cells in bone marrow of breast cancer patients.

    PubMed

    Braun, S; Pantel, K

    2001-01-01

    The early and clinically occult spread of viable tumor cells to the organism is increasingly considered a hallmark in cancer progression, as emerging data suggest that these cells are precursors of subsequent distant relapse. Using monoclonal antibodies to epithelial cytokeratins or tumor-associated cell membrane glycoproteins, individual carcinoma cells can be detected on cytologic bone marrow preparations at frequencies of 10(-5) to 10(-6). Prospective clinical studies have shown that the presence of these immunostained cells in bone marrow, as a frequent site of overt metastases, is prognostically relevant with regard to relapse-free and overall survival. This screening approach may be, therefore, used to improve tumor staging and guide the stratification of patients for adjuvant therapy in clinical trials. Another promising application is monitoring the response of micrometastatic cells to adjuvant therapies, which, at present, can only be assessed retrospectively after an extended period of clinical follow-up. The present review summarizes the current data on the clinical significance of occult metastatic breast cancer cells in bone marrow.

  9. Clinical significance of molecular diagnosis for gastric cancer lymph node micrometastasis

    PubMed Central

    Sonoda, Hiromichi; Tani, Tohru

    2014-01-01

    Advances in molecular diagnostic tools have allowed the identification of lymph node micrometastasis (LNM), including isolated tumor cells, in cancer patients. While immunohistochemistry and reverse transcription-polymerase chain reaction have been used to identify LNM in patients with gastric cancer, the clinical significance of this finding remains unclear. Recently, minimally invasive treatments, such as endoscopic submucosal dissection and laparoscopic surgery, are widely performed to help improve postsurgical quality of life (QOL). However, it is important to maintain the balance between QOL and curability when making treatments decision for patients with gastric cancer. If minimally invasive surgery based on accurate intraoperative LNM diagnosis was established, it could be performed safely. Therefore, we reviewed the clinical significance of LNM detected by molecular techniques as an important target for treatment decision making with gastric cancer patients. PMID:25320510

  10. The clinical significance of brain microbleeds in patients with Alzheimer's disease: Preliminary study

    PubMed Central

    Heo, Jae-Hyeok; Im, Dong-Gyu; Lee, Seung-Hyeon; Ahn, Jin-Young

    2016-01-01

    Background: Microbleeds (MBs) are observed frequently in Alzheimer's disease (AD) and suggested to play a crucial role in the pathophysiology, but their clinical significance remains unclear. Materials and Methods: The study recruited 100 patients with AD who were diagnosed at the memory clinic in Seoul Medical Center in 2014. For each patient, baseline characteristics, neuropsychological tests, cerebrovascular risk factors, medial temporal lobe atrophy (MTLA), and severity of small vessel disease (SVD) according to the existence of MBs were evaluated. Results: The prevalence of MBs in patients with AD was 33%. The percentage of male gender, the severity of SVD and MTLA were significantly increased in MB(+) group. The MB(+) group showed more severe MTLA and SVD than MB(−) group. Conclusions: These results suggested that MBs might reflect the burden of amyloid and ischemic vascular pathology. PMID:27994360

  11. Clinically significant hemodynamic alterations after propacetamol injection in the emergency department: prevalence and risk factors.

    PubMed

    Bae, June-Il; Ahn, Shin; Lee, Yoon-Seon; Kim, Won Young; Lee, Jae Ho; Oh, Bum Jin; Lim, Kyung Soo

    2017-04-01

    Propacetamol, a water-soluble prodrug form of paracetamol, is hydrolyzed by esterase to generate paracetamol in the blood. Each gram of propacetamol is equal to 0.5 g of paracetamol. It has been reported to cause hypotension in critically ill patients with a fever. We aimed to investigate the hemodynamic effects of propacetamol for the control of fever in patients with diverse severities of illness who were managed in the emergency department (ED). We also aimed to identify clinical factors related to significant hemodynamic alterations in ED patients. This was a retrospective study of 1507 ED patients who received propacetamol. Significant hemodynamic alterations were defined as systolic blood pressure (SBP) <90 mmHg or diastolic blood pressure (DBP) <60 mmHg, or a drop in SBP >30 mmHg, which required treatments with a bolus of fluid or vasopressor administration. Postinfusion SBP and DBP were significantly lower than the preinfusion SBP and DBP. A clinically significant drop in BP occurred in 162 (10.7 %) patients, and interventions were necessary. Among the predictors assessed, congestive heart failure (OR 6.21, 95 % CI 2.67-14.45) and chills (OR 3.10, 95 % CI 2.04-4.70) were independent factors for a significant hemodynamic change. Administration of propacetamol can provoke a reduction in BP in ED patients. This reduction was clinically significant for 10 % of infusions. Clinicians should be aware of this potential deleterious effect, especially in patients with congestive heart failure or who experience chills prior to the administration of propacetamol.

  12. 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

  13. Significance of molecular identification and antifungal susceptibility of clinically significant yeasts and moulds in a global antifungal surveillance programme.

    PubMed

    Pfaller, Michael A; Woosley, Leah N; Messer, Shawn A; Jones, Ronald N; Castanheira, Mariana

    2012-10-01

    The increasing diversity of opportunistic fungi causing serious invasive fungal infections (IFI) has been documented. Accurate identification (ID) is important in guiding therapy, determining prognosis for IFIs and in epidemiological surveys. We assessed the utility of PCR-based methods for the ID of yeasts and moulds that either were uncommon, failed conventional ID, or represented unusual biochemical or phenotypic profiles of common species. Among 1,790 viable fungal clinical isolates received during the SENTRY Program in 2010, 322 strains from 40 study sites had ID confirmed by molecular methods. Isolates were previously identified in participant institutions. Yeasts that were not confirmed by morphology on CHROMagar, growth at 45 °C (Candida albicans/dubliniensis), or assimilation of trehalose (C. glabrata) as well as non-Candida yeasts and all moulds were amplified and sequenced using primers amplifying one or more of the following genes: ITS, 28S, β-tubulin (Aspergillus spp.), TEF (Fusarium spp.), IGS (Trichosporon spp.). The isolates selected for molecular ID included 149 isolates of Candida species, 77 of Aspergillus species, 73 non-Candida yeasts, and 23 other moulds (a total of 41 different species). Overall, the ID determined by the submitting site was confirmed for 189 isolates (58.7 %): Aspergillus spp. (64.1 % correct); Candida spp. (60.1 % correct); non-Candida yeasts (58.9 % correct); non-Aspergillus moulds (30.4 % correct). Species with high levels of concordance between conventional and molecular ID included A. fumigatus (95.0  %), C. lusitaniae (100 %), C. dubliniensis (92.3 %), C. kefyr (100 %), and C. neoformans (90.2 %). Only 50.0 % of isolates of C. albicans and 59.1 % of C. glabrata selected due to unusual phenotypic or biochemical features were found to be correctly identified by the submitting site. Molecular methods for the identification of fungal pathogens are an important adjunct to the conventional identification of

  14. MMSA-1 expression pattern in multiple myeloma and its clinical significance.

    PubMed

    Meng, Shan; Lu, Chenyang; Zhang, Wanggang; Shen, Wenjun; Wei, Yongchang; Su, Dan; Zhou, Fuling

    2016-11-01

    Multiple myeloma-associated antigen-1 (MMSA-1) is a novel multiple myeloma (MM)-associated antigen which has been recently identified. Herein, we have tried to examine its clinical significance by studying the relationship between its expression and selected clinicopathological features. We extracted mononuclear cells from the bone marrow of MM patients and healthy donors and compared the MMSA-1 expression by RT-PCR and Western blot analysis. In addition, we also analyzed MMSA-1 expression in patients that were grouped based on selected clinical parameters. Moreover, the impact of MMSA-1 on patients' survival was also explored. MMSA-1 mRNA and protein were significantly upregulated in MM patients in comparison with healthy donors. Moreover, among the newly diagnosed and relapsed/refractory patients, the MMSA-1 expression was higher in relapsed/refractory patients. In addition, MMSA-1 mRNA expression not only showed significantly higher correlation with clinical parameters such as age, Durie and Salmon stage, bone lesion condition, albumin, creatinine and lactate dehydrogenase but also has a close relationship with myeloma bone disease-related cytokines, genetic abnormalities and treatment response. Multivariate COX analysis predicted MMSA-1 and LDH levels to be independently associated with a poor progression-free survival and overall survival in myeloma patients. Our findings provide initial proof of concept that MMSA-1 is a potent gene that is specifically expressed in MM patients and could be a feasible biomarker and independent prognostic factor.

  15. Monoscopic versus stereoscopic photography in screening for clinically significant macular edema.

    PubMed

    Welty, Christopher J; Agarwal, Anita; Merin, Lawrence M; Chomsky, Amy

    2006-01-01

    The purpose of the study was to determine whether monoscopic photography could serve as an accurate tool when used to screen for clinically significant macular edema. In a masked randomized fashion, two readers evaluated monoscopic and stereoscopic retinal photographs of 100 eyes. The photographs were evaluated first individually for probable clinically significant macular edema based on the Early Treatment Diabetic Retinopathy Study criteria and then as stereoscopic pairs. Graders were evaluated for sensitivity and specificity individually and in combination. Individually, reader one had a sensitivity of 0.93 and a specificity of 0.77, and reader two had a sensitivity of 0.88 and a specificity of 0.94. In combination, the readers had a sensitivity of 0.91 and a specificity of 0.86. They correlated on 0.76 of the stereoscopic readings and 0.92 of the monoscopic readings. These results indicate that the use of monoscopic retinal photography may be an accurate screening tool for clinically significant macular edema.

  16. Overexpression and clinical significance of MYC-associated zinc finger protein in pancreatic carcinoma

    PubMed Central

    Zhu, Xiaonian; Luo, Wei; Liang, Wenjin; Tang, Fen; Bei, Chunhua; Ren, Yuan; Qin, Linyuan; Tan, Chao; Zhang, Ying; Tan, Shengkui

    2016-01-01

    This study aimed to investigate the expression and clinical significance of MYC-associated zinc finger protein (MAZ) in pancreatic carcinoma (PC), and the biological functions of MAZ in PC cells. MAZ expression was detected in 57 PC tissues and 41 paired adjacent nontumor tissues by immunohistochemistry. Compared to the expression in adjacent nontumor tissues, MAZ was significantly higher expressed in PC tissues (P<0.0001). In addition, MAZ expression had a significant correlation with certain clinical characteristics of PC patients, such as age, tumor diameter, tumor number, and the serum level of CA199 (P<0.05). The survival analysis showed that the survival time of PC patients with high expression of MAZ was significantly lower than patients with low expression of MAZ (P=0.0365). After MAZ was knocked down in PANC-1 cells by RNA interference, the cells’ ability to proliferate, invade, and migrate was decreased significantly (P<0.01). Moreover, MAZ expression was found to be associated with Ki-67, a cell proliferation marker, in PC tissues, further supporting the idea that MAZ promotes PC cell proliferation. Our study clarifies an oncogenic role of MAZ in pathogenesis of PC and provides MAZ as a biomarker in the treatment and prognosis of PC. PMID:28008270

  17. [Clinical diagnose and significance of congenital sensorineural hearing loss combined with BPES].

    PubMed

    Ao, Liying; Liu, Yongzhi

    2015-09-01

    To analyze congenital sensorineural hearing loss combined with blepharophimosis-ptosis-epicanthus inversus syndrome (BPES). For the case of cochlear implantation to child with congenital sensorineural deafness combined BPES, accomplish routine examination and assessment, combining with literature to analyze the clinical diagnosis of this disease and its significance. Sensorineural hearing loss is a common congenital diseases with neonatal incidence of 1 per thousand - 3 per thousand, 50%-70% of deafness is associated with genetic factors, the incidence of congenital sensorineural hearing loss combined with eye disease is about 40%-60%, mainly reflected in ametropia and retinopathy. BPES's main clinical manifestations is blepharophimosis, ptosis, epicanthus inversus, and telecanthus. BPES is a rare autosomal dominant disease caused by FOXL 2 gene mutation, sometimes associated with retarded growth, delayed development, congenital heart disease, and microcephaly. Suffering from both sensorineural hearing loss and BPES is rare in reported literature. This case is diagnosed by clinical examination, without visual impairment. Facial nerve dysplasia has been found during the surgery. For congenital deafness patients with eye disease or other diseases, timely and correct diagnosis has important clinical significance, which can improve the diagnostic rate and make it coming true to early intervention, and then, effectively improve the quality of the patients. There are few literature reports, of patients with two kinds of genetic diseases. Our inference is that the cases are rare or the patients has visited different departments and ignored the other systems' signs. Therefore, in such doubtful cases, we should do the professional comprehensive examination in daily clinical work in order to avoid missed diagnosis or delayed treatment and intervention. By analyzing this case, the patient may also suffer from facial nerve dysplasia. Preoperatively viewing CT scan and

  18. 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

  19. Mechanism of an unusual, but clinically significant, digoxin-bupropion drug interaction.

    PubMed

    He, Jiake; Yu, Yang; Prasad, Bhagwat; Chen, Xijing; Unadkat, Jashvant D

    2014-07-01

    An unusual, but clinically significant, digoxin (DIG)-bupropion (BUP) drug interaction (DDI), in which BUP increased DIG renal clearance by 80% is reported. To investigate the mechanism(s) of this unusual DDI, first the effect of BUP, its circulating metabolites or their combination on [(3) H]-DIG transport by cells expressing human P-gp or human OATP4C1 was determined. Second, the study asked whether this DDI could be replicated in the rat so that it could be used to conduct mechanistic studies. Then, the effect of BUP and its rat metabolites on [(3) H]-DIG transport were tested by cells expressing rat Oatp4c1. Bupropion and its metabolites had no effect on human P-gp mediated transepithelial transport of [(3) H]-DIG. Bupropion and hydroxybupropion (HBUP) significantly stimulated H-OATP4C1 mediated transport of [(3) H]-DIG. In addition, BUP cocktail (BUP plus its metabolites) significantly increased the H-OATP4C1 mediated transport of [(3) H]-DIG, and partially reversed the inhibition by 100 µm DIG. However, erythro-hydrobupropion (EBUP) and threo-hydrobupropion (TBUP) did not affect the [(3) H]-DIG uptake by H-OATP4C1 cells. Bupropion administration significantly increased digoxin renal clearance in rats. Surprisingly, bupropion significantly inhibited r-Oatp4c1 mediated transport of [(3) H]-DIG at clinically relevant unbound plasma concentrations of BUP or those observed in the rat study, while HBUP or TBUP did not. These data support our hypothesis that at clinically relevant plasma concentrations, bupropion and its metabolites activate H-OATP4C1 mediated DIG tubular secretion, and could possibly explain the increase in digoxin renal clearance produced by bupropion. While bupropion increased digoxin renal clearance in the rat, it appeared to do so by inhibiting r-Oatp4c1-mediated digoxin renal reabsorption.

  20. Clinical Significance of Commensal Gram-Positive Rods Routinely Isolated from Patient Samples.

    PubMed

    Leal, Sixto M; Jones, Melissa; Gilligan, Peter H

    2016-12-01

    Commensal bacteria from the skin and mucosal surfaces are routinely isolated from patient samples and considered contaminants. The majority of these isolates are catalase-positive Gram-positive rods from multiple genera routinely classified as diphtheroids. These organisms can be seen upon Gram staining of clinical specimens or can be isolated as the predominant or pure species in culture, raising a priori suspicion of a possible involvement in infection. With the development and adoption of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), suspicious isolates are now routinely identified to the species level. In this study, we performed a retrospective data review (2012 to 2015) and utilized site-specific laboratory criteria and chart reviews to identify species within the diphtheroid classification representative of true infection versus contamination. Our data set included 762 isolates from 13 genera constituting 41 bacterial species. Only 18% represented true infection, and 82% were deemed contaminants. Clinically significant isolates were identified in anaerobic wounds (18%), aerobic wounds (30%), blood (5.5%), urine (22%), cerebrospinal fluid (24%), ophthalmologic cultures (8%), and sterile sites (20%). Organisms deemed clinically significant included multiple Actinomyces species in wounds, Propionibacterium species in joints and cerebrospinal fluid associated with central nervous system hardware, Corynebacterium kroppenstedtii (100%) in breast, and Corynebacterium striatum in multiple sites. Novel findings include clinically significant urinary tract infections by Actinomyces neuii (21%) and Corynebacterium aurimucosum (21%). Taken together, these findings indicate that species-level identification of diphtheroids isolated with a priori suspicion of infection is essential to accurately determine whether an isolate belongs to a species associated with specific types of infection.

  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. Occurrence and clinical significance of Aelurostrongylus abstrusus and other endoparasites in Danish cats.

    PubMed

    Hansen, Alice P; Skarbye, Line K; Vinther, Lene M; Willesen, Jakob L; Pipper, Christian B; Olsen, Caroline S; Mejer, Helena

    2017-01-30

    Feline endoparasites are highly prevalent worldwide and may cause a variety of clinical signs in infected cats. Prevalence rates are dynamic and there is limited knowledge of the current prevalence in Denmark and the clinical manifestation and significance of especially the lungworm Aelurostrongylus abstrusus. This study investigated the total and local prevalence of Aelurostrongylus abstrusus and other endoparasites in Danish cats. The clinical significance of feline aelurostrongylosis was also examined through identification of frequency and severity of selected clinical signs. Faecal samples (n=327) and clinical data (n=312) were collected from August to October 2015, primarily from outdoor cats located at shelters distributed across Denmark. A modified Baermann method and a concentration McMaster technique was used to diagnose A. abstrusus first stage larvae and eggs/oocysts of other endoparasites. The total A. abstrusus prevalence was 8.3% [95% CI: 5.6-11.9] but local prevalence rates varied from 0% [95% CI: 0.0-8.8] to 31.4% [95% CI: 16.9-49.3]. A rural habitat appeared to increase the risk of A. abstrusus and this accounted for most of the local variation. Furthermore, the risk of infection was lower in kittens younger than 11 weeks compared to older cats (p=0.002). The cats were also infected with Toxocara cati (44.4% [95% CI: 38.3-50.7]), taeniid species (8.9% [95% CI: 5.7-13.0]), Capillaria aerophila (3.1% [95% CI: 1.3-6.0]), Aonchotheca putorii (3.9% [95% CI: 1.9-7.0]), Cystoisospora felis (3.1% [95% CI: 1.3-6.0]) and Cystoisospora rivolta (2.3% [95% CI: 0.9-5.0]), but there was no difference in local distribution. Co-infection was common, as 66.7% of A. abstrusus infected cats were also infected with one or more other parasites, the most common being T. cati. However, none of these parasites were significantly associated with A. abstrusus. The vast majority of the A. abstrusus infected cats displayed mild to moderate clinical signs. The main symptoms

  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.

  4. Clinical and molecular significance of microvascular inflammation in transplant kidney biopsies.

    PubMed

    Gupta, Anjali; Broin, Pilib Ó; Bao, Yi; Pullman, James; Kamal, Layla; Ajaimy, Maria; Lubetzky, Michelle; Colovai, Adriana; Schwartz, Daniel; de Boccardo, Graciela; Golden, Aaron; Akalin, Enver

    2016-01-01

    The diagnostic criteria for antibody-mediated rejection (AMR) are continuously evolving. Here we investigated the clinical and molecular significance of different Banff microvascular inflammation (MVI) scores in transplant kidney biopsies. A total of 356 patients with clinically indicated kidney transplant biopsies were classified into three groups based on MVI scores of 0, 1, 2, or more for Groups 1-3, respectively. Gene expression profiles were assessed using arrays on a representative subset of 93 patients. The incidence of donor-specific anti-HLA antibodies was increased from 25% in Group 1 to 36% in Group 2 and to 54% in Group 3. Acute and chronic AMR were significantly more frequent in Group 3 (15% and 35%) compared with the Group 2 (3% and 15%) and Group 1 (0% and 5%), respectively. Gene expression profiles showed increased interferon-γ and rejection-induced, cytotoxic and regulatory T-cell, natural killer cell-associated and donor-specific antibody (DSA)-selective transcripts in Group 3 compared with Groups 1 and 2. There was no significant difference in gene expression profiles between the Groups 1 and 2. Increased intragraft expression of DSA-selective transcripts was found in the biopsies of C4d- Group 3 patients. Thus, an MVI score of 2 or more was significantly associated with a histological diagnosis of acute and chronic antibody-mediated rejection. Hence, increased intragraft DSA-selective gene transcripts may be used as molecular markers for AMR, especially in C4d- biopsies.

  5. Contextual cognitive-behavioral therapy for severely disabled chronic pain sufferers: effectiveness and clinically significant change.

    PubMed

    McCracken, Lance M; MacKichan, Fiona; Eccleston, Christopher

    2007-04-01

    Interdisciplinary pain management programs have an established record of significantly improving the functioning of persons disabled with chronic pain. There is a group of pain sufferers, however, who have difficulty accessing these programs and for whom the effectiveness of these treatments in unknown, these are patients whose mobility and self-care deficits leave them unable to meet the practical demands of many treatment environments. The purpose of this study was to examine the results of a treatment program designed to meet the needs of these highly disabled individuals (n=53) in comparison to results obtained from a standard less-disabled group attending treatment at the same facility (n=234). Results from the highly disabled patients showed statistically significant change after treatment in eight of nine outcome variables, including improvements in pain-related distress, disability, depression, pain-related anxiety, daytime rest, and performance during an activity tolerance test. Effect size calculations showed a number of large treatment effects, for psychosocial disability, depression, and acceptance of pain. Analysis of reliable change and clinical significance demonstrated that results were not merely statistically significant but clinically meaningful. Results appeared stable at three months following treatment. This research plays an important part in establishing an evidence base to inform service development, ensuring that chronic pain services do not exclude people on the basis of the severity of their disability.

  6. Clinical significance of a new autoantibody against a human eye muscle soluble antigen, detected by immunofluorescence.

    PubMed Central

    Mengistu, M; Laryea, E; Miller, A; Wall, J R

    1986-01-01

    The clinical significance of a circulating autoantibody against a recently identified soluble human eye muscle-derived antigen was studied in patients with Graves' ophthalmopathy and autoimmune thyroid disorders. Tests were positive in 73% of patients with Graves' ophthalmopathy, including six of seven with no associated thyroid disease (euthyroid Graves' disease). Tests were also positive in 27% of patients with hyperthyroidism but no clinically apparent eye disease, in 13% of patients with Hashimoto's thyroiditis without eye disease, in two of 12 patients with subacute thyroiditis, in one of 20 patients with nonimmunological thyroid disorders but in none of 39 normal subjects. There were significant positive correlations between serum levels of the antibody (expressed as a titre) and the severity of the eye muscle component quantified as an index as well as the duration of the eye disease. Antibodies were detected in three of five patients with only lid lag and state who subsequently developed active ophthalmopathy, in six of nine patients who developed eye disease after treatment of their hyperthyroidism and in one of eight first degree relatives of patients with Graves' ophthalmopathy. In addition three of the 12 patients with autoimmune thyroid disease without apparent eye involvement, but positive antibody tests, have developed ophthalmopathy since the time of testing. These findings suggest that tests for antibodies against a soluble human eye muscle antigen may be useful clinically as a diagnostic test and to predict the onset of eye disease in predisposed patients and subjects. PMID:3539423

  7. The clinical significance of the Ezrin gene and circulating tumor cells in osteosarcoma

    PubMed Central

    Zhong, Guang-Xian; Feng, Shao-Dan; Shen, Rongkai; Wu, Zhao-Yang; Chen, Fei; Zhu, Xia

    2017-01-01

    Purpose The aim of this study was to investigate the clinical significance of circulating tumor cells (CTCs) in the peripheral blood of an osteosarcoma and the Ezrin gene expressed in CTCs. Patients and methods CTC enrichment was done with CanPatrol™ CTC enrichment technique in 41 patients with osteosarcoma. The characterization of CTCs was performed using a multiple messenger RNA in situ analysis (MRIA). The expression of the Ezrin gene in CTCs was detected by RNA probe technology. The correlations of CTC counts, cell type and the expression level of the Ezrin gene with clinical stage and metastasis of osteosarcoma were analyzed using SPSS 16.0 software. Results The CTC counts correlated significantly with Enneking stage (P<0.001). The ratio of mesenchymal CTCs correlated with the distant metastases (P<0.001). Ezrin gene expression in CTCs correlated significantly with distant metastases (χ2=152.51, P=0.000). Conclusion The ratio of mesenchymal CTCs in the peripheral blood of osteosarcoma correlates with distant metastases. High expression of Ezrin gene in CTCs correlates with distant metastases. PMID:28223819

  8. Clinical significance of radiation-induced CD133 expression in residual rectal cancer cells after chemoradiotherapy.

    PubMed

    Kawamoto, Aya; Tanaka, Koji; Saigusa, Susumu; Toiyama, Yuji; Morimoto, Yuhki; Fujikawa, Hiroyuki; Iwata, Takashi; Matsushita, Kohei; Yokoe, Takeshi; Yasuda, Hiromi; Inoue, Yasuhiro; Miki, Chikao; Kusunoki, Masato

    2012-03-01

    CD133 and CD44 have been considered as markers for colorectal cancer stem cells (CSCs). The association of CD133 and CD44 expression with radiation has not been fully examined in rectal cancer. Both CD133 (PROM) and CD44 mRNA levels were measured in post-chemoradiotherapy (CRT) specimens of 52 rectal cancer patients using real-time RT-PCR and compared to clinicopathological variables and clinical outcome. Their protein levels were examined in the radiation-treated HT29 human colon cancer cell line. Post-CRT CD133 in residual cancer cells was significantly higher than matched pre-CRT CD133 in biopsy specimens (n=30). By contrast, CD44 was significantly lower in post-CRT specimens (P<0.01). CD133 was associated with distant recurrence after CRT followed by surgery (P<0.05). Patients with elevated CD133 in residual cancer cells showed poor disease-free survival (P<0.05). No significant association between post-CRT CD44 and clinical outcome was found. The in vitro study showed that CD133 protein was increased in a radiation dose-dependent manner, despite of the decreased number of clonogenic radiation-surviving cells. CD44 protein was decreased after irradiation. CD133, but not CD44, was increased in radiation-resistant surviving colon cancer cells. Post-CRT CD133 in residual cancer cells may predict metachronous distant recurrence and poor survival of rectal cancer patients after CRT.

  9. Managing clinically significant findings in research: the UK10K example.

    PubMed

    Kaye, Jane; Hurles, Matthew; Griffin, Heather; Grewal, Jasote; Bobrow, Martin; Timpson, Nic; Smee, Carol; Bolton, Patrick; Durbin, Richard; Dyke, Stephanie; Fitzpatrick, David; Kennedy, Karen; Kent, Alastair; Muddyman, Dawn; Muntoni, Francesco; Raymond, Lucy F; Semple, Robert; Spector, Tim

    2014-09-01

    Recent advances in sequencing technology allow data on the human genome to be generated more quickly and in greater detail than ever before. Such detail includes findings that may be of significance to the health of the research participant involved. Although research studies generally do not feed back information on clinically significant findings (CSFs) to participants, this stance is increasingly being questioned. There may be difficulties and risks in feeding clinically significant information back to research participants, however, the UK10K consortium sought to address these by creating a detailed management pathway. This was not intended to create any obligation upon the researchers to feed back any CSFs they discovered. Instead, it provides a mechanism to ensure that any such findings can be passed on to the participant where appropriate. This paper describes this mechanism and the specific criteria, which must be fulfilled in order for a finding and participant to qualify for feedback. This mechanism could be used by future research consortia, and may also assist in the development of sound principles for dealing with CSFs.

  10. Managing clinically significant findings in research: the UK10K example

    PubMed Central

    Kaye, Jane; Hurles, Matthew; Griffin, Heather; Grewal, Jasote; Bobrow, Martin; Timpson, Nic; Smee, Carol; Bolton, Patrick; Durbin, Richard; Dyke, Stephanie; Fitzpatrick, David; Kennedy, Karen; Kent, Alastair; Muddyman, Dawn; Muntoni, Francesco; Raymond, Lucy F; Semple, Robert; Spector, Tim

    2014-01-01

    Recent advances in sequencing technology allow data on the human genome to be generated more quickly and in greater detail than ever before. Such detail includes findings that may be of significance to the health of the research participant involved. Although research studies generally do not feed back information on clinically significant findings (CSFs) to participants, this stance is increasingly being questioned. There may be difficulties and risks in feeding clinically significant information back to research participants, however, the UK10K consortium sought to address these by creating a detailed management pathway. This was not intended to create any obligation upon the researchers to feed back any CSFs they discovered. Instead, it provides a mechanism to ensure that any such findings can be passed on to the participant where appropriate. This paper describes this mechanism and the specific criteria, which must be fulfilled in order for a finding and participant to qualify for feedback. This mechanism could be used by future research consortia, and may also assist in the development of sound principles for dealing with CSFs. PMID:24424120

  11. 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

  12. Clinically Significant Behavior Problems among Young Children 2 Years after the Great East Japan Earthquake

    PubMed Central

    Fujiwara, Takeo; Yagi, Junko; Homma, Hiroaki; Mashiko, Hirobumi; Nagao, Keizo; Okuyama, Makiko

    2014-01-01

    Background On March 11, 2011, a massive undersea earthquake and tsunami struck East Japan. Few studies have investigated the impact of exposure to a natural disaster on preschool children. We investigated the association of trauma experiences during the Great East Japan Earthquake on clinically significant behavior problems among preschool children 2 years after the earthquake. Method Participants were children who were exposed to the 2011 disaster at preschool age (affected area, n = 178; unaffected area, n = 82). Data were collected from September 2012 to June 2013 (around 2 years after the earthquake), thus participants were aged 5 to 8 years when assessed. Severe trauma exposures related to the earthquake (e.g., loss of family members) were assessed by interview, and trauma events in the physical environment related to the earthquake (e.g. housing damage), and other trauma exposure before the earthquake, were assessed by questionnaire. Behavior problems were assessed by caregivers using the Child Behavior Checklist (CBCL), which encompasses internalizing, externalizing, and total problems. Children who exceeded clinical cut-off of the CBCL were defined as having clinically significant behavior problems. Results Rates of internalizing, externalizing, and total problems in the affected area were 27.7%, 21.2%, and 25.9%, respectively. The rate ratio suggests that children who lost distant relatives or friends were 2.36 times more likely to have internalizing behavior problems (47.6% vs. 20.2%, 95% CI: 1.10–5.07). Other trauma experiences before the earthquake also showed significant positive association with internalizing, externalizing, and total behavior problems, which were not observed in the unaffected area. Conclusions One in four children still had behavior problems even 2 years after the Great East Japan Earthquake. Children who had other trauma experiences before the earthquake were more likely to have behavior problems. These data will be

  13. 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

  14. The Clinical Significance of CD169-Positive Lymph Node Macrophage in Patients with Breast Cancer

    PubMed Central

    Yamamoto-Ibusuki, Mutsuko; Yamamoto, Yutaka; Iwase, Hirotaka; Takeya, Motohiro; Komohara, Yoshihiro

    2016-01-01

    The immune status of patients can impact on the clinical course of cancer. Lymph node (LN) macrophages play critical roles in anti-cancer immunity via the activation of cytotoxic T-lymphocytes (CTLs). In this study, the prognostic significance of CD169+ LN macrophages was examined in patients with breast cancer. For this purpose the number of CD169+ cells and their ratio relative to total macrophages (CD68+) in regional LNs (RLNs), as well as the number of CD8+ CTLs in tumor tissues, were investigated using immunohistochemistry of paraffin-embedded tissue samples from 146 patients with breast cancer. The association of these data with clinicopathological factors was then analyzed. The number of cells positive for the pan-macrophage marker CD68 remained relatively uniform, while the number of CD169+ cells varied across all cases. Moreover, a high density of CD169+ cells correlated with early clinical stage and no LN metastasis, while a higher CD169+ to CD68+ ratio was significantly associated with small tumor size and a low Ki-67+ rate. There was also a significant correlation between the number of CD8+ CTLs and that of CD169+ macrophages in high grade breast cancer cases with a Ki-67 index greater than 40%. However, neither the density nor the ratio of CD169+ cells, nor the density of CD8+ CTLs, were associated with relapse-free survival, distant relapse-free survival, or breast cancer-specific survival. These findings suggest that CD169+ macrophages in RLNs might be a useful marker for assessing clinical stage, including LN states, in patients with breast cancer. PMID:27861544

  15. Diagnostic value and clinical significance of stress hormones in patients with tinnitus.

    PubMed

    Kim, Dong-Kee; Chung, Dae Young; Bae, Seung Chun; Park, Kyoung-Ho; Yeo, Sang Won; Park, Shi-Nae

    2014-11-01

    Tinnitus has been found to be modulated by stress and is also closely related to the emotional state and the limbic system. In the present study, we evaluated the diagnostic and clinical values of several stress hormones in a large number of tinnitus patients. This study included 344 patients with sensorineural tinnitus and 87 normal controls. A questionnaire about tinnitus was administered to the participants, and blood levels of norepinephrine (NE), epinephrine (Epi), a metabolite of serotonin (5-hydroxyindoleacetic acid, 5-HIAA) and cortisol were compared between groups. In results, the mean values of Beck's depression inventory (BDI), Brief Encounter Psychosocial Instrument (BEPSI), NE, and 5-HIAA levels were higher in the tinnitus group, although there was no statistical significance. But, the proportion of participants with elevated 5-HIAA was significantly higher in the tinnitus group (21.8 vs. 8.0 %, P < 0.05), and the 5-HIAA level significantly correlated with the duration of tinnitus, NE and cortisol. Elevated stress-related hormones, as well as hearing loss, BDI, and BEPSI were the most related factors with tinnitus in multiple regression test with age adjustment. However, levels of stress-related hormones did not correlate with subjective measures including BDI, BEPSI and severity of tinnitus. In conclusion, blood stress hormones seemed to have some diagnostic and clinical value in patients with tinnitus, and serotonin is supposed to be the most important hormone in tinnitus. Further studies about the values of stress and stress hormones in tinnitus patients may lead to new approaches regarding diagnosis and clinical management of the disease.

  16. [Rethinking clinical significance of tear osmolarity measurement for dry eye diagnosis and therapeutic efficacy evaluation].

    PubMed

    Liang, Lingyi; Ke, Hongming; Liu, Zuguo

    2014-09-01

    Increased tear osmolarity is one of the core mechanisms of dry eye and has been considered as an important diagnostic criterion, if not"gold standard", of dry eye. However, recent studies showed the limitations of tear osmolarity measurement not only in the diagnosis, but also in the therapeutic efficacy evaluation of dry eye. The clinical significance of tear osmolarity measurement has become a hot topic of argument. Herein, we review the publications on this topic and try to find the underlying causes of such argument.

  17. [Transmissing electron microscopy of the vitreo-macular border in clinically significant diabetic macular edema].

    PubMed

    Synek, S; Pác, L; Synková, M

    2007-09-01

    The authors examined samples of the epimacular tissue in clinically significant macular edema by means of the transmissing electron microscopy. They did not found morphological differences between samples from patients already treated by means of laser photocoagulation before the pars plana vitrectomy and those without the laser treatment. Findings may be divided into three groups: (1) the inner limiting membrane (ILM) covered with collagen vitreous fibers, (2) cells' elements of the fibroblasts category, and (3) fibrous astrocytes in the vitreous cortex constituting one- or multilayer cellular membranes.

  18. Environmental pollution and DNA methylation: carcinogenesis, clinical significance, and practical applications.

    PubMed

    Cao, Yi

    2015-09-01

    Environmental pollution is one of the main causes of human cancer. Exposures to environmental carcinogens result in genetic and epigenetic alterations which induce cell transformation. Epigenetic changes caused by environmental pollution play important roles in the development and progression of environmental pollution-related cancers. Studies on DNA methylation are among the earliest and most conducted epigenetic research linked to cancer. In this review, the roles of DNA methylation in carcinogenesis and their significance in clinical medicine were summarized, and the effects of environmental pollutants, particularly air pollutants, on DNA methylation were introduced. Furthermore, prospective applications of DNA methylation to environmental pollution detection and cancer prevention were discussed.

  19. A Case of Traumatic Unilateral Internuclear Ophthalmoplegia: Clinical Significance of Susceptibility-Weighted Imaging

    PubMed Central

    Lee, Shin-heon; Park, Yong-sook; Kwon, Jeong-taik

    2016-01-01

    A 43-year-old man was admitted for head trauma after falling backward. The patient complained of diplopia. Unilateral internuclear ophthalmoplegia (INO) was diagnosed during the neurologic examination. Initially, no specific finding was shown on T2-weighted, T1-weighted, and fluid attenuated inversion recovery brain magnetic resonance image (MRI) or brain computed tomography (CT). However, susceptibility-weighted imaging (SWI) definitively demonstrated a tiny hemorrhage at the midline of the pontomesencephalic junction. The patient's symptom improved after 12 weeks. We discuss the clinical significance of SWI when traumatic INO due to a tiny hemorrhage is suspected. PMID:27857923

  20. [Clinical significance and distribution of BRCA genes mutation in sporadic high grade serous ovarian cancer].

    PubMed

    Liu, W L; Wang, Z Z; Zhao, J Z; Hou, Y Y; Wu, X X; Li, W; Dong, B; Tong, T T; Guo, Y J

    2017-01-25

    Objective: To investigate the mutations of BRCA genes in sporadic high grade serous ovarian cancer (HGSOC) and study its clinical significance. Methods: Sixty-eight patients between January 2015 and January 2016 from the Affiliated Cancer Hospital of Zhengzhou University were collected who were based on pathological diagnosis of ovarian cancer and had no reported family history, and all patients firstly hospitalized were untreated in other hospitals before. (1) The BRCA genes were detected by next-generation sequencing (NGS) method. (2) The serum tumor markers included carcinoembryonic antigen (CEA), CA(125), CA(199), and human epididymis protein 4 (HE4) were detected by the chemiluminescence methods, and their correlation was analyzed by Pearson linear correlation. Descriptive statistics and comparisons were performed using two-tailed t-tests, Pearson's chi square test, Fisher's exact tests or logistic regression analysis as appropriate to research the clinicopathologic features associated with BRCA mutations, including age, International Federation of Gynecology and Obstetrics (FIGO) stage, platinum-based chemotherapy sensitivity, distant metastases, serum tumor markers (STM) . Results: (1) Fifteen cases (22%, 15/68) BRCA mutations were identified (BRCA1: 11 cases; BRCA2: 4 cases), and four novel mutations were observed. (2) The levels of CEA, CA(199), and HE4 were lower in BRCA mutations compared to that in control group, while no significant differences were found (P>0.05), but the level of CA(125) was much higher in BRCA mutation group than that in controls (t=-3.536, P=0.003). Further linear regression analysis found that there was a significant linear correlation between CA(125) and HE4 group (r=0.494, P<0.01), and the same correlation as CEA and CA(199) group (r=0.897, P<0.01). (3) Single factor analysis showed that no significant differences were observed in onset age, FIGO stage, distant metastasis, and STM between BRCA(+) and BRCA(-) group (P>0

  1. Clinical significance of home blood pressure measurements for the prevention and management of high blood pressure.

    PubMed

    Imai, Yutaka; Hosaka, Miki; Elnagar, Noha; Satoh, Michihiro

    2014-01-01

    1. Ambulatory blood pressure (ABP) monitoring (M) provides BP information at many points on any particular day during unrestricted routine daily activities, whereas home blood pressure (HBP) monitoring provides a lot of BP information obtained under fixed times and conditions over a long period of time, thus mean values of HBP provide high reproducibility, and thus an overall superiority compared with ABP.  2. HBP is at least equally or better able than ABP to predict hypertensive target organ damage and prognosis of cardiovascular disease.  3. HBPM allows for ongoing disease monitoring by patients, improves adherence to antihypertensive treatment, and can provide health-care providers with timely clinical data and direct and immediate feedback regarding diagnosis and treatment of hypertension.  4. HBPM provides BP information in relation to time; that is, BP in the morning, in the evening and at night during sleep, and it is an essential tool for the diagnosis of white-coat and masked hypertension.  5. HBPM yields minimal alerting affects and no or minimal placebo effect, and can therefore distinguish small, but significant, serial changes in BP. It is thus the most practical method for monitoring BP in the day-to-day management of hypertension. 6. The superiority of HBPM over ABPM and clinic BPM is apparent from almost all practical and clinical research perspectives.

  2. 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

  3. Clinical Significance of an Alloantibody against the Kell Blood Group Glycoprotein

    PubMed Central

    Mattaloni, Stella Maris; Arnoni, Carine; Céspedes, Rosario; Nonaka, Claudia; Trucco Boggione, Carolina; Luján Brajovich, Melina Eliana; Trejo, Andrea; Zani, Néstor; Biondi, Claudia Silvia; Castilho, Lilian; Cotorruelo, Carlos Miquel

    2017-01-01

    Background Kell null (K0) individuals can produce anti-Ku, an antibody against many epitopes in the Kell glycoprotein, after transfusion and/or pregnancy. Since sensitized K0 patients are rare, little is known about anti-Ku clinical relevance and in particular about its association to hemolytic disease of the fetus and newborn. Case Report This work describes a case of neonatal hyperbilirubinemia due to immune-mediated erythrocyte destruction by an alloantibody directed against the Kell glycoprotein. Serologic and molecular approaches identified an anti-Ku alloantibody in maternal serum. A homozygous IVS3 + 1g>a point mutation (KEL*02N.06 allele) was found to be responsible for the lack of Kell antigen expression in the mother's red blood cell and subsequent alloimmunization after a previous pregnancy. Even though in most cases Kell antibodies are clinically severe and may cause suppression of erythropoiesis, in our case the newborn had a moderate anemia and hyperbilirubinemia that was successfully treated with phototherapy without requiring exchange transfusion. Serological and molecular studies performed in the proband's family members allowed us to provide them with proper counseling regarding alloimmunization after transfusion and/or pregnancy. Conclusions This case enlarges the understanding of the clinical significance of alloantibodies against Kell blood group antigens.

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

    PubMed

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

    2015-09-27

    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.

  5. 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

  6. Markers of Collagen Remodeling Detect Clinically Significant Fibrosis in Chronic Hepatitis C Patients

    PubMed Central

    Nielsen, Mette J.; Kazankov, Konstantin; Leeming, Diana J.; Karsdal, Morten A.; Krag, Aleksander; Barrera, Francisco; McLeod, Duncan; George, Jacob; Grønbæk, Henning

    2015-01-01

    Background and Aim Detection of advanced fibrosis (Metavir F≥3) is important to identify patients with a high urgency of antiviral treatments vs. those whose treatment could be deferred (F≤2). The aim was to assess the diagnostic value of novel serological extracellular matrix protein fragments as potential biomarkers for clinically significant and advanced fibrosis. Methods Specific protein fragments of matrix metalloprotease degraded type I, III, IV and VI collagen (C1M, C3M, C4M, C6M) and type III and IV collagen formation (Pro-C3 and P4NP7S) were assessed in plasma from 403 chronic hepatitis C patients by specific ELISAs. Patients were stratified according to Metavir Fibrosis stage; F0 (n = 46), F1 (n = 161), F2 (n = 95), F3 (n = 44) and F4 (n = 33) based on liver biopsy. Results Pro-C3 was significantly elevated in patients with significant fibrosis (≥F2) compared to F0-F1 (p<0.05), while the markers C3M, C4M, C6M and P4NP7S were significantly elevated in patients with advanced fibrosis (≥F3) compared to F0-F2 (p<0.05). C1M showed no difference between fibrosis stages. Using Receiver Operating Characteristics analysis, the best marker for detecting ≥F2 and ≥F3 was Pro-C3 with AUC = 0.75 and AUC = 0.86. Combination of Pro-C3 and C4M with age, BMI and gender in a multiple ordered logistic regression model improved the diagnostic value for detecting ≥F2 and ≥F3 with AUC = 0.80 and AUC = 0.88. Conclusion The Pro-C3 protein fragment provided clinically relevant diagnostic accuracy as a single marker of liver fibrosis. A model combining Pro-C3 and C4M along with patient’s age, body mass index and gender increased the diagnostic power for identifying clinically significant fibrosis. PMID:26406331

  7. Clinical significance of multidetector-row computed tomography in breast surgery.

    PubMed

    Doihara, Hiroyoshi; Fujita, Takeo; Takabatake, Daisuke; Takahashi, Hirotoshi; Ogasawara, Yutaka; Shimizu, Nobuyoshi

    2006-01-01

    Several reports support the association of higher ipsilateral breast tumor recurrence rates with positive or intermediate margins compared with negative pathologic margins. Precise evaluation of tumor extension and adequate surgical margin are important factors affecting tumor recurrence after breast-conserving surgery (BCS). Many studies have reported the utility of magnetic resonance imaging (MRI) for diagnosing the tumor extension of breast cancer, but few have evaluated the utility of multidetector-row computed tomography (MDCT). The results of this study show the clinical significance of MDCT for detecting cancer extension and demonstrate the clinical role of MDCT in BCS. Subjects comprised 136 patients grouped into two categories based on whether or not tumor extension was evaluated with MDCT preoperatively. The positive surgical margin rate and breast conservation rate were analyzed in each group and the clinical role of MDCT in BCS was evaluated. Moreover, evaluation of intraductal extension was done both with MDCT and histologically, and computed tomography (CT)-pathologic correlations were examined retrospectively. Finally, the margin-positive cases were analyzed in relation to their clinical characteristics. Sensitivity, specificity, positive predictive value, and negative predictive value for detection of the intraductal component were 71.8%, 85.7%, 82.1%, and 76.9%, respectively. The positive surgical margin rate and conservation rate are 7.46% and 81.9%, respectively, for those who were diagnosed with MDCT preoperatively; their corresponding rates without MDCT were 16.67% and 67.9%. Most margin-positive patients have remarkable lymphatic space invasion. Positive surgical margins were often recognized toward the nipple. For diagnosing the intraductal extension, MDCT shows sufficient diagnosability. Moreover, MDCT can provide appropriate information for the determination of adequate surgical margins and contribute to increases in breast conservation

  8. Clinical Significance of Pre- and Post-Transplant BAFF Levels in Kidney Transplant Recipients

    PubMed Central

    Min, Ji Won; Kim, Kyoung Woon; Kim, Bo-Mi; Doh, Kyoung Chan; Choi, Min Seok; Choi, Bum Soon; Park, Cheol Whee; Yang, Chul Woo; Kim, Yong-Soo

    2016-01-01

    It is well known that pre-transplant B cell activating factor (BAFF) levels are associated with the development of de novo anti-HLA antibodies and antibody mediated rejection post-transplant. However, the clinical significance of BAFF values at allograft rejection has not been determined. In this study, we investigated the clinical significance of pre-transplant BAFF level as well as post-transplant BAFF levels measured when indication biopsy was done. We checked for anti-HLA antibodies in 115 kidney transplant recipients who required allograft biopsy due to an increase in serum creatinine. With the same serum specimen, we measured BAFF levels, and in 78 of these patients, pre-transplant BAFF and anti-HLA antibody levels were detected as well. Patients in each group were divided into tertiles according to BAFF levels. We investigated the relationship between BAFF levels and the occurrence of anti-HLA antibodies. Pre-transplant BAFF levels showed significant association with pre-transplant sensitization, and also with early rejection (Tertile 3, 26.9% vs. Tertile 1, 11.5%; P<0.05). Post-transplant BAFF levels showed significant association with pre-transplant sensitization, but did not show association with anti-HLA antibodies and positive donor-specific antibodies at the time of biopsy. We did not find any association between post-transplant BAFF levels and allograft biopsy results, Banff scores and microvascular inflammation scores. In conclusion, pre-transplant BAFF levels are associated with pre-transplant sensitization and are useful in predicting allograft rejection. But post-transplant BAFF levels measured at the time of indication biopsy are not associated with the appearance of de novo HLA-DSA, allograft rejection, biopsy findings and other allograft outcomes. PMID:27631619

  9. 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

  10. Lipoprotein Subfractions in Metabolic Syndrome and Obesity: Clinical Significance and Therapeutic Approaches

    PubMed Central

    Nikolic, Dragana; Katsiki, Niki; Montalto, Giuseppe; Isenovic, Esma R.; Mikhailidis, Dimitri P.; Rizzo, Manfredi

    2013-01-01

    Small, dense low density lipoprotein (sdLDL) represents an emerging cardiovascular risk factor, since these particles can be associated with cardiovascular disease (CVD) independently of established risk factors, including plasma lipids. Obese subjects frequently have atherogenic dyslipidaemia, including elevated sdLDL levels, in addition to elevated triglycerides (TG), very low density lipoprotein (VLDL) and apolipoprotein-B, as well as decreased high density lipoprotein cholesterol (HDL-C) levels. Obesity-related co-morbidities, such as metabolic syndrome (MetS) are also characterized by dyslipidaemia. Therefore, agents that favourably modulate LDL subclasses may be of clinical value in these subjects. Statins are the lipid-lowering drug of choice. Also, anti-obesity and lipid lowering drugs other than statins could be useful in these patients. However, the effects of anti-obesity drugs on CVD risk factors remain unclear. We review the clinical significance of sdLDL in being overweight and obesity, as well as the efficacy of anti-obesity drugs on LDL subfractions in these individuals; a short comment on HDL subclasses is also included. Our literature search was based on PubMed and Scopus listings. Further research is required to fully explore both the significance of sdLDL and the efficacy of anti-obesity drugs on LDL subfractions in being overweight, obesity and MetS. Improving the lipoprotein profile in these patients may represent an efficient approach for reducing cardiovascular risk. PMID:23507795

  11. Characterization of Change and Significance for Clinical Findings in Radiology Reports Through Natural Language Processing.

    PubMed

    Hassanpour, Saeed; Bay, Graham; Langlotz, Curtis P

    2017-01-03

    We built a natural language processing (NLP) method to automatically extract clinical findings in radiology reports and characterize their level of change and significance according to a radiology-specific information model. We utilized a combination of machine learning and rule-based approaches for this purpose. Our method is unique in capturing different features and levels of abstractions at surface, entity, and discourse levels in text analysis. This combination has enabled us to recognize the underlying semantics of radiology report narratives for this task. We evaluated our method on radiology reports from four major healthcare organizations. Our evaluation showed the efficacy of our method in highlighting important changes (accuracy 99.2%, precision 96.3%, recall 93.5%, and F1 score 94.7%) and identifying significant observations (accuracy 75.8%, precision 75.2%, recall 75.7%, and F1 score 75.3%) to characterize radiology reports. This method can help clinicians quickly understand the key observations in radiology reports and facilitate clinical decision support, review prioritization, and disease surveillance.

  12. 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.

  13. 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

  14. Clinical significance of pharmacogenomic studies in tardive dyskinesia associated with patients with psychiatric disorders

    PubMed Central

    Chang, Florence CF; Fung, Victor SC

    2014-01-01

    Pharmacogenomics is the study of the effects of genetic polymorphisms on medication pharmacokinetics and pharmacodynamics. It offers advantages in predicting drug efficacy and/or toxicity and has already changed clinical practice in many fields of medicine. Tardive dyskinesia (TD) is a movement disorder that rarely remits and poses significant social stigma and physical discomfort for the patient. Pharmacokinetic studies show an association between cytochrome P450 enzyme-determined poor metabolizer status and elevated serum antipsychotic and metabolite levels. However, few prospective studies have shown this to correlate with the occurrence of TD. Many retrospective, case-control and cross-sectional studies have examined the association of cytochrome P450 enzyme, dopamine (receptor, metabolizer and transporter), serotonin (receptor and transporter), and oxidative stress enzyme gene polymorphisms with the occurrence and severity of TD. These studies have produced conflicting and confusing results secondary to heterogeneous inclusion criteria and other patient characteristics that also act as confounding factors. This paper aims to review and summarize the pharmacogenetic findings in antipsychotic-associated TD and assess its clinical significance for psychiatry patients. In addition, we hope to provide insight into areas that need further research. PMID:25378945

  15. Serum BAFF and APRIL levels in patients with autoimmune hemolytic anemia and their clinical significance.

    PubMed

    Xu, Zi-Zhen; Zhao, Bing-Bing; Xiong, Hong; Wei, Bei-Wen; Wang, Ye-Fei

    2015-10-01

    B cell-activating factor of the tumor necrosis factor family (BAFF) and a proliferation-inducing ligand (APRIL) play crucial roles in B cell development, survival, and antibody production. Autoimmune hemolytic anemia (AIHA) is an acquired autoimmune disease that occurs when antibodies target autologous red blood cells. Here, we analyzed the serum levels of BAFF and APRIL and their respective clinical associations in patients with AIHA. Serum BAFF and APRIL levels in patients with AIHA were significantly higher (P < 0.01) than in healthy individuals. Serum BAFF and APRIL levels were significantly augmented in patients with lower hemoglobin levels (hemoglobin was <8 g/dL) and higher LDH activity (LDH > 480 IU/mL). Glucocorticoid treatment dramatically reduced serum levels of BAFF and APRIL. Thus, serum BAFF and APRIL levels may reflect the clinical activity of this disease. Our results indicate that analysis of serum concentrations of BAFF and APRIL potentially represents a useful tool for the assessment of AIHA disease activity and progression.

  16. [Prevalence and clinical significance of interactions drug-enteral nutrition in Intensive Care Units].

    PubMed

    Reis, Adriano Max Moreira; de Carvalho, Rhanna Emanuela Fontenele Lima; de Faria, Leila Marcia Pereira; de Oliveira, Regina Célia; Zago, Karine Santana de Azevedo; Cavelagna, Milena Ferreira; Silva, Adriano Gomes; Neto, Manoel Luis; Cassiani, Silvia Helena de Bortoli

    2014-01-01

    This is a multicenter, cross-sectional retrospective study, which aimed to determine the prevalence of interactions drug-enteral nutrition (EN) in Intensive Care Units (ICU) of seven teaching hospitals in Brazil, and to analyze the clinical significance of them. Information on medications and EN administered with 24 hours and 120 hours of hospitalization were collected. For identification of drug-EN interaction was employed software Drug Reax®. It was investigated 1.124 records. Of these, 320 patients, with 24 hours of hospitalization, were on EN, and 20 (6.3%) had drug-EN interaction. Of the 504 patients with 120 hours of hospitalization, 39 (7.7%) had drug-EN interaction. The most frequent drug-EN interactions of clinical significance were phenytoin-EN, warfarin-EN and levothyroxine-EN. Drug-EN interactions may interfere with the quality and cost effectiveness of care in ICU, so it is essential that the health team has knowledge about them.

  17. 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

  18. Clinical significance in oral cavity squamous cell carcinoma of pathogenic somatic mitochondrial mutations.

    PubMed

    Lai, Chih-Hsiung; Huang, Shiang-Fu; Liao, Chun-Ta; Chen, I-How; Wang, Hung-Ming; Hsieh, Ling-Ling

    2013-01-01

    Somatic mutations affecting the mitochondrial DNA (mtDNA) have been frequently observed in human cancers and proposed as important oncological biomarkers. However, the clinical significance of mtDNA mutations in cancer remains unclear. This study was therefore performed to explore the possible clinical use in assessing oral squamous cell carcinoma (OSCC) of pathogenic mtDNA mutations. The entire mitochondrial genome of 300 OSCC with their matched control DNAs was screened by direct sequencing and criteria were set to define a pathogenic somatic mutation. The patients' TP53 R72P genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism. The relationships between pathogenic somatic mutations, clinicopathogical features, TP53 R72P genotype and clinical prognosis were analyzed. Overall, 645 somatic mtDNA mutations were identified and 91 of these mutations were defined as pathogenic. About one quarter (74/300) of the OSCC tumor samples contained pathogenic mutations. Individuals with the TP53 R allele had a higher frequency of pathogenic somatic mutation than those with the PP genotype. Kaplan-Meier analysis indicated that TP53 R allele patients with pathogenic somatic mutations demonstrated a significant association with a poorer disease-free survival than other individuals (HR = 1.71; 95% CI, 1.15-2.57; p = 0.009) and this phenomenon still existed after adjusting for mtDNA haplogroup, tumor stage with treatment regimens, differentiation and age at diagnosis (HR = 1.59; 95% CI, 1.06-2.40; p = 0.03). Subgroup analyses showed that this phenomenon was limited to patients who received adjuvant radiotherapy/chemo-radiotherapy after surgery. The results strongly indicated that pathogenic mtDNA mutations are a potential prognostic marker for OSCCs. Furthermore, functional mitochondria may play an active role in cancer development and the patient's response to radiotherapy/chemo-radiotherapy.

  19. 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.

  20. Orientation feedback during simulated simple translation tests has little clinical significance on the magnitude and precision of glenohumeral joint translations.

    PubMed

    Musahl, Volker; Moore, Susan M; McMahon, Patrick J; Debski, Richard E

    2006-11-01

    The repeatability of shoulder instability clinical examinations has been reported to be poor, producing a large range of translations. The objective of this study was to determine the effect of providing the clinician with joint orientation feedback on the magnitude and precision of glenohumeral joint kinematics. A 6-degree of freedom magnetic tracking system was used to determine the kinematics of the humerus with respect to the scapula (n=8 cadaveric shoulders). The joints were preconditioned with simple loading tests five times. At 60 degrees of glenohumeral abduction and 0 degrees of flexion/extension, a clinician then applied an anterior and posterior load to the humerus until a manual maximum simulating a simple translation test (STT) was achieved at 0, 30, and 60 degrees of external rotation with and without angular orientation feedback of the humerus with respect to the scapula. The precision for the external rotation was within 4.3 degrees for the feedback group and 17.5 degrees for the no feedback group over all external rotations. For achieving the target external rotation of 30 degrees , there was a significant difference in precision between the feedback and no feedback groups (p<0.05). The magnitudes of the anterior translations were 18.2+/-5.3, 15.5+/-5.1, and 9.9+/-5.5 mm for the feedback group and 19.3+/-6.6, 17.5+/-4.9, and 11.5+/-5.3 mm for the no feedback group, at 0, 30, and 60 degrees of external rotation, respectively. There was a significant difference in the precision of anterior translation at 30 and 60 degrees of external rotation for 4 of 8 specimens (p<0.05). Significant differences in the precision of the posterior translation was only detected at 0 degrees of external rotation for 3 of 8 specimens (p<0.05). Based on the data obtained, providing orientation feedback to a clinician performing a simulated STT results in increased precision for not only the target external rotations but also the resulting glenohumeral translations. While

  1. Near Infrared Spectrometry of Clinically Significant Fatty Acids Using Multicomponent Regression

    NASA Astrophysics Data System (ADS)

    Kalinin, A. V.; Krasheninnikov, V. N.; Sviridov, A. P.; Titov, V. N.

    2016-11-01

    We have developed methods for determining the content of clinically important fatty acids (FAs), primarily saturated palmitic acid, monounsaturated oleic acid, and the sum of polyenoic fatty acids (eicosapentaenoic + docosahexaenoic), in oily media (food products and supplements, fish oils) using different types of near infrared (NIR) spectrometers: Fourier-transform, linear photodiode array, and Raman. Based on a calibration method (regression) by means of projections to latent structures, using standard samples of oil and fat mixtures, we have confirmed the feasibility of reliable and selective quantitative analysis of the above-indicated fatty acids. As a result of comparing the calibration models for Fourier-transform spectrometers in different parts of the NIR range (based on different overtones and combinations of fatty acid absorption), we have provided a basis for selection of the spectral range for a portable linear InGaAs-photodiode array spectrometer. In testing the calibrations of a linear InGaAs-photodiode array spectrometer which is a prototype for a portable instrument, for palmitic and oleic acids and also the sum of the polyenoic fatty acids we have achieved a multiple correlation coefficient of 0.89, 0.85, and 0.96 and a standard error of 0.53%, 1.43%, and 0.39% respectively. We have confirmed the feasibility of using Raman spectra to determine the content of the above-indicated fatty acids in media where water is present.

  2. 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.

  3. Prevalence, predictors and clinical significance of Blastocystis sp. in Sebha, Libya

    PubMed Central

    2013-01-01

    Background Blastocystis sp. has a worldwide distribution and is often the most common human intestinal protozoan reported in children and adults in developing countries. The clinical relevance of Blastocystis sp. remains controversial. This study was undertaken to determine the prevalence of Blastocystis infection and its association with gastrointestinal symptoms among outpatients in Sebha city, Libya. Methods A total of 380 stool samples were collected from outpatients attending the Central Laboratory in Sebha, Libya for routine stool examination. The presence of Blastocystis sp. was screened comparing light microscopy of direct smears against in vitro cultivation. Demographic and socioeconomic information were collected with a standardized questionnaire. Results The overall prevalence of Blastocystis infection was 22.1%. The prevalence was significantly higher among patients aged ≥18 years compared to those aged < 18 years (29.4% vs 9.9%; x2 = 19.746; P < 0.001), and in males compared to females (26.4% vs 17.5%; x2 = 4.374; P = 0.036). Univariate analysis showed significant associations between Blastocystis infection and the occupational status (P = 0.017), family size (P = 0.023) and educational level (P = 0.042) of the participants. Multiple logistic regression analysis confirmed that the age of ≥ 18 years (OR = 5.7; 95% CI = 2.21; 9.86) and occupational status (OR = 2.2; 95% CI = 1.02, 4.70) as significant predictors of Blastocystis infection among this population. In those who had only Blastocystis infection but no other gastrointestinal parasitic infections, the prevalence of gastrointestinal symptoms was higher compared to those without Blastocystis infection (35.3% vs 13.2%; x2 = 25.8; P < 0.001). The most common symptoms among these patients were abdominal pain (76.4%), flatulence (41.1%) and diarrhoea (21.5%). Conclusions Blastocystis sp. is prevalent and associated with

  4. Clinical significance of noncalcified lung nodules in patients with breast cancer.

    PubMed

    Li, Feng; Armato, Samuel G; Giger, Maryellen L; MacMahon, Heber

    2016-09-01

    Patients with breast cancer are increasingly likely to have chest computed tomography (CT) performed. In many cases, small lung nodules will be detected, raising concern for metastases and causing considerable patient anxiety. The majority of these nodules, however, are benign, though the specific probability of malignancy is uncertain in any given case. Therefore, we analyzed the results of chest CT scans of a large number of patients with breast cancer, to determine characteristics and clinical significance of noncalcified lung nodules. 3313 patients were investigated, and 4889 CT scans from 1325 patients were retrospectively reviewed. Among the 1325 patients, 812 (59 %) had at least one noncalcified lung nodule, of which 330 (41 %) had malignant nodules, 197 (24 %) had large (≥10 mm) nodules, and 586 (72 %) had multiple nodules. Large nodules were more often malignant than benign (P < 0.001). In patients with multiple large nodules, the rate of malignancy rate was 83 %, and most of these were metastases. In the case of very small (2-4 mm) nodules, the malignancy rates for solitary and multiple nodules were 8 and 20 %, respectively. Lung metastases were more likely with breast cancer cell grade 3 (22 %) than grade 1-2 (10 %) (P < 0.001) and when patients were clinical stage 2-3 (14 %) than stage 0-1 (7.9 %) (P = 0.03). Lung metastases are highly likely in patients with multiple nodules greater than 10 mm. Higher cancer cell grades and clinical stage are also related to an increased likelihood of lung metastases. The great majority of small lung nodules in breast cancer patients are benign.

  5. Expression and clinical significance of obesity-associated gene STEAP4 in obese children.

    PubMed

    Xu, H M; Cui, Y Z; Wang, W G; Cheng, H X; Sun, Y J; Zhao, H Y; Yan, Y Q

    2016-10-05

    The aim of this study was to investigate the expression and clinical significance of the obesity-associated gene STEAP4 in obese children. Fifty-three obese children and 33 children with a standard body weight (control) from our hospital were recruited to this study. The expression of STEAP4 mRNA and protein in the adipose tissue were detected by reverse transcriptase polymerase chain reaction and enzyme-linked immunosorbent assay, respectively, in order to analyze the relationship between STEAP4 mRNA and protein levels and blood pressure, blood lipid profile, blood glucose levels, and inflammation in obese children. Obese children showed significantly lower levels of STEAP4 mRNA and protein in the adipose tissue compared to the control subjects (P < 0.05). The obese subjects exhibited significantly higher diastolic blood pressure (DBP), systolic blood pressure (SBP), total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), fasting plasma glucose (FPG), interleukin (IL)-6, and tumor necrosis factor (TNF)-α levels, and a significantly lower high-density lipoprotein (HDL) level, compared to the control subjects (P < 0.05). Correlation analysis revealed that STEAP4 expression was negatively correlated with the DBP, SBP, TC, TG, LDL, FPG, IL-6, and TNF-α levels, and was positively correlated with the HDL level (P < 0.05). In conclusion, the expression of STEAP4 was significantly downregulated in the adipose tissue of obese children and was closely related to the blood pressure, blood lipid, blood glucose, and inflammation in these patients; therefore, these results could provide a theoretical basis for the treatment of childhood obesity.

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

    PubMed

    Tas, Faruk; Bilgin, Elif; Karabulut, Senem; Duranyildiz, Derya

    2016-07-01

    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.

  7. The clinical significance of CDK1 expression in oral squamous cell carcinoma

    PubMed Central

    Chen, Xin; Chen, Qiao-Er; Wang, Yuan-Yin; Wang, Yin-Long; He, Jia-Cai; Zhou, Jian

    2015-01-01

    Objectives: To evaluate the clinical significance of cyclin-dependent kinase 1 (CDK1) in 77 oral squamous cell carcinomas (OSCC) using immunohistochemical methods. Study Design: Immunohistochemical expression of CDK1 was compared with various clinicopathological features in 77 OSCC and 60 controlled epithelia adjacent to the tumours. In addition, correlation of CDK1 expression and prognostic and the 5-year accumulative survival rate of OSCC were investigated. Results: The CDK1 protein was expressed in 52 cases of 77 tumor tissues (67.5%), compared with 21 cases of 60 controlled (35.0%). The expression of CDK1 was significantly correlated with the histological grade of OSCC (P<0.05). The CDK1 protein was over-expressed in recurrent tumors or in those with lymph node metastasis. Statistical analysis showed a significant reduction in the 5-year accumulative survival rate in CDK1 positive cases compared with CDK1 negative cases (P<0.05). Namely, the CDK1 positive patients had poor prognosis. Conclusions: The expression of CDK1 might serve as malignant degree and prognostic markers for the survival of OSCC. Key words:Cyclin-dependent kinase 1 (CDK1), oral squamous cell carcinoma (OSCC), immunohistochemistry, cell proliferation. PMID:25129248

  8. 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

  9. Refractory anemia with severe dysplasia: clinical significance of morphological features in refractory anemia.

    PubMed

    Matsuda, A; Jinnai, I; Yagasaki, F; Kusumoto, S; Minamihisamatsu, M; Honda, S; Murohashi, I; Bessho, M; Hirashima, K

    1998-04-01

    Refractory anemia (RA) in myelodysplastic syndromes (MDS) are very heterogeneous diseases regarding their morphology, clinical features and survival. We proposed the new designations 'RA with severe dysplasia (RASD)' and 'RA with minimal dysplasia (RAminiD)'. In our criteria, RASD is considered present if a bone marrow (BM) examination shows Pseudo-Pelger-Huet anomalies of mature neutrophils > or =3% and/or micromegakaryocytes (mMgk) of megakaryocytes > or =10% in RA patients. RAminiD is defined as RA cases other than RASD. After the reclassification of 58 primary RA patients, the group was composed of 45 RAminiD and 13 RASD patients. The blast percentage in the BM and the frequency of cytogenetic abnormalities observed in the RASD patients were intermediate between those in the RAminiD and RAEB patients. The analysis of survival curves revealed differences among the three groups; the RASD patients had lower survival probabilities than those of the RAminiD group, and significantly higher probabilities than those of the RAEB group. (RAminiD vs RASD, P=0.06; RASD vs RAEB, P=0.004.) Our data indicate that in RA patients, RASD is a distinct subset of RA with an unfavorable clinical outcome.

  10. Clinical features of congenital adrenal insufficiency including growth patterns and significance of ACTH stimulation test.

    PubMed

    Koh, Ji Won; Kim, Gu Hwan; Yoo, Han Wook; Yu, Jeesuk

    2013-11-01

    Congenital adrenal insufficiency is caused by specific genetic mutations. Early suspicion and definite diagnosis are crucial because the disease can precipitate a life-threatening hypovolemic shock without prompt treatment. This study was designed to understand the clinical manifestations including growth patterns and to find the usefulness of ACTH stimulation test. Sixteen patients with confirmed genotyping were subdivided into three groups according to the genetic study results: congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH, n=11), congenital lipoid adrenal hyperplasia (n=3) and X-linked adrenal hypoplasia congenita (n=2). Bone age advancement was prominent in patients with CAH especially after 60 months of chronologic age (n=6, 67%). They were diagnosed in older ages in group with bone age advancement (P<0.05). Comorbid conditions such as obesity, mental retardation, and central precocious puberty were also prominent in this group. In conclusion, this study showed the importance of understanding the clinical symptoms as well as genetic analysis for early diagnosis and management of congenital adrenal insufficiency. ACTH stimulation test played an important role to support the diagnosis and serum 17-hydroxyprogesterone levels were significantly elevated in all of the CAH patients. The test will be important for monitoring growth and puberty during follow up of patients with congenital adrenal insufficiency.

  11. Clinical Features of Congenital Adrenal Insufficiency Including Growth Patterns and Significance of ACTH Stimulation Test

    PubMed Central

    Koh, Ji Won; Kim, Gu Hwan; Yoo, Han Wook

    2013-01-01

    Congenital adrenal insufficiency is caused by specific genetic mutations. Early suspicion and definite diagnosis are crucial because the disease can precipitate a life-threatening hypovolemic shock without prompt treatment. This study was designed to understand the clinical manifestations including growth patterns and to find the usefulness of ACTH stimulation test. Sixteen patients with confirmed genotyping were subdivided into three groups according to the genetic study results: congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH, n=11), congenital lipoid adrenal hyperplasia (n=3) and X-linked adrenal hypoplasia congenita (n=2). Bone age advancement was prominent in patients with CAH especially after 60 months of chronologic age (n=6, 67%). They were diagnosed in older ages in group with bone age advancement (P<0.05). Comorbid conditions such as obesity, mental retardation, and central precocious puberty were also prominent in this group. In conclusion, this study showed the importance of understanding the clinical symptoms as well as genetic analysis for early diagnosis and management of congenital adrenal insufficiency. ACTH stimulation test played an important role to support the diagnosis and serum 17-hydroxyprogesterone levels were significantly elevated in all of the CAH patients. The test will be important for monitoring growth and puberty during follow up of patients with congenital adrenal insufficiency. PMID:24265530

  12. 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.

  13. The clinical significance and biological function of olfactomedin 4 in triple negative breast cancer.

    PubMed

    Xiong, Bin; Lei, Xuefeng; Zhang, Lei; Fu, Jia

    2017-02-01

    Olfactomedin 4 abnormal expression has been observed in several types of human cancer, but the status of olfactomedin 4 in triple negative breast cancer is still unknown. The aim of our study is to explore the clinical significance and biological function of olfactomedin 4 in triple negative breast cancer. The mRNA and protein expression of olfactomedin 4 in triple negative breast cancer tissues and cell lines was detected, and the correlation between olfactomedin 4 expression and clinicopathological factors was analyzed by immunohistochemistry. The biological function of olfactomedin 4 on tumor-metastasis was explored by Transwell migration assay and invasion assay in vitro. In our results, olfactomedin 4 mRNA and protein expression is decreased in triple-negative breast cancer tissues and cell lines. Olfactomedin 4 protein low-expression associated with lymph node metastasis, distant metastasis, clinical stage and poor prognosis of triple-negative breast cancer patients. Up-regulation of olfactomedin 4 suppresseed triple-negative breast cancer cells migration and invasion, and reduced cell metastasis-associated protein MMP 9 expression. In conclusion, olfactomedin 4 is a novel biomarker of triple-negative breast cancer for predicting prognosis and developing targeted molecular therapies.

  14. Clinical significance of cytomegalovirus infection in patients with inflammatory bowel disease.

    PubMed

    Garrido, Elena; Carrera, Elisa; Manzano, Rebeca; Lopez-Sanroman, Antonio

    2013-01-07

    Cytomegalovirus (CMV) infection is common in humans. The virus then enters a "latency phase" and can reactivate to different stimuli such as immunosuppression. The clinical significance of CMV infection in inflammatory bowel disease is different in Crohn's disease (CD) and ulcerative colitis (UC). CMV does not interfere in the clinical course of CD. However, CMV reactivation is frequent in severe or steroid-resistant UC. It is not known whether the virus exacerbates the disease or simply appears as a bystander of a severe disease. Different methods are used to diagnose CMV colitis. Diagnosis is classically based on histopathological identification of viral-infected cells or CMV antigens in biopsied tissues using haematoxylin-eosin or immunohistochemistry, other tests on blood or tissue samples are currently being investigated. Polymerase chain reaction performed in colonic mucosa has a high sensitivity and a positive result could be associated with a worse prognosis disease; further studies are needed to determine the most appropriate strategy with positive CMV-DNA in colonic mucosa. Specific endoscopic features have not been described in active UC and CMV infection. CMV colitis is usually treated with ganciclovir for several weeks, there are different opinions about whether or not to stop immunosuppressive therapy. Other antiviral drugs may be used. Multicenter controlled studies would needed to determine which subgroup of UC patients would benefit from early antiviral treatment.

  15. Are all significant P values created equal? The analogy between diagnostic tests and clinical research.

    PubMed

    Browner, W S; Newman, T B

    1987-05-08

    Just as diagnostic tests are most helpful in light of the clinical presentation, statistical tests are most useful in the context of scientific knowledge. Knowing the specificity and sensitivity of a diagnostic test is necessary, but insufficient: the clinician must also estimate the prior probability of the disease. In the same way, knowing the P value and power, or the confidence interval, for the results of a research study is necessary but insufficient: the reader must estimate the prior probability that the research hypothesis is true. Just as a positive diagnostic test does not mean that a patient has the disease, especially if the clinical picture suggests otherwise, a significant P value does not mean that a research hypothesis is correct, especially if it is inconsistent with current knowledge. Powerful studies are like sensitive tests in that they can be especially useful when the results are negative. Very low P values are like very specific tests; both result in few false-positive results due to chance. This Bayesian approach can clarify much of the confusion surrounding the use and interpretation of statistical tests.

  16. 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.

  17. Trombone tongue: a new clinical sign for significant medullary compression at the craniovertebral junction. Case report.

    PubMed

    Lee, Cheong H; Casey, Adrian T H; Allibone, James B; Chelvarajah, Ramesh

    2006-12-01

    The authors describe a previously unreported clinical sign that may indicate the onset of significant compression of the medulla oblongata in cases of craniovertebral junction abnormalities. This 17-year-old boy presented with mild bilateral leg weakness. Imaging studies revealed severe basilar invagination and a marked Chiari malformation. While awaiting surgery, his tongue developed an involuntary constant protrusion-intrusion repetitive motion. The onset of this so-named "trombone tongue" sign was followed shortly afterward by rapidly progressive spastic tetraparesis. After the authors performed a transmaxillary clivectomy, foramen magnum decompression, and occipitocervical fusion, they noted that the abnormal tongue motion promptly resolved and the tetraparesis gradually improved. The authors discuss their current understanding of the central control of tongue movements and present a hypothesis on the pathogenesis of trombone tongue based on the neuroanatomical basis of another abnormal tongue movement sign, lingual myoclonus.

  18. WW domain-containing oxidoreductase's role in myriad cancers: clinical significance and future implications.

    PubMed

    Gardenswartz, Aliza; Aqeilan, Rami I

    2014-03-01

    The WW domain-containing oxidoreductase (WWOX) gene, encodes a tumor suppressor located on 16q23.1, spanning FRA16D, one of the most active common fragile sites in the human genome, that is altered in numerous types of cancer. WWOX's alteration in these myriad cancers is due to disparate mechanisms including loss of heterozygosity, homozygous deletion and epigenetic changes. In vitro, WWOX has been found to be reduced or absent in numerous cancer cell lines and WWOX restoration has been found to inhibit tumor cell growth and invasion. Wwox knockout mice developed femoral focal lesions resembling osteosarcomas within one month of their life and aging Wwox heterozygous mice have an increased incidence of spontaneous lung and mammary tumors as well as B-cell lymphomas. We herein review WWOX's role that has been unearthed thus far in different types of malignancies, its clinical significance and future implications.

  19. Clinical significance of in vivo cytarabine-induced gene expression signature in AML.

    PubMed

    Lamba, Jatinder K; Pounds, Stanley; Cao, Xueyuan; Crews, Kristine R; Cogle, Christopher R; Bhise, Neha; Raimondi, Susana C; Downing, James R; Baker, Sharyn D; Ribeiro, Raul C; Rubnitz, Jeffrey E

    2016-01-01

    Despite initial remission, ∼60-70% of adult and 30% of pediatric patients experience relapse or refractory AML. Studies so far have identified base line gene expression profiles of pathogenic and prognostic significance in AML; however, the extent of change in gene expression post-initiation of treatment has not been investigated. Exposure of leukemic cells to chemotherapeutic agents such as cytarabine, a mainstay of AML chemotherapy, can trigger adaptive response by influencing leukemic cell transcriptome and, hence, development of resistance or refractory disease. It is, however, challenging to perform such a study due to lack of availability of specimens post-drug treatment. The primary objective of this study was to identify in vivo cytarabine-induced changes in leukemia cell transcriptome and to evaluate their impact on clinical outcome. The results highlight genes relevant to cytarabine resistance and support the concept of targeting cytarabine-induced genes as a means of improving response.

  20. Role of multifaceted regulators in cancer glucose metabolism and their clinical significance

    PubMed Central

    Zhao, Luqing; Mao, Yitao; Zhao, Yuelong; Cao, Ya; Chen, Xiang

    2016-01-01

    Aberrant glucose metabolism, “aerobic glycolysis” or “Warburg effect”, is a hallmark of human cancers. There is a cluster of “multifaceted regulators”, which plays a pivotal role in the regulation of glucose metabolism. They can not only modulate the activities of specific enzymes, but also act as transcriptional activators to regulate the expression of metabolism related genes. Additionally, they can crosstalk with other key factors involved in glucose metabolism and work together to initiate multiple oncogenic processes. These “multifaceted regulators”, especially p53, HIF-1, TIGAR and microRNA, will be focused in this review. And we will comprehensively illustrate their regulatory effects on cancer glucose metabolism, and further elaborate on their clinical significance. In-depth elucidation the role of “multifaceted regulators” in cancer glucose metabolism will provide us novel insights in cancer research field and offer promising therapeutic targets for anti-cancer therapies. PMID:26934324

  1. 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

  2. Paraneoplastic syndromes in patients with laryngeal neuroendocrine carcinomas: clinical manifestations and prognostic significance.

    PubMed

    Ferlito, Alfio; Rinaldo, Alessandra; Bishop, Justin A; Hunt, Jennifer L; Vander Poorten, Vincent; Williams, Michelle D; Triantafyllou, Asterios; Devaney, Kenneth O; Gnepp, Douglas R; Kusafuka, Kimihide; Halmos, Gyorgy B; Westra, William H; Takes, Robert P; Thompson, Lester D R

    2016-03-01

    Paraneoplastic syndromes are associated with a variety of malignant neoplasms and are systemic and non-metastatic manifestations that develop in a minority of cancer patients. This review examines all published cases of paraneoplastic syndromes associated with neuroendocrine carcinomas of the larynx. There are a total of ten patients reported with paraneoplastic syndromes associated with laryngeal neuroendocrine carcinomas in the literature. Of these, nine died and the tenth is alive with liver metastases. There were five cases of small-cell neuroendocrine carcinoma, four cases of moderately differentiated neuroendocrine carcinoma, and one case of well-differentiated neuroendocrine carcinoma associated with paraneoplastic syndromes. As these syndromes have significant clinical relevance, physicians should be aware of the possible presence of paraneoplastic syndromes in the diagnostic process of patients with neuroendocrine carcinoma of the larynx.

  3. [Viridans streptococci isolated from cerebrospinal fluid. Clinical significance of 9 cases].

    PubMed

    Alba, D; Guerra, A; Peña, P; Molina, F

    1997-02-01

    Viridans streptococci (VS) are often isolated from cerebrospinal fluid (CSF). However, the significance of such isolates is poorly understood. In the present study we carry out a retrospective analysis of 9 patients in whom VS were isolated from CSF during a 1-year period at La Paz Hospital. Two patients (22.2%) had meningitis diagnosed through clinical, laboratory and bacteriologic findings. Both patients had predisposition diseases (previous difficult spinal tap, ventriculo-peritoneal shunt). The other isolations were considered as contaminants. Three patients (33.3%) with no VS meningitis had other different serious disease (sepsis without bacteriologic confirmation). VS are isolated with relative frequency from CSF, although they cause meningitis in less than one-quarter of the cases (those who have a predisposition disease). In the other cases, VS are isolated as contaminants of CSF and other disease should be search as cause of patient symptoms.

  4. 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

  5. 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

  6. The clinical significance of platelet microparticle-associated microRNAs.

    PubMed

    Provost, Patrick

    2017-05-01

    Circulating blood platelets play a central role in the maintenance of hemostasis. They adhere to subendothelial extracellular matrix proteins that become exposed upon vessel wall damage, which is followed by platelet activation, further platelet recruitment, platelet aggregation and formation of an occlusive, or non-occlusive, platelet thrombus. Platelets host a surprisingly diverse transcriptome, which is comprised of ~9500 messenger RNAs (mRNAs) and different classes of non-coding RNAs, including microRNAs, as well as a significant repertoire of proteins that contribute to their primary (adhesion, aggregation, granule secretion) and alternative (RNA transfer, mRNA translation, immune regulation) functions. Platelets have the propensity to release microparticles (MPs; 0.1-1 μm in diameter) upon activation, which may mediate inflammatory responses and contribute to exacerbate inflammatory diseases and conditions. Carrying components of the platelets' cytoplasm, platelet MPs may exert their effects on recipient cells by transferring their content in platelet-derived bioactive lipid mediators, cytokines, mRNAs and microRNAs. Platelet MP-associated microRNAs may thus function also outside of platelets and play an important role in intercellular signaling and gene expression programming across the entire circulatory system. The role and importance of platelet MP-associated microRNAs in various aspects of biology and pathophysiology are increasingly recognized, and now provide the scientific basis and rationale to support further translational research and clinical studies. The clinical significance, pathophysiological role as well as the diagnostic and therapeutic potential of platelet MP-associated microRNAs in cardiovascular diseases, platelet transfusion and cancer will be discussed.

  7. Distinguishing between statistical significance and practical/clinical meaningfulness using statistical inference.

    PubMed

    Wilkinson, Michael

    2014-03-01

    Decisions about support for predictions of theories in light of data are made using statistical inference. The dominant approach in sport and exercise science is the Neyman-Pearson (N-P) significance-testing approach. When applied correctly it provides a reliable procedure for making dichotomous decisions for accepting or rejecting zero-effect null hypotheses with known and controlled long-run error rates. Type I and type II error rates must be specified in advance and the latter controlled by conducting an a priori sample size calculation. The N-P approach does not provide the probability of hypotheses or indicate the strength of support for hypotheses in light of data, yet many scientists believe it does. Outcomes of analyses allow conclusions only about the existence of non-zero effects, and provide no information about the likely size of true effects or their practical/clinical value. Bayesian inference can show how much support data provide for different hypotheses, and how personal convictions should be altered in light of data, but the approach is complicated by formulating probability distributions about prior subjective estimates of population effects. A pragmatic solution is magnitude-based inference, which allows scientists to estimate the true magnitude of population effects and how likely they are to exceed an effect magnitude of practical/clinical importance, thereby integrating elements of subjective Bayesian-style thinking. While this approach is gaining acceptance, progress might be hastened if scientists appreciate the shortcomings of traditional N-P null hypothesis significance testing.

  8. A hybrid approach to achieving both marginal and conditional balances for stratification variables in sequential clinical trials.

    PubMed

    Lin, Yunzhi; Su, Zheng

    2013-01-01

    Various methods exist in the literature for achieving marginal balance for baseline stratification variables in sequential clinical trials. One major limitation with balancing on the margins of the stratification variables is that there is an efficiency loss when the primary analysis is stratified. To preserve the efficiency of a stratified analysis one recently proposed approach balances on the crossing of the stratification variables included in the analysis, which achieves conditional balance for the variables. A hybrid approach to achieving both marginal and conditional balances in sequential clinical trials is proposed, which is applicable to both continuous and categorical stratification variables. Numerical results based on extensive simulation studies and a real dataset show that the proposed approach outperforms the existing ones and is particularly useful when both additive and stratified models are planned for a trial.

  9. 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

  10. Clinical significance of Cox-2, Survivin and Bcl-2 expression in hepatocellular carcinoma (HCC).

    PubMed

    Yang, Yu; Zhu, Jiang; Gou, Hongfeng; Cao, Dan; Jiang, Ming; Hou, Mei

    2011-09-01

    Cox-2, Survivin and Bcl-2 are frequently overexpressed in numerous types of cancers. They are known to be the important regulators of apoptosis. This study was designed to investigate the correlation between the clinical characteristics and the expression of Cox-2, Survivin and Bcl-2 in hepatocellular carcinoma. A total of 63 postoperative hepatocellular carcinoma (HCC) samples, 10 adjacent non-tumor samples and 10 normal liver samples were immunochemically detected for the expression of Cox-2, Survivin and Bcl-2. A median follow-up of 4 years for the 63 HCC patients was conducted. Univariate tests and multivariate Cox regression were performed for statistical analysis. The Kaplan-Meier method was used to analyze the survival. Positive expression of Cox-2 (84.3%) and Survivin (77.8%) was detected significantly more frequently in the HCC samples than in the normal liver tissues (30% and 0, respectively). Bcl-2 was highly expressed in the adjacent non-tumor tissue. Cox-2 was positively correlative to Survivin. Survivin and Bcl-2 were significantly associated with the pathological grade of HCC (P<0.05). Expression of both Cox-2 and Survivin was significantly associated with the poor overall survival (OS) (P=0.0141, P=0.0039). Furthermore, multivariate analysis confirmed the independent prognostic value of Survivin expression, along with tumor size and hepatic function. Cox-2 and Survivin were highly expressed in the HCC tissue. Survivin and Bcl-2 were significantly associated with the pathological grade of HCC. The expression of Survivin was an independent prognostic factor for HCC after a hepatectomy. Treatment that inhibits Survivin may be a promising targeted approach in HCC.

  11. Clinical significance of putative markers of cancer stem cells in gastric cancer: A retrospective cohort study

    PubMed Central

    He, Du; Lu, Zheng-Hao; Liu, Kai; Zhang, Wei-Han; Wang, Wei; Li, Chang-Chun; Xue, Lian; Zhao, Lin-Yong; Yang, Kun; Liu, Jian-Ping; Zhou, Zong-Guang; Hu, Jian-Kun; Mo, Xian-Ming

    2016-01-01

    Cancer stem cells (CSCs) are thought as the source of tumor maintaining and many CSCs markers have been identified. Regarding the heterogeneity in gastric cancer (GC), TNM stage is not enough to accurately predict the prognosis. The aim of this study was to investigate the clinical significance of CSCs markers (Lgr5, Oct4, CD133, EpCAM, CD54 and Sox2) and establish a new model based on these markers to accurately predict prognosis of GC. We retrospectively enrolled 377 GC tissues from January 2006 to October 2012 to perform immunohistochemistry (IHC), and 93 pairs of GC tissues and corresponding adjacent normal gastric tissues to perform quantitative PCR (qPCR) from December 2011 to October 2012. The clinicopathological and follow-up characteristics were collected. In IHC, Oct4, CD133 and EpCAM were independently related to tumor progression, while Sox2 were associated with well or moderate differentiation (all p<0.05). Cox regression showed that Oct4-EpCAM was an independently prognostic factor, indicating that double low expression of Oct4-EpCAM group had significantly better prognosis than control group (p=0.035). Regarding qPCR, CD133 was an independent prognostic factor, showing that the prognosis of patients with CD133 high expression was significantly worse than that of patients with CD133 low expression (p<0.001). The prognostic prediction accuracy of nomogram based on Oct4-EpCAM expression in IHC was significantly better than TNM stage alone (p=0.003). Low expressions of Oct4-EpCAM in IHC and CD133 in qPCR were favorable prognostic factors in GC. The nomogram based on Oct4-EpCAM was valuable in prognostic prediction of GC patients. PMID:27557490

  12. The rotational model and microdialysis: Significance for dopamine signalling, clinical studies, and beyond.

    PubMed

    Herrera-Marschitz, Mario; Arbuthnott, Gordon; Ungerstedt, Urban

    2010-02-09

    The detailed anatomy of the monoamine pathways of the rat by the students of Nils-Ake Hillarp provided the basis for a neurocircuitry targeting pharmacology. Further progress was achieved by the introduction of 6-hydroxydopamine as a tool for performing specific lesions, leading to the first stereotaxic mapping of the monoamine pathways in the rat brain by Urban Ungerstedt at the Karolinska Institutet, Stockholm, Sweden. Unilateral intracerebral injections with 6-hydroxydopamine led to the proposal of 'Rotational Behaviour', as a classical model for screening drugs useful for alleviating Parkinson's disease and other neuropathologies. The direction of the rotational behaviour induced by drugs administrated to lesioned rats reveals their mechanisms of action on dopamine synapses, as demonstrated when rotational behaviour was combined with microdialysis. The model was useful for proposing a role of dopamine receptors in the gating of the flow of information through different efferent pathways of the basal ganglia. It is established now that the coupling of dopamine receptors is regulated by a number of proteins acting as GTPases, the regulators of G-protein signalling (RGS) family. More than 20 RGS proteins have been identified, organised into subfamilies based on structural features and specificity for different G-protein subunits. These protein subfamilies represent alternative pathways gating the flow of information generated in the basal ganglia. Microdialysis has been developed as a general tool for studying tissue and organ chemistry, leading to a truly translational venture as microdialysis is brought into clinical use, monitoring energy metabolism following global or focal ischemia in the neurosurgery and general medicine scenario.

  13. Clinical significance of circulating dendritic cells in patients with systemic lupus erythematosus.

    PubMed Central

    Robak, E; Smolewski, P; Woźniacka, A; Sysa-Jedrzejowska, A; Robak, T

    2004-01-01

    Dendritic cells are a complex group of mainly bone-marrow-derived leukocytes that play a role in autoimmune diseases. The total number of circulating dendritic cells (tDC), and their plasmacytoid dendritic cell (pDC) and myeloid dendritic cell (mDC1 and mDC2) subpopulations were assessed using flow cytometry. The number of tDC and their subsets were significantly lower in systemic lupus erythematosus patients than in the control group. The count of tDC and their subsets correlated with the number of T cells. The number of tDC and pDC subpopulation were lower in the patients with lymphopenia and leukopenia than in the patients without these symptoms. Our data suggest that fluctuations in blood dendritic cell count in systemic lupus erythematosus patients are much more significant in pDC than in mDC, what may be caused by their migration to the sites of inflammation including skin lesions. Positive correlation between dendritic cell number and TCD4+, TCD8+ and CD19+ B cells, testify of their interactions and influence on SLE pathogenesis. The association between dendritic cell number and clinical features seems to be less clear. PMID:15223608

  14. Expression of O(6)-methylguanine DNA methyltransferase (MGMT) and its clinical significance in gastroenteropancreatic neuroendocrine neoplasm.

    PubMed

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

    2014-01-01

    O(6)-methylguanine-DNA methyltransferase (MGMT) is a widespread DNA repair enzyme defending against mutation caused by guanine O(6)-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 (χ(2) = 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.

  15. Clinical significance of serum vascular endothelial growth factor in young male asthma patients

    PubMed Central

    Lee, Hea Yon; Min, Kyung Hoon; Lee, Sang Min; Lee, Ji Eun; Rhee, Chin Kook

    2017-01-01

    Background/Aims Vascular endothelial growth factor (VEGF) is an important mediator of angiogenesis. However, little is known about the potential use of serum levels of VEGF as a biomarker for asthma. We investigated the differences in VEGF levels among normal controls, stable asthma patients, and those with exacerbation of acute asthma. All subjects were young males. Methods We measured VEGF levels in each patient group, and examined any serial changes in those with acute exacerbation. Results VEGF levels were significantly higher in stable asthmatic patients and even more so in acute asthmatic patients, compared to healthy controls. However, there was no correlation between VEGF levels and forced expiratory volume in 1 second in patients with stable asthma. In addition, there were no correlations between VEGF levels and asthma control test scores. In patients with acute exacerbation, VEGF levels significantly increased during the acute period; their levels decreased gradually at 7 and 14 days after treatment. Conclusions Compared to normal control patients, the serum levels of VEGF were elevated in stable asthma patients and even more elevated in patients with acute exacerbation. However, the role of VEGF as a biomarker in stable asthma is limited. In patients with acute exacerbation, VEGF levels were associated with clinical improvements. PMID:26996348

  16. Expression and clinical significance of matrix metalloproteinase-17 and -25 in gastric cancer

    PubMed Central

    WANG, YING; YU, SHI-JIE; LI, YAN-XIA; LUO, HE-SHENG

    2015-01-01

    The aim of the present study was to investigate the expression and clinicopathological features of matrix metalloproteinase 17 (MMP17; also known as MT4-MMP) and MMP25 (also known as MT6-MMP) in gastric cancer. Immunohistochemistry and reverse transcription-quantitative polymerase chain reaction were used to detect the expression of MMP17 and MMP25 in 42 cases of gastric carcinoma and normal tissues, and 40 cases of atrophic gastritis. The expression of MMP17 in the normal gastric and atrophic gastritis tissues was significantly lower than that in the gastric cancer tissues (P<0.05). The expression of MMP25 in the gastric cancer and atrophic gastritis tissues was markedly higher compared with the normal gastric tissues (P<0.05). The expression of MMP17 and MMP25 was significantly associated with the depth of tumor invasion, lymph node metastasis and serous membrane involvement (P<0.05), but not with patient age and gender, or lesion length, site and histological grade (P>0.05). Therefore, this indicates that the expression of MMP17 and MMP25 is increased with the degree of progress of gastric carcinoma. The detection of MMP17 and MMP25 expression may have clinical value in predicting the prognosis of patients with gastric cancer. PMID:25621036

  17. Clinical and biological significance of CXCR5 expressed by prostate cancer specimens and cell lines.

    PubMed

    Singh, Shailesh; Singh, Rajesh; Singh, Udai P; Rai, Shesh N; Novakovic, Kristian R; Chung, Leland W K; Didier, Peter J; Grizzle, William E; Lillard, James W

    2009-11-15

    Chemokines and chemokine receptors have been shown to be involved in metastatic process of prostate cancer (PCa). In this study, we show primary PCa tissues and cell lines (LNCaP and PC3) express CXCR5, a specific chemokine receptor for CXCL13. Expression of CXCR5 was significantly higher (p < 0.001) in PCa cases than compared to normal match (NM) tissues. CXCR5 intensity correlated (R(2) = 0.97) with Gleason score. While prostate tumor tissues with Gleason scores >or= 7, displayed predominantly nuclear CXCR5 expression patterns, PCa specimens with Gleason scores significantly more CXCR5 than normal prostatic epithelial cells (PrECs), and CXCR5 expression was distributed among intracellular and extracellular compartments. Functional in vitro assays showed higher migratory and invasive potentials toward CXCL13, an effect that was mediated by CXCR5. In both PCa cell lines, CXCL13 treatment increased the expression of collagenase-1 or matrix metalloproteinase-1 (MMP-1), collagenase-3 (MMP-13), stromelysin-1 (MMP-3), stromelysin-2 (MMP-10) and stromelysin-3 (MMP-11). These data demonstrate the clinical and biological relevance of the CXCL13-CXCR5 pathway and its role in PCa cell invasion and migration.

  18. Clinical significance of serum anti-annexin V antibodies in Egyptian patients with scleroderma.

    PubMed

    El Serougy, Iman M; Shahin, Amira A; Soliman, Doaa A; Akhnoukh, Amany F; Mousa, Somaia M

    2009-01-01

    The pathogenesis of scleroderma encompasses vascular, immunological, and fibrotic processes, which contribute to clinical manifestations. We investigated the prevalence of anti-annexin V IgG and IgM antibodies in sera of scleroderma patients and their relation to the presence of other antibodies and development of disease morbidity. Sera of 40 scleroderma patients and 15 healthy controls were examined for IgG and IgM anti-annexin V antibodies by ELISA and anticentromere antibodies by indirect immunofluorescence. Serum level of anti-annexin V IgG antibodies in scleroderma patients was significantly higher than that of the control (P < 0.001) and correlated significantly with the presence of digital ischemia (P = 0.023) and pulmonary fibrosis (P = 0.02). IgM isotype was comparable between patients and controls (P = 0.317). Anticentromere antibodies are more prevalent in the limited cutaneous subtype (P = 0.017). In conclusion, measurement of serum anti-annexin V IgG antibodies in scleroderma patients may be important for early diagnosis of vascular and pulmonary complications.

  19. Clinical significance of peripheral blood erythroblastosis after hematopoietic stem cell transplantation.

    PubMed

    Goyama, Susumu; Kanda, Yoshinobu; Nannya, Yasuhito; Ogawa, Seishi; Asano-Moki, Yuki; Ogawa, Natsu; Nakagawa, Masahiro; Sakata-Yanagimoto, Mamiko; Kawazu, Masahito; Komeno, Yukiko; Imai, Yoichi; Hangaishi, Akira; Kurokawa, Mineo; Tsujino, Shiho; Aoki, Katsunori; Chiba, Shigeru; Motokura, Toru; Hirai, Hisamaru

    2004-12-01

    Erythroblasts (EBL) are normally not observed in peripheral blood, but may be found in patients suffering from a variety of severe diseases. The detection of EBL in peripheral blood has been shown to be associated with a poor prognosis. However, the clinical significance of peripheral erythroblastosis after hematopoietic stem cell transplantation (HSCT) has not been evaluated. We retrospectively analyzed the records of 161 patients who underwent HSCT at our hospital from June 1995 to October 2001. EBL at any level were detected in 94% of the patients. Forty-four and 11 patients experienced erythroblastosis exceeding 200 and 1,000/ul, respectively. The erythroblast count was higher in patients who died than in the survivors (geometric mean value 184 vs. 100/ul, P=0.01). High-level erythroblastosis ( >1,000/ul) within 180 days after HSCT was associated with an extremely poor prognosis (median survival 22.5 days). Among the possible confounding factors, the use of total body irradiation (RR 2.35, 95% CI 1.22 - 4.54, P=0.011) and the disease status before transplantation (RR 2.51, 95% CI 1.15 - 5.49, P=0.021) were independent significant factors for erythroblastosis after HSCT. As for post-transplant events, a high EBL concentration was frequently preceded by graft-vs.-host disease, thrombotic microangiopathy, hypoxia, and hematological relapse.

  20. 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

  1. 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.

  2. The clinical significance of preoperative brain magnetic resonance imaging in pediatric cochlear implant recipients.

    PubMed

    Moon, Il Joon; Kim, Eun Yeon; Park, Ga-Young; Jang, Min Seok; Kim, Ji Hye; Lee, Jeehun; Chung, Won-Ho; Cho, Yang-Sun; Hong, Sung Hwa

    2012-01-01

    Although central nervous system abnormalities are incidentally detected in preoperative brain magnetic resonance imaging (MRI) studies in pediatric cochlear implant (CI) candidates, the clinical significance of the abnormalities remains unclear. We aimed to assess post-implantation auditory and speech performance in patients with brain lesions seen on MRI. Pediatric CI recipients (n = 177) who underwent preoperative MRI scans of the brain between January 2002 and June 2009 were included in this study. Patients with brain lesions on MRI were reviewed and categorized into the following groups: brain parenchymal lesions (focal vs. diffuse), ventriculomegaly, and extra-axial lesion. The main communication mode as well as progress in auditory perception and speech production were evaluated preoperatively and at 3, 6, 12, and 24 months postoperatively. Performance in patients with brain lesions was compared with the age- and sex-matched control group. Various brain lesions were found in 27 out of 177 patients. Children with brain lesions who received CIs showed gradual progress in auditory and speech outcomes for 2 years, though performance was reduced compared with the control group. In addition, there was a significant difference in the main communication mode between the two groups at 2 years following cochlear implantation. This difference was especially significant in patients with diffuse brain parenchymal lesions after further stratification of the brain lesion group. Preoperative brain MRI may have a role in improving the prediction of adverse outcomes in pediatric CI recipients. In particular, children with diffuse brain parenchymal lesions should be counseled regarding the poor prognosis preoperatively, and followed up with special attention.

  3. Clinical significance of antibody to hepatitis B core antigen in multitransfused hemodialysis patients

    PubMed Central

    Elghannam, Doaa M.; Aly, Rabab M.; Goda, Enas F.; Eltoraby, Ehab E.; Farag, Raghda E.

    2009-01-01

    Background: In spite of the progress made in the prevention of transfusion transmitted infections over the last few years, transmission of HBV infection through transfusion of HBsAg negative blood has been documented. Objectives: To assess the frequency and clinical significance of anti-HBc in multitransfused hemodialysis patients. Materials and Methods: One hundred and forty-three hemodialysis patients who had been receiving blood regularly with an average of 39.4 ± 7.579 months on hemodialysis were enrolled in this study. HBV markers (HBsAg, anti-HBc, anti-HBs) were measured in these patients and in 100 healthy controls by the ELISA technique. The following data were obtained for all patients: socio demographic data, number of blood transfusions and some laboratory investigations. Results: In our patients, anti-HBc was positive in 9%, anti HBs in 7%, coexistant HbsAg/anti-HBc in 2.8% and anti HBc/anti HBs in 18.9%, meanwhile no patients were positive for HBsAg alone. In patients with only positive anti-HBc, the levels of anti-HBc were significantly related to abnormal results of liver function. In patients with positive anti-HBs/anti-HBc (n = 27), 18 patients had abnormal liver function, and 9 patients had normal liver function with no significant difference between them. Conclusions: This study suggests that hepatitis B prevalence in our multitransfused hemodialysis patients is far in excess of that anticipated on the basis of HBsAg prevalence. Absence of HBsAg in the blood of hemodialyzed patients may not be sufficient to ensure lack of circulating HBV, and isolated positivity of anti-HBc may be a possible indicator of active hepatitis B infection. PMID:20041091

  4. Expression pattern and clinical significance of DNA methyltransferase 3B variants in gastric carcinoma.

    PubMed

    Su, Xianwei; Lv, Chengyu; Qiao, Fengchang; Qiu, Xuemei; Huang, Wenbin; Wu, Qingxiang; Zhao, Zhujiang; Fan, Hong

    2010-03-01

    The aim of this study was to detect the expression pattern of DNA methyltransferase 3B (DNMT3B) variants in primary gastric cancer (GC) and to explore the clinical significance of DNMT3B variants in gastric carcinogenesis. Specific polymerase chain reaction (PCR) primer sets were designed to distinguish individual DNMT3B variants according to their splicing patterns. Expression levels of DNMT3B variants were assessed by quantitative real-time RT-PCR in gastric cancer tissue, normal gastric mucosae and GC cell lines. The relationship between the expression patterns of the DNMT3B variants and corresponding clinical information was analyzed by observing the expression levels of different variants in the tumors. These results demonstrate that DNMT3B overexpression is related to late phase invasion (P=0.029) and intestinal type (P=0.012) in GC. DNMT3B3 expression was higher in normal tissue, compared to tumor tissue (P=0.033). In contrast, only 18, 32 and 35% of the patient tumors overexpressed DNMT3B1, DNMT3B4 and DNMT3B5, respectively. While taking into account environmental factors (H. pylori, Epstein-Barr virus infection), H. pylori infection elevated DNMT3B1 and DNMT3B3 variants in tumors, while increasing DNMT3B4 in both tumor and non-cancerous tissues. Our findings indicated that the expression of DNMT3B3 is the major splice variant in normal gastric mucosae and may be affected by H. pylori infection. Elevated DNMT3B variants may influence the progression of gastric cancer and may possibly be a powerful indicator for the disease.

  5. 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

  6. Clinical significance of antibodies against neutrophils in patients with inflammatory bowel disease and primary sclerosing cholangitis.

    PubMed Central

    Seibold, F; Weber, P; Klein, R; Berg, P A; Wiedmann, K H

    1992-01-01

    The presence of perinuclear antibodies against neutrophils (pANCA) has been detected recently in sera of patients with inflammatory bowel disease and primary sclerosing cholangitis. In order to evaluate their clinical significance, sera from 126 patients with inflammatory bowel disease (80 Crohn's disease and 46 ulcerative colitis and 22 patients with primary sclerosing cholangitis were examined for pANCA by indirect immunofluorescence on liver sections and cytocentrifuge slides of neutrophils and by immunoblot. Perinuclear antibodies against neutrophils were found in 83% of patients with ulcerative colitis in 88% of patients with primary sclerosing cholangitis and inflammatory bowel disease, in 40% of patients with primary sclerosing cholangitis but without inflammatory bowel disease, and in 25% of patients with Crohn's disease using the immunofluorescence test. Titres of pANCA ranged from 1:10 to 1:1000 in ulcerative colitis and primary sclerosing cholangitis (median 1:100), whereas in Crohn's disease only four patients had titres of more than 1:10. The occurrence of pANCA did not correlate with clinical activity of Crohn's disease and primary sclerosing cholangitis whereas in ulcerative colitis high titres of pANCA were found mainly in active disease. Using an immunoblot system with sonified neutrophils as antigen, 82% of sera from patients with primary sclerosing cholangitis reacted with up to five different determinants, whereas only 12% of sera from patients with Crohn's disease and 11% of sera with ulcerative colitis detected one of the determinants, suggesting different antigens involved in pANCA reaction. Images Figure 1 Figure 3 Figure 4 Figure 5 PMID:1612483

  7. Internight sleep variability: its clinical significance and responsiveness to treatment in primary and comorbid insomnia.

    PubMed

    Sánchez-Ortuño, María M; Edinger, Jack D

    2012-10-01

    Although sleep diary and actigraphy data are usually collected daily for 1 or 2 weeks, traditional analytical approaches aggregate these data into mean values. Internight variability of sleep often accompanies insomnia. However, few studies have explored the relevance of this 'construct' in the context of diagnosis, clinical impact, treatment effects and/or whether having 'variable sleep' carries any prognostic significance. We explored these questions by conducting secondary analyses of data from a randomized clinical trial. The sample included primary (PI: n = 40) and comorbid insomnia (CMI: n = 41) sufferers receiving four biweekly sessions of cognitive-behavioural therapy (CBT) or sleep hygiene education. Using the within-subject standard deviations of diary- and actigraphy-derived measures collected for 2-week periods [sleep onset latency (SOL), wake after sleep onset (WASO), total sleep time (TST) and sleep efficiency (SE)], we found that CMI sufferers displayed more variable self-reported SOLs and SEs than PI sufferers. However, higher variability in diary and actigraphy-derived measures was related to poorer sleep quality only within the PI group, as measured by the Pittsburgh Sleep Quality Index (PSQI). Within both groups, the variability of diary-derived measures was reduced after CBT, but the variability of actigraphy-derived measures remained unchanged. Interestingly, the variability of actigraphy measures at baseline was correlated with PSQI scores at 6-month follow-up. Higher SOL variability was associated with worse treatment outcomes within the PI group, whereas higher WASO variability was correlated with better treatment outcomes within the CMI group. Sleep variability differences across insomnia diagnoses, along with their distinctive correlates, suggest that mechanisms underlying the sleep disruption/complaint and treatment response in both patient groups are distinct. Further studies are warranted to support variability as a useful metric in

  8. 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

  9. Clinical significance of the appearance of abnormal protein band in patients with multiple myeloma.

    PubMed

    Jo, Jae-Cheol; Yoon, Dok Hyun; Kim, Shin; Lee, Kyoungmin; Kang, Eun Hee; Jang, Seongsoo; Park, Chan-Jeoung; Chi, Hyun-Sook; Huh, Jooryung; Park, Chan-Sik; Suh, Cheolwon

    2014-03-01

    Multiple myeloma (MM) is characterized by clonal expansion of malignant bone marrow cells producing a unique monoclonal immunoglobulin. The appearance of abnormal protein band (APB) in MM has been reported during follow-up. We aimed to evaluate the clinical characteristics and outcomes of patients with APB in a single center cohort. A total of 377 consecutive MM patients were treated at the Asan Medical Center between January 2002 and December 2012. We compared clinical characteristics and survival outcome between those with and without APB. Of the 377 patients, 34 (9 %) experienced APB. They comprised 18.2 % (27/148) of patients treated with autologous stem cell transplantation (ASCT) and 3.1 % (7/229) of those not receiving ASCT. APB occurred after a median of 7.9 months (range, 2.2-95.7 months) from diagnosis. Immunoglobulin isotypes at diagnosis were as follows: IgG (n = 10), IgA (n = 8), IgD (n = 5), free κ (n = 4), and free λ (n = 7). Nine patients experienced a second APB. With a median follow-up of 54.1 months, the median overall survival (OS) has not been reached in patients with APB and was 38.3 months in patients without (P < 0.001). Multivariate analysis indicated that the development of APB was a significant favorable prognostic factor for OS (hazard ratio 0.21; 95 % confidence interval 0.08-0.52). Serum β₂-microglobulin, albumin, creatinine, and ASCT were also independent prognostic factors for OS. Further investigation is required to establish the mechanisms underlying APB in MM.

  10. [Monoclonal gammopathies of indetermined significance: diagnosis and clinical follow-up guidelines].

    PubMed

    Parreira, Joana; Lúcio, Paulo; João, Cristina; Macedo, Ana; Sarmento, Ana Bela; Geraldes, Catarina; Gonçalves, Cristina; Esteves, Graça

    2014-01-01

    The Portuguese group of multiple myeloma of the Portuguese Society of Hematology proposes a national protocol for diagnosis and clinical follow-up of monoclonal gammopathies. The proposed protocol aims to standardize clinical management of monoclonal gammopathies. Furthermore, it would also define the major risk factors for progression to Multiple Myeloma that require a precocious close articulation between general practitioners and a Hematology Clinic.

  11. Scope-of-practice laws for nurse practitioners limit cost savings that can be achieved in retail clinics.

    PubMed

    Spetz, Joanne; Parente, Stephen T; Town, Robert J; Bazarko, Dawn

    2013-11-01

    Retail clinics have the potential to reduce health spending by offering convenient, low-cost access to basic health care services. Retail clinics are often staffed by nurse practitioners (NPs), whose services are regulated by state scope-of-practice regulations. By limiting NPs' work scope, restrictive regulations could affect possible cost savings. Using multistate insurance claims data from 2004-07, a period in which many retail clinics opened, we analyzed whether the cost per episode associated with the use of retail clinics was lower in states where NPs are allowed to practice independently and to prescribe independently. We also examined whether retail clinic use and scope of practice were associated with emergency department visits and hospitalizations. We found that visits to retail clinics were associated with lower costs per episode, compared to episodes of care that did not begin with a retail clinic visit, and the costs were even lower when NPs practiced independently. Eliminating restrictions on NPs' scope of practice could have a large impact on the cost savings that can be achieved by retail clinics.

  12. [Abnormality of blood coagulation indexes in patients with de novo acute leukemia and its clinical significance].

    PubMed

    Xiao, Fang-Fang; Hu, Kai-Xun; Guo, Mei; Qiao, Jian-Hui; Sun, Qi-Yun; Ai, Hui-Sheng; Yu, Chang-Lin

    2013-04-01

    To explore hemorrhage risk and the clinical significance of abnormal change of prothrombin time (PT), activated partial thromboplastin time (APTT), plasma fibrinogen (FIB), plasma thrombin time (TT) and d-dimer (D-D) in de novo acute leukemia (except for APL), the different bleeding manifestations of 114 cases of de novo acute leukemia with different coagulation indexes were analyzed retrospectively. The correlation between these blood coagulation indexes and the possible correlative clinical characteristics were analysed, including age, sex, type of acute leukemia, initial white blood cell(WBC) and platelet(Plt) count, the proportion of blast cells in bone marrow and cytogenetic abnormality of patients at diagnosis. The results indicated that the incidence of abnormal blood coagulation was as high as 78.1% for de novo AL patients. These patients with 5 normal blood coagulation indexes may have mild bleeding manifestation, but the more abnormal indexes, the more severe bleeding. Both PT and D-D were sensitive indexes for diagnosis of level II bleeding. Incidence of abnormal blood coagulation significantly correlates with the proportion of blast cells in bone marrow (χ(2) = 4.184, OR = 1.021, P < 0.05) and more with D-D (P < 0.01), while age, sex, type of AL, WBC count, Plt count and abnormality of cytogenetics did not correlate with abnormal blood coagulation. It is concluded that the coagulation and fibrinolysis are abnormal in most patients with de novo acute leukemia. More abnormal indexes indicate more severe bleeding, and both PT and D-D are sensitive indexes for diagnosis of level II bleeding. Higher proportion of blast cells in bone marrow predicts higher incidence of abnormal blood clotting. Acute leukemia with elderly age, high white blood cell count and adverse cytogenetics do not predict severer abnormal blood clotting. Detection of PT, APTT, TT, FIB, and D-D may help to judge whether the patients are in a state of hypercoagulability or disseminated

  13. Relationships between Preferred Learning and Clinical Achievement of Baccalaureate Nursing Students.

    ERIC Educational Resources Information Center

    Wilkerson, Norma Neahr

    Paper presented at the Regional achievement in a nursing course in an integrated curriculum were studied. The theoretical framework was based on Kolb's model of experiential learning, which posited four phases: concrete experience, reflective observation, abstract conceptualization, and active experimentation. Kolb's Learning Style Inventory was…

  14. [Possible mechanism of production of the musical second heart sound and its clinical significance].

    PubMed

    Fukuda, N; Hosoi, K; Iuchi, A; Ogawa, S; Kageji, Y; Hayashi, M; Yoshimoto, K; Tanimoto, M; Oki, T

    1991-01-01

    To investigate the predisposing factors and the clinical significance of the musical aortic component of the second heart sound (musical S2), 18 patients with musical S2 (musical group) among the consecutive 2,000 patients with phonocardiographic examination were noninvasively studied by analyzing underlying diseases, phonocardiographic findings, organic changes of the aortic valve, severity of aortic regurgitation and left ventricular dysfunction. Organic changes of the aortic valve were assessed by two-dimensional echocardiography, and aortic regurgitation was assessed by color Doppler flow imaging. Twenty-two normal subjects (normal group) and 17 patients with essential hypertension (hypertensive group) served as controls. Mean ages were matched among the three groups. 1. Left ventricular dilatation (seven patients) and hypertension (six patients) were the dominant part of underlying disease in the musical group. 2. Musical S2 was classified in the following two types based on the phonocardiographic characteristics; musical vibrations followed immediately after the accentuated S2, and the S2 which was replaced by regular vibratory waves. 3. Frequency of the musical vibrations ranged from 120 to 200 Hz, and its duration ranged from 60 to 120 msec. Amplitude of the musical vibrations decreased by inhalation of amyl nitrite, but increased by infusion of methoxamine. In a case with mild rheumatic valve disease, methoxamine induced marked intensification of the amplitude and prolongation of the duration of the musical vibrations, finally giving a typical cooing murmur. 4. Echo intensity of the aortic valve tended to be higher in the musical group than in the other two groups. 5. Echocardiographically, aortic regurgitation appeared more frequently in the musical group (88%) than in the normal (36%) and hypertensive (41%) groups. Area of the aortic regurgitant signal was significantly larger in the musical group (4.1 +/- 1.4 cm2) than in the normal (1.2 +/- 0.8 cm2

  15. Clinical significance of para-aortic lymph node dissection and prognosis in ovarian cancer.

    PubMed

    Li, Xianxian; Xing, Hui; Li, Lin; Huang, Yanli; Zhou, Min; Liu, Qiong; Qin, Xiaomin; He, Min

    2014-03-01

    Lymph node metastasis has an important effect on prognosis of patients with ovarian cancer. Moreover, the impact of para-aortic lymph node (PAN) removal on patient prognosis is still unclear. In this study, 80 patients were divided into groups A and B. Group A consisted of 30 patients who underwent PAN + pelvic lymph node (PLN) dissection, whereas group B consisted of 50 patients who only underwent PLN dissection. Analysis of the correlation between PAN clearance and prognosis in epithelial ovarian cancer was conducted. Nineteen cases of lymph node metastasis were found in group A, among whom seven cases were positive for PAN, three cases for PLN, and nine cases for both PAN and PLN. In group B, 13 cases were positive for lymph node metastasis. Our study suggested that the metastatic rate of lymph node is 40.0%. Lymph node metastasis was significantly correlated with FIGO stage, tumor differentiation, and histological type both in groups A and B (P < 0.05). In groups A and B, the three-year survival rates were 77.9% and 69.0%, and the five-year survival rates were 46.7% and 39.2%, respectively. However, the difference was not statistically significant (P > 0.05). The three-year survival rates of PLN metastasis in groups A and B were 68.5% and 41.4%, and the five-year survival rates were 49.7% and 26.4%, respectively. Furthermore, PLN-positive patients who cleared PAN had significantly higher survival rate (P = 0.044). In group A, the three-year survival rates of positive and negative lymph nodes were 43.5% and 72.7%, and the five-year survival rates were 27.2% and 58.5%, respectively. The difference was statistically significant (P = 0.048). Cox model analysis of single factor suggested that lymph node status affected the survival rate (P < 0.01), which was the death risk factor. Consequently, in ovarian carcinoma cytoreductive surgery, resection of the para-aortic lymph node, which has an important function in clinical treatment and prognosis of patients with

  16. Busulphan is active against neuroblastoma and medulloblastoma xenografts in athymic mice at clinically achievable plasma drug concentrations

    PubMed Central

    Boland, I; Vassal, G; Morizet, J; Terrier-Lacombe, M-J; Valteau-Couanet, D; Kalifa, C; Hartmann, O; Gouyette, A

    1999-01-01

    High-dose busulphan-containing chemotherapy regimens have shown high response rates in children with relapsed or refractory neuroblastoma, Ewing's sarcoma and medulloblastoma. However, the anti-tumour activity of busulfan as a single agent remains to be defined, and this was evaluated in athymic mice bearing advanced stage subcutaneous paediatric solid tumour xenografts. Because busulphan is highly insoluble in water, the use of several vehicles for enteral and parenteral administration was first investigated in terms of pharmacokinetics and toxicity. The highest bioavailability was obtained with busulphan in DMSO administered i.p. When busulphan was suspended in carboxymethylcellulose and given orally or i.p., the bioavailability was poor. Then, in the therapeutic experiments, busulphan in DMSO was administered i.p. on days 0 and 4. At the maximum tolerated total dose (50 mg kg−1), busulphan induced a significant tumour growth delay, ranging from 12 to 34 days in the three neuroblastomas evaluated and in one out of three medulloblastomas. At a dose level above the maximum tolerated dose, busulphan induced complete and partial tumour regressions. Busulphan was inactive in a peripheral primitive neuroectodermal tumour (PNET) xenograft. When busulphan pharmacokinetics in mice and humans were considered, the estimated systemic exposure at the therapeutically active dose in mice (113 μg h ml−1) was close to the mean total systemic exposure in children receiving high-dose busulphan (102.4 μg h ml−1). In conclusion, busulphan displayed a significant anti-tumour activity in neuroblastoma and medulloblastoma xenografts at plasma drug concentrations which can be achieved clinically in children receiving high-dose busulphan-containing regimens. 1999 Cancer Research Campaign PMID:10070870

  17. Radiation-induced bystander effect in healthy G(o) human lymphocytes: biological and clinical significance.

    PubMed

    Belloni, Paola; Latini, Paolo; Palitti, Fabrizio

    2011-08-01

    To study the bystander effects, G(0) human peripheral blood lymphocytes were X-irradiated with 0.1, 0.5 and 3 Gy. After 24h, cell-free conditioned media from irradiated cultures were transferred to unexposed lymphocytes. Following 48 h of medium transfer, viability, induction of apoptosis, telomere shortening, reactive oxygen species (ROS) levels and micronuclei (after stimulation) were analyzed. A statistically significant decrement in cell viability, concomitant with the loss of mitochondrial membrane potential, telomere shortening, increases in hydrogen peroxide (H(2)O(2)) and superoxide anion (O(2)(-)) with depletion of intracellular glutathione (GSH) level, and higher frequencies of micronuclei, were observed in bystander lymphocytes incubated with medium from 0.5 and 3 Gy irradiated samples, compared to lymphocytes unexposed. Furthermore, no statistically significant difference between the response to 0.5 and 3 Gy of irradiation in bystander lymphocytes, was found. However, when lymphocytes were irradiated with 0.1 Gy, no bystander effect with regard to viability, apoptosis, telomere length, and micronuclei was observed, although a high production of ROS level persisted. Radiation in the presence of the radical scavenger dimethyl sulfoxide (DMSO) suppressed oxidative stress induced by 3 Gy of X-rays with the effective elimination of bystander effects, suggesting a correlation between ROS and bystander signal formation in irradiated cells. The data propose that bystander effect might be mostly due to the reactions of radiation induced free radicals on DNA, with the existence of a threshold at which the bystander signal is not operative (0.1 Gy dose of X-rays). Our results may have clinical implications for health risk associated with radiation exposure.

  18. 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

  19. Androgen Receptor Expression in Early Triple-Negative Breast Cancer: Clinical Significance and Prognostic Associations

    PubMed Central

    Pistelli, Mirco; Caramanti, Miriam; Biscotti, Tommasina; Santinelli, Alfredo; Pagliacci, Alessandra; De Lisa, Mariagrazia; Ballatore, Zelmira; Ridolfi, Francesca; Maccaroni, Elena; Bracci, Raffaella; Berardi, Rossana; Battelli, Nicola; Cascinu, Stefano

    2014-01-01

    Background: Triple-negative breast cancers (TNBC) are characterized by aggressive tumour biology resulting in a poor prognosis. Androgen receptor (AR) is one of newly emerging biomarker in TNBC. In recent years, ARs have been demonstrated to play an important role in the genesis and in the development of breast cancer, although their prognostic role is still debated. In the present study, we explored the correlation of AR expression with clinical, pathological and molecular features and its impact on prognosis in early TNBC. Patients and Methods: ARs were considered positive in case of tumors with >10% nuclear-stained. Survival distribution was estimated by the Kaplan Meier method. The univariate and multivariate analyses were performed. The difference among variables were calculated by chi-square test. Results: 81 TNBC patients diagnosed between January 2006 and December 2011 were included in the analysis. Slides were stained immunohistochemically for estrogen and progesterone receptors, HER-2, Ki-67, ALDH1, e-cadherin and AR. Of the 81 TNBC samples, 18.8% showed positive immunostaining for AR, 23.5% and 44.4% of patients were negative for e-cadherin and ALDH1, respectively. Positive AR immunostaining was inversely correlated with a higher Ki-67 (p < 0.0001) and a lympho-vascular invasion (p = 0.01), but no other variables. Univariate survival analysis revealed that AR expression was not associated with disease-free survival (p = 0.72) or overall survival (p = 0.93). Conclusions: The expression of AR is associated with some biological features of TNBC, such as Ki-67 and lympho-vascular invasion; nevertheless the prognostic significance of AR was not documented in our analysis. However, since ARs are expressed in a significant number of TNBC, prospective studies in order to determine the biological mechanisms and their potential role as novel treatment target. PMID:24978437

  20. Expression and clinical significance of erb-B receptor family in hepatocellular carcinoma

    PubMed Central

    Ito, Y; Takeda, T; Sakon, M; Tsujimoto, M; Higashiyama, S; Noda, K; Miyoshi, E; Monden, M; Matsuura, N

    2001-01-01

    In order to elucidate the clinical significance of the erbB family, epidermal growth factor receptor (EGF-R), c-erbB-2, c-erbB-3 and c-erbB-4 in hepatocellular carcinoma (HCC), we investigated the expression of these proteins by means of immunohistochemistry for HCC as well as adjacent noncancerous lesions. EGF-R was expressed in 68% of the HCC examined and showed correlation with the proliferating activity, stage, intrahepatic metastasis and carcinoma differentiation. c-erbB-2 was expressed in only 21% of the cases and showed no relationships with the clinicopathological parameters. c-erbB-3 protein was observed in 84% of the HCC and 38.1% of the noncancerous lesions. Its expression in HCC was equal to or greater than noncancerous lesions in 90.5% of the cases, and was related to the stage, portal invasion, cell proliferating activity, tumour size, intrahepatic metastasis and carcinoma differentiation. c-erbB-4 protein was expressed in 61.0% of HCC and in as much as 86.1% of the noncancerous lesions. Unlike the expression of c-erbB-3, that of c-erbB-4 in HCC was less than that of the adjacent noncancerous lesions in 51.2% of the cases. No statistical significance could be established between this protein expression in HCC and clinicopathological features. EGF-R and c-erbB-3 affected disease-free survival, but were not recognized as independent prognostic factors by multivariate analysis. The present study suggests that, of the four receptors, EGF-R and c-erbB-3 play important roles in the progression of HCC. © 2001 Cancer Research Campaign www.bjcancer.com PMID:11355950

  1. 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

  2. Expression of RUNX3 gene in pancreatic adenocarcinoma and its clinical significance.

    PubMed

    Xue, L-N; Bai, F H; Wang, X-Y; Lin, M; Tan, Y; Yao, X-Y; Xu, K-Q

    2014-05-23

    We investigated the clinical significance of RUNX3 gene expression in human pancreatic carcinoma. Five samples of pancreatic tissues and 30 samples of pancreatic cancer tissues and paracancerous tissues were collected. RUNX3 expression was detected by real-time PCR and immunohistochemistry. The relationships between clinicopathological findings and the expression of RUNX3 were analyzed. The relative quantification level of RUNX3 mRNA expression in human pancreatic carcinoma tissues and paracancerous tissues was 2.60 (0.42-12.82) and 1.02 (0.19-3.58), respectively (P < 0.05). The percentage of positive cells expressing RUNX3 protein in human pancreatic tissues and paracancerous tissues was 45.5 ± 26.2 and 6.9 ± 6.0%, respectively (P < 0.01). The high RUNX3 group (N = 9) with 45.5% or more of the cancer cells staining for RUNX3 and the low RUNX3 group (N = 21) with less than 45.5% cancer cells staining for RUNX3. Low expression of RUNX3 correlated significantly with an advanced TNM stage (χ(2) = 6.897, P = 0.045), lymph node metastasis (χ(2) = 4.739, P = 0.029) and neural invasion (χ(2) = 5.44, P = 0.020). On the other hand, no association could be found between RUNX3 expression and clinicopathological variables including age, gender, tumor location, tumor size, tumor differentiation or the serum concentration of CEA and CA199. The expression of RUNX3 in pancreatic cancer tissues was obviously higher than that in the paracancerous tissues. Low expression of RUNX3 may have an important role in aggressiveness, lymph node metastasis and neural invasion in pancreatic cancer. In pancreatic carcinoma tissues, low expression of RUNX3 may indicate a poor prognosis.

  3. Locations and Clinical Significance of Non-Hemorrhagic Brain Lesions in Diffuse Axonal Injuries

    PubMed Central

    Chung, Sang Won; Nam, Taek Kyun; Kwon, Jeong Taik; Min, Byung Kook; Hwang, Sung Nam

    2012-01-01

    Objective Detection of focal non-hemorrhagic lesion (NHL) has become more efficient in diffuse axonal injury (DAI) patients using an MRI. The aims of this study are to find out the radiological distribution, progress of NHL and its clinical significance. Methods Between September 2005 and October 2011, 32 individuals with NHLs on brain MRI were enrolled. NHLs were classified by brain location into 4 major districts and 13 detailed locations including cortical and subcortical, corpus callosum, deep nuclei and adjacent area, and brainstem. The severity of NHL was scored from grades 1 to 4, according to the number of districts involved. Fourteen patients with NHL were available for MRI follow-up and an investigation of the changes was conducted. Results Thirty-two patients had 59 NHLs. The most common district of NHL was cortical and subcortical area; 15 patients had 20 NHSs. However the most common specific location was the splenium of the corpus callosum; 14 patients had 14 lesions. The more lesions patients had, the lower the GCS, however, this was not a statistically meaningful difference. On follow-up MRI in 14 patients, out of 24 lesions, 13 NHLs resolved, 5 showed cystic change, and 6 showed atrophic changes. Conclusion NHLs were located most commonly in the splenium and occur frequently in the thalamus and the mesial temporal lobe. Because most NHS occur concomitantly with hemorrhagic lesions, it was difficult to determine their effects on prognosis. Since most NHLs resolve completely, they are probably less significant to prognosis than hemorrhagic lesions. PMID:23133728

  4. Compression Angle of Ossification of the Posterior Longitudinal Ligament and Its Clinical Significance in Cervical Myelopathy

    PubMed Central

    Lee, Nam; Yoon, Do Heum; Kim, Keung Nyun; Shin, Hyun Chul; Shin, Dong Ah

    2016-01-01

    Objectives The correction of clinical and radiologic abnormalities in patients with symptomatic ossification of the posterior longitudinal ligament (OPLL) is the current mainstay of treatment. This study aimed to identify radiographic predictors of severity of myelopathy in patients with symptomatic OPLL. Methods Fifty patients with symptomatic cervical OPLL were enrolled. Based on Japanese Orthopedic Association (JOA) scores, patients were divided into either the mild myelopathy (n=31) or severe myelopathy (n=19) group. All subjects underwent preoperative plain cervical roentgenogram, computed tomography (CT), and MR imaging (MRI). Radiological parameters (C2–7 sagittal vertical axis, SVA; C2–7 Cobb angle; C2–7 range of motion, ROM; OPLL occupying ratio; and compression angle) were compared. Compression angle of OPLL was defined as the angle between the cranial and caudal surfaces of OPLL at the maximum level of cord compression Results The occupying ratio of the spinal canal, C2–7 Cobb angle, C2–7 SVA, types of OPLL, and C2–7 ROM of the cervical spine were not statistically different between the two groups. However, the OPLL compression angle was significantly greater (p=0.003) in the severe myelopathy group than in the mild myelopathy group and was inversely correlated with JOA score (r=-0.533, p<0.01). Furthermore, multivariate regression analysis demonstrated that the compression angle (B=-0.069, p<0.001) was significantly associated with JOA scores (R=0.647, p<0.005). Conclusion Higher compression angles of OPLL have deleterious effects on the spinal cord and decrease preoperative JOA scores. PMID:27651865

  5. Incidence, Prevalence, and Clinical Significance of Abnormal Hematologic Indices in Compensated Cirrhosis

    PubMed Central

    Qamar, Amir A.; Grace, Norman D.; Groszmann, Roberto J.; Garcia–Tsao, Guadalupe; Bosch, Jaime; Burroughs, Andrew K.; Ripoll, Cristina; Maurer, Rie; Planas, Ramon; Escorsell, Angels; Garcia–Pagan, Juan Carlos; Patch, David; Matloff, Daniel S.; Makuch, Robert; Rendon, Gabriel

    2011-01-01

    Background & Aims Patients with cirrhosis develop abnormal hematologic indices (HI) from multiple factors, including hypersplenism. We aimed to analyze the sequence of events and determine whether abnormal HI has prognostic significance. Methods We analyzed a database of 213 subjects with compensated cirrhosis without esophageal varices. Subjects were followed for approximately 9 years until the development of varices or variceal bleeding or completion of the study; 84 subjects developed varices. Abnormal HI was defined as anemia at baseline (hemoglobin, ≤13.5 g/dL for men and 11.5 g/dL for women), leukopenia (white blood cell counts, ≤4000/mm3), or thrombocytopenia (platelet counts, ≤150,000/mm3). The primary end points were death or transplant surgery. Results Most subjects had thrombocytopenia at baseline. Kaplan–Meier analysis showed that leukopenia occurred by 30 months (95% confidence interval, 18.5–53.6), and anemia occurred by 39.6 months (95% confidence interval, 24.1–49.9). Baseline thrombocytopenia (P = .0191) and leukopenia (P = .0383) were predictors of death or transplant, after adjusting for baseline hepatic venous pressure gradient (HVPG), and Child–Pugh scores. After a median of 5 years, a significant difference in death or transplant, mortality, and clinical decompensation was observed in patients who had leukopenia combined with thrombocytopenia at baseline compared with patients with normal HI (P < .0001). HVPG correlated with hemoglobin and white blood cell count (hemoglobin, r = −0.35, P < .0001; white blood cell count, r = −0.31, P < .0001). Conclusions Thrombocytopenia is the most common and first abnormal HI to occur in patients with cirrhosis, followed by leukopenia and anemia. A combination of leukopenia and thrombocytopenia at baseline predicted increased morbidity and mortality. PMID:19281860

  6. Calcareous concretions and psammoma bodies in sputum smears: do these similar structures have different clinical significance?

    PubMed

    Martínez-Girón, Rafael; Martínez-Torre, Santiago; Tamargo-Peláez, María Luisa; López-Cabanilles, María Dolores; Torre-Bayón, Concepción

    2014-09-01

    Different noncellular elements, such as round concentric calcified laminated structures, may be found in sputum smears. If these structures appear isolated on the background of the smear, the term usually used to describe them is "calcareous concretions" (CC). On the contrary, when the structures are part of epithelial cell groups or small tissue fragments, the term used to describe them is "Psammoma bodies" (PB). The aim of this work is to establish the relationship between these structures and pulmonary disease, especially lung carcinoma, by searching for the presence of CC and/or PB in sputum smears. Our study has taken as a basis 16.716 sputum smears from 696 patients obtained during a 7-year period (2003-2009). After reviewing them, it was found that from the total, 66 cases (0.39%) contained round calcified structures, 57 of them (0.34%) corresponding to CC, and the remaining 9 ones (0.05%) corresponding to PB. From these 57 CC cases, 56 corresponded to benign entities, and only one was found with lung carcinoma. On the other hand, from the 9 PB cases all of them (100%) were related to lung adenocarcinoma. We conclude that, even having a similar morphological structure, these aforementioned calcified structures we have observed in sputum smears have different and relevant clinical significance.

  7. Clinical significance of leukocyte-associated immunoglobulin-like receptor-1 expression in human cervical cancer

    PubMed Central

    Wang, Yue; Zhang, Xueshan; Miao, Fang; Cao, Yanning; Xue, Jiangnan; Cao, Qizhi; Zhang, Xiaoshu

    2016-01-01

    Leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is broadly expressed on the majority of immune cells; however, the biological role of LAIR in solid tumors has yet to be elucidated. In the present study, using immunohistochemical staining analysis, the expression of LAIR-1 in human cervical cancer (HCC) and nontumor-adjacent tissue specimens was determined, and the results indicated that the expression of LAIR-1 in HCC tissue was higher compared with that in noncancerous tissue. The χ2 test was used to analyze the correlation between the expression of LAIR-1 in tumor tissues with clinicopathological parameters. The results showed that the expression of LAIR-1 in the cancer cell nucleus was significantly associated with tumor size, pathological differentiation, T classification and clinical stage. In addition, the expression in the cytoplasm was evidently associated with the number of positive lymph nodes. The HCC cell line, ME-180, which does not express LAIR-1, was stably transfected using LAIR-1 cDNA. Cell Counting Kit-8 and an annexin V assay showed that the overexpression of LAIR-1 in ME-180 cells suppressed the proliferation and anti-apoptosis capacity of the cells. These findings demonstrated that LAIR-1 is markedly overexpressed in HCC tissue, and that its expression status is associated with tumor progression. LAIR-1 may be a biomarker and target in the diagnosis and treatment of patients with HCC. PMID:28105100

  8. 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.

  9. Clinical significance and prognostic value of Vav1 expression in Non-small cell lung cancer

    PubMed Central

    Qi, Yao; Kong, Fan-Ming; Deng, Qi; Li, Jing-Yi; Cui, Rui; Pu, Ye-Di; Zhai, Qiong-Li; Jia, Ying-Jie; Li, Yu-Ming

    2015-01-01

    Vav1 has been reported to be involved in human cancers, however, the expression and clinical significance of Vav1 in NSCLC are not fully understood. In the present study, we examined the expression of Vav1 in 170 NSCLC patients who underwent radical resection by the immunohistochemical analyses. The association between the Vav1 expression and clinicopathological variables was analyzed. The multivariate Cox proportional hazards model was conducted to determine the prognostic value of Vav1 on the long-term survival. The results showed that the elevated Vav1 expression was correlated positively with lymph node metastasis (P<0.001), T stage (P<0.001) and poor histological differentiation (P<0.001). Patients with negative or low Vav1 expression had better prognoses than those with high Vav1 expression (P<0.001). Multivariate analysis indicated that Vav1 was independent prognostic factor for overall survival (OS) (HR 2.079, 95% CI 1.564 to 2.762, P<0.001) and disease-free survival (DFS) (HR 1.810, 95% CI 1.391 to 2.356, P<0.001). Our findings showed that overexpressed Vav1 was correlated with aggressive tumor behavior. Val1 was an independent factor for NSCLC prognosis, which may serve as a novel prognostic factor and potential target to improve the long-term outcome of NSCLC. PMID:26396925

  10. Lymph node, peritoneal and bone marrow micrometastases in gastric cancer: Their clinical significance.

    PubMed

    Griniatsos, John; Michail, Othon; Dimitriou, Nikoletta; Karavokyros, Ioannis

    2012-02-15

    The 7th TNM classification clearly states that micrometastases detected by morphological techniques (HE stain and immunohistochemistry) should always be reported and calculated in the staging of the disease (pN1mi or M1), while patients in whom micrometastases are detected by non-morphological techniques (e.g., flow cytometry, reverse-transcriptase polymerase chain reaction) should still be classified as N0 or M0. In gastric cancer patients, micrometastases have been detected in lymph nodes, the peritoneal cavity and bone marrow. However, the clinical implications and/or their prognostic significance are still a matter of debate. Current literature suggests that lymph node micrometastases should be encountered for the loco-regional staging of the disease, while skip lymph node micrometastases should also be encountered in the total number of infiltrated lymph nodes. Peritoneal fluid cytology examination should be obligatorily performed in pT3 or pT4 tumors. A positive cytology classifies gastric cancer patients as stage IV. Although a curative resection is not precluded, these patients face an overall dismal prognosis. Whether patients with a positive cytology should be treated similarly to patients with macroscopic peritoneal recurrence should be evaluated further. Gastric cancer cells are detected with high incidence in the bone marrow. However, the published results make comparison of data between groups almost impossible due to severe methodological problems. If these methodological problems are overcome in the future, specific target therapies may be designed for specific groups of patients.

  11. Lymph node, peritoneal and bone marrow micrometastases in gastric cancer: Their clinical significance

    PubMed Central

    Griniatsos, John; Michail, Othon; Dimitriou, Nikoletta; Karavokyros, Ioannis

    2012-01-01

    The 7th TNM classification clearly states that micrometastases detected by morphological techniques (HE stain and immunohistochemistry) should always be reported and calculated in the staging of the disease (pN1mi or M1), while patients in whom micrometastases are detected by non-morphological techniques (e.g., flow cytometry, reverse-transcriptase polymerase chain reaction) should still be classified as N0 or M0. In gastric cancer patients, micrometastases have been detected in lymph nodes, the peritoneal cavity and bone marrow. However, the clinical implications and/or their prognostic significance are still a matter of debate. Current literature suggests that lymph node micrometastases should be encountered for the loco-regional staging of the disease, while skip lymph node micrometastases should also be encountered in the total number of infiltrated lymph nodes. Peritoneal fluid cytology examination should be obligatorily performed in pT3 or pT4 tumors. A positive cytology classifies gastric cancer patients as stage IV. Although a curative resection is not precluded, these patients face an overall dismal prognosis. Whether patients with a positive cytology should be treated similarly to patients with macroscopic peritoneal recurrence should be evaluated further. Gastric cancer cells are detected with high incidence in the bone marrow. However, the published results make comparison of data between groups almost impossible due to severe methodological problems. If these methodological problems are overcome in the future, specific target therapies may be designed for specific groups of patients. PMID:22403737

  12. The clinical significance of the gut microbiota in cystic fibrosis and the potential for dietary therapies.

    PubMed

    Li, Li; Somerset, Shawn

    2014-08-01

    Cystic fibrosis (CF) is characterised by many comorbidities related to aberrant mucosa and chronic inflammation in the respiratory and digestive systems. The intestinal mucosa serves as the primary interface between the gut microbiota and endocrine, neural and immune systems. There is emerging evidence that aberrant intestinal mucosa in CF may associate with an altered gut microbiota. Compared to healthy subjects, the overall bacterial abundance and species richness seems to be reduced in CF, accompanied by a trend in suppression of Firmicutes and Bacteroidetes spp. and an augmentation of potentially pathogenic species. There is also some concordance of gut and respiratory microbiotas in CF infants over time. The clinical significance of these observations awaits investigation. The gut microbiota have some potential in CF management by affecting inflammatory and immune responses, and influencing aberrant mucosa. As an important modifiable factor, diet therapies such as probiotics and prebiotics have shown initial promise in improving CF related conditions associated with chronic inflammation. More studies are needed to confirm this, as well as the efficacy of other dietary strategies such as modulating dietary fat and indigestible carbohydrate. Similarly, dietary modification of gut microbiota to optimise nutritional status in CF may be feasible, although more CF-specific studies are warranted.

  13. The prevalence and clinical significance of intestinal parasites in HIV-infected patients in Denmark.

    PubMed

    Stensvold, Christen Rune; Nielsen, Susanne Dam; Badsberg, Jens-Henrik; Engberg, Jørgen; Friis-Møller, Nina; Nielsen, Sanne Søgaard; Nielsen, Henrik Vedel; Friis-Møller, Alice

    2011-02-01

    To investigate the prevalence and clinical significance of intestinal parasites in human immunodeficiency virus (HIV)-infected patients, faecal specimens from 96 HIV-infected patients were submitted to microbiological analyses, including microscopy and polymerase chain reaction for protozoa and enteropathogenic bacteria. Results of microbiological analyses were compared with self-reported gastrointestinal complaints collected using a validated questionnaire. Thirty-two (33%) patients were positive for parasites. However, opportunistic parasites (Isospora and Cryptosporidium) were detected in only 2 instances. Entamoeba dispar was detected in 10 cases, 9 of which represented men who have sex with men (MSM). Despite generally low HIV RNA loads and high CD4+ T-cell counts, 42% of the 76 patients reporting symptoms complained of diarrhoea, 31% of whom were parasite-positive. The presence of diarrhoea was not associated with the presence or absence of parasites; neither was it associated with receiving highly active anti-retroviral therapy (HAART) in general, or protease inhibitors (PI) in particular. A CD4+ T-cell count <200 cells/mm³ was not associated with parasitic infection or with diarrhoea. The data show that diarrhoea is a common symptom among HIV-infected patients in Denmark, but do not indicate that the diarrhoea is due to intestinal parasites.

  14. Blastocystis: unravelling potential risk factors and clinical significance of a common but neglected parasite.

    PubMed

    Stensvold, C R; Lewis, H C; Hammerum, A M; Porsbo, L J; Nielsen, S S; Olsen, K E P; Arendrup, M C; Nielsen, H V; Mølbak, K

    2009-11-01

    Two independent studies were conducted to describe symptoms and potential risk factors associated with Blastocystis infection. Isolates were subtyped by molecular analysis. In the NORMAT study (126 individuals randomly sampled from the general population) 24 (19%) were positive for Blastocystis. Blastocystis was associated with irritable bowel syndrome (P=0.04), contact with pigs (P<0.01) and poultry (P=0.03). In the Follow-up (FU) study (follow-up of 92 Blastocystis-positive patients), reports on bloating were associated with subtype (ST) 2 (P<0.01), and blood in stool to mixed subtype infection (P=0.06). ST1 was more common in FU individuals (32%) than in NORMAT individuals (8%), whereas single subtype infections due to ST3 or ST4 were seen in 63% of the NORMAT cases and 28% of the FU cases. Only FU individuals hosted ST7, and ST6/7 infections due to ST7 or ST9 were characterized by multiple intestinal symptoms. The data indicate subtype-dependent differences in the clinical significance of Blastocystis.

  15. DNA methylation Profiles in Primary Cutaneous Melanomas are Associated with Clinically Significant Pathologic Features

    PubMed Central

    Thomas, Nancy E.; Slater, Nathaniel A.; Edmiston, Sharon N.; Zhou, Xin; Kuan, Pei-Fen; Groben, Pamela A.; Carson, Craig C.; Hao, Honglin; Parrish, Eloise; Moschos, Stergios J.; Berwick, Marianne; Ollila, David W.; Conway, Kathleen

    2014-01-01

    Summary DNA methylation studies have elucidated a methylation signature distinguishing primary melanomas from benign nevi and provided new insights about genes that may be important in melanoma development. However, it is unclear whether methylation differences among primary melanomas are related to tumor pathologic features with known clinical significance. We utilized the Illumina Golden Gate Cancer Panel array to investigate the methylation profiles of 47 primary cutaneous melanomas. Array-wide methylation patterns revealed a positive association of methylation with Breslow thickness and mutated BRAF, a negative association with mitotic rate, and a weak association with ulceration. Hierarchical clustering on CpG sites exhibiting the most variable methylation (n=235) divided the melanoma samples into three clusters, including a highly-methylated cluster that was positively associated with Breslow thickness and an intermediately-methylated cluster associated with Breslow thickness and mitotic rate. Our findings provide support for the existence of methylation-defined subsets in melanomas, with increased methylation associated with Breslow thickness. PMID:24986547

  16. Clinical and biological significance of glucocorticoid receptor (GR) expression in breast cancer.

    PubMed

    Abduljabbar, Rezvan; Negm, Ola H; Lai, Chun-Fui; Jerjees, Dena A; Al-Kaabi, Methaq; Hamed, Mohamed R; Tighe, Patrick J; Buluwela, Lakjaya; Mukherjee, Abhik; Green, Andrew R; Ali, Simak; Rakha, Emad A; Ellis, Ian O

    2015-04-01

    The glucocorticoid receptor (GR) is a member of the nuclear receptor superfamily of transcription factors, which exerts anti-proliferative and anti-apoptotic activities. The GR is expressed in a large proportion of breast cancer (BC) although levels generally decrease during cancer progression. This study aimed to determine the clinical and biological significance of GR expression using a large series of early-stage BC with long-term follow-up and BC cell lines. Immunohistochemistry was used to assess the expression of GR in 999 cases of primary invasive BC prepared as tissue microarrays. Reverse phase protein microarray was used to assess the expression of GR in MCF7 and MDA-MB-231 cell lines. Nuclear expression of GR was observed in 61.6 % of breast tumours and was associated with features of good prognosis including smaller tumour size and lower grade with less pleomorphism and low mitotic count. GR expression was positively correlated with expression of oestrogen (ER) and progesterone receptors. In ER-positive tumours, GR was associated with other features of favourable outcome including FOXA1, GATA3 and BEX1 expression, while low GR expression was associated with high Ki67, p53 and CD71 expression. GR expression is associated with features of good outcome but does not provide prognostic information independent of size, stage and grade. Understanding the receptor and its effects on BC behaviour is essential for avoiding any unwanted effects from the use of glucocorticoids in routine oncology practice.

  17. Clinical Significance of Molecular Diagnostic Tools for Bacterial Bloodstream Infections: A Systematic Review

    PubMed Central

    Nyirahabimana, Therese

    2016-01-01

    Bacterial bloodstream infection (bBSI) represents any form of invasiveness of the blood circulatory system caused by bacteria and can lead to death among critically ill patients. Thus, there is a need for rapid and accurate diagnosis and treatment of patients with septicemia. So far, different molecular diagnostic tools have been developed. The majority of these tools focus on amplification based techniques such as polymerase chain reaction (PCR) which allows the detection of nucleic acids (both DNA and small RNAs) that are specific to bacterial species and sequencing or nucleic acid hybridization that allows the detection of bacteria in order to reduce delay of appropriate antibiotic therapy. However, there is still a need to improve sensitivity of most molecular techniques to enhance their accuracy and allow exact and on time antibiotic therapy treatment. In this regard, we conducted a systematic review of the existing studies conducted in molecular diagnosis of bBSIs, with the main aim of reporting on clinical significance and benefits of molecular diagnosis to patients. We searched both Google Scholar and PubMed. In total, eighteen reviewed papers indicate that shift from conventional diagnostic methods to molecular tools is needed and would lead to accurate diagnosis and treatment of bBSI. PMID:27974890

  18. [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.

  19. The different functions and clinical significances of caveolin-1 in human adenocarcinoma and squamous cell carcinoma

    PubMed Central

    Fu, Pin; Chen, Fuchun; Pan, Qi; Zhao, Xianda; Zhao, Chen; Cho, William Chi-Shing; Chen, Honglei

    2017-01-01

    Caveolin-1 (Cav-1), a major structural protein of caveolae, is an integral membrane protein which plays an important role in the progression of carcinoma. However, whether Cav-1 acts as a tumor promoter or a tumor suppressor still remains controversial. For example, the tumor-promoting function of Cav-1 has been found in renal cancer, prostate cancer, tongue squamous cell carcinoma (SCC), lung SCC and bladder SCC. In contrast, Cav-1 also plays an inhibitory role in esophagus adenocarcinoma, lung adenocarcinoma and cutaneous SCC. The role of Cav-1 is still controversial in thyroid cancer, hepatocellular carcinoma, gastric adenocarcinoma, colon adenocarcinoma, breast cancer, pancreas cancer, oral SCC, laryngeal SCC, head and neck SCC, esophageal SCC and cervical SCC. Besides, it has been reported that the loss of stromal Cav-1 might predict poor prognosis in breast cancer, gastric cancer, pancreas cancer, prostate cancer, oral SCC and esophageal SCC. However, the accumulation of stromal Cav-1 has been found to be promoted by the progression of tongue SCC. Taken together, Cav-1 seems playing a different role in different cancer subtypes even of the same organ, as well as acting differently in the same cancer subtype of different organs. Thus, we hereby explore the functions of Cav-1 in human adenocarcinoma and SCC from the perspective of clinical significances and pathogenesis. We envision that novel targets may come with the further investigation of Cav-1 in carcinogenesis. PMID:28243118

  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. Unilateral ectopic insertion of the pectoralis minor: Clinical and functional significance.

    PubMed

    Goldman, E; Vasan, C; Lopez-Cardona, H; Vasan, N

    2016-03-01

    During routine dissection of a 70-year-old female, we observed a unilateral ectopic insertion of the left pectoralis minor muscle. The tendon was cord-like and passed through a tendon sheath superior to the coracoid process to insert on the greater tubercle of the humerus. Additionally, an aponeurosis extended from the distal aspect of the muscle's tendon and passed medially to insert near the base of the coracoid process. This is the first report of an additional aponeurosis extending from the tendon of the pectoralis minor and attaching to the coracoid process. We also observed that the pectoralis minor tendon caused an unusually smooth deep indentation on the superior aspect of the coracoid process; considering its insertion on the humerus, we hypothesize that the muscle acted as an abductor of the shoulder along with the supraspinatus. The medial extension of an aponeurotic tendon from the pectoralis minor tendon near its insertion, to the base of the coracoid process further suggests that the muscle provided stability to the glenohumeral joint while acting as an abductor. Pectoralis minor variations have been described since 1897; however, few studies have demonstrated functional or clinical significance. The redundancy of the actions of this muscle along with its long tendon suggests a potential source for autograft.

  2. The role of effective communication in achieving informed consent for clinical trials.

    PubMed

    Pick, Andrew; Gilbert, Kayleigh; McCaul, James

    2014-11-11

    Informed consent is fundamental to the protection of the rights, safety and wellbeing of patients in clinical research. For consent to be valid, patients must first be given all the information they need about the proposed research to be able to decide whether they would like to take part. This material should be presented in a way that is easy for them to understand. This article explores the importance of communication in clinical research, and how more effective communication with patients during the informed consent process can ensure they are fully informed.

  3. Predicting clinically significant response to cognitive behavior therapy for chronic insomnia in general medical practice: analysis of outcome data at 12 months posttreatment.

    PubMed

    Espie, C A; Inglis, S J; Harvey, L

    2001-02-01

    The clinical efficacy of cognitive behavior therapy (CBT) for chronic insomnia has been established, yet clinical effectiveness is less clear. This study presents data on 109 patients from general practice during a formal evaluation of clinical effectiveness. Two thirds achieved normative values of < or =30 min for sleep latency and wakefulness during the night after CBT. Furthermore, almost half of the sample reduced sleeplessness by > or =50%. Logistic regression revealed that initial severity did not contraindicate good outcome. Rather, greater sleep disturbance was positively associated with large symptom reduction, although lower endpoint scores were less likely. Similarly, symptoms of anxiety, depression, and thinking errors positively predicted good outcome. Hypnotic using patients responded equally well to CBT, and demographic factors were of no significant predictive value. It is concluded that CBT is clinically and durably effective for persistent insomnia in routine practice.

  4. Clinical significance of the fractional excretion of anions in metabolic acidosis.

    PubMed

    Kim, H Y; Han, J S; Jeon, U S; Joo, K W; Earm, J H; Ahn, C; Kim, S; Lee, J S; Kim, G H

    2001-06-01

    The fractional excretion of anions has been proposed as a new index for the differential diagnosis of metabolic acidosis, identifying the properties of the conjugate base by examining the renal handling of the anion. Here, we investigated clinical significance of the fractional excretion of anions in pathophysiologic diagnosis of metabolic acidosis by measuring urine ammonium (NH4+) excretion, the ratio of A plasma anion gap/delta plasma HCO3- concentration (deltaAG/deltaHCO3-), and fractional excretion of anions in three different groups of metabolic acidosis: acid overproduction (8 patients with lactic acidosis, 8 with diabetic ketoacidosis, 3 with hippuric acidosis following glue sniffing), acid underexcretion (10 patients with chronic renal failure) and normal controls (10 normal volunteers who underwent 3-day NH4Cl loading). As expected, urine NH4+ excretion was higher in overproduction acidosis than in acid-loaded normal controls (88.1 +/- 12.3 vs. 54.0 +/- 3.7 mmol/day, p < 0.05), and it was lower in chronic renal failure than in acid-loaded normal controls (12.8 +/- 1.7 vs. 54.0 +/- 3.7 mmol/day, p < 0.05). The fractional excretion of anions had no difference between overproduction acidosis and chronic renal failure (41.2 +/- 42.8% vs. 41.0 +/- 8.1%). However, the fractional excretion of anions showed significant differences between the subgroups in acid overproduction (lactic acidosis, 4.7 +/- 0.3%; diabetic ketoacidosis, 45.8 +/- 3.1%; hippuric acidosis, 126.0 +/- 14.4%; p < 0.05). The ratio of plasma deltaAG/deltaHCO3- also exhibited significant differences between the subgroups in acid overproduction (lactic acidosis, 1.5 +/- 0.1; diabetic ketoacidosis, 1.0 +/- 0.1; hippuric acidosis, 0.3 +/- 0.1; p < 0.05). There was an inverse linear correlation between the fractional excretion of anions and the ratio of plasma deltaAG/deltaHCO3- (r2 =-0.89, p < 0.05). In conclusion, determination of the fractional excretion of anions may provide a useful clue to the

  5. The Frequency and Clinical Significance of IDH1 Mutations in Chinese Acute Myeloid Leukemia Patients

    PubMed Central

    Wang, Lili; Li, Meng; Yin, Yue; Yu, Li; Gao, Chunji

    2013-01-01

    Objective Mutations in the gene encoding isocitrate dehydrogenease 1 (IDH1) occur in various hematopoietic tumors including acute myeloid leukemia (AML), myeloproliferative neoplasms and myelodysplastic syndromes. IDH1 mutations are significant in both diagnosis and prognosis of these conditions. In the present study we determined the prevalence and clinical significance of IDH1 mutations in 349 samples from newly diagnosed AML patients. Results Of the 349 AML patient specimens analyzed, 35 (10.03%) were found to have IDH1 mutations including 4 IDH1 R132 mutations and 31 non-R132 mutations. IDH1 non-R132 mutations were largely concentrated within AML-M1 (35.72%, p<0.01). We identified five IDH1 mutations that were novel to AML: (1) c.299 G>A, p.R100Q; (2) c.311G>T, p.G104V; (3) c.322T>C, p.F108L; (4) c.356G>A, p.R119Q; and (5) c.388A>G, p.I130V. In addition, we identified three IDH1 mutations that were previously described in AML. The frequency of IDH1 mutations in AML patients with normal karyotype was 9.9%. IDH1 non-R132 mutations were concurrent with mutations in FLT3-ITD (p<0.01), CEBPA (p<0.01), and NRAS (p<0.01), as well as the overexpression of MN1 (p<0.01) and WT1(p<0.01). The overall survival (OS) in the patients with IDH1 non-R132 mutations compared to patients without IDH1 mutations don't reach statistically significance (median 521 days vs median: not reached; n.s.). Conclusion IDH1 non-R132 mutations occurred frequently in newly diagnosed adult Chinese AML patients, and these mutations were associated with genetic alterations. The OS was not influenced by IDH1 non-R132 mutations in the present study. PMID:24376688

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

    PubMed Central

    2012-01-01

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

  7. Clinically significant drug interactions among HIV-infected patients receiving antiretroviral therapy.

    PubMed

    So-Ngern, Apichot; Montakantikul, Preecha; Manosuthi, Weerawat

    2014-09-01

    We conducted a cross sectional study of the outpatient medical records of 1000 HIV-infected patients receiving antiretroviral therapy (ART) in 2011 to determine the incidence of clinically significant drug interactions (CSDI). The severities of the CSDI were graded following the Micromedex" 2.0 database and the Department of Health and Human Services (DHHS) 2012 HIV treatment guidelines. Three hundred thirty-five patients (34%) had 554 episodes of CSDI. Of which 337 episodes (61%), 163 episodes (29%) and 54 episodes (10%) had grades 2, 3 and 4 severity CSDI, respectively. The CSDI were caused by protease inhibitor (PI)-based drug regimens in 79%, by efavirenz-based regimens in 34% and by nevirapine-based regimens in 10% (p<0.001). The three most common grade 4 CSDI were: a PI with simvastatin (n=24), simvastatin with gemfibrozil (n=24) and didanosine with allopurinol (n=2). The three most common grade 3 CSDI were: a PI with a statin drug except simvastatin (n=56), fenofibrate with a statin drug (n=28) and amlodipine with simvastatin (n=14). On multivariate analysis, risk factors associated with CSDI were: receiving a PI-based regimen (OR 14.44; 95% CI: 9.10-22.88), having dyslipidemia (OR 3.94; 95% CI: 1.89-8.21), having >5 items prescribed at a time (OR 1.80; 95% CI: 1.23-2.63), seeing a doctor >4 times a year (OR 1.72; 95% CI: 1.20-2.46), having hypertension (OR 0.60; 95% CI: 0.37-0.98), having a duration of receiving ART of >5 years (OR 0.46; 95% CI: 0.28-0.77) and having a CD4 count of >200 cells/mm3 (OR 0.46; 95%CI: 0.26-0.84). CSDI were common among HIV-infected patients receiving ARV in our outpatient clinic. Patients having a low CD, count, having dyslipidemia, receiving PI-based ART, having a frequent number of visits per year and having a large number of items prescribed at each visit had a greater chance of a CSDI.

  8. [The significance, development and prospects of healthcare data integration in new drug clinical trials].

    PubMed

    Cai, Hong-wei; Li, Yan-hong; Zhang, Zi-bao; Deng, Ya-zhong

    2015-11-01

    With the deployment of electronic medical records systems, more and more routine clinical data are recorded electronically, which become a potential data source for new drug clinical trials. In this paper, we summarized the opportunities, challenges, obstacles and the latest development in this field.

  9. Nuclear imaging of the breast: translating achievements in instrumentation into clinical use.

    PubMed

    Hruska, Carrie B; O'Connor, Michael K

    2013-05-01

    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.

  10. 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

  11. Biological and clinical significance of tryptophan-catabolizing enzymes in cutaneous T-cell lymphomas

    PubMed Central

    Maliniemi, Pilvi; Dettmer, Katja; Lipsanen, Tuomas; Jeskanen, Leila; Bessede, Alban; Oefner, Peter J.; Kadin, Marshall E.

    2017-01-01

    ABSTRACT Indoleamine 2,3-deoxygenase 1 (IDO1) induces immune tolerance in the tumor microenvironment (TME) and is recognized as a potential therapeutic target. We studied the expression of both IDO1 and the related tryptophan 2,3-dioxygenase (TDO) in several different subtypes of cutaneous T-cell lymphoma (CTCL), and evaluated the kynurenine (KYN) pathway in the local TME and in patient sera. Specimens from the total of 90 CTCL patients, including mycosis fungoides (MF, n = 37), lymphomatoid papulosis (LyP, n = 36), primary cutaneous anaplastic large cell lymphoma (pcALCL, n = 4), subcutaneous panniculitis-like T-cell lymphoma (SPTCL n = 13), and 10 patients with inflammatory lichen ruber planus (LRP), were analyzed by immunohistochemistry (IHC), immunofluorescence (IF), quantitative PCR, and/or liquid chromatography–tandem mass spectrometry (LC–MS/MS). Three CTCL cell lines also were studied. Expression of both IDO1 and TDO was upregulated in CTCL. In MF specimens and in the MF cell line MyLa2000, IDO1 expression exceeded that of TDO, whereas the opposite was true for LyP, ALCL, and corresponding Mac1/2A cell lines. The spectrum of IDO1-expressing cell types differed among CTCL subtypes and was reflected in the clinical behavior. In MF, SPTCL, and LyP, IDO1 was expressed by malignant cells and by CD33+ myeloid-derived suppressor cells, whereas in SPTCL CD163+ tumor-associated macrophages also expressed IDO1. Significantly elevated serum KYN/Trp ratios were found in patients with advanced stages of MF. Epacadostat, an IDO1 inhibitor, induced a clear decrease in KYN concentration in cell culture. These results show the importance of IDO1/TDO-induced immunosuppression in CTCL and emphasize its role as a new therapeutic target.

  12. Pathogenic features of clinically significant coagulase-negative staphylococci in hospital and community infections in Benin.

    PubMed

    Nanoukon, Chimène; Argemi, Xavier; Sogbo, Frédéric; Orekan, Jeanne; Keller, Daniel; Affolabi, Dissou; Schramm, Frédéric; Riegel, Philippe; Baba-Moussa, Lamine; Prévost, Gilles

    2017-01-01

    In West Africa, very little consideration has been given to coagulase negative Staphylococci (CNS). Herein, we describe the features contributing to the pathogenicity of 99 clinically-significant independent CNS isolates associated with infections encountered at the National Teaching Hospital Center of Cotonou (Benin). The pathogenic potentials of nosocomial strains were compared with community strains. S. haemolyticus (44%), S. epidermidis (22%) and S. hominis (7%) were the most frequently isolated while bacteremia (66.7%) and urinary tract infections (24.2%) were the most commonly encountered infections. Most strains were resistant to multiple antibiotics, including penicillin (92%), fosfomycin (81%), methicillin (74%) and trimethoprim-sulfamethoxazole (72%). The most frequently isolated species were also the most frequently resistant to methicillin: S. hominis (100%), S. haemolyticus (93%) and S. epidermidis (67%). Screening of toxic functions or toxin presence revealed hemolytic potential in 25% of strains in over 50% of human erythrocytes in 1h. Twenty-six percent of strains exhibited protease activity with low (5%), moderate (10%) and high activity (11%), while 25% of strains displayed esterase activity. Three percent of strain supernatants were able to lyse 100% of human polymorphonuclear cells after 30min. Polymerase chain reaction and latex agglutination methods revealed staphylococcal enterotoxin C gene expression in 9% of S. epidermidis. A majority of hospital-associated CNS strains (68%) had at least one important virulence feature, compared with only 32% for community-acquired strains. The present investigation confirms that these microorganisms can be virulent, at least in some individual cases, possibly through genetic transfer from S. aureus.

  13. Characteristics, clinical outcome, and prognostic significance of IDH mutations in AML.

    PubMed

    DiNardo, Courtney D; Ravandi, Farhad; Agresta, Sam; Konopleva, Marina; Takahashi, Koichi; Kadia, Tapan; Routbort, Mark; Patel, Keyur P; Mark Brandt; Pierce, Sherry; Garcia-Manero, Guillermo; Cortes, Jorge; Kantarjian, Hagop

    2015-08-01

    The pathophysiology of IDH mutations in tumorigenesis is increasingly described, yet the prognostic significance of IDH1 and IDH2 mutations in AML remains controversial. The primary objective of this study was to define the natural history and prognosis of patients with AML and IDH1 or IDH2 mutations and provide historical survival expectations. A total of 826 patients treated from 2010 to 2014 at a single institution were evaluated, including 167 patients (20%) with AML and IDH1 or IDH2 mutations. Median age was 62 years (range 18-92). There were 59 IDH1-R132, 83 IDH2-R140, and 23 IDH2-R172 mutations. Clinicopathologic characteristics associated with IDH-mutations included older age, less frequent therapy-related status, and increased incidence of intermediate-risk cytogenetics, FLT3-ITD mutations, and NPM1 mutations. Remission rates (CR/CRi) by AML treatment status were: induction, 68%; Salvage-1 (S1), 42%; and Salvage-2 and beyond (S2+), 27%. No difference in response was identified by IDH mutation status. Similarly, overall survival (OS) was not dependent on IDH status within any cohort. The median OS was 15.4 months in induction, 8.7 months in S1, and 4.8 months in S2+. This analysis defines the clinical outcome associated with IDH-mutations in both the front-line and salvage AML treatment settings, and confirms that response rate and OS for both IDH-mutated and IDH wild-type AML patients is comparable. This provides contemporary data to be used for comparison with results of novel investigational (e.g., selective IDH inhibitor) strategies.

  14. 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

  15. Clinical significance of sunitinib-associated macrocytosis in metastatic renal cell carcinoma.

    PubMed

    Bourlon, Maria T; Gao, Dexiang; Trigero, Sara; Clemons, Julia E; Breaker, Kathryn; Lam, Elaine T; Flaig, Thomas W

    2016-12-01

    Increases in the mean corpuscular volume (MCV) have been observed in patients with metastatic renal cell carcinoma (mRCC) on tyrosine kinase inhibitor (TKI) treatment; however, its association with progression-free-survival (PFS) is unknown. We aimed to characterize TKI-associated macrocytosis in mRCC and its relationship with PFS. Retrospective review of data on macrocytosis and thyroid dysfunction on mRCC patients treated with sunitinib and/or sorafenib. These results are evaluated in the context of our previous report on the association of hypothyroidism in this setting. We assessed PFS as clinically defined by the treating physician. Seventy-four patients, 29 of whom received both drugs, were included. A treatment period was defined as time from initiation to discontinuation of either sunitinib or sorafenib; 103 treatment periods [sorafenib (47), sunitinib (56)] were analyzed. Macrocytosis was found in 55 and 8% of sunitinib- and sorafenib-treated patients, respectively, P < 0.001. The median time to developing macrocytosis was 3 months (m, range 1-7). Median PFS in sunitinib-treated patients was 11 m (95% CI: 6-19). Median PFS was higher among those with macrocytosis compared to normocytosis (21 m [95% CI: 11-25] vs. 4 m [95% CI: 3-8] P = 0.0001). Macrocytosis and hypothyroidism were two significant predictors of PFS. The greatest difference in PFS among all patients was observed in patients with both macrocytosis and hypothyroidism (25 m), compared to the normocytic and euthyroid patients (5 m) (P < 0.0001). Sunitinib-related macrocytosis was associated with prolonged PFS, and concurrent development of hypothyroidism and macrocytosis further prolonged PFS. Increased MCV may have a role as a predictive biomarker for sunitinib. Prospective studies accounting for other known prognostic factors are needed to confirm this finding.

  16. Achieving clinical statement interoperability using R-MIM and archetype-based semantic transformations.

    PubMed

    Kilic, Ozgur; Dogac, Asuman

    2009-07-01

    Effective use of electronic healthcare records (EHRs) has the potential to positively influence both the quality and the cost of health care. Consequently, sharing patient's EHRs is becoming a global priority in the healthcare information technology domain. This paper addresses the interoperability of EHR structure and content. It describes how two different EHR standards derived from the same reference information model (RIM) can be mapped to each other by using archetypes, refined message information model (R-MIM) derivations, and semantic tools. It is also demonstrated that well-defined R-MIM derivation rules help tracing the class properties back to their origins when the R-MIMs of two EHR standards are derived from the same RIM. Using well-defined rules also enable finding equivalences in the properties of the source and target EHRs. Yet an R-MIM still defines the concepts at the generic level. Archetypes (or templates), on the other hand, constrain an R-MIM to domain-specific concepts, and hence, provide finer granularity semantics. Therefore, while mapping clinical statements between EHRs, we also make use of the archetype semantics. Derivation statements are inferred from the Web Ontology Language definitions of the RIM, the R-MIMs, and the archetypes. Finally, we show how to transform Health Level Seven clinical statement instances to EHRcom clinical statement instances and vice versa by using the generated mapping definitions.

  17. De Garengeot's hernia in an 82-year-old man: a case report and clinical significance

    PubMed Central

    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

  18. Lies, damned lies and statistics: Clinical importance versus statistical significance in research.

    PubMed

    Mellis, Craig

    2017-02-28

    Correctly performed and interpreted statistics play a crucial role for both those who 'produce' clinical research, and for those who 'consume' this research. Unfortunately, however, there are many misunderstandings and misinterpretations of statistics by both groups. In particular, there is a widespread lack of appreciation for the severe limitations with p values. This is a particular problem with small sample sizes and low event rates - common features of many published clinical trials. These issues have resulted in increasing numbers of false positive clinical trials (false 'discoveries'), and the well-publicised inability to replicate many of the findings. While chance clearly plays a role in these errors, many more are due to either poorly performed or badly misinterpreted statistics. Consequently, it is essential that whenever p values appear, these need be accompanied by both 95% confidence limits and effect sizes. These will enable readers to immediately assess the plausible range of results, and whether or not the effect is clinically meaningful.

  19. [The Coordinating Centres for Clinical Trials Network. Objectives and significance for research sites].

    PubMed

    Bruns, I; Maier-Lenz, H; Wolff, S

    2009-04-01

    In the late 1990s a funding program was set up by the federal German government to help keep stride with developments in the international research arena. Within this programme, Coordinating Centres for Clinical Trials ("Koordinierungszentren für Klinische Studien", KKS) were established at 12 German universities aiming at supporting all processes of academic clinical trials according to international standards. A close network infrastructure was chosen in order to reap maximum benefit from synergy effects and to promote the harmonisation of standards. Continuing to grow, the KKS Network currently has 16 research institutions as members. More than 400 employees within the KKS Network provide scientific services to clinical trials at universities, hospitals and in industry. In cooperation with study clinics, surgeries, study groups and competence networks in medicine within Europe and beyond, the KKS supports many different research projects covering all areas of medicine. The KKS Network contributes expertise to legislative processes within Germany and Europe through its work in professional committees and working groups. A wide range of education and training concepts supports clinical research as a scientific field in its own right. After nearly ten years the KKS Network has established itself as an indispensable partner in the field of clinical research.

  20. Neuroblastoma and bone metastases: clinical significance and prognostic value of Dickkopf 1 plasma levels.

    PubMed

    Granchi, Donatella; Corrias, Maria Valeria; Garaventa, Alberto; Baglìo, Serena Rubina; Cangemi, Giuliana; Carlini, Barbara; Paolucci, Paolo; Giunti, Armando; Baldini, Nicola

    2011-01-01

    The critical role of the Wnt pathway inhibition in sustaining the onset of bone lesions has been demonstrated in a variety of bone diseases and tumors, and it has been associated with cancer aggressiveness. We have previously demonstrated that neuroblastoma cells express Dickkopf 1 (Dkk1), an inhibitor of the canonical Wnt pathway which prevents the differentiation of bone-forming cells. Since Dkk1 is a secreted factor, it could have potential clinical application as tumor marker for detecting bone metastasis and monitoring of disease. In this study, we investigated the diagnostic and prognostic value of Dkk1 plasma levels in 92 children affected by neuroblastoma, including 32 with bone metastases. Fifty-seven children hospitalized for minor surgical problems served as control group. Circulating levels of Dkk1 were higher in healthy children than in normal adults and were comparable to those found in adult patients with aggressive tumors. No significant differences were found between neuroblastoma patients and controls and between patients with and without bone metastases. However, when only patients with metastatic neuroblastoma were considered, the highest Dkk1 levels were detected in patients that poorly responded to induction chemotherapy and in subjects with unamplified MYCN and three or more different metastatic sites. The 'Receiver Operating Characteristic' curve enabled us to identify a threshold value to distinguish patients who were unresponsive to induction treatment. The relationship between Dkk1 and drug resistance was supported by in vitro experiments, since an increased sensitivity to doxorubicin was found in neuroblastoma cells releasing low Dkk1 levels, either constitutively or experimentally following the treatment with specific siRNA. In conclusion, Dkk1 is released by neuroblastoma cells and is able to affect the balance between osteoblastogenesis and osteoclastogenesis, thus favoring the onset of osteolytic metastases. Nevertheless, Dkk1 plasma

  1. Clinically significant differences in acute pain measured on self-report pain scales in children

    PubMed Central

    Tsze, Daniel S.; Hirschfeld, Gerrit; von Baeyer, Carl L.; Bulloch, Blake; Dayan, Peter S.

    2015-01-01

    Objectives The objective was to determine the minimum and ideal clinically significant differences (MCSD, ICSD) of the Faces Pain Scale–Revised (FPS-R) and the Color Analog Scale (CAS) in children and to identify any differences in these estimates based on patient characteristics. Methods This was a prospective study of children aged 4 to 17 years with acute pain presenting to two urban pediatric emergency departments. Participants self-reported their pain severity using the FPS-R and CAS and qualitatively described their changes in pain. Changes in pain score reported using the FPS-R and CAS that were associated with “a little less” and “much less” pain (MCSD and ICSD, respectively) were identified using a receiver operating characteristic–based method and expressed as raw change score and percent reductions. Estimates of MCSD and ICSD were determined for each category of initial pain severity (mild, moderate, and severe) and patient characteristics (age, sex, and ethnicity). Post hoc exploratory analyses evaluated categories of race, primary language, and etiology of pain. Results A total of 314 children with acute pain were enrolled; mean (±SD) age was 9.8 (±3.8) years. The FPS-R raw change score and percent reduction MCSD estimates were 2/10 and 25%, with ICSD estimates of 3/10 and 60%. For the CAS, raw change score and percent reduction MCSD estimates were 1/10 and 15%, with ICSD estimates of 2.75/10 and 52%. For both scales, raw change score and percent reduction estimates of the MCSD remained unchanged in children with either moderate or severe pain. For both scales, estimates of ICSD were not stable across categories of initial pain severity. There was no difference in MCSD or ICSD based on age, sex, ethnicity, race, primary language, or etiology of pain. Conclusions The MCSD estimates can be expressed as raw change score and percent reductions for the FPS-R and CAS. These estimates appear stable for children with moderate to severe pain

  2. 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

  3. Significance of Kampo, Japanese traditional medicine, in the treatment of obesity: basic and clinical evidence.

    PubMed

    Yamakawa, Jun-Ichi; Moriya, Junji; Takeuchi, Kenji; Nakatou, Mio; Motoo, Yoshiharu; Kobayashi, Junji

    2013-01-01

    The cause of obesity includes genetic and environmental factors, including cytokines derived from adipocytes (adipo-cytokines). Although drug therapy is available for obesity, it is highly risky. Our main focus in this review is on the traditional form of Japanese medicine, Kampo, in the treated of obesity. Two Kampo formulas, that is, bofutsushosan () and boiogito (), are covered by the national health insurance in Japan for the treatment of obesity. Various issues related to their action mechanisms remain unsolved. Considering these, we described the results of basic experiments and presented clinical evidence and case reports on osteoarthritis as examples of clinical application of their two Kampo medicine. Traditional medicine is used not only for treatment but also for prevention. In clinical practice, it is of great importance to prove the efficacy of combinations of traditional medicine and Western medicine and the utility of traditional medicine in the attenuation of adverse effects of Western medicine.

  4. Progress in Metabolomics Standardisation and its Significance in Future Clinical Laboratory Medicine

    PubMed Central

    Koal, Therese

    2016-01-01

    Today, the technology of ‘targeted’ based metabolomics is pivotal in the clinical analysis workflow as it provides information of metabolic phenotyping (metabotypes) by enhancing our understanding of metabolism of complex diseases, biomarker discovery for disease development, progression, treatment, and drug function and assessment. This review is focused on surveying and providing a gap analysis on metabolic phenotyping with a focus on targeted based metabolomics from an instrumental, technical point-of-view discussing the state-of-the-art instrumentation, pre- to post- analytical aspects as well as an overall future necessity for biomarker discovery and future (pre-) clinical routine application. PMID:28149265

  5. On achieving a clinically useful D-T neutron isocentric therapy system

    SciTech Connect

    Hilton, J.L.; Hendry, G.O.

    1981-04-01

    The Cyclotron Corporation's Model 4100 Neutron Cancer Therapy System with its output of 8 x 10/sup 12/ (14 MeV) neutron/sec designed for 500 hours is made up of: a factory recyclable miniature 200 kV sealed tube which radially accelerates up to 450 mA of deuterium and tritium ions from four duoplasmatron-type ion sources onto a central target; hand changeable radiation collimators; boronated hydrogenous shielding; isocentric gantry mounting; clinical diagnostics; and controls. The self-contained gas handling system which provides the needed differential gas pressure also stores, pumps, cleans, and recycles the D-T inventory. It is composed of a reversible getter high vacuum pump, a selective noble gas sputter ion pump, and a specialized uranium trap which, by controlled thermal decomposition of uranium hydride, regulates the ion source pressure. A D-T gas inventory of 3.7 k curies provides beam-on time of about three hours, while the gas recycle requires one to two hours. The four-sided target is made up from an array of heat transfer-optimized small copper tubes and their metal surface cladding which results in relatively high neutron output and long target life. The double vacuum walls, providing redundant tritium containment, are combined with other safety features.

  6. 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…

  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. Prognostic and Clinical Significance of miRNA-205 in Endometrioid Endometrial Cancer.

    PubMed

    Wilczynski, Milosz; Danielska, Justyna; Dzieniecka, Monika; Szymanska, Bozena; Wojciechowski, Michal; Malinowski, Andrzej

    2016-01-01

    Endometrial cancer is one of the most common malignancies of the reproductive female tract, with endometrioid endometrial cancer being the most frequent type. Despite the relatively favourable prognosis in cases of endometrial cancer, there is a necessity to evaluate clinical and prognostic utility of new molecular markers. MiRNAs are small, non-coding RNA molecules that take part in RNA silencing and post-transcriptional regulation of gene expression. Altered expression of miRNAs may be associated with cancer initiation, progression and metastatic capabilities. MiRNA-205 seems to be one of the key regulators of gene expression in endometrial cancer. In this study, we investigated clinical and prognostic role of miRNA-205 in endometrioid endometrial cancer. After total RNA extraction from 100 archival formalin-fixed paraffin-embedded tissues, real-time quantitative RT-PCR was used to define miRNA-205 expression levels. The aim of the study was to evaluate miRNA-205 expression levels in regard to patients' clinical and histopathological features, such as: survival rate, recurrence rate, staging, myometrial invasion, grading and lymph nodes involvement. Higher levels of miRNA-205 expression were observed in tumours with less than half of myometrial invasion and non-advanced cancers. Kaplan-Maier analysis revealed that higher levels of miRNA-205 were associated with better overall survival (p = 0,034). These results indicate potential clinical utility of miRNA-205 as a prognostic marker.

  9. Prognostic and Clinical Significance of miRNA-205 in Endometrioid Endometrial Cancer

    PubMed Central

    Wilczynski, Milosz; Wojciechowski, Michal; Malinowski, Andrzej

    2016-01-01

    Endometrial cancer is one of the most common malignancies of the reproductive female tract, with endometrioid endometrial cancer being the most frequent type. Despite the relatively favourable prognosis in cases of endometrial cancer, there is a necessity to evaluate clinical and prognostic utility of new molecular markers. MiRNAs are small, non-coding RNA molecules that take part in RNA silencing and post-transcriptional regulation of gene expression. Altered expression of miRNAs may be associated with cancer initiation, progression and metastatic capabilities. MiRNA-205 seems to be one of the key regulators of gene expression in endometrial cancer. In this study, we investigated clinical and prognostic role of miRNA-205 in endometrioid endometrial cancer. After total RNA extraction from 100 archival formalin-fixed paraffin-embedded tissues, real-time quantitative RT-PCR was used to define miRNA-205 expression levels. The aim of the study was to evaluate miRNA-205 expression levels in regard to patients’ clinical and histopathological features, such as: survival rate, recurrence rate, staging, myometrial invasion, grading and lymph nodes involvement. Higher levels of miRNA-205 expression were observed in tumours with less than half of myometrial invasion and non-advanced cancers. Kaplan-Maier analysis revealed that higher levels of miRNA-205 were associated with better overall survival (p = 0,034). These results indicate potential clinical utility of miRNA-205 as a prognostic marker. PMID:27737015

  10. Antibiotic use in acne vulgaris and rosacea: clinical considerations and resistance issues of significance to dermatologists.

    PubMed

    Del Rosso, James Q; Leyden, James J; Thiboutot, Diane; Webster, Guy F

    2008-08-01

    Antibiotics are commonly prescribed in dermatology practice for a variety of disorders, including acne vulgaris and rosacea. Importantly, they often are used long-term for these inflammatory dermatoses. Changes in bacterial ecology related to antibiotic prescribing have led to the decreased sensitivity of some bacterial organisms, such as Propionibacterium acnes, to antibiotics commonly prescribed by dermatologists. The potential clinical outcomes of altered bacterial sensitivities may vary among specific disease states and include decreased therapeutic response and the need to alter approaches in disease management. Additionally, changing patterns of antibiotic sensitivity and the emergence of more virulent pathogens, such as community-acquired methicillin-resistant Staphylococcus aureus, macrolide-resistant staphylococci and streptococci, and mupirocin-resistant S aureus, have led to marked changes in how clinicians use antibiotics in clinical practice. This article reviews antibiotic prescribing in dermatology practice and provides important clinical perspectives and recommendations to preserve the therapeutic value of antibiotics based on a thorough review of current literature and clinical experience.

  11. 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

  12. 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.

  13. Achieving hemostasis with topical hemostats: making clinically and economically appropriate decisions in the surgical and trauma settings.

    PubMed

    Schreiber, Martin A; Neveleff, Deborah J

    2011-11-01

    Achieving hemostasis is a crucial focus of clinicians working in surgical and trauma settings. Topical hemostatic agents-including mechanical hemostats, active hemostats, flowable hemostats, and fibrin sealants-are frequently used in efforts to control bleeding, and new options such as hemostatic dressings, initially used in combat situations, are increasingly being used in civilian settings. To achieve successful hemostasis, a number of vital factors must be considered by surgeons and perioperative nurses, such as the size of the wound; bleeding severity; and the efficacy, possible adverse effects, and method of application of potential hemostatic agents. Understanding how and when to use each of the available hemostatic agents can greatly affect clinical outcomes and help to limit the overall cost of treatment.

  14. The antiplatelet effects of nitrates: is it of clinical significance in patients with cardiovascular disease?

    PubMed

    Zhou, Rui-Hai; Frishman, William H

    2010-01-01

    Organic nitrates have been used for over a century in cardiovascular therapy and are still widely used in the treatment of acute coronary syndromes, chronic angina pectoris, and congestive heart failure. Nitrates, together with sodium nitroprusside, generally referred to as nitrovasodilators, exert their biologic effects via the release of nitric oxide. They are also known as nitric oxide donors. The mechanism of action of these drugs is traditionally believed to lie in their arterial vasodilation and venodilation effects, resulting in an improvement of coronary artery blood supply and/or reduction of cardiac workload in the treatment of coronary artery disease and congestive heart failure. Recently it has been recognized that these drugs also have intrinsic antiplatelet and antithrombotic effects, demonstrated both in vitro and in vivo, which would add further rationale for the use of these drugs in atherothrombotic diseases. Research has shown that nitrovasodilators can nonselectively inhibit platelet aggregation induced by multiple stimuli. However, clinical trials have yielded conflicting results regarding clinical outcome, especially with long-term nitrate use. The potentially beneficial effects of nitrates could be negated by the development of tolerance and the generation of deleterious oxidative stress causing endothelial dysfunction during continuous nitrate administration. Much progress has been made in the development of new nitric oxide donors devoid of oxidant-generating properties. Novel combination therapies with nitrovasodilators plus antioxidants or agents with antioxidant properties have shown promise in reducing or reversing tolerance, potentiating antiplatelet effects, and improving clinical outcome. It is expected that clinical introduction of novel nitrovasodilator regimens will provide a new approach to the prevention and treatment of atherothrombotic diseases. Large-scale clinical trials will ultimately provide the evidence-based answers.

  15. 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

  16. Digit Symbol-Incidental Learning in the WAIS-III: construct validity and clinical significance.

    PubMed

    Joy, Stephen; Kaplan, Edith; Fein, Deborah

    2003-05-01

    We analyzed WAIS-III/WMS-III standardization data for evidence of the construct validity and clinical utility of the Digit Symbol-Incidental Learning procedures (Pairing and Free Recall). Scores on both tests correlated moderately with WMS-III memory index scores (mean r=.38 for Pairing and .36 for Free Recall). Cutoff scores can be used to identify younger and older adults likely to suffer from memory impairment. In the standardization sample (which excludes neurological patients), these have moderate positive predictive power (averaging .56 if either test yields a positive finding), moderate negative predictive power (.76), and high specificity (.88), but low sensitivity (.35). In a clinical sample, the same cutoff scores were much more sensitive, correctly identifying 88% of a group of patients with Alzheimer's Disease. Examinees who obtain these low scores should receive follow-up memory testing. Very high scores are associated with a reduced risk of memory impairment.

  17. 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

  18. Clinical Significance and Pathogenesis of Staphylococcal Small Colony Variants in Persistent Infections

    PubMed Central

    Becker, Karsten; Löffler, Bettina

    2016-01-01

    SUMMARY 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. Prevalence and Dimensions of Complete Sella Turcica Bridges and Its Clinical Significance.

    PubMed

    Brahmbhatt, Ritesh Jyotindra; Bansal, Minaxi; Mehta, Chandrakant; Chauhan, Ketan Bharat

    2015-12-01

    The ossification of ligamentous structures in various part of the body may result in clinical problems. The complete sella turcica bridge corresponds to the complete ossification of the interclinoid ligaments. Fifty dry adult skull bones were studied for presence of ossified interclinoid ligaments. Three skull bones show sella turcica bridge, of which one shows bilateral and two show unilateral. The ligamentous or bony interclinoid connections have important neuronal and vascular relations and are both clinically and surgically important. The knowledge of detailed anatomy of the interclinoid ligament can increase the success of diagnostic evaluation and surgical approaches to the region. The existence of a bony caroticoclinoid foramen may cause compression, tightening, or stretching of the internal carotid artery. Further, removing the anterior clinoid process is an important step in regional surgery; the presence of a bony caroticoclinoid foramen may have high risk.

  20. Clinically significant persistence and enlargement of an antenatally diagnosed isolated choroid plexus cyst.

    PubMed

    Becker, S; Niemann, G; Schöning, M; Wallwiener, D; Mielke, G

    2002-12-01

    Isolated choroid plexus cysts are usually diagnosed at the time of screening ultrasonography during the second trimester. While they raise the question of underlying chromosomal abnormalities, their clinical course is almost invariably benign with complete resolution often by the third trimester. We report the highly unusual case of a choroid plexus cyst diagnosed at 14 weeks of gestational age with subsequent further enlargement of the cyst, necessitating postpartum neurosurgical intervention.

  1. Clinical significance of antibodies to Ro52/TRIM21 in systemic sclerosis

    PubMed Central

    2012-01-01

    Introduction Autoantibodies to Ro52 recently identified as TRIM21 are among the most common autoantibodies in systemic autoimmune rheumatic diseases, but their clinical association remains poorly understood. We undertook this study to determine the clinical and serologic associations of anti-Ro52/TRIM21 antibodies in patients with systemic sclerosis (SSc). Methods Detailed clinical data and sera from 963 patients with SSc enrolled in a multicenter cohort study were collected and entered into a central database. Antibodies to Ro52/TRIM21 and other autoantibodies were detected with an addressable laser-bead immunoassay and different enzyme-linked immunosorbent assay (ELISA) systems. Associations between anti-Ro52/TRIM21 antibodies and clinical and other serologic manifestations of SSc were investigated. Results Anti-Ro52/TRIM21 antibodies were present in 20% of SSc patients and overlapped with other main SSc-related antibodies, including anti-centromere (by immunofluorescence and centromere protein (CENP)-A and CENP-B ELISA), anti-topoisomerase I, anti-RNA polymerase III, and anti-Pm/Scl antibodies. Anti-Ro52/TRIM21 antibodies were strongly associated with interstitial lung disease (odds ratio (OR), 1.53; 95% confidence interval (CI), 1.11 to 2.12; P = 0.0091) and overlap syndrome (OR, 2.06; 95% CI, 1.01 to 4.19; P = 0.0059). Conclusions Anti-Ro52/TRIM21 antibodies were the second most common autoantibodies in this SSc cohort. In SSc, anti-Ro52/TRIM21 antibodies may be a marker of interstitial lung disease and overlap syndrome. PMID:22394602

  2. 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

  3. Significance of Kampo, Japanese Traditional Medicine, in the Treatment of Obesity: Basic and Clinical Evidence

    PubMed Central

    Yamakawa, Jun-ichi; Moriya, Junji; Takeuchi, Kenji; Nakatou, Mio; Motoo, Yoshiharu; Kobayashi, Junji

    2013-01-01

    The cause of obesity includes genetic and environmental factors, including cytokines derived from adipocytes (adipo-cytokines). Although drug therapy is available for obesity, it is highly risky. Our main focus in this review is on the traditional form of Japanese medicine, Kampo, in the treated of obesity. Two Kampo formulas, that is, bofutsushosan (防風通聖散) and boiogito (防己黄耆湯), are covered by the national health insurance in Japan for the treatment of obesity. Various issues related to their action mechanisms remain unsolved. Considering these, we described the results of basic experiments and presented clinical evidence and case reports on osteoarthritis as examples of clinical application of their two Kampo medicine. Traditional medicine is used not only for treatment but also for prevention. In clinical practice, it is of great importance to prove the efficacy of combinations of traditional medicine and Western medicine and the utility of traditional medicine in the attenuation of adverse effects of Western medicine. PMID:23662155

  4. Prevalence and clinical significance of occult fractures in children with radiograph-negative acute ankle injury

    PubMed Central

    Najaf-Zadeh, Abolfazl; Nectoux, Eric; Dubos, François; Happiette, Laurent; Demondion, Xavier; Gnansounou, Magloire; Herbaux, Bernard; Martinot, Alain

    2014-01-01

    Background and purpose Plain radiographs may fail to reveal an ankle fracture in children because of developmental and anatomical characteristics. In this systematic review and meta- analysis, we estimated the prevalence of occult fractures in children with acute ankle injuries and clinical suspicion of fracture, and assessed the diagnostic accuracy of ultrasound (US) in the detection of occult fractures. Methods We searched the literature and included studies reporting the prevalence of occult fractures in children with acute ankle injuries and clinical suspicion of fracture. Proportion meta-analysis was performed to calculate the pooled prevalence of occult fractures. For each individual study exploring the US diagnostic accuracy, we calculated US operating characteristics. Results 9 studies (involving 187 patients) using magnetic resonance imaging (MRI) (n = 5) or late radiographs (n = 4) as reference standard were included, 2 of which also assessed the diagnostic accuracy of US. Out of the 187 children, 41 were found to have an occult fracture. The pooled prevalence of occult fractures was 24% (95% CI: 18–31). The operating characteristics for detection of occult ankle fractures by US ranged in positive likelihood ratio (LR) from 9 to 20, and in negative LR from 0.04 to 0.08. Interpretation A substantial proportion of fractures may be overlooked on plain radiographs in children with acute ankle injuries and clinical suspicion of fracture. US appears to be a promising method for detection of ankle fractures in such children when plain radiographs are negative. PMID:24875057

  5. Proficiency testing linked to the national reference system for the clinical laboratory: a proposal for achieving accuracy.

    PubMed

    Lasky, F D

    1992-07-01

    I propose using proficiency testing (PT) to achieve one of the important goals of CLIA: accurate and reliable clinical testing. Routine methods for the clinical laboratory are traceable to Definitive (DM) or Reference Methods (RM) or to Methodological Principles (MP) through a modification of the National Reference System for the Clinical Laboratory. PT is the link used to monitor consistent field performance. Although PT has been effective as a relative measure of laboratory performance, the technical limitations of PT fluids and of routine methods currently in use make it unlikely that PT alone can be used as a reliable measure of laboratory accuracy. Instead, I recommend calibration of routine systems through correlation to DM, RM, or MP with use of patients' specimens. The manufacturer is in the best position to assume this responsibility because of also being responsible for consistent, reliable product. Analysis of different manufactured batches of reagent would be compared with predetermined goals for precision and accuracy, as illustrated with data from product testing of Kodak Ektachem clinical chemistry slides. Adoption of this proposal would give manufacturers of PT materials, manufacturers of analytical systems, PT providers, and government agencies time to understand and resolve sources of error that limit the utility of PT for the job required by law.

  6. Identification of Variants in Breast Cancer Susceptibility Genes and Determination of Functional and Clinical Significance of Novel Mutations

    DTIC Science & Technology

    2014-10-01

    cancer susceptibility genes in over 30% of patients with early onset breast cancer. However, only rare patients (2.5%) have definitively actionable...CONTRACT NUMBER Genes and Determination of Functional and Clinical 5b. GRANT NUMBER W81XWH-13-1-0338 Significance of Novel Mutations 5c...Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Purpose: Clinical testing for germline variation in multiple cancer susceptibility genes is

  7. 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

  8. Bicuspid aortic valve aortopathy in adults: Incidence, etiology, and clinical significance.

    PubMed

    Michelena, Hector I; Della Corte, Alessandro; Prakash, Siddharth K; Milewicz, Dianna M; Evangelista, Artur; Enriquez-Sarano, Maurice

    2015-12-15

    Bicuspid aortic valve is the most common congenital heart defect and is associated with an aortopathy manifested by dilatation of the ascending thoracic aorta. The clinical consequences of this aortopathy are the need for periodic monitoring of aortic diameters, elective prophylactic surgical aortic repair, and the occurrence of aortic dissection or rupture. This review describes the current knowledge of BAV aortopathy in adults, including incidence, pathophysiologic insights into its etiology, contemporary hypothesis-generating observations into its complications, and recommendations for monitoring and intervention.

  9. Clinical significance of airway mucus hypersecretion in chronic obstructive pulmonary disease

    PubMed Central

    Tian, Pan-wen; Wen, Fu-qiang

    2015-01-01

    Airway mucus hypersecretion is one of the most important features of chronic obstructive pulmonary disease (COPD). Airway mucus hypersecretion in COPD patients results in outcomes such as rapid decline of lung function, poor quality of life, and high rate of acute exacerbation, hospitalization and mortality. Nonpharmacologic treatments for airway mucus hypersecretion in COPD include smoking cessation and physical rehabilitation. Pharmacologic therapies include expectorants, mucolytics, methylxanthines, beta-adrenergic receptor agonists, anticholinergics, glucocorticoids, phosphodiesterase-4 inhibitors, antioxidants, and antibiotics. Novel drugs with promising prospects are currently under clinical trials. PMID:27847895

  10. A variant of the classical superficial brachioulnoradial artery: morphology and clinical significances.

    PubMed

    Ariyo, Olutayo; Fenderson, Bruce

    2016-08-01

    We report a superficial brachioulnoradial artery (SBURA) presenting as a variant of the normal, originating from the proximal third of the right brachial artery of a 75-year-old female cadaver which bifurcated yielding a brachiointerosseous artery laterally and a SBURA medially, and the latter bifurcating 5 cm proximal to the elbow yielding a brachioradial artery laterally and the superficial brachioulnar artery medially, resulting in the formation of three instead of two brachial arteries as in the classical SBURA said to bifurcate at the elbow into the radial and ulnar arteries. Clinical implications of this variant are discussed.

  11. Biomarkers: important clues to the pathogenesis of infantile haemangioma and their clinical significance.

    PubMed

    Jia, Jun; Zhao, Yi Fang

    2010-01-01

    Infantile haemangioma is the most common tumour of infancy, yet the pathogensis of this lesion remains unknown and the predictable life cycle is poorly understood. Though much new information on infantile haemangioma has emerged over the past decade, researchers continue to debate the fundamental features; including cells of origin, nonrandom distribution, and mechanisms regulating the sometimes explosive growth and slow involution. The development of biomarkers has shed light on the pathogenesis and management of infantile haemangioma. Several useful biomarkers and their suggestions as to the aetiology of infantile haemangioma are reviewed. In addition, the application in clinical diagnosis and choice of treatment methods of infantile haemangioma is summarised.

  12. Immunological and clinical significance of HLA class I antigen processing machinery component defects in malignant cells

    PubMed Central

    Concha-Benavente, Fernando; Srivastava, Raghvendra; Ferrone, Soldano; Ferris, Robert L.

    2017-01-01

    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

  13. History and clinical significance of mechanical symptoms in blistering dermatoses: a reappraisal.

    PubMed

    Grando, Sergei A; Grando, Alexander A; Glukhenky, Boris T; Doguzov, Vasiliy; Nguyen, Vu Thuong; Holubar, Karl

    2003-01-01

    In the era before the advent of routine microscopy and immunopathology, mechanical symptoms were described in an attempt to facilitate clinical diagnosis of blistering dermatoses. A plethora of eponyms and signs were described, but no proper original quotations exist. All the eponyms haunt the student and specialist. In the case of an ominous and, therefore, very important clinical phenomenon termed the Nikolskiy sign, this creates confusion about the specific meaning of the term, obscuring diagnosis and delaying initiation of an adequate treatment of pemphigus. We try to set this record straight and go to the sources. Russian, German, French, and English, at the least, are required to properly interpret the relevant descriptions. We provide an accurate interpretation of the major mechanical symptoms pathognomonic for acantholysis, dermoepidermal separation, and peeling of the entire epidermis. Correct performance of the tests and proper interpretation of the results can serve as an invaluable diagnostic tool to assist in the preliminary bedside diagnosis of serious and potentially lethal bullous dermatoses.

  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.

  15. Determination of clinical significance of coagulase-negative staphylococci in blood cultures.

    PubMed

    Karakullukçu, Asiye; Kuşkucu, Mert Ahmet; Ergin, Sevgi; Aygün, Gökhan; Midilli, Kenan; Küçükbasmaci, Ömer

    2017-03-01

    The aim of this study was to investigate the criteria used to distinguish coagulase-negative staphylococci (CoNS) bacteremia from contamination. We evaluated 162 adult patients with CoNS-positive blood cultures (BCs). Of the 162 patients, 35 (21.6%) had at least 2 positive BCs and 127 (78.4%) had a single positive BC. According to the Laboratory-Confirmed Bloodstream Infection (LCBI) criteria, 24 (14.8%) patients with the same species of CoNS had true bacteremia, and 138 (85.2%) patients had contaminants. Despite the detection of the same CoNS species, 9 of the 24 patients had different CoNS genotypes. Using clinical assessments, only 20 patients were diagnosed with true bacteremia, 8 of them had a single positive BC. We concluded that only using the LCBI criteria or clinical evaluations of a patient were not sufficient to distinguish CoNS bacteremia from contamination. Molecular identification should also be performed as a diagnostic laboratory parameter for CoNS bacteremia.

  16. Paroxysmal Atrial Fibrillation in the Course of Acute Pulmonary Embolism: Clinical Significance and Impact on Prognosis

    PubMed Central

    Krajewska, Agnieszka; Kiluk, Izabela; Kosacka, Urszula; Krajewski, Jacek; Musial, Wlodzimierz Jerzy

    2017-01-01

    The relationship and clinical implications of atrial fibrillation (AF) in acute pulmonary embolism (PE) are poorly investigated. We aimed to analyze clinical characteristics and prognosis in PE patients with paroxysmal AF episode. Methods. From the 391 patients with PE 31 subjects with paroxysmal AF were selected. This group was compared with patients with PE and sinus rhythm (SR) and 32 patients with PE and permanent AF. Results. Paroxysmal AF patients were the oldest. Concomitant DVT varies between groups: paroxysmal AF 32.3%, SR 49.5%, and permanent AF 28.1% (p = 0.02). The stroke history frequency was 4.6% SR, 12.9% paroxysmal AF, and 21.9% permanent AF (p < 0.001). Paroxysmal AF comparing to permanent AF and SR individuals had higher estimated SPAP (56 versus 48 versus 47 mmHg, p = 0.01) and shorter ACT (58 versus 65 versus 70 ms, p = 0.04). Patients with AF were more often classified into high-risk group according to revised Geneva score and sPESI than SR patients. In-hospital mortality was lower in SR (5%) and paroxysmal AF (6.5%) compared to permanent AF group (25%) (p < 0.001). Conclusions. Patients with PE-associated paroxysmal AF constitute a separate population. More severe impairment of the parameters reflecting RV afterload may indicate relation between PE severity and paroxysmal AF episode. Paroxysmal AF has no impact on short-term mortality. PMID:28280732

  17. Night eating syndrome in young adults: delineation from other eating disorders and clinical significance.

    PubMed

    Fischer, Sophia; Meyer, Andrea H; Hermann, Ernst; Tuch, Alex; Munsch, Simone

    2012-12-30

    The Night Eating Syndrome (NES) is a recently described disordered eating style whose status in current diagnostic systems needs to be further clarified. The aim of this study was to increase knowledge about the clinical features of NES in a sample of 1514 young adults aged 18-26 years from the general population who participated in an anonymous Internet survey. We first examined characteristics of NES and tried to delineate it from healthy controls as well as from other eating disorders in terms of socio-demography, eating disorder pathology and general psychopathology. Second, we attempted to further clarify the clinical utility of the NES by assessing the degree of distress as well as impairment. Twenty (1.3%) participants with NES were identified and there was only modest overlap between NES and both Binge Eating Disorder (BED) and Bulimia nervosa (BN) according to questionnaire-based DSM-IV criteria. Compared to healthy controls, NES individuals reported more pronounced eating disorder pathology as well as general psychopathology (depressive symptoms, chronic social stress). NES seems to be associated with considerable distress and impairment. Implications for the validity and classification of NES are discussed.

  18. Clinical significance and antimicrobial susceptibilities of Aerococcus sanguinicola and Aerococcus urinae.

    PubMed

    Shelton-Dodge, Kelsey; Vetter, Emily A; Kohner, Peggy C; Nyre, Lisa M; Patel, Robin

    2011-08-01

    A retrospective chart review was performed on 92 patients from whom 118 isolates of Aerococcus sanguinicola (n = 52) or Aerococcus urinae (n = 66) were obtained from urine cultures between October 2007 and June 2008 to assess clinical presentation and antimicrobial susceptibilities. The mean patient age was 82 (range 24-101) years. The majority was female (76% and 87% for A. sanguinicola and A. urinae, respectively) and institutionalized (61% and 60%, respectively). The majority of male patients had underlying prostatic disease (55% and 63%, respectively). Thirty-one of 46 patients with A. sanguinicola and 45 of 57 patients with A. urinae isolated from the urine had a clinical diagnosis of urinary tract infection. One subject had A. sanguinicola isolated from blood cultures. A. sanguinicola and A. urinae had low ceftriaxone, penicillin, and vancomycin MICs. MICs to erythromycin and levofloxacin were ≥0.5 and >4 μg/mL in 41% and 78% of A. sanguinicola and 17% and 23% of A. urinae isolates, respectively. In conclusion, A. sanguinicola and A. urinae are not infrequent causes of urinary tract infection and most A. sanguinicola isolates have elevated MICs to levofloxacin.

  19. Drug-induced sleep endoscopy changes snoring management plan very significantly compared to standard clinical evaluation.

    PubMed

    Pilaete, Karen; De Medts, Joris; Delsupehe, Kathelijne Godelieve

    2014-05-01

    Drug-induced sleep endoscopy (DISE) is a new tool in the work-up of patients with sleep-disordered breathing (SDB). We assessed the impact of DISE on the treatment plan of snoring patients. This is a single institution prospective longitudinal clinical trial. The setting is a private teaching hospital. A consecutive series of 100 snoring patients prospectively underwent a standardised questionnaire, clinical examination, rhinomanometry, allergy skin prick testing, DISE and polysomnography. Management plan before and after DISE evaluation was compared. In 61 patients (excluding 16 patients sent for continuous positive airway pressure, three patients refused sleep endoscopy and 20 were lost to follow-up), we compared the treatment plans. DISE showed single level airway collapse in 13 and multilevel collapse in 48 patients. The site of flutter did not add additional information as compared to the pattern and the location of the collapse. After DISE, the initial management plan changed in 41% of patients irrespective of the type of initial management plan. The only somewhat accurate initial treatment plan was uvulopalatopharyngoplasty (unchanged in 11/13 patients). Excluding moderate to severe obstructive sleep apnea patients DISE is an indispensable tool in treatment decision in all SDB patients. We suggest to simplify the protocol for DISE reporting.

  20. Exemplary Care and Learning Sites: A Model for Achieving Continual Improvement in Care and Learning in the Clinical Setting

    PubMed Central

    Ogrinc, Greg; Hoffman, Kimberly G.; Stevenson, Katherine M.; Shalaby, Marc; Beard, Albertine S.; Thörne, Karin E.; Coleman, Mary T.; Baum, Karyn D.

    2016-01-01

    Problem Current models of health care quality improvement do not explicitly describe the role of health professions education. The authors propose the Exemplary Care and Learning Site (ECLS) model as an approach to achieving continual improvement in care and learning in the clinical setting. Approach From 2008–2012, an iterative, interactive process was used to develop the ECLS model and its core elements—patients and families informing process changes; trainees engaging both in care and the improvement of care; leaders knowing, valuing, and practicing improvement; data transforming into useful information; and health professionals competently engaging both in care improvement and teaching about care improvement. In 2012–2013, a three-part feasibility test of the model, including a site self-assessment, an independent review of each site’s ratings, and implementation case stories, was conducted at six clinical teaching sites (in the United States and Sweden). Outcomes Site leaders reported the ECLS model provided a systematic approach toward improving patient (and population) outcomes, system performance, and professional development. Most sites found it challenging to incorporate the patients and families element. The trainee element was strong at four sites. The leadership and data elements were self-assessed as the most fully developed. The health professionals element exhibited the greatest variability across sites. Next Steps The next test of the model should be prospective, linked to clinical and educa tional outcomes, to evaluate whether it helps care delivery teams, educators, and patients and families take action to achieve better patient (and population) outcomes, system performance, and professional development. PMID:26760058

  1. Chronic Pulmonary Histoplasmosis and its Clinical Significance: an Under-reported Systemic Fungal Disease

    PubMed Central

    Vaish, Ritu; Palange, Padmavali; Bhoomagiri, Mohan Rao

    2016-01-01

    Histoplasmosis is a systemic fungal mycosis caused by Histoplasma capsulatum. It is a dimorphic fungus which lives as a saprophyte in the environment and occasionally infects immunosuppressed people. H capsulatum is a ubiquitous fungus present throughout the globe and is more common in the temperate world. Human infection with H capsulatum occurs through respiratory route by inhalation of spores present in the air as droplet nuclei. Pulmonary histoplasmosis is difficult to diagnose, more so in the regions where tuberculosis is endemic, and many infected patients remain asymptomatic. In the case of immunosuppression, clinical symptoms of pulmonary infection may be seen along with chances of dissemination. We report a case of chronic pulmonary histoplasmosis in an immunocompetent individual. PMID:27688988

  2. 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

  3. Oral pemphigus: clinical significance of esophageal involvement: report of eight cases.

    PubMed

    Mignogna, M D; Lo Muzio, L; Galloro, G; Satriano, R A; Ruocco, V; Bucci, E

    1997-08-01

    The extension of the blisters of pemphigus to the esophagus is relatively uncommon, especially in patients treated with corticosteroids who appear to be in clinical remission. The aim of this study was to evaluate the esophagus in eight patients affected by oral pemphigus in various stages of the disease. Upper gastrointestinal endoscopy revealed esophageal involvement in five patients (two men and three women); three had blisters or erosions in the upper esophagus, whereas two showed red longitudinal lines along the entire organ. Direct immunofluorescence was positive in all eight patients. It is suggested that endoscopic examination of esophageal mucosa is an objective criterion by which to judge the success of therapy of pemphigus vulgaris.

  4. Wharton's Jelly Derived Mesenchymal Stem Cells: Future of Regenerative Medicine? Recent Findings and Clinical Significance

    PubMed Central

    Kalaszczynska, Ilona; Ferdyn, Katarzyna

    2015-01-01

    Around 5 million annual births in EU and 131 million worldwide give a unique opportunity to collect lifesaving Wharton's jelly derived mesenchymal stem cells (WJ-MSC). Evidences that these cells possess therapeutic properties are constantly accumulating. Collection of WJ-MSC is done at the time of delivery and it is easy and devoid of side effects associated with collection of adult stem cells from bone marrow or adipose tissue. Likewise, their rate of proliferation, immune privileged status, lack of ethical concerns, nontumorigenic properties make them ideal for both autologous and allogeneic use in regenerative medicine applications. This review provides an outline of the recent findings related to WJ-MSC therapeutic effects and possible advantage they possess over MSC from other sources. Results of first clinical trials conducted to treat immune disorders are highlighted. PMID:25861624

  5. New concepts in liver cirrhosis: clinical significance of sarcopenia in cirrhotic patients.

    PubMed

    Montano-Loza, A J

    2013-06-01

    The natural history of cirrhotic patients is highly variable due to several factors including hepatic synthetic function, presence and degree of portal hypertension, the cause of cirrhosis, the possibility of resolution of the underlying damaging process, and the occurrence of liver cancer. Currently, D'Amico stage classification and Child-Pugh and Model for End-Stage Liver Disease (MELD) scores constitute the best tools to predict mortality in patients with cirrhosis; however, one of their main limitations is the lack of evaluation of the nutritional and functional status. Most widely recognized complications in cirrhotic patients include ascites, hepatic encephalopathy, variceal bleeding, kidney dysfunction, and hepatocellular carcinoma; however, sarcopenia or severe muscle wasting is one of the most common and frequently hidden complications which negatively impact survival, quality of life, and response to stressor, such as infection and surgery. In this review, we discuss the current accepted and new methods to evaluate prognosis in cirrhosis, and also analyze the current knowledge regarding incidence and clinical impact of malnutrition and sarcopenia in cirrhosis and their impact after liver transplantation. We also discuss existing and potential novel therapeutic strategies for malnutrition in cirrhosis, emphasizing the recognition of sarcopenia in cirrhosis in an effort to improve survival and reduced morbidity related to cirrhosis. Finally, we propose that future studies including sarcopenia with the MELD score may allow better prediction of mortality among cirrhotic patients waiting for liver transplantation; however, due to the worldwide shortage of organs for transplants, one of the vital clinical questions is the feasibility to treat sarcopenia in cirrhosis without the need of liver transplant.

  6. 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.

  7. Clinical significance of routine lacrimal sac biopsy during dacryocystorhinostomy: A comprehensive review of literature

    PubMed Central

    Koturović, Zoran; Knežević, Miroslav; Rašić, Dejan M.

    2017-01-01

    The main purpose of this paper is to provide the information about the incidence and types of pathology of secondary acquired obstructions of the lacrimal excretory outflow system caused by primary lacrimal sac non-neoplastic and neoplastic lesions. After a thorough literature search, 17 case-control studies were found and selected, data were extracted and categorized, to evaluate specific lacrimal sac pathology mimicking inflammation. A total of 3865 histopathologically examined lacrimal sac wall biopsy specimens from 3662 patients, taken during dacryocystorhinostomy for clinically presumed primary chronic dacryocystitis, were analyzed. The most common reported histopathological finding was non-specific chronic inflammation with or without fibrosis (94.15% of cases). Lacrimal sac-specific pathologies were present in 226 (5.85%) cases. Unsuspected lacrimal sac-specific pathologies were present in 55/226 (24.34%) cases. Almost 45% of primary lacrimal sac malignant neoplasms were not suspected, preoperatively and intraoperatively. Tumor-like lesions of the lacrimal sac were the most common pathology found: (1) lacrimal stones-dacryoliths, (2) pyogenic granuloma, (3) granulation tissues, (4) reactive lymphoid hyperplasia, and (5) lacrimal sac-specific inflammation (Wegener’s granulomatosis and sarcoidosis). Neoplastic pathology was found in 55/3865 (1.42%) lacrimal sac wall biopsy specimens; of those, malignant cases were 2.24 times more frequent than benign. Lymphoma was the most common preoperatively unsuspected or intraoperatively unexpected neoplastic pathology. This analysis of the relevant literature highlights the value of routine lacrimal sac biopsy during surgery for clinically presumed primary acquired nasolacrimal duct obstruction. PMID:27754826

  8. Clinical significance of routine lacrimal sac biopsy during dacryocystorhinostomy: A comprehensive review of literature.

    PubMed

    Koturović, Zoran; Knežević, Miroslav; Rašić, Dejan M

    2017-02-21

    The main purpose of this paper is to provide the information about the incidence and types of pathology of secondary acquired obstructions of the lacrimal excretory outflow system caused by primary lacrimal sac non-neoplastic and neoplastic lesions. After a thorough literature search, 17 case-control studies were found and selected, data were extracted and categorized, to evaluate specific lacrimal sac pathology mimicking inflammation. A total of 3865 histopathologically examined lacrimal sac wall biopsy specimens from 3662 patients, taken during dacryocystorhinostomy for clinically presumed primary chronic dacryocystitis, were analyzed. The most common reported histopathological finding was non-specific chronic inflammation with or without fibrosis (94.15% of cases). Lacrimal sac-specific pathologies were present in 226 (5.85%) cases. Unsuspected lacrimal sac-specific pathologies were present in 55/226 (24.34%) cases. Almost 45% of primary lacrimal sac malignant neoplasms were not suspected, preoperatively and intraoperatively. Tumor-like lesions of the lacrimal sac were the most common pathology found: (1) lacrimal stones-dacryoliths, (2) pyogenic granuloma, (3) granulation tissues, (4) reactive lymphoid hyperplasia, and (5) lacrimal sac-specific inflammation (Wegener's granulomatosis and sarcoidosis). Neoplastic pathology was found in 55/3865 (1.42%) lacrimal sac wall biopsy specimens; of those, malignant cases were 2.24 times more frequent than benign. Lymphoma was the most common preoperatively unsuspected or intraoperatively unexpected neoplastic pathology. This analysis of the relevant literature highlights the value of routine lacrimal sac biopsy during surgery for clinically presumed primary acquired nasolacrimal duct obstruction.

  9. Clinical Significance of Component Allergens in Fagales Pollen-Sensitized Peanut Allergy in Korea

    PubMed Central

    Park, Kyung Hee; Son, Young Woong; Lee, Sang Chul; Jeong, Kyunguk; Sim, Da Woon; Park, Hye Jung; Lee, Sooyoung; Lee, Jae-Hyun

    2016-01-01

    Purpose Clinical features of peanut allergy can range from localized to systemic reactions. Because peanut and birch pollen have cross-reactivity, peanut can lead to localized allergic reaction in Fagales pollen-sensitized oral allergy syndrome (OAS) patients without peanut sensitization per se. The purpose of this study was to discriminate true peanut food allergy from cross-reactive hypersensitivity in birch-sensitized peanut allergy. Methods Birch-sensitized (n=81) and peanut anaphylaxis patients (n=12) were enrolled. Peanut-related allergic reactions and sensitization profiles were examined. Specific IgE to Fagales tree pollens (birch, oak), peanut, and their component allergens (Bet v 1, Bet v 2, Ara h 1, Ara h 2, Ara h 3, Ara h 8, and Ara h 9) were evaluated. Based on these specific IgEs and clinical features, the patients were classified into 4 groups: group 1 (Fagales pollen allergy without OAS), group 2 (Fagales pollen allergy with OAS), group 3 (OAS with peanut anaphylaxis), and group 4 (peanut anaphylaxis). Results After peanut consumption, one-third of OAS patients experienced oral symptoms not associated with peanut sensitization. Ara h 1 or Ara h 2 was positive in peanut anaphylaxis patients, whereas Ara h 8 was positive in OAS patients. There were 4 patients with both peanut anaphylaxis and OAS (group 3). Both Ara h 2 and Ara h 8 were positive in these patients. Foods associated with OAS in Korea showed unique patterns compared to Westernized countries. Conclusions Ara h 2 and Ara h 8 may be important component allergens for discriminating peanut allergy. PMID:27582401

  10. 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

  11. 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.

  12. Decreased Expression of Hsa_circ_00001649 in Gastric Cancer and Its Clinical Significance

    PubMed Central

    Li, Wen-han; Song, Yong-chun; Zhou, Zhang-jian; Xie, Xin; Zeng, Qing-nuo; Guo, Kun; Wang, Ting; Xia, Peng

    2017-01-01

    Background. It has been reported that circRNAs are differentially expressed in a wide range of cancers and could be used as a new biomarker for diagnosis. However, the correlation between circRNAs and gastric cancer (GC) it is still unclear. Materials and Methods. In this study, by using real-time quantitative reverse transcription-polymerase chain reactions (qRT-PCRs), we detected the expression level of hsa_circ_0001649 in tissue and serum samples from GC patients. Results. We found that hsa_circ_0001649 expression was significantly downregulated in GC tissue compared with their paired paracancerous histological normal tissues (PCHNTs) (P < 0.01). We next analyzed the expression level of hsa_circ_0001649 in serum samples between preoperative and postoperative GC patients. We found that its level in serum was significantly upregulated after surgery (P < 0.01). The area under the receiver operating characteristic (ROC) curve was 0.834. Moreover, the expression level of hsa_circ_0001649 was significantly correlated with pathological differentiation (P = 0.039). Conclusion. Our test suggested that hsa_circ_0001649 was significantly downregulated in GC and may become a novel potential biomarker in the diagnosis of GC. PMID:28167847

  13. Effects of dutasteride on serum free-testosterone and clinical significance of testosterone changes.

    PubMed

    Enatsu, N; Miyake, H; Haraguchi, T; Chiba, K; Fujisawa, M

    2016-12-01

    Sixty-two patients with benign prostate hyperplasia (BPH) who were being treated with dutasteride participated in this study. Prostate volume, uroflowmetry, blood tests, the International Prostate Symptom Score (IPSS) and International Index of Erectile Function (IIEF-5) were determined before and 1, 3 and 12 months after the treatment with dutasteride. Patients were divided into two groups based on changes in serum testosterone after 1 month: Group A (>20% increase; n = 33) or Group B (<20% increase; n = 29). Serum free-testosterone levels were 20.4% higher after 1 month and remained constant thereafter. When Groups A and B were compared, baseline free-testosterone levels were significantly lower in Group A, IPSS QOL was significantly better in Group A at 3 and 12 months, and no significant differences were observed in uroflowmetry, prostate volume, IPSS or IIEF-5. A univariate analysis identified serum free-testosterone levels and the IPSS storage symptom subscore as significant factors influencing IPSS QOL at 12 months, and only the IPSS storage symptom subscore appeared to be independently related to IPSS QOL. These results indicate that dutasteride increases serum free-testosterone levels in BPH patients, particularly with low baseline free-testosterone levels, and the increase in free-testosterone may have further add-on impacts on their urinary tract symptoms.

  14. Clinical significance of plasminogen activator inhibitor activity in patients with exercise-induced ischemia

    SciTech Connect

    Sakata, K.; Kurata, C.; Taguchi, T.; Suzuki, S.; Kobayashi, A.; Yamazaki, N.; Rydzewski, A.; Takada, Y.; Takada, A. )

    1990-10-01

    To assess the fibrinolytic system in patients with exercise-induced ischemia and its relation to ischemia and severity of coronary artery disease (CAD), 47 patients with CAD confirmed by results of coronary angiography underwent symptom-limited multistage exercise thallium-201 emission computed tomography. All patients with CAD had exercise-induced ischemia as assessed from thallium-201 images. Pre- and peak exercise blood samples from each patient and preexercise blood samples from control subjects were assayed for several fibrinolytic components and were also assayed for plasma adrenaline. The extent of ischemia was defined as delta visual uptake score (total visual uptake score in delayed images minus total visual uptake score in initial images) and the severity of CAD as the number of diseased vessels. In the basal condition, plasminogen activator inhibitor (PAI) activity was significantly higher in patients with exercise-induced ischemia as compared to control subjects (p less than 0.01), although there were no significant differences in other fibrinolytic variables between the two groups. Moreover, PAI activity in the basal condition displayed a significantly positive correlation with the extent of ischemia (r = 0.47, p less than 0.01). Patients with exercise-induced ischemia were divided into two groups (24 with single-vessel disease and 23 with multivessel disease). There were no significant differences in coronary risk factors, hemodynamics, or plasma adrenaline levels during exercise between single-vessel and multivessel disease except that delta visual uptake score was significantly higher in multivessel disease (p less than 0.01).

  15. Prevalence and characteristics of clinically significant retained common bile duct stones after laparoscopic cholecystectomy for symptomatic cholelithiasis

    PubMed Central

    Lee, Doo-ho; Lee, Hae Won; Chung, Jung Kee; Jung, In Mok

    2016-01-01

    Purpose To investigate the prevalence and clinical features of retained symptomatic common bile duct (CBD) stone detected after laparoscopic cholecystectomy (LC) in patients without preoperative evidence of CBD or intrahepatic duct stones. Methods Of 2,111 patients who underwent cholecystectomy between September 2007 and December 2014 at Seoul Metropolitan Government-Seoul National University Boramae Medical Center, 1,467 underwent laparoscopic cholecystectomy for symptomatic gallbladder stones and their medical records were analyzed. We reviewed the clinical data of patients who underwent postoperative endoscopic retrograde cholangiopancreatography (ERCP) for clinically significant CBD stones (i.e., symptomatic stones requiring therapeutic intervention). Results Overall, 27 of 1,467 patients (1.84%) underwent postoperative ERCP after LC because of clinical evidence of retained CBD stones. The median time from LC to ERCP was 152 days (range, 60–1,015 days). Nine patients had ERCP-related complications. The median hospital stay for ERCP was 6 days. Conclusion The prevalence of clinically significant retained CBD stone after LC for symptomatic cholelithiasis was 1.84% and the time from LC to clinical presentation ranged from 2 months to 2 years 9 months. Therefore, biliary surgeons should inform patients that retained CBD stone may be detected several years after LC for simple gallbladder stones. PMID:27847796

  16. Hepatocellular carcinoma associated microRNA expression signature: integrated bioinformatics analysis, experimental validation and clinical significance

    PubMed Central

    Shi, Ke-Qing; Lin, Zhuo; Chen, Xiang-Jian; Song, Mei; Wang, Yu-Qun; Cai, Yi-Jing; Yang, Nai-Bing; Zheng, Ming-Hua; Dong, Jin-Zhong; Zhang, Lei; Chen, Yong-Ping

    2015-01-01

    microRNA (miRNA) expression profiles varied greatly among current studies due to different technological platforms and small sample size. Systematic and integrative analysis of published datesets that compared the miRNA expression profiles between hepatocellular carcinoma (HCC) tissue and paired adjacent noncancerous liver tissue was performed to determine candidate HCC associated miRNAs. Moreover, we further validated the confirmed miRNAs in a clinical setting using qRT-PCR and Tumor Cancer Genome Atlas (TCGA) dataset. A miRNA integrated-signature of 5 upregulated and 8 downregulated miRNAs was identified from 26 published datesets in HCC using robust rank aggregation method. qRT-PCR demonstrated that miR-93-5p, miR-224-5p, miR-221-3p and miR-21-5p was increased, whereas the expression of miR-214-3p, miR-199a-3p, miR-195-5p, miR-150-5p and miR-145-5p was decreased in the HCC tissues, which was also validated on TCGA dataset. A miRNA based score using LASSO regression model provided a high accuracy for identifying HCC tissue (AUC = 0.982): HCC risk score = 0.180E_miR-221 + 0.0262E_miR-21 - 0.007E_miR-223 - 0.185E_miR-130a. E_miR-n = Log 2 (expression of microRNA n). Furthermore, expression of 5 miRNAs (miR-222, miR-221, miR-21 miR-214 and miR-130a) correlated with pathological tumor grade. Cox regression analysis showed that miR-21 was related with 3-year survival (hazard ratio [HR]: 1.509, 95%CI: 1.079–2.112, P = 0.016) and 5-year survival (HR: 1.416, 95%CI: 1.057–1.897, P = 0.020). However, none of the deregulated miRNAs was related with microscopic vascular invasion. This study provides a basis for further clinical application of miRNAs in HCC. PMID:26231037

  17. Significant differences in drug lag in clinical development among various strategies used for regulatory submissions in Japan.

    PubMed

    Ueno, T; Asahina, Y; Tanaka, A; Yamada, H; Nakamura, M; Uyama, Y

    2014-05-01

    Although the number of global clinical trials (GCTs) conducted in multiple countries including Japan has increased recently, it is not clear how much these GCTs help in reducing the lag in drug development (LDD: difference between the submission dates for new drug applications (NDAs) in the United States and Japan). We examined the effects of various clinical development strategies on LDD because the development period depends on what types of clinical trials were conducted for the Japanese NDA. Although various drug development strategies are available, deciding early on an appropriate strategy is a key to minimizing the LDD in Japan. The inclusion of GCTs in the clinical development strategy is also important; simultaneously, the smaller sample size of the Japanese population should be taken into consideration. Furthermore, reinforcement of Japan's capability to lead drug development may also be important in providing innovative drugs to Japanese patients without any significant LDD.

  18. Serum hepcidin level and its clinical significance in maintenance hemodialysis patients.

    PubMed

    Zhang, P; Yang, L-N; Wang, G; Li, F-E; Tang, F

    2014-11-27

    Hepcidin is a key protein of iron metabolism, which may play an important role in the prognosis of patients with chronic renal failure on maintenance hemodialysis. The purpose of this study was to investigate the relationship between the prognosis of maintenance hemodialysis patients and serum hepcidin level. We enrolled 60 patients on maintenance hemodialysis and 30 healthy controls from March 2012 to December 2012 in our hospital. Peripheral blood samples were collected to determine hepcidin by an ELISA method. Hepcidin levels of hemodialysis patients were significantly higher than those of the healthy control group. Hepcidin level was positively correlated with the degree of anemia in the dialysis group. Therefore, we conclude that hepcidin level is significantly increased in patients with chronic renal failure on maintenance hemodialysis and that increased hepcidin seriously affects the prognosis of chronic renal failure.

  19. Clinical and Epidemiological Significance of Carbapenem Resistance in Acinetobacter baumannii Infections

    PubMed Central

    Tal-Jasper, Ruthy; Katz, David E.; Amrami, Nadav; Ravid, Dor; Avivi, Dori; Zaidenstein, Ronit; Lazarovitch, Tsilia; Dadon, Mor; Kaye, Keith S.

    2016-01-01

    Carbapenems are considered the treatment of choice for Acinetobacter baumannii infections. Many facilities implement preventive measures toward only carbapenem-resistant A. baumannii (CRAB). However, the independent role of the carbapenem resistance determinant on patient outcomes remains controversial. In a 6-year analysis of adults with A. baumannii bloodstream infection (BSI), the outcomes of 149 CRAB isolates were compared to those of 91 patients with carbapenem-susceptible A. baumannii. In bivariable analyses, CRAB BSIs were significantly associated with worse outcomes and with a delay in the initiation of appropriate antimicrobial therapy (DAAT). However, in multivariable analyses, carbapenem resistance status was no longer associated with poor outcomes, while DAAT remained an independent predictor. The epidemiological significance of A. baumannii should not be determined by its resistance to carbapenems. PMID:26883694

  20. 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

  1. 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

  2. Clinical and Biological Significance of KISS1 Expression in Prostate Cancer

    PubMed Central

    Wang, Honghe; Jones, Jacqueline; Turner, Timothy; He, Qinghua P.; Hardy, Shana; Grizzle, William E.; Welch, Danny R.; Yates, Clayton

    2012-01-01

    For men in the United States, prostate cancer (PCa) is the most frequent malignancy and the second leading cause of cancer mortality. The metastatic spread of PCa is responsible for most deaths related to PCa. Although KISS1 functions as a metastasis suppressor in various cancers, its expression levels and functions in PCa development and progression remain undetermined. The goals of this study were to correlate the expression levels of KISS1 in PCas with clinicopathologic characteristics and to assess the biological relevance of KISS1 to the viability and motility of PCa cells. Strong KISS1 staining was detected in benign prostate tissues, but the staining was weaker in primary and metastatic PCas (both P < 0.001, t-test). Furthermore, the low expression levels of KISS1 in PCas correlated with clinical stage (P < 0.01) and with KISS1R expression (P < 0.001). Overexpression of full-length KISS1 in low KISS1-expressing PC-3M cells, but not KFMΔSS, which lacks the secretion signal sequence, induced re-sensitization of cells to anoikis, although it had no effect on either cell proliferation or apoptosis. Overexpression of KISS1 also suppressed steps in the metastatic cascade, including motility and invasiveness. Moreover, cells overexpressing KISS1 were found to enhance chemosensitivity to paclitaxel. Collectively, our data suggest that KISS1 functions as a metastasis suppressor in PCas and may serve as a useful biomarker as well as a therapeutic target for aggressive PCas. PMID:22226740

  3. Diagnosis and treatment of spontaneous coronary artery pseudoaneurysm: Rare anomaly with potentially significant clinical implications.

    PubMed

    Kar, Subrata; Webel, Richard R

    2017-03-04

    Spontaneous coronary artery pseudoaneurysm (PSA, false aneurysm) is an extremely rare occurrence with the precise incidence unknown. It is defined as an outwardly bulging monolayer or double layer within the coronary artery that lacks all 3 layers (intima, media, and adventitia) of the arterial wall. Coronary PSA commonly occurs from arterial dissection or perforation induced by catheter intervention, infection, pregnancy, or trauma. Traumatic dissection or perforation of the coronary artery after a percutaneous coronary intervention (PCI) remains the most common cause. Such cases may progress to myocardial ischemia, acute myocardial infarction, or acute coronary artery rupture causing death from cardiac tamponade. Intravascular ultrasound or cardiac computed tomography may aid in the diagnosis. Treatment options include PCI with a covered stent, bare or drug-eluting stent, coil embolization, coronary artery bypass graft with isolation of the PSA, or conservative management with vigilant clinical follow-up. In this review, we sought to describe the diagnosis, etiology, treatment, and the limited literature on spontaneous coronary artery PSA. © 2017 Wiley Periodicals, Inc.

  4. The TGF-β/Smad4 Signaling Pathway in Pancreatic Carcinogenesis and Its Clinical Significance

    PubMed Central

    Ahmed, Sunjida; Bradshaw, Azore-Dee; Gera, Shweta; Dewan, M. Zahidunnabi; Xu, Ruliang

    2017-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal human cancers due to its complicated genomic instability. PDAC frequently presents at an advanced stage with extensive metastasis, which portends a poor prognosis. The known risk factors associated with PDAC include advanced age, smoking, long-standing chronic pancreatitis, obesity, and diabetes. Its association with genomic and somatic mutations is the most important factor for its aggressiveness. The most common gene mutations associated with PDAC include KRas2, p16, TP53, and Smad4. Among these, Smad4 mutation is relatively specific and its inactivation is found in more than 50% of invasive pancreatic adenocarcinomas. Smad4 is a member of the Smad family of signal transducers and acts as a central mediator of transforming growth factor beta (TGF-β) signaling pathways. The TGF-β signaling pathway promotes many physiological processes, including cell growth, differentiation, proliferation, fibrosis, and scar formation. It also plays a major role in the development of tumors through induction of angiogenesis and immune suppression. In this review, we will discuss the molecular mechanism of TGF-β/Smad4 signaling in the pathogenesis of pancreatic adenocarcinoma and its clinical implication, particularly potential as a prognostic factor and a therapeutic target. PMID:28067794

  5. Clinical and biological significance of KISS1 expression in prostate cancer.

    PubMed

    Wang, Honghe; Jones, Jacqueline; Turner, Timothy; He, Qinghua P; Hardy, Shana; Grizzle, William E; Welch, Danny R; Yates, Clayton

    2012-03-01

    For men in the United States, prostate cancer (PCa) is the most frequent malignancy and the second leading cause of cancer mortality. The metastatic spread of PCa is responsible for most deaths related to PCa. Although KISS1 functions as a metastasis suppressor in various cancers, its expression levels and functions in PCa development and progression remain undetermined. The goals of this study were to correlate the expression levels of KISS1 in PCas with clinicopathologic characteristics and to assess the biological relevance of KISS1 to the viability and motility of PCa cells. Strong KISS1 staining was detected in benign prostate tissues, but the staining was weaker in primary and metastatic PCas (both P < 0.001, t-test). Furthermore, the low expression levels of KISS1 in PCas correlated with clinical stage (P < 0.01) and with KISS1R expression (P < 0.001). Overexpression of full-length KISS1 in low KISS1-expressing PC-3M cells, but not KFMΔSS, which lacks the secretion signal sequence, induced re-sensitization of cells to anoikis, although it had no effect on either cell proliferation or apoptosis. Overexpression of KISS1 also suppressed steps in the metastatic cascade, including motility and invasiveness. Moreover, cells overexpressing KISS1 were found to enhance chemosensitivity to paclitaxel. Collectively, our data suggest that KISS1 functions as a metastasis suppressor in PCas and may serve as a useful biomarker as well as a therapeutic target for aggressive PCas.

  6. Heterogeneity and clinical significance of ETV1 translocations in human prostate cancer

    PubMed Central

    Attard, G; Clark, J; Ambroisine, L; Mills, I G; Fisher, G; Flohr, P; Reid, A; Edwards, S; Kovacs, G; Berney, D; Foster, C; Massie, C E; Fletcher, A; De Bono, J S; Scardino, P; Cuzick, J; Cooper, C S

    2008-01-01

    A fluorescence in situ hybridisation (FISH) assay has been used to screen for ETV1 gene rearrangements in a cohort of 429 prostate cancers from patients who had been diagnosed by trans-urethral resection of the prostate. The presence of ETV1 gene alterations (found in 23 cases, 5.4%) was correlated with higher Gleason Score (P=0.001), PSA level at diagnosis (P=<0.0001) and clinical stage (P=0.017) but was not linked to poorer survival. We found that the six previously characterised translocation partners of ETV1 only accounted for 34% of ETV1 re-arrangements (eight out of 23) in this series, with fusion to the androgen-repressed gene C15orf21 representing the commonest event (four out of 23). In 5′-RACE experiments on RNA extracted from formalin-fixed tissue we identified the androgen-upregulated gene ACSL3 as a new 5′-translocation partner of ETV1. These studies report a novel fusion partner for ETV1 and highlight the considerable heterogeneity of ETV1 gene rearrangements in human prostate cancer. PMID:18594527

  7. 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.

  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.

  9. Heterogeneity and clinical significance of ETV1 translocations in human prostate cancer.

    PubMed

    Attard, G; Clark, J; Ambroisine, L; Mills, I G; Fisher, G; Flohr, P; Reid, A; Edwards, S; Kovacs, G; Berney, D; Foster, C; Massie, C E; Fletcher, A; De Bono, J S; Scardino, P; Cuzick, J; Cooper, C S

    2008-07-22

    A fluorescence in situ hybridisation (FISH) assay has been used to screen for ETV1 gene rearrangements in a cohort of 429 prostate cancers from patients who had been diagnosed by trans-urethral resection of the prostate. The presence of ETV1 gene alterations (found in 23 cases, 5.4%) was correlated with higher Gleason Score (P=0.001), PSA level at diagnosis (P=<0.0001) and clinical stage (P=0.017) but was not linked to poorer survival. We found that the six previously characterised translocation partners of ETV1 only accounted for 34% of ETV1 re-arrangements (eight out of 23) in this series, with fusion to the androgen-repressed gene C15orf21 representing the commonest event (four out of 23). In 5'-RACE experiments on RNA extracted from formalin-fixed tissue we identified the androgen-upregulated gene ACSL3 as a new 5'-translocation partner of ETV1. These studies report a novel fusion partner for ETV1 and highlight the considerable heterogeneity of ETV1 gene rearrangements in human prostate cancer.

  10. The Clinical Significance of the Biological False Positive Serologic Reactor: A Study of 113 Cases

    PubMed Central

    Knight, Allan; Wilkinson, R. D.

    1963-01-01

    Biological false positive serologic reactors were studied during a long-term follow-up of asymptomatic patients with chronic false positive serology for syphilitic reagin. This was done with a view to facilitating the early diagnosis of systemic disease, particularly collagen disorders, which are frequently associated with this finding in women. One hundred and thirteen cases were studied. Thirty-eight were “acute”, i.e. positive for less than six months, 58 were “chronic”, i.e. positive for more than six months, and the remainder still positive but followed for less than six months. Of 39 female chronic reactors, 10 were diagnosed as having collagen disease, and in six the BFP reaction preceded clinical diagnosis of the disease. Five had no apparent disease. In 19 male chronic reactors, there was no evidence of collagen disorders and five were free of any recognizable pathology. The remainder in both sexes were found to have a wide variety of systemic illnesses. PMID:14033756

  11. Clinical determinants and prognostic significance of the electrocardiographic strain pattern in chronic kidney disease patients.

    PubMed

    Cordeiro, Antonio C; Moraes, Aline A I; Cerutti, Virginia; França, Faustino; Quiroga, Borja; Amodeo, Celso; Picotti, Juliano C; Dutra, Lucas V; Rodrigues, Gabriel D; Amparo, Fernanda C; Lindholm, Bengt; Carrero, Juan Jesús

    2014-05-01

    The electrocardiographic (ECG) strain pattern (Strain) is a marker of left ventricular hypertrophy (LVH) severity that provides additional prognostic information beyond echocardiography (ECHO) in the community level. We sought to evaluate its clinical determinants and prognostic usefulness in chronic kidney disease (CKD) patients. We evaluated 284 non-dialysis-dependent patients with CKD stages 3 to 5 (mean age, 61 years [interquartile range, 53-67 years]; 62% men). Patients were followed for 23 months (range, 13-32 months) for cardiovascular (CV) events and/or death. Strain patients (n = 37; 13%) were using more antihypertensive drugs, had higher prevalence of peripheral vascular disease and smoking, and higher levels of C-reactive protein, cardiac troponin, and brain natriuretic peptide (BNP). The independent predictors of Strain were: left ventricular mass index (LVMI), BNP, and smoking. During follow-up, there were 44 cardiovascular events (fatal and non-fatal) and 22 non-CV deaths; and Strain was associated with a worse prognosis independently of LVMI. Adding Strain to a prognostic model of LVMI improved in 15% the risk discrimination for the composite endpoint and in 12% for the CV events. Strain associates with CV risk factors and adds prognostic information over and above that of ECHO-assessed LVMI. Its routine screening may allow early identification of high risk CKD patients.

  12. Short sleep is a questionable risk factor for obesity and related disorders: statistical versus clinical significance.

    PubMed

    Horne, Jim

    2008-03-01

    Habitually insufficient sleep could contribute towards obesity, metabolic syndrome, etc., via sleepiness-related inactivity and excess energy intake; more controversially, through more direct physiological changes. Epidemiological studies in adult/children point to small clinical risk only in very short (around 5h in adults), or long sleepers, developing over many years, involving hundreds of hours of 'too little' or 'too much' sleep. Although acute 4h/day sleep restriction leads to glucose intolerance and incipient metabolic syndrome, this is too little sleep and cannot be sustained beyond a few days. Few obese adults/children are short sleepers, and few short sleeping adults/children are obese or suffer obesity-related disorders. For adults, about 7h uninterrupted daily sleep is 'healthy'. Extending sleep, even with hypnotics, to lose weight, may take years, compared with the rapidity of utilising extra sleep time to exercise and evaluate one's diet. The real health risk of inadequate sleep comes from a sleepiness-related accident.

  13. The significance of arterial hypertension at the onset of clinical lupus nephritis.

    PubMed

    Naiker, I P; Chrystal, V; Randeree, I G; Seedat, Y K

    1997-04-01

    The prognostic importance of hypertension at the onset of clinical lupus nephritis is not well established. We studied retrospectively 44 patients with lupus nephritis in order to ascertain the prevalence of hypertension at presentation and to investigate a possible association between hypertension and renal functional impairment. A correlation was also sought between hypertension and histological class of lupus nephritis. Hypertension was graded as mild (diastolic 95-99 mmHg), moderate (100-114) or severe (> 115). Impaired renal function (creatinine > 120 mumol/l) was graded as mild (120-200 mumol/l), moderate (200-350 mumol/l), or severe (> 350 mumol/l). Histological class and the presence of hypertensive renal vascular lesions was recorded. The prevalence of hypertension was 38%. There were 17 hypertensives and 27 normotensives. The incidence of renal impairment was greater in the hypertensives, 47% vs 18.5% (p = 0.04). Mean serum creatinine was also higher higher in this group (p = 0.02). The presence of hypertensive renal vascular lesions identified a high-risk subgroup who had a higher incidence of renal functional impairment and worse renal function than the hypertensive group as a whole. Even at an early stage, hypertension and hypertensive renal vascular lesions correlated well with renal functional impairment. Aggressive treatment of hypertension is therefore essential in early lupus nephritis in order to prevent further deterioration of renal function as the disease evolves.

  14. Implant-abutment gap versus microbial colonization: Clinical significance based on a literature review.

    PubMed

    Passos, Sheila Pestana; Gressler May, Liliana; Faria, Renata; Özcan, Mutlu; Bottino, Marco Antonio

    2013-10-01

    Microorganisms from the oral cavity may settle at the implant-abutment interface (IAI). As a result, tissue inflammation could occur around these structures. The databases MEDLINE/PubMed and PubMed Central were used to identify articles published from 1981 through 2012 related to the microbial colonization in the implant-abutment gap and its consequence in terms of crest bone loss and osseointegration. The following considerations could be put forward, with respect to the clinical importance of IAI: (a) the space present at the IAI seems to allow bacterial leakage to occur, in spite of the size of this space; (b) bacterial leakage seems to occur at the IAI, irrespective of the type of connection. More studies are necessary to clarify the relationship between leakage at IAI and abutment connection designs; (c) losses at the peri-implant bone crests cannot be related to the IAI size, since few studies have shown no relationship. Also, the microbial leakage at the IAI cannot be related to the bone crest loss, since there are no articles reporting this relationship; remains controversial the influence of the IAI position on the bone crest losses.

  15. Isolated microscopic haematuria of glomerular origin: clinical significance and diagnosis in the 21st century.

    PubMed

    Chan, Melanie My; Gale, Daniel P

    2015-12-01

    Isolated microscopic, or non-visible, haematuria of glomerular origin was previously regarded a benign finding, but it is now known that, even in the absence of proteinuria, hypertension or renal impairment at presentation, haematuria is associated with increased risk of kidney failure in the long term. The most common causes of isolated microscopic haematuria among children and young adults are IgA nephropathy, Alport syndrome (AS), and thin basement membrane nephropathy (TBMN). AS, which is usually inherited as an X-linked or autosomal recessive trait, and TBMN, which is usually autosomal dominant, are caused by mutations in the genes encoding type-IV collagen, an abundant component of the glomerular basement membrane. A detailed family history with screening of at-risk relatives is important, allowing prompt diagnosis of affected relatives and helping determine the mode of transmission. As costs fall and availability increases, genetic testing is increasingly being used in clinical practice to provide diagnostic and predictive information for patients and their families.

  16. Multiple Heads of Gastrocnemius with Bipennate Fiber Arrangement- A Clinically Significant Variation

    PubMed Central

    Rodrigues, Vincent; Nayak, Shivananda

    2016-01-01

    It is common to have additional muscles or muscle slips in the extremities. Some of them may compress the nerves and vessels or restrict the movements, while others may enhance the muscular activity. However, a small number of them may go unnoticed. Knowledge of such variant muscles becomes important for plastic surgeons while performing various reconstructive surgeries and for clinicians while managing the pain. A case of multiple heads of gastrocnemius muscle was observed during routine dissection of the right lower limb of about 70-year-old male cadaver. It was observed that the medial head of gastrocnemius was attached to the femur with 3 thick heads and lateral head was arising from the lateral condyle of femur by 3 thick heads. All the heads of the muscles remained separate till they formed tendocalcaneus. Some of these heads showed bipinnate fiber arrangement. All the heads were innervated by the branches of tibial nerve. As the muscle heads passed down from their origin, they entrapped the sural nerve and sural nerve was seen emerging at the beginning of tendocalcaneus. Further, detailed literature and the clinical and surgical importance of the case are discussed. PMID:27656426

  17. Expression and clinical significance of tyrosine phosphatase SHP-2 in colon cancer.

    PubMed

    Cai, Peifen; Guo, Wenjie; Yuan, Huaqin; Li, Qian; Wang, Weicheng; Sun, Yang; Li, Xiaomin; Gu, Yanhong

    2014-04-01

    Protein-tyrosine phosphatase SHP-2, encoded by gene PTPN11, has been identified as a tumor-promoting factor in several types of leukemia and is hyper-activated by other mechanisms in some solid tumors including gastric cancer, breast cancer, non-small cell lung cancer (NSCLC), etc. But few were reported on the expression and significances of SHP-2 in colon cancer. Here, we detect SHP-2 expression in colon cancer cells, colon cancer-induced by AOM+DSS in mice and 232 human colon cancer specimens, including 58 groups of self-matched adjacent peritumor tissues and normal tissues. We found that compared to the normal colon tissues, SHP-2 significantly decreased in tumor tissues (P<0.001). The same results were got in colon tumor cells as well as mice colon tumors. And in humans samples, low SHP-2 expression showed a significantly correlation with poor tumor differentiation (P<0.05), late TNM stage (P=0.1666) and lymph node metastasis (P<0.05).

  18. Different Volumetric Measurement Methods for Pituitary Adenomas and Their Crucial Clinical Significance

    PubMed Central

    Chuang, Chi-Cheng; Lin, Shinn-Yn; Pai, Ping-Ching; Yan, Jiun-Lin; Toh, Cheng-Hong; Lee, Shih-Tseng; Wei, Kuo-Chen; Liu, Zhuo-Hao; Chen, Chung-Ming; Wang, Yu-Chi; Lee, Cheng-Chi

    2017-01-01

    Confirming the status of residual tumors is crucial. In stationary or spontaneous regression cases, early treatments are inappropriate. The long-used geometric calculation formula is 1/2 (length × width × height). However, it yields only rough estimates and is particularly unreliable for irregularly shaped masses. In our study, we attempted to propose a more accurate method. Between 2004 and 2014, 94 patients with pituitary tumors were enrolled in this retrospective study. All patients underwent transsphenoidal surgery and received magnetic resonance imaging (MRI). The pre- and postoperative volumes calculated using the traditional formula were termed A1 and A2, and those calculated using the proposed method were termed O1 and O2, respectively. Wilcoxon signed rank test revealed no significant difference between the A1 and O1 groups (P = 0.1810) but a significant difference between the A2 and O2 groups (P < 0.0001). Significant differences were present in the extent of resection (P < 0.0001), high-grade cavernous sinus invasion (P = 0.0312), and irregular shape (P = 0.0116). Volume is crucial in evaluating tumor status and determining treatment. Therefore, a more scientific method is especially useful when lesions are irregularly shaped or when treatment is determined exclusively based on the tumor volume. PMID:28098212

  19. A Long-Gap Peripheral Nerve Injury Therapy Using Human Skeletal Muscle-Derived Stem Cells (Sk-SCs): An Achievement of Significant Morphological, Numerical and Functional Recovery

    PubMed Central

    Hirata, Maki; Nakajima, Nobuyuki; Saito, Kosuke; Hashimoto, Hiroyuki; Soeda, Shuichi; Uchiyama, Yoshiyasu; Watanabe, Masahiko

    2016-01-01

    Losses in vital functions of the somatic motor and sensory nervous system are induced by severe long-gap peripheral nerve transection injury. In such cases, autologous nerve grafts are the gold standard treatment, despite the unavoidable sacrifice of other healthy functions, whereas the prognosis is not always favorable. Here, we use human skeletal muscle-derived stem cells (Sk-SCs) to reconstitute the function after long nerve-gap injury. Muscles samples were obtained from the amputated legs from 9 patients following unforeseen accidents. The Sk-SCs were isolated using conditioned collagenase solution, and sorted as CD34+/45- (Sk-34) and CD34-/45-/29+ (Sk-DN/29+) cells. Cells were separately cultured/expanded under optimal conditions for 2 weeks, then injected into the athymic nude mice sciatic nerve long-gap model (7-mm) bridging an acellular conduit. After 8–12 weeks, active cell engraftment was observed only in the Sk-34 cell transplanted group, showing preferential differentiation into Schwann cells and perineurial/endoneurial cells, as well as formation of the myelin sheath and perineurium/endoneurium surrounding regenerated axons, resulted in 87% of numerical recovery. Differentiation into vascular cell lineage (pericyte and endothelial cells) were also observed. A significant tetanic tension recovery (over 90%) of downstream muscles following electrical stimulation of the sciatic nerve (at upper portion of the gap) was also achieved. In contrast, Sk-DN/29+ cells were completely eliminated during the first 4 weeks, but relatively higher numerical (83% vs. 41% in axon) and functional (80% vs. 60% in tetanus) recovery than control were observed. Noteworthy, significant increase in the formation of vascular networks in the conduit during the early stage (first 2 weeks) of recovery was observed in both groups with the expression of key factors (mRNA and protein levels), suggesting the paracrine effects to angiogenesis. These results suggested that the human Sk

  20. Prevalence, Predictive Factor, and Clinical Significance of White-Coat Hypertension and Masked Hypertension in Korean Hypertensive patients

    PubMed Central

    Hwang, Eui-Seock; Choi, Kee-Joon; Kang, Duk-Hyun; Nam, Gi-Byoung; Jang, Jae-Sik; Jeong, Young-Hoon; Lee, Chang-Hoon; Lee, Ji-Young; Park, Hyun-Koo

    2007-01-01

    Background The prevalence and clinical significance of white-coat hypertension (WCHT) and masked hypertension (MHT) are unknown in Koreans. Here we measure the frequency of WCHT and MHT in hypertensive subjects and identify the epidemiologic and/or clinical factors that predict it in Korean subjects. Methods This study is a retrospective analysis of a random sample from February 2004 to October 2005. All patients had measurements of blood pressure (BP) in the clinic and 24-hour ambulatory blood pressure monitoring (ABPM). Subjects were classified into four groups on the basis of daytime ambulatory BP and clinic BP level: 1) Normotension (NT), 2) MHT, 3) WCHT, and 4) sustained hypertension (SHT). Results For all 967 patients, the mean clinic BP was 157.7±22.0/ 95.3±13.1 mmHg, and the mean daytime ambulatory BP was 136.4±15.0/ 86.2±10.7 mmHg. The NT, MHT, WCHT, and SHT groups consisted of 51 (5.3%), 55 (5.7%), 273 (28.2%), and 588 (60.8%) subjects, respectively. The left ventricular mass index was significantly higher in SHT than in the other groups, and was positively correlated with BP, especially ABPM. Compared with NT, the factors associated with MHT were younger age, male gender, higher BMI, clinic BP ≥130 mmHg, and alcohol consumption. Compared with SHT, the factors associated with WCHT were female gender, lower BMI, and clinic BP < 150 mmHg. Conclusions WCHT and MHT were prevalent in the hypertensive population. ABPM was more predictive of target organ damage than clinic BP, and could be useful in identifying subjects at risk for WCHT and MHT. PMID:18309684

  1. 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

  2. EXPRESSION MECHANISM AND CLINICAL SIGNIFICANCE OF NOB1 IN GASTRIC CANCER TISSUE AND ADJACENT NORMAL TISSUE.

    PubMed

    Zhou, W-P; Liu, X; Yang, Y; Liu, Y-F

    2015-01-01

    This paper studies the effect and relationship of NOB1 in the development of gastric cancer, based on an analysis of NOB1expression in gastric cancer tissue and adjacent tissue. Thirty gastric cancer tissue samples taken during surgery with complete pathological data and their related adjacent normal tissue were examined in this study. NOB1 protein expression in gastric cancer tissue and adjacent normal tissue was detected by immunohistochemistry (IHC). Real-time PCR was used to detect NOB1 mRNA expression, which provided a basis on which to explore the clinical pathological characteristics for patients with gastric cancer. Results show that NOB1 protein in gastric cancer tissue and adjacent normal tissue were diffusely expressed both in the cytoplasm and nucleus. The positive expression rate in gastric cancer tissue was 73%, higher than that in adjacent normal tissue (47%). Both the reference NAPDH and NOB1 amplification are reflected in the amplification curve in standard S-shape and the unimodal solubility curve which was not altered by non-specific amplification and primer dimer. NOB1 mRNA relative expression in cancer tissue was 4.899∓1.412. NOB1 expression had no direct relationship with the patients’ age, gender, tumor differentiation or infiltration degree, lymphatic metastasis, distant metastasis nor pTNM periodization, but was directly related to the size of the tumor. All the findings in this paper suggest that NOB1 can be one of the focuses for diagnosing and treating gastric cancer and that its protein expression is likely to increase with the growth of tumor, thus playing a great role in the incidence and development of gastric cancer.

  3. [Physiological significance and interpretation of plasma lactate concentration and pH in clinical exercise testing].

    PubMed

    Péronnet, F; Aguilaniu, B

    2014-06-01

    According to a widely accepted model, based on the theory of the anaerobic threshold (AT), the increase in plasma lactate concentration which develops after the first ventilatory threshold (VT1, considered as an AT) is due to compensation for insufficient aerobic metabolism by anaerobic glycolysis, with accumulation of lactic acid resulting in a decrease in pH. Bicarbonate is the main buffer of protons (>90%) producing non-metabolic CO2 in muscle and thus increasing the CO2 flux to the lungs. This phenomenon, along with the low pH, triggers hyperventilation. Because of this model, great importance has been placed on plasma lactate and pH. We argue that this importance is excessive and these variables should be used with caution in the interpretation of clinical exercise testing, because the model based on AT is not valid: there is no aerobic failure above VT1 and, thus, there is no evidence of an AT; the increase in plasma lactate does not reflect anaerobiosis but is the marker of the increase in the error signal needed for the stimulation of mitochondrial respiration; bicarbonate is not the main buffer during exercise (these are proteins and phosphocreatine breakdown in the muscle; hemoglobin in the blood); non-metabolic CO2 is not produced in the muscle but in the lung because of the low pH and hyperventilation (the control of which remains unknown); and the flux of CO2 to the lung does not increase at faster rate after than before VT1.

  4. Clinically Significant Endometrial Cancer Risk Following a Diagnosis of Complex Atypical Hyperplasia

    PubMed Central

    COSTALES, Anthony B.; SCHMELER, Kathleen M.; BROADDUS, Russell; SOLIMAN, Pamela T.; WESTIN, Shannon N.; RAMIREZ, Pedro T.; FRUMOVITZ, Michael

    2014-01-01

    Objectives Because of the frequent detection of carcinoma in surgical specimens after hysterectomy for endometrial complex atypical hyperplasia (CAH), it has been suggested that patients with a preoperative diagnosis of CAH be referred to gynecologic oncology for potential lymphadenectomy. However, the risk of lymph node metastasis in such patients is unknown. We sought to determine the risk of endometrial cancer and to estimate the risk of lymphatic spread in women with a preoperative diagnosis of CAH. Study Design We retrospectively reviewed the medical records of 150 consecutive patients with a preoperative diagnosis of CAH who subsequently underwent hysterectomy. Clinical characteristics and pathologic information were abstracted. Risk of lymphatic spread was modeled using previously published criteria and nomograms. Results Fifty-five of the 150 patients (36.7%) had an incidental endometrial carcinoma at the time of hysterectomy. Among patients with a preoperative office biopsy compared to dilation and curettage, the rate of an incidental finding of cancer was 43.5% and 28.1%, respectively (p=0.054). Of patients with cancer, 1 (1.8%) had a grade 3 endometrial carcinoma, 4 (7.3%) had lymphovascular space involvement, and 6 (10.9%) had deep (>50%) myometrial invasion. For the 10 patients who underwent lymphadenectomy, one (10%) had lymph node metastases. Based on multiple models, the estimated risk of lymph node spread was 1.6-2.1% for all women with a preoperative diagnosis of CAH and 4.4-6.8% for the 55 women with endometrial cancer. Conclusions Given the high rates of underlying endometrial cancer and the potential need for lymphadenectomy, care for patients with a preoperative diagnosis of CAH desiring definitive management with hysterectomy should be referred to a gynecologic oncologist. PMID:25316176

  5. Sentinel lymph nodes and breast carcinoma: which micrometastases are clinically significant?

    PubMed

    Weaver, Donald L

    2003-06-01

    Sentinel lymph node biopsy is changing surgical management of breast cancer and pathologic evaluation of lymph nodes. Although it has long been known that lymph nodes contain occult metastases, pathologists have not generally pursued their identification. Compared with level I-II axillary dissection, the reduced number of sentinel lymph nodes has made additional evaluation more attractive; however, the consequences of increased detection of micrometastases has not been fully explored or appreciated. National data suggest that the composition of traditional TNM stage groupings is changing, with a recent increase in node-positive, stage II breast cancer, most likely the result of increased pathologic scrutiny. Clinical management of this new group of stage II patients is complicated by the lack of a historic prognostic comparison group because many of these patients would have been classified as stage I, node-negative in the past. Early outcome data in sentinel lymph node biopsy suggest no adverse outcome for patients with metastases no larger than 2.0 mm, a finding aligned with the current definition of micrometastasis. When sentinel lymph nodes are sliced at 2.0-mm intervals and totally embedded, the probability of identifying all metastases >2.0 mm is high. Using reasonable sampling strategies, minute metastases have a nearly equal chance of being missed or detected. New staging guidelines have established a lower limit for micrometastases and defined metastases no larger than 0.2 mm as isolated tumor cells or tumor cell clusters; nodes with isolated tumor cells will be classified as node negative (pN0) for stage grouping. Rigorous strategies designed to reliably detect single cells or small cell clusters in sentinel nodes remain time-intensive and cost prohibitive.

  6. Clinical significance of pyloric aperture in the aetiology of peptic ulcer disease: a prospective study.

    PubMed

    Saha, Sisir Kumar

    2009-04-01

    Despite so much contributions reported in the literature, the aetiology of the duodenal ulcer remains an enigmatic subject to the medical profession. Findings of Helicobacter pylori seem to have overshadowed the real issue, in that, how a small area of the duodenal mucosa could be inflicted with the acid-pepsin injury has not been questioned? One hundred and sixty-eight consecutive patients, presented with epigastric pain were included in the endoscopic study. The aim of the study was to find out the prevalence and its clinical importance on the sizes of the pyloric aperture in the aetiology of peptic ulcer disease. Demographic data on the sizes of the pyloric aperture were divided into two groups, in that, those up to 3 mm in diameter were included in one and those over the size of 3 mm in another. Among the 168 cases, the gastric ulcer was found in 12 and duodenal ulcer in 27 patients. The sex ratio of men to women was 1.4:1 found in the former and 8:1 in the latter. Among other findings, a knuckle of duodenal mucoa was noticed prolapsing through the large pyloric aperture. It could be postulated that a knuckle of the mucosa that keeps peeping through the pylorus acts as a mucosal plug in empty stomach, like a cork in the acid bottle. The main physiological function is to protect the mucosa from being damaged by the acid-pepsin injury or by the reflux of bile, but the tip of the plug seems to be subjected to such injury. Furthermore, the surface epithelial cells could also be subjected to ischaemic change while prolapsing through the pylorus. This may lead to reduced production of the mucosal gel and bicarbonate secretion, thus exposing the damaged mucosa to acid bath. This supports the concept, how a small area of the stomach or duodenum could be inflicted with ulceration.

  7. 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

  8. Expression and clinical significance of LXRα and SREBP-1c in placentas of preeclampsia

    PubMed Central

    Jianhua, Li; Xueqin, Miao

    2016-01-01

    Abstract Objective To evaluate the expression and correlations of liver X receptor alpha (LXRa) and its target gene sterol regulatory element-binding protein-1c (SREBP-1c) in placentas of preeclampsia (PE) and their significance in PE. Methods Pregnancies were divided into two groups, 60 cases (29 cases of mild and 31 cases of severe) of PE group and 56 cases of normal group. The level of mRNA and protein of LXRa and SREBP-1c were analyzed by reverse transcription-polymerase chain reaction (RTPCR) and immunohistochemistry (IHC) in the placentas. Results RT-PCR and IHC results showed that the mRNA and protein expression of both LXRa and SREBP-1c increased gradually with the extent of PE among normal pregnancy, mild PE and severe PE groups, and the differences were of statistically significance (P<0.01 or P<0.05). There were positive correlations between the expression of LXRa mRNA and SREBP-1c mRNA, also between LXRa mRNA and LXRa protein (r=0.521, P<0.01; r=0.422, P<0.01). The expression of SREBP-1c mRNA positively correlated with its protein level (r=0.598, P<0.01). There were positive correlations between the expression of LXRa protein and SREBP-1c protein (r=0.612, P<0.01). Conclusion The expression of LXRa is elevated significantly in placentas of PE patients, and might contribute for promoting the transcription and translation of its target gene SREBP1-c, which is related to the occurrence and development of PE. PMID:28352810

  9. Frequency and clinical significance of short cervix in patients with preterm premature rupture of membranes

    PubMed Central

    Lee, Seung Mi; Park, Kyo Hoon; Jung, Eun Young; Jang, Ji Ae; Yoo, Ha-Na

    2017-01-01

    Objective Cervical length measurement has been uggested as a useful tool for predicting intra-amniotic infection/inflammation in preterm labor, but little information is available in the setting of preterm premature rupture of membranes (pPROM). We aimed to determine whether a short cervical length is independently associated with an increased risk of intra-amniotic infection or inflammation and impending preterm delivery in women with pPROM. Methods This was a retrospective cohort study involving 171 consecutive singleton pregnant women with pPROM (21+0–33+6 weeks’ gestation), who underwent amniocentesis. Amniotic fluid (AF) was cultured, and assayed for interleukin (IL)-6 and IL-8. Cervical length was measured at the time of amniocentesis by transvaginal ultrasonography with an aseptic technique. Short cervical length was defined as a cervical length of ≤15 mm. Intra-amniotic infection was defined as a positive AF culture for microorganisms and intra-amniotic inflammation was defined as elevated AF concentrations of IL-6 or IL-8 (IL-6 ≥1.5 ng/mL and/or IL-8 ≥1.3 ng/mL). Results Fifty (29.2%) women had a sonographic cervical length of ≤15mm. On univariate analysis, short cervical length was associated with an increased risk for intra-amniotic infection and/or inflammation; no other parameters studied showed a significant association. Multivariable analyses indicated that short cervical length was significantly associated with a higher risk of impending preterm delivery (within 2 days of measurement, within 7 days of measurement, and before 34 weeks), and remained significant after adjustment for potential confounders. Conclusion In women with pPROM, short cervical length is associated with an increased risk for intra-amniotic infection/inflammation and associated with impending preterm delivery, independent of the presence of intra-amniotic infection/inflammation. PMID:28358839

  10. Expression, clinical significance, and receptor identification of the newest B7 family member HHLA2 protein

    PubMed Central

    Janakiram, Murali; Chinai, Jordan M; Fineberg, Susan; Fiser, Andras; Montagna, Cristina; Medaverepu, Ramadevi; Castano, Ekaterina; Jeon, Hyungjun; Ohaegbulam, Kim C; Zhao, Ruihua; Zhao, Aimin; Almo, Steven C.; Sparano, Joseph A; Zang, Xingxing

    2014-01-01

    Purpose HHLA2 (B7H7/B7-H5/B7y) is a newly identified B7 family member that regulates human T cell functions. However, its protein expression in human organs and significance in human diseases are unknown. The objective of this study was to analyze HHLA2 protein expression in normal human tissues and cancers, its prognostic significance, to explore mechanisms regulating HHLA2 expression, and to identify candidate HHLA2 receptors. Experimental Design An immunohistochemistry protocol and a flow cytometry assay with newly generated monoclonal antibodies were developed to examine HHLA2 protein. HHLA2 gene copy number variation was analyzed from cancer genomic data. The combination of bioinformatics analysis and immunological approaches was established to explore HHLA2 receptors. Results HHLA2 protein was detected in trophoblastic cells of the placenta and the epithelium of gut, kidney, gallbladder and breast, but not in most other organs. In contrast, HHLA2 protein was widely expressed in human cancers from the breast, lung, thyroid, melanoma, pancreas, ovary, liver, bladder, colon, prostate, kidney, and esophagus. In a cohort of 50 patients with stage I–III triple negative breast cancer, 56% of patients had aberrant expression of HHLA2 on their tumors, and high HHLA2 expression was significantly associated with regional lymph node metastasis and stage. The Cancer Genome Atlas revealed that HHLA2 copy number gains were present in 29% of basal breast cancers, providing a potential mechanism for increased HHLA2 protein expression in breast cancer. Finally, Transmembrane and Immunoglobulin Domain Containing 2 (TMIGD2) was identified as one of the receptors for HHLA2. Conclusion Wide expression of HHLA2 in human malignancies, association with poor prognostic factors and its T cell coinhibitory capability, suggests that the HHLA2 pathway represents a novel immunosuppressive mechanism within the tumor microenvironment and an attractive target for human cancer therapy. PMID

  11. The clinical significance of isocitrate dehydrogenase 2 in esophageal squamous cell carcinoma

    PubMed Central

    Chen, Xuan; Xu, Wenzhe; Wang, Cong; Liu, Fang; Guan, Shanghui; Sun, Yi; Wang, Xintong; An, Dianzheng; Wen, Zhihua; Chen, Pengxiang; Cheng, Yufeng

    2017-01-01

    Isocitrate dehydrogenase 2 (IDH2) is the rate-limiting enzyme in the tricarboxylic acid (TCA) cycle in cellular metabolism. Growing evidence indicates that IDH2 plays a crucial role in the development of cancer. We aimed to investigate the expression level of IDH2 and its prognostic value in esophageal squamous cell cancer (ESCC). We evaluate the IDH2 expression and prognostic value in ESCC by immunohistochemical (IHC) staining, quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. The cell counting kit-8 (CCK8), clonogenic and invasion assays were performed to verify the IDH2 function in vitro. The protein expression level of IDH2 was significantly upregulated in ESCC tissues (IHC, Western blotting, all P<0.001) despite no significant difference at mRNA expression level (P>0.05). Kaplan-Meier analysis showed that IDH2 overexpression in ESCC patients was significantly related to worse overall survival (OS) and progression-free survival (PFS), P = 0.003 and 0.002, respectively. The univariate and multivariate analyses revealed that IDH2 overexpression served as an independent prognostic factor for OS and PFS (all P<0.005) in ESCC. The OD450 value, colony formation and invasive cell number were decreased in the shIDH2 groups (all P<0.0001). The upregulation of IDH2 in ESCC cells showed opposite effects (all P<0.05). Additionally, IDH2 knockdown phenotype can be rescued by shRNA-resistant IDH2 (all P<0.05). These results demonstrated that IDH2 was upregulated in ESCC and could be used as a valuable prognostic marker for ESCC patients.

  12. The clinical significance of isocitrate dehydrogenase 2 in esophageal squamous cell carcinoma.

    PubMed

    Chen, Xuan; Xu, Wenzhe; Wang, Cong; Liu, Fang; Guan, Shanghui; Sun, Yi; Wang, Xintong; An, Dianzheng; Wen, Zhihua; Chen, Pengxiang; Cheng, Yufeng

    2017-01-01

    Isocitrate dehydrogenase 2 (IDH2) is the rate-limiting enzyme in the tricarboxylic acid (TCA) cycle in cellular metabolism. Growing evidence indicates that IDH2 plays a crucial role in the development of cancer. We aimed to investigate the expression level of IDH2 and its prognostic value in esophageal squamous cell cancer (ESCC). We evaluate the IDH2 expression and prognostic value in ESCC by immunohistochemical (IHC) staining, quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. The cell counting kit-8 (CCK8), clonogenic and invasion assays were performed to verify the IDH2 function in vitro. The protein expression level of IDH2 was significantly upregulated in ESCC tissues (IHC, Western blotting, all P<0.001) despite no significant difference at mRNA expression level (P>0.05). Kaplan-Meier analysis showed that IDH2 overexpression in ESCC patients was significantly related to worse overall survival (OS) and progression-free survival (PFS), P = 0.003 and 0.002, respectively. The univariate and multivariate analyses revealed that IDH2 overexpression served as an independent prognostic factor for OS and PFS (all P<0.005) in ESCC. The OD450 value, colony formation and invasive cell number were decreased in the shIDH2 groups (all P<0.0001). The upregulation of IDH2 in ESCC cells showed opposite effects (all P<0.05). Additionally, IDH2 knockdown phenotype can be rescued by shRNA-resistant IDH2 (all P<0.05). These results demonstrated that IDH2 was upregulated in ESCC and could be used as a valuable prognostic marker for ESCC patients.

  13. [The arterio-alveolar CO2 gradient. Physiopathological and clinical significance].

    PubMed

    Foscale, M; Giacone, A; Cardellino, G; Garbagni, R

    1978-05-09

    The arterio-alveolar CO(2) gradient was examined in 20 patients with various ventilation diseases. It increased or became negative in obstruction. The tendency to increase was attributable to distribution disturbances, particularly the marked increase in the "dead space" effect. The same picture, though to a lesser degree, owing to a smaller dead space increase, was even more frequent in restriction cases. The appearance of a gradient in healthy subjects is referable to uneven air and blood distribution in the alveoli under physiological conditions. The physiopathological significance of negative gradients is discussed in the light of the results and the findings of other workers.

  14. Clinically significant CYP2C inhibition by noscapine but not by glucosamine.

    PubMed

    Rosenborg, S; Stenberg, M; Otto, S; Ostervall, J; Masquelier, M; Yue, Q-Y; Bertilsson, L; Eliasson, E

    2010-09-01

    Noscapine and glucosamine reportedly interact with warfarin. We investigated the effects of these drugs on various cytochrome P450 (CYP) activity markers. Twelve healthy subjects were phenotyped at baseline and during separate treatments with noscapine and glucosamine. Whereas glucosamine had no significant effect on CYP activity, noscapine caused marked inhibition of CYP2C9 (4.9-fold increase in urinary losartan/E3174 ratio) and CYP2C19 (3.6-fold increase in the plasma omeprazole/5-hydroxyomeprazole ratio). Noscapine-dependent inhibition of CYP2C9 may explain the interaction with warfarin.

  15. 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

  16. The periosteal microcirculation in health and disease: An update on clinical significance.

    PubMed

    Szabó, Andrea; Janovszky, Ágnes; Pócs, Levente; Boros, Mihály

    2017-03-01

    Apart from its nutritive functions, the periosteum critically affects bone regeneration via its stem/osteoprogenitor cell content. Normal healing after bone fractures, trauma-orthopedic interventions and invasive dental procedures is critically linked to the reestablishment of the periosteal microcirculation, but the reconstruction, replacement or repair of lost tissues may also be performed with autologous periosteum. Besides the initiation of cell differentiation during bone repair and remodeling processes, the periosteum together with the endosteum plays significant roles in the pathogenesis of both hormone-related and trauma-induced osteoporotic alterations in the bone metabolism. Nevertheless, the axial bones, and in particular the jawbones, and the appendicular bones display differences not only in their blood supply and fracture healing characteristics, but also in respect of the development of osteoporosis and their reactions to treatment modalities (i.e. bisphosphonates). These reactions may also be linked to the differences in periosteal microcirculatory reactions. The present overview summarizes the relevant data of microcirculatory studies focusing on the periosteal reactions in different anatomical locations together with the optimal background methodologies, study models and the most significant observations.

  17. Expression and Clinical Significance of Androgen Receptor in Triple-Negative Breast Cancer

    PubMed Central

    Asano, Yuka; Kashiwagi, Shinichiro; Goto, Wataru; Tanaka, Sayaka; Morisaki, Tamami; Takashima, Tsutomu; Noda, Satoru; Onoda, Naoyoshi; Ohsawa, Masahiko; Hirakawa, Kosei; Ohira, Masaichi

    2017-01-01

    Background: Triple-negative breast cancer (TNBC) has a poor prognosis because of frequent recurrence. Androgen receptor (AR) is involved in the pathogenesis of breast cancer, but its role is not clearly defined. The aim of this study was to explore the expression of AR and its relationship with clinicopathologic features in TNBC. Methods: This study investigated 1036 cases of sporadic invasive breast carcinoma. Immunohistochemical assays were performed to determine the expression of AR in 190 TNBC samples. The relationships between AR expression and clinicopathologic data and prognosis were analyzed. Results: In 190 TNBC cases, the prognosis of AR-positive patients was significantly better (p = 0.019, log-rank) than AR-negative patients, and in multivariate analysis, AR expression was an independent indicator of good prognosis (p = 0.039, hazard ratio = 0.36). In patients with disease relapse, AR positivity was significantly correlated with better prognosis (p = 0.034, log-rank). Conclusions: AR expression may be useful as a subclassification marker for prognosis in TNBC. PMID:28067809

  18. A Survey Study of Significent Achievements Accomplished By Snon-mainstreamt Seismologists In ¸ Earthquake Monitoring and Prediction Science In China Since 1970

    NASA Astrophysics Data System (ADS)

    Chen, I. W.

    Since 1990, the author, a British U Chinese consultant, has studied and followed the significant achievements accomplished by Snon-mainstreamT seismologists in & cedil;earthquake prediction in China since 1970. The scientific systems used include: (1) Astronomy-seismology: The relativity between special positions of certain planets (especially the moon and another planet) relative to the seismic active areas on the earth and the occurrence time of major damaging earthquakes in these areas on the earth, the relativity between the dates of magnetic storms on the earth caused by so- lar flare on the sun and the occurrence dates of major damaging earthquakes on the earth, as well as certain cycle relativity between the occurrence dates of major his- torical earthquakes occurring in relative areas on the earth. (2) Precursor analysis: With own-developed sensors and instruments, different to conventional seismologi- cal instruments, numerous precursors, abnormality signs, and earthquake imminent signals were recorded. In most cases, these precursors can not be detected by conven- tional seismological sensors/instruments. Through exploratory practice and theoreti- cal studies, various relativity between different characteristics of the precursors, and the occurrence time, epicenter location and magnitude of the developing earthquake were identified and can be calculated. Through approaches quite different to conven- tional methods, successful predictions of quite a large number of earthquakes have been achieved, including earthquakes that occurred in mainland China, Taiwan and Japan. (3) Earthquake imminent affirmative confirmation: With a special instrument, the background of imminent state of earthquakes can be identified, and a universal earthquake imminent signal is further identified. It can be used to confirm if an earlier predicted earthquake is entering its imminent state, if it will definitely occur, or if an earlier prediction can be released. (4) 5km, 7km and

  19. [Anthropometry: the modern statistical analysis and significance for clinics of internal diseases and nutrition].

    PubMed

    Petykhov, A B; Maev, I V; Deriabin, V E

    2012-01-01

    extremal lipopexia. Importance of anthropometry complex application of was proved at epidemiological researches for healthy individuals and patients with various diseases. The revealed morphological features confirm the necessary of the development of this medical anthropology direction for clinic of internal diseases.

  20. 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

  1. Clinical significance of intraventricular gradient during effort in an adolescent karate player

    PubMed Central

    Cotrim, Carlos; Almeida, Ana G; Carrageta, Manuel

    2007-01-01

    The authors report the case of a 16-year-old boy who practices karate, who underwent medical evaluation because of atypical chest discomfort, related to strenuous effort. The ECG and echocardiogram findings were normal. The young boy did a treadmill stress test which was positive for myocardial ischemia. Late during the investigation, he underwent treadmill stress echocardiography, during which he developed intraventricular gradient of over 130 mmHg with end-systolic peak and systolic anterior movement (SAM) of the mitral valve. These echocardiographic findings were not present at rest and disappeared shortly after termination of exercise. The authors discuss the significance of this event. This leads us to advise withdrawal from participation in competitive sport according to the recomendations of the European Society of Cardiology. A possible role of exercise stress echo for intraventricular pressure gradient assessment in symptomatic athletes with structurally normal hearts is suggested. PMID:18021434

  2. Clinical Significance and Prognostic Relevance of Microsatellite Instability in Sporadic Colorectal Cancer Patients

    PubMed Central

    Copija, Angelika; Waniczek, Dariusz; Witkoś, Andrzej; Walkiewicz, Katarzyna; Nowakowska-Zajdel, Ewa

    2017-01-01

    Microsatellite instability (MSI) is a marker of the replication error phenotype. It is caused by impaired DNA mismatch repair processes (MMR), resulting in ineffectiveness of the mechanisms responsible for the DNA replication precision and postreplicative DNA repair. MSI underlies the pathogenesis of 10%–20% of colorectal cancer (CRC) cases. The data about the potential value of MMR status as a predictive factor for 5-fluorouracil (FU)-based chemotherapy remain unclear. According to National Comprehensive Cancer Network updated guidelines, MSI testing is recommended for all patients with stage II CRC because patients with MSI-H (high-frequency MSI) tumour may have a good prognosis and obtain no benefit from 5-FU-based adjuvant chemotherapy. The significance of the MSI status as a predictive factor for patients with metastatic disease was not confirmed. The association between the MSI status and the efficacy of the therapy based on anti-programmed death-1 receptor inhibitors requires further studies. PMID:28067827

  3. 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.

  4. The dynamic and clinical significance of autoantibodies and immunoglobulins in liver transplant recipients.

    PubMed

    Stanca, Carmen M; Aloman, Costica; Fiel, Maria Isabel; Raja, Kaiser; Uskudar, Oguz; Florman, Sander; Schiano, Thomas D

    2016-03-01

    Little is known about autoantibody pattern in liver transplantation (LT). The aim of the study was to examine autoantibodies (AAB) and immunoglobulins in patients with end-stage liver disease before and after LT. Patients with LT who underwent post-LT biopsies between 10/2008 and 8/2011 were enrolled. AAB were assessed at the time of LT and liver biopsy. Demographics, serum immunoglobulins, AAB, and liver histology (explant, post-LT biopsies) were analyzed. Two hundred and twenty patients (M/F 143/77; age at LT 54 (19-73)) were included; AAB and immunoglobulins were evaluated in 76 patients. Length of follow-up from LT was 285 (30-1462) days. Sixty-one percent of patients had hepatitis C (HCV); 83% developed recurrent HCV. A significant decrease in IgG, IgA, IgM (p < 0.001 each), anticardiolipin antibodies IgG and IgM (p = 0.02), and beta-2 microglobulin (p = 0.004) was observed post-LT. HCV patients had higher IgG (p = 0.005), rheumatoid factor (p = 0.044) before LT; elevated IgM was associated with increased inflammation in the explant (p = 0.007). Lower IgG levels and antismooth muscle antibodies were present before LT in a higher percentage in patients who would develop recurrent HCV (p = 0.004, p = 0.077, respectively). In conclusion, AAB change significantly after LT and have a different pattern in HCV. Some immunological markers are associated with HCV recurrence and advanced inflammation on explant.

  5. Clinical and prognostic significance of Merkel cell polyomavirus in nonsmall cell lung cancer

    PubMed Central

    Kim, Gun-Jik; Lee, Jae-Ho; Lee, Deok Heon

    2017-01-01

    Abstract Recently, an association between Merkel cell polyomavirus (MCPyV) and epidermal growth factor receptor (EGFR) mutations in nonsmall cell lung cancer (NSCLC) was reported. However, the underlying carcinogenic effects and the prognosis related to MCPyV are still unclear. The aim of this study was to clarify the incidence and prognosis related to MCPyV infections in NSCLC. Tissue samples from 167 NSCLC patients (92 with squamous cell carcinomas [SCCs] and 75 with adenocarcinomas) were analyzed for the presence of MCPyV and EGFR mutations. Clinicopathological characteristics, disease-free survival rate, and overall survival rate were assessed with respect to MCPyV. MCPyV DNA was detected in 30 patients (18.0%) out of 167 patients, and EGFR mutations were found in 31 out of 127 patients (24.4%). EGFR mutations were more frequently detected in MCPyV-positive patients than in MCPyV-negative patients; however, this did not reach statistical significance (P = 0.075). There was no difference in overall survival between patients with and without MCPyV infections. The disease-free survival rate of patients with pN0 stage, SCC, or EGFR mutations was lower for patients with MCPyV than without MCPyV (P = 0.036, 0.042, and 0.050, respectively). Although the prevalence of MCPyV infection was relatively low, the presence of MCPyV DNA was significantly correlated with cancer prognosis in subgroups of NSCLC patients. These results suggest that MCPyV may be partly associated with pathogenesis and prognosis in some cases of NSCLC. PMID:28099328

  6. Organizational Designs for Achieving High Treatment Trial Enrollment: A Fuzzy-Set Analysis of the Community Clinical Oncology Program

    PubMed Central

    Weiner, Bryan J.; Jacobs, Sara R.; Minasian, Lori M.; Good, Marjorie J.

    2012-01-01

    Purpose: To examine the organizational design features that were consistently associated in 2010 with high levels of patient enrollment onto National Cancer Institute (NCI) cancer treatment trials among the oncology practices and hospitals participating in the NCI Community Clinical Oncology Program (CCOP). Methods: Fuzzy-set qualitative comparative analysis was used to identify the recipes (ie, combinations of organizational design features) that CCOPs used to achieve high levels of patient enrollment onto NCI treatment trials in 2010. Four organizational design features were examined: number of open treatment trials with at least one patient enrolled, number of newly diagnosed patients with cancer, number of CCOP-affiliated physicians, and number of CCOP-affiliated hospitals or practices where patient enrollment could occur. Data were obtained from NCI data systems and CCOP grant progress reports. Results: Two recipes were consistently associated with high levels of patient enrollment onto NCI treatment trials in 2010: having many open treatment trials and many new patients with cancer, and having many open treatment trials and many affiliated hospitals or practices. Together, these recipes accounted for nearly two thirds of CCOP membership in the high-performance set in 2010. Conclusion: No single organizational design feature, by itself, was consistently associated with high levels of patient enrollment onto NCI treatment trials in 2010. Having a large menu of active treatment trials may be necessary to achieve high–patient enrollment performance, but this is not sufficient unless combined with either large patient volume or many participating sites. PMID:23277765

  7. Effects of Achieving Target Measures in Rheumatoid Arthritis on Functional Status, Quality of Life, and Resource Utilization: Analysis of Clinical Practice Data

    PubMed Central

    Joo, Seongjung; Kawabata, Hugh; Al, Maiwenn J.; Allison, Paul D.; Rutten‐van Mölken, Maureen P. M. H.; Frits, Michelle L.; Iannaccone, Christine K.; Shadick, Nancy A.; Weinblatt, Michael E.

    2016-01-01

    Objective To evaluate associations between achieving guideline‐recommended targets of disease activity, defined by the Disease Activity Score in 28 joints using C‐reactive protein level (DAS28‐CRP) <2.6, the Simplified Disease Activity Index (SDAI) ≤3.3, or the Clinical Disease Activity Index (CDAI) ≤2.8, and other health outcomes in a longitudinal observational study. Methods Other defined thresholds included low disease activity (LDA), moderate (MDA), or severe disease activity (SDA). To control for intraclass correlation and estimate effects of independent variables on outcomes of the modified Health Assessment Questionnaire (M‐HAQ), the EuroQol 5‐domain (EQ‐5D; a quality‐of‐life measure), hospitalization, and durable medical equipment (DME) use, we employed mixed models for continuous outcomes and generalized estimating equations for binary outcomes. Results Among 1,297 subjects, achievement (versus nonachievement) of recommended disease targets was associated with enhanced physical functioning and lower health resource utilization. After controlling for baseline covariates, achievement of disease targets (versus LDA) was associated with significantly enhanced physical functioning based on SDAI ≤3.3 (ΔM‐HAQ −0.047; P = 0.0100) and CDAI ≤2.8 (−0.073; P = 0.0003) but not DAS28‐CRP <2.6 (−0.022; P = 0.1735). Target attainment was associated with significantly improved EQ‐5D (0.022–0.096; P < 0.0030 versus LDA, MDA, or SDA). Patients achieving guideline‐recommended disease targets were 36–45% less likely to be hospitalized (P < 0.0500) and 23–45% less likely to utilize DME (P < 0.0100). Conclusion Attaining recommended target disease‐activity measures was associated with enhanced physical functioning and health‐related quality of life. Some health outcomes were similar in subjects attaining guideline targets versus LDA. Achieving LDA is a worthy clinical objective in some patients. PMID:26238974

  8. Clinical significance of interval changes in breast lesions initially categorized as probably benign on breast ultrasound

    PubMed Central

    Jang, Ja Yoon; Kim, Sun Mi; Kim, Jin Hwan; Jang, Mijung; La Yun, Bo; Lee, Jong Yoon; Lee, Soo Hyun; Kim, Bohyoung

    2017-01-01

    Abstract The aims of this study were to determine the malignancy rate of probably benign lesions that show an interval change on follow-up ultrasound and to evaluate the differences seen on imaging between benign and malignant lesions initially categorized as probably benign but with interval change on follow-up breast ultrasound. We retrospectively reviewed 11,323 lesions from ultrasound-guided core-biopsies performed between June 2004 and December 2014 and identified 289 lesions (266 patients) with an interval change from probably benign (Breast Imaging Reporting and Data System [BI-RADS] category 3) in the previous 2 years. Malignancy rates were compared according to the ultrasound findings and the characteristics of the interval changes, including changes in morphology and/or diameter. The malignancy rate for probably benign lesions that showed an interval change on follow-up ultrasound was 6.9% (20/289). The malignancy rate was higher for clustered cysts (33.3%) and irregular or noncircumscribed masses (12.7%) than for circumscribed oval masses (5%) or complicated cysts (5%) seen on initial ultrasound (P = 0.043). Fifty-five percent of the malignancies were found to be ductal carcinoma in situ and there was 1 case of lymph node metastasis among the patients with invasive disease in whom biopsy was delayed by 6 to 15 months. The extent of invasiveness was greater in missed cases. There was a significant difference in the maximal diameter change between the 20 malignant lesions and the 269 benign lesions (4.0 mm vs 2.7 mm, P = 0.002). The cutoff value for maximal diameter change per initial diameter was 39.0% for predicting malignancy (sensitivity 95%, specificity 53.5%). The malignancy rate for morphologically changed lesions was significantly higher than for morphologically stable lesions (13.6% vs 4.9%; P = 0.024) Our 6.9% of probably benign lesions that showed an interval change finally turned out to be malignancy was mostly DCIS. The

  9. Clinical Significance of MET Gene Copy Number in Patients with Curatively Resected Gastric Cancer

    PubMed Central

    Kang, Byung Woog; Park, Heyoung; Park, Bo Eun; Jeon, Seong Woo; Bae, Han Ik; Kwon, Oh-kyoung; Chung, Ho Young; Yu, Wansik

    2015-01-01

    The present study analyzed the prognostic impact of MET gene copy number in patients with curatively resected gastric cancer who received a combination regimen of cisplatin and S-1. The MET gene copy number was analyzed by use of quantitative real-time polymerase chain reaction. From January 2006 to July 2010, 70 tumor samples from 74 patients enrolled in a pilot study were analyzed. According to a cutoff MET gene copy number of ≥2 copies, a high MET gene copy number was observed in 38 patients (54.3%). The characteristics of the 2 groups divided according to MET gene copy number were similar. With a median follow-up duration of 26.4 months (range, 2.6-73.2 months), the estimated 3-year relapse-free survival and overall survival rates were 54.3% and 77.4%, respectively. No significant association was observed between the MET gene copy number and survival in a multivariate analysis. The MET gene copy number investigated in this study was not found to be associated with prognosis in patients with curatively resected gastric cancer. PMID:26306302

  10. Low Prevalence of Clinically Significant Endoscopic Findings in Outpatients with Dyspepsia

    PubMed Central

    Abdeljawad, Khaled; Wehbeh, Antonios

    2017-01-01

    Background. The value of endoscopy in dyspeptic patients is questionable. Aims. To examine the prevalence of significant endoscopic findings (SEFs) and the utility of alarm features and age in predicting SEFs in outpatients with dyspepsia. Methods. A retrospective analysis of outpatient adults who had endoscopy for dyspepsia. Demographic variables, alarm features, and endoscopic findings were recorded. We defined SEFs as peptic ulcer disease, erosive esophagitis, malignancy, stricture, or findings requiring specific therapy. Results. Of 650 patients included in the analysis, 51% had a normal endoscopy. The most common endoscopic abnormality was nonerosive gastritis (29.7%) followed by nonerosive duodenitis (7.2%) and LA-class A esophagitis (5.4%). Only 10.2% had a SEF. Five patients (0.8%) had malignancy. SEFs were more likely present in patients with alarm features (12.6% versus 5.4%, p = 0.004). Age ≥ 55 and presence of any alarm feature were associated with SEFs (aOR 1.8 and 2.3, resp.). Conclusion. Dyspeptic patients have low prevalence of SEF. The presence of any alarm feature and age ≥ 55 are associated with higher risk of SEF. Endoscopy in young patients with no alarm features has a low yield; these patients can be considered for nonendoscopic approach for diagnosis and management. PMID:28210269

  11. 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

  12. [Blood-stasis and toxin causing catastrophe hypothesis and acute cardiovascular events: proposal of the hypothesis and its clinical significance].

    PubMed

    Xu, Hao; Shi, Da-Zhu; Yin, Hui-Jun

    2008-10-01

    A hypothesis of " blood-stasis and toxin causing catastrophe engender acute cardiovascular event (ACE)" was put forward according to TCM cognition on blood-stasis and toxin, in combining with the up to date concept of atherosclerosis and coronary heart disease, and together with our clinical practical experiences. The etiology, pathogenesis, evolving law, initial characteristics, clinical manifestation, therapeutic methods, prescriptions and their compatibility, as well as the well-suited time for applying TCM intervention were discussed. The authors stressed that it is of great significance for further reducing the morbidity of ACE and improving the effect of integrative medicine for preventing and treating cardiovascular thrombotic disease.

  13. [Clinical significance of ID4 methylation detection by quantitative methylation-specific PCR in acute leukemia].

    PubMed

    Liu, Yang; Zhong, Wen-Wen; Kang, Hui-Yuan; Wang, Li-Li; Lu, Xue-Chun; Yu, Li; Zhu, Hong-Li

    2014-06-01

    The advances of treatment improved the prognosis of the patients with acute leukemia (AL) in the last decade, but the lack of general biomarker for predicting relapse in AL, which is one of the most important factors influencing the survival and prognosis. DNA methylation of ID4 gene promoter occurred frequently in patients with AL and was found to be highly related to the tumor progression. Based on the previous work of the setup of methylation-specific quantitative PCR system for ID4 gene, this study was designed to investigate the relation between the quantitative indicator of methylation density, percentage of methylation reference(PMR) value, and different disease status of AL. PMR of ID4 was detected by MS-PCR in bone marrow (BM) samples of 17 healthy persons and 54 AL patients in the status of newly diagnosis, complete remission and disease relapse. The results showed that at different disease status, PMR value in newly diagnosed group was significantly lower than that in complete remission group (P = 0.031). Among serial samples, PMR value remained very low at the status of patients with continuous complete remission (<1.5‰), and increased along with the accumulation of tumor cells at relapse. In 1 relapse case, the abnormal rise of PMR value occurred prior to morphological relapse. PMR value seemed to be related to body tumor cell load. It is concluded that the quantitative indicator of methylation density and PMR value may reflect the change of tumor cell load in acute leukemia patients. Dynamic monitoring of PMR maybe predict leukemia relapse.

  14. Percutaneous Perineal Electrostimulation Induces Erection: Clinical Significance in Patients With Spinal Cord Injury and Erectile Dysfunction

    PubMed Central

    Shafik, Ahmed; Shafik, Ali A; Shafik, Ismail A; Sibai, Olfat El

    2008-01-01

    Objectives: Approximately one third to one half of the penis is embedded in the pelvis and can be felt through the scrotum and in the perineum. The main arteries and nerves enter the penis through this perineal part of the penis, which seems to represent a highly sensitive area. We investigated the hypothesis that percutaneous perineal stimulation evokes erection in patients with neurogenic erectile dysfunction. Methods: Percutaneous electrostimulation of the perineum (PESP) with synchronous intracorporeal pressure (ICP) recording was performed in 28 healthy volunteers (age 36.3 ± 7.4 y) and 18 patients (age 36.6 ± 6.8 y) with complete neurogenic erectile dysfunction (NED). Current was delivered in a sine wave summation fashion. Average maximal voltages and number of stimulations delivered per session were 15 to 18 volts and 15 to 25 stimulations, respectively. Results: PESP of healthy volunteers effected an ICP increase (P < 0.0001), which returned to the basal value upon stimulation cessation. The latent period recorded was 2.5 ± 0.2 seconds. Results were reproducible on repeated PESP in the same subject but with an increase of the latent period. Patients with NED recorded an ICP increase that was lower (P < 0.05) and a latent period that was longer (P < 0.0001) than those of healthy volunteers. Conclusion: PESP effected ICP increase in the healthy volunteers and patients with NED. The ICP was significantly higher and latent period shorter in the healthy volunteers than in the NED patients. PESP may be of value in the treatment of patients with NED, provided that further studies are performed to reproduce these results. PMID:18533410

  15. 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

  16. Clinical Significance of Bis-GMA and HEMA Orthodontic Resins Bonding to Enamel and Ceramic Materials.

    PubMed

    Reichheld, Timothy; Monfette, Gregory; Perry, Ronald D; Finkelman, Matthew; Gheewalla, Eric; Kugel, Gerard

    The advancement of new ceramic materials for dental crowns has prompted the need for improved methods of bonding orthodontic brackets to these surfaces. Currently, lithium-disilicate is the primary material being used for anterior crowns, while zirconia is the primary material being used in the posterior. The purpose of this study was to compare the shear bond strength of HEMA (Assure® Universal Bonding Resin) and bis-GMA (Assure® PLUS All Surface Bonding Resin) orthodontic bonding resins on enamel, lithium-disilicate, and zirconia materials. Two groups were formed, with three tested surfaces per group (n = 20). The categories included premolars, zirconia rods, and lithium-disilicate rods. Group 1 was treated with Assure, and group 2 was treated with Assure PLUS. Zirconia rods (1 cm x 1 cm x 4 cm) were used to represent zirconia crowns, and IPS e.max CAD rods (1 cm x 1 cm x 2 cm) were used to represent lithium-disilicate crowns. Assure and Assure PLUS bonding agents were applied according to the manufacturer's specifications, and standard edgewise universal premolar brackets were secured using Light Bond™ paste without fluoride. After 24 hours the brackets were sheared with a universal testing machine (Instron® 5566A) and the results were recorded. Data were analyzed using a combination of ANOVA and Tukey tests. A P value of less than .05 was considered statistically significant. Although group 1 and group 2 gave statistically equivalent results, the authors found that the ease of use when applying the group 2 bonding agent made it a safer, superior product within the confines of this study. It did not require a 4-minute hydrofluoric acid-etch and needed half the curing time of the group 1 agent when bonding to ceramic materials.

  17. Two Flavonolignans from Milk Thistle (Silybum marianum) Inhibit CYP2C9-Mediated Warfarin Metabolism at Clinically Achievable Concentrations

    PubMed Central

    Brantley, Scott J.; Oberlies, Nicholas H.; Kroll, David J.

    2010-01-01

    Milk thistle (Silybum marianum) is a popular herbal product used for hepatoprotection and chemoprevention. Two commercially available formulations are the crude extract, silymarin, and the semipurified product, silibinin. Silymarin consists of at least seven flavonolignans, of which the most prevalent are the diastereoisomers silybin A and silybin B; silibinin consists only of silybin A and silybin B. Based on a recent clinical study showing an interaction between a silymarin product and the CYP2C9 substrate losartan, the CYP2C9 inhibition properties of silybin A and silybin B and corresponding regioisomers, isosilybin A and isosilybin B, were evaluated using human liver microsomes (HLMs), recombinant CYP2C9 (rCYP2C9) enzymes, and the clinically relevant probe, (S)-warfarin. Silybin B was the most potent inhibitor in HLMs, followed by silybin A, isosilybin B, and isosilybin A (IC50 of 8.2, 18, 74, and >100 μM, respectively). Next, silybin A and silybin B were selected for further characterization. As with HLMs, silybin B was more potent than silybin A toward rCYP2C9*1 (6.7 versus 12 μM), rCYP2C9*2 (9.3 versus 19 μM), and rCYP2C9*3 (2.4 versus 9.3 μM). Using a matrix of five substrate (1–15 μM) and six inhibitor (1–80 μM) concentrations and HLMs, both diastereoisomers inhibited (S)-warfarin 7-hydroxylation in a manner described best by a mixed-type inhibition model (Ki values of 4.8 and 10 μM for silybin B and silybin A, respectively). These observations, combined with the high systemic silibinin concentrations (>5–75 μM) achieved in a phase I study involving prostate cancer patients, prompt clinical evaluation of a potential warfarin-milk thistle interaction. PMID:19934397

  18. [Clinical significance of myocardial 123I-BMIPP imaging in patients with myocardial infarction].

    PubMed

    Narita, M; Kurihara, T; Shindoh, T; Honda, M

    1997-03-01

    In order to clarify the characteristics of fatty acid metabolism in patients with myocardial infarction (MI), we performed myocardial imaging with 123I-beta-methyl-p-iodophenylpentadecanoic acid (BMIPP) and we compared these findings with exercise stress (Ex) and resting myocardial perfusion imaging with 99mTc-methoxyisobutylisonitrile (MIBI) and left ventricular wall motion index (WMI) which were obtained by left ventriculography. We studied 55 patients with MI, 14 patients with recent MI (RMI) and 41 patients with old MI (OMI), and myocardial images were divided into 17 segments and myocardial uptake of the radionuclide was graded from 0 (normal) to 3 (maximal abnormality). In 28 patients we compared segmental defect score (SDS) with WMI which were obtained by centerline method at the corresponded segments. As a whole, the mean total defect scores (TDSs) of BMIPP and Ex were similar and they were greater than the mean TDS of resting perfusion. In 30 patient (55%) TDS of BMIPP was greater than that of TDS of resting perfusion. In 24 patients perfusion abnormality developed by Ex and the location of BMIPP abnormality coincided with the abnormality of Ex. But in the other 6 patients Ex did not induce any abnormality and they were all RMI and infarcted coronary artery was patent. However in the group with TDS of BMIPP identical to TDS of resting perfusion (25 patients), 92% did not show myocardial perfusion abnormality after Ex. In the comparison of SDS and WMI, myocardial segments were divided into 3 groups; both SDSs of BMIPP and resting perfusion were normal or borderline abnormality (Group 1, 82 segments), SDS of resting perfusion was normal or borderline and SDS of BMIPP was definitely abnormal (Group 2, 10 segments) and both SDSs of BMIPP and resting perfusion were definitely abnormal (Group 3, 48 segments). In Group 1, WMS (-0.41 +/- 0.77) was significantly (p < 0.001) greater than those of Group 2 (-2.14 +/- 0.50) and Group 3 (-2.32 +/- 0.67). But there was

  19. The Significance of Language and Cultural Education on Secondary Achievement: A Survey of Chinese-American and Korean-American Students.

    ERIC Educational Resources Information Center

    Lee, Steven K.

    2002-01-01

    Surveys of 105 U.S.-born, Chinese-American and Korean-American students in southern California high schools found that those who adapted to the mainstream culture while maintaining their heritage language and culture had higher academic achievement than those who wholly adopted mainstream values and lifestyles. (Contains 21 references.) (SV)

  20. External Beam Radiotherapy for Clinically Localized Hormone-Refractory Prostate Cancer: Clinical Significance of Nadir Prostate-Specific Antigen Value Within 12 Months

    SciTech Connect

    Ogawa, Kazuhiko Nakamura, Katsumasa; Sasaki, Tomonari; Onishi, Hiroshi; Koizumi, Masahiko; Shioyama, Yoshiyuki; Araya, Masayuki; Mukumoto, Nobutaka M.S.; Mitsumori, Michihide; Teshima, Teruki

    2009-07-01

    Purpose: To analyze retrospectively the results of external beam radiotherapy for clinically localized hormone-refractory prostate cancer and investigate the clinical significance of nadir prostate-specific antigen (PSA) value within 12 months (nPSA12) as an early estimate of clinical outcomes after radiotherapy. Methods and Materials: Eighty-four patients with localized hormone-refractory prostate cancer treated with external beam radiotherapy were retrospectively reviewed. The total radiation doses ranged from 30 to 76 Gy (median, 66 Gy), and the median follow-up period for all 84 patients was 26.9 months (range, 2.7-77.3 months). Results: The 3-year actuarial overall survival, progression-free survival (PFS), and local control rates in all 84 patients after radiotherapy were 67%, 61%, and 93%, respectively. Although distant metastases and/or regional lymph node metastases developed in 34 patients (40%) after radiotherapy, local progression was observed in only 5 patients (6%). Of all 84 patients, the median nPSA12 in patients with clinical failure and in patients without clinical failure was 3.1 ng/mL and 0.5 ng/mL, respectively. When dividing patients according to low (<0.5 ng/mL) and high ({>=}0.5 ng/mL) nPSA12 levels, the 3-year PFS rate in patients with low nPSA12 and in those with high nPSA12 was 96% and 44%, respectively (p < 0.0001). In univariate analysis, nPSA12 and pretreatment PSA value had a significant impact on PFS, and in multivariate analysis nPSA12 alone was an independent prognostic factor for PFS after radiotherapy. Conclusions: External beam radiotherapy had an excellent local control rate for clinically localized hormone-refractory prostate cancer, and nPSA12 was predictive of clinical outcomes after radiotherapy.

  1. A pilot study of the clinical and statistical significance of a program to reduce eating disorder risk factors in children.

    PubMed

    Escoto Ponce de León, M C; Mancilla Díaz, J M; Camacho Ruiz, E J

    2008-09-01

    The current study used clinical and statistical significance tests to investigate the effects of two forms (didactic or interactive) of a universal prevention program on attitudes about shape and weight, eating behaviors, the influence of body aesthetic models, and self-esteem. Three schools were randomly assigned to one, interactive, didactic, or a control condition. Children (61 girls and 59 boys, age 9-11 years) were evaluated at pre-intervention, post-intervention, and at 6-month follow-up. Programs comprised eight, 90-min sessions. Statistical and clinical significance tests showed more changes in boys and girls with the interactive program versus the didactic intervention and control groups. The findings support the use of interactive programs that highlight identified risk factors and construction of identity based on positive traits distinct to physical appearance.

  2. Isolation of Mycobacterium fortuitum in sputum specimens of a patient with chronic cough: Is it clinically significant?

    PubMed

    Radzniwan, M R; Tohid, H; Ahmad, S; Mohd, Ali F; Md Anshar, F

    2014-01-01

    Managing chronic cough is diagnostically challenging especially in primary care. This case report highlights the difficulties experienced in approaching a case of chronic cough from a primary care perspective. The discussion also involves the clinical significance and treatment dilemma of M. fortuitum chelonae complex that was isolated from the sputum cultures of an elderly woman who presented with chronic cough for more than a year.

  3. An evidence-based approach to establish the functional and clinical significance of CNVs in intellectual and developmental disabilities

    PubMed Central

    Kaminsky, Erin B.; Kaul, Vineith; Paschall, Justin; Church, Deanna M.; Bunke, Brian; Kunig, Dawn; Moreno-De-Luca, Daniel; Moreno-De-Luca, Andres; Mulle, Jennifer G.; Warren, Stephen T.; Richard, Gabriele; Compton, John G.; Fuller, Amy E.; Gliem, Troy J.; Huang, Shuwen; Collinson, Morag N.; Beal, Sarah J.; Ackley, Todd; Pickering, Diane L.; Golden, Denae M.; Aston, Emily; Whitby, Heidi; Shetty, Shashirekha; Rossi, Michael R.; Rudd, M. Katharine; South, Sarah T.; Brothman, Arthur R.; Sanger, Warren G.; Iyer, Ramaswamy K.; Crolla, John A.; Thorland, Erik C.; Aradhya, Swaroop; Ledbetter, David H.; Martin, Christa L.

    2013-01-01

    Purpose Copy number variants (CNVs) have emerged as a major cause of human disease such as autism and intellectual disabilities. Because CNVs are common in normal individuals, determining the functional and clinical significance of rare CNVs in patients remains challenging. The adoption of whole-genome chromosomal microarray analysis (CMA) as a first-tier diagnostic test for individuals with unexplained developmental disabilities provides a unique opportunity to obtain large CNV datasets generated through routine patient care. Methods A consortium of diagnostic laboratories was established [the International Standards for Cytogenomic Arrays (ISCA) consortium] to share CNV and phenotypic data in a central, public database. We present the largest CNV case-control study to date comprising 15,749 ISCA cases and 10,118 published controls, focusing our initial analysis on recurrent deletions and duplications involving 14 CNV regions. Results Compared to controls, fourteen deletions, and seven duplications were significantly overrepresented in cases, providing a clinical diagnosis as pathogenic. Conclusion Given the rapid expansion of clinical CMA testing, very large datasets will be available to determine the functional significance of increasingly rare CNVs. This data will provide an evidenced-based guide to clinicians across many disciplines involved in the diagnosis, management, and care of these patients and their families. PMID:21844811

  4. Clinical Significance of the Number of Depressive Symptoms in Major Depressive Disorder: Results from the CRESCEND Study

    PubMed Central

    2016-01-01

    Our study aimed to establish the relationship between the number of depressive symptoms and the clinical characteristics of major depressive disorder (MDD). This would enable us to predict the clinical significance of the number of depressive symptoms in MDD patients. Using data from the Clinical Research Center for Depression (CRESCEND) study in Korea, 853 patients with DSM-IV MDD were recruited. The baseline and clinical characteristics of groups with different numbers of depressive symptoms were compared using the χ2 test for discrete variables and covariance (ANCOVA) for continuous variables. In addition, the scores of these groups on the measurement tools were compared by ANCOVA after adjusting the potential effects of confounding variables. After adjusting the effects of monthly income and history of depression, a larger number of depressive symptoms indicated higher overall severity of depression (F [4, 756] = 21.458, P < 0.001) and higher levels of depressive symptoms (F [4, 767] = 19.145, P < 0.001), anxiety symptoms (F [4, 765] = 12.890, P < 0.001) and suicidal ideation (F [4, 653] = 6.970, P < 0.001). It also indicated lower levels of social function (F [4, 760] = 13.343, P < 0.001), and quality of life (F [4, 656] = 11.975, P < 0.001). However, there were no significant differences in alcohol consumption (F [4, 656] = 11.975, P < 0.001). The number of depressive symptoms can be used as an index of greater illness burden in clinical psychiatry. PMID:27051248

  5. Clinical Significance of the Number of Depressive Symptoms in Major Depressive Disorder: Results from the CRESCEND Study.

    PubMed

    Park, Seon-Cheol; Sakong, Jeongkyu; Koo, Bon Hoon; Kim, Jae-Min; Jun, Tae-Youn; Lee, Min-Soo; Kim, Jung-Bum; Yim, Hyeon-Woo; Park, Yong Chon

    2016-04-01

    Our study aimed to establish the relationship between the number of depressive symptoms and the clinical characteristics of major depressive disorder (MDD). This would enable us to predict the clinical significance of the number of depressive symptoms in MDD patients. Using data from the Clinical Research Center for Depression (CRESCEND) study in Korea, 853 patients with DSM-IV MDD were recruited. The baseline and clinical characteristics of groups with different numbers of depressive symptoms were compared using the χ(2) test for discrete variables and covariance (ANCOVA) for continuous variables. In addition, the scores of these groups on the measurement tools were compared by ANCOVA after adjusting the potential effects of confounding variables. After adjusting the effects of monthly income and history of depression, a larger number of depressive symptoms indicated higher overall severity of depression (F [4, 756] = 21.458, P < 0.001) and higher levels of depressive symptoms (F [4, 767] = 19.145, P < 0.001), anxiety symptoms (F [4, 765] = 12.890, P < 0.001) and suicidal ideation (F [4, 653] = 6.970, P < 0.001). It also indicated lower levels of social function (F [4, 760] = 13.343, P < 0.001), and quality of life (F [4, 656] = 11.975, P < 0.001). However, there were no significant differences in alcohol consumption (F [4, 656] = 11.975, P < 0.001). The number of depressive symptoms can be used as an index of greater illness burden in clinical psychiatry.

  6. The clinical relevance and management of monoclonal gammopathy of undetermined significance and related disorders: recommendations from the European Myeloma Network.

    PubMed

    van de Donk, Niels W C J; Palumbo, Antonio; Johnsen, Hans Erik; Engelhardt, Monika; Gay, Francesca; Gregersen, Henrik; Hajek, Roman; Kleber, Martina; Ludwig, Heinz; Morgan, Gareth; Musto, Pellegrino; Plesner, Torben; Sezer, Orhan; Terpos, Evangelos; Waage, Anders; Zweegman, Sonja; Einsele, Hermann; Sonneveld, Pieter; Lokhorst, Henk M

    2014-06-01

    Monoclonal gammopathy of undetermined significance is one of the most common pre-malignant disorders. IgG and IgA monoclonal gammopathy of undetermined significance are precursor conditions of multiple myeloma; light-chain monoclonal gammopathy of undetermined significance of light-chain multiple myeloma; and IgM monoclonal gammopathy of undetermined significance of Waldenström's macroglobulinemia and other lymphoproliferative disorders. Clonal burden, as determined by bone marrow plasma cell percentage or M-protein level, as well as biological characteristics, including heavy chain isotype and light chain production, are helpful in predicting risk of progression of monoclonal gammopathy of undetermined significance to symptomatic disease. Furthermore, alterations in the bone marrow microenvironment of monoclonal gammopathy of undetermined significance patients result in an increased risk of venous and arterial thrombosis, infections, osteoporosis, and bone fractures. In addition, the small clone may occasionally be responsible for severe organ damage through the production of a monoclonal protein that has autoantibody activity or deposits in tissues. These disorders are rare and often require therapy directed at eradication of the underlying plasma cell or lymphoplasmacytic clone. In this review, we provide an overview of the clinical relevance of monoclonal gammopathy of undetermined significance. We also give general recommendations of how to diagnose and manage patients with monoclonal gammopathy of undetermined significance.

  7. The clinical relevance and management of monoclonal gammopathy of undetermined significance and related disorders: recommendations from the European Myeloma Network

    PubMed Central

    van de Donk, Niels W.C.J.; Palumbo, Antonio; Johnsen, Hans Erik; Engelhardt, Monika; Gay, Francesca; Gregersen, Henrik; Hajek, Roman; Kleber, Martina; Ludwig, Heinz; Morgan, Gareth; Musto, Pellegrino; Plesner, Torben; Sezer, Orhan; Terpos, Evangelos; Waage, Anders; Zweegman, Sonja; Einsele, Hermann; Sonneveld, Pieter; Lokhorst, Henk M.

    2014-01-01

    Monoclonal gammopathy of undetermined significance is one of the most common pre-malignant disorders. IgG and IgA monoclonal gammopathy of undetermined significance are precursor conditions of multiple myeloma; light-chain monoclonal gammopathy of undetermined significance of light-chain multiple myeloma; and IgM monoclonal gammopathy of undetermined significance of Waldenström’s macroglobulinemia and other lymphoproliferative disorders. Clonal burden, as determined by bone marrow plasma cell percentage or M-protein level, as well as biological characteristics, including heavy chain isotype and light chain production, are helpful in predicting risk of progression of monoclonal gammopathy of undetermined significance to symptomatic disease. Furthermore, alterations in the bone marrow microenvironment of monoclonal gammopathy of undetermined significance patients result in an increased risk of venous and arterial thrombosis, infections, osteoporosis, and bone fractures. In addition, the small clone may occasionally be responsible for severe organ damage through the production of a monoclonal protein that has autoantibody activity or deposits in tissues. These disorders are rare and often require therapy directed at eradication of the underlying plasma cell or lymphoplasmacytic clone. In this review, we provide an overview of the clinical relevance of monoclonal gammopathy of undetermined significance. We also give general recommendations of how to diagnose and manage patients with monoclonal gammopathy of undetermined significance. PMID:24658815

  8. Decreased Sperm Motility Retarded ICSI Fertilization Rate in Severe Oligozoospermia but Good-Quality Embryo Transfer Had Achieved the Prospective Clinical Outcomes

    PubMed Central

    Zheng, Jufeng; Lu, Yongning; Qu, Xianqin; Wang, Peng; Zhao, Luiwen; Gao, Minzhi; Shi, Huijuan; Jin, Xingliang

    2016-01-01

    Introduction Spermatozoa motility is the critical parameter to affect the treatment outcomes during assisted reproductive technologies (ART), but its reproductive capability remains a little informed in condition of severe male factor infertility. This retrospective cohort study aimed to evaluate the effects of reduced sperm motility on the embryological and clinical outcomes in intra-cytoplasmic sperm injection (ICSI) treatment of severe oligozoospermia. Patients and Methods 966 cycles (812 couples) of severe oligozoospermia diagnosed by spermatozoa count ≤ 5 × 106/mL and motile spermatozoa ≤ 2 × 106/mL were divided into four groups in according to the number of motile spermatozoa in one ejaculate on the day of oocyte retrieval (Group B—E). The control (Group A) was 188 cycles of moderate oligozoospermia with spermatozoa count > 5 × 106/mL and motile spermatozoa > 2 × 106/mL. All female partners were younger than 35 years of age. Logistic regression analyzed embryological outcomes (the rates of fertilization, cleavage and good-quality embryo) and clinical outcomes (the rates of pregnancy, implantation, early miscarriage and live birth). Quality of embryo transfer (ET) was divided into three classes as continuous factor to test the effects of embryo quality on clinical outcomes. Results The reduction in the number of motile sperm in four groups of severe oligozoospermia gave rise to comparable inability of the fertilization (p < 0.001) and a decreased rate of good-quality embryo at Day 3 (p < 0.001) by compared to the control. The cleavage rate of the derived zygotes was similar to the control. ET classes significantly affected the clinical outcomes (p < 0.001). Class I ET gave rise to similar rates of clinical outcomes between five groups, but Class II and Class III ET retarded the rates of pregnancy, implantation and live birth and this particularly occurred in Group C, D and E. The rate of early miscarriage was not comparably different between groups

  9. Novel one-stop multidisciplinary follow-up clinic significantly improves cancer risk management in BRCA1/2 carriers.

    PubMed

    Pichert, G; Jacobs, C; Jacobs, I; Menon, U; Manchanda, R; Johnson, M; Hamed, H; Firth, C; Evison, M; Tutt, A; de Silva, L; Langman, C; Izatt, L

    2010-09-01

    The purpose of this study is to measure the impact of a multidisciplinary one-stop follow-up clinic (MDOSC) on breast and ovarian surveillance, risk reducing surgery and enrolment in clinical trials in BRCA1/2 carriers. All BRCA1/2 carriers in our region were invited and chose which specialists to see in our MDOSC offering best practice using clinical protocols based on national guidelines and published data. Uptake was evaluated over 24 months recording numbers of individuals undergoing breast and ovarian surveillance, risk reducing surgery, newly diagnosed cancers, their method of detection and participation in clinical trials. 172 (60%) of invited BRCA1/2 carriers chose to attend the MDOSC. Breast surveillance was initiated in 88% and screening frequency altered in 14% of women to comply with national guidelines. Risk reducing salpingo-oophorectomy was chosen by 47% of women and an additional 39% were considering it. The rate of failure to remove fallopian tubes fell from 15 to 3% of procedures (P < 0.01) and peritoneal washings and serial sectioning of tubes and ovaries rose from 25% and 14% before, to 67% (P < 0.001) and 63% (P < 0.001) procedures, respectively, after initiation of our MDOSC. 24% of women considered and 18% decided to undergo risk reducing mastectomy during the follow-up period. Participation in clinical trials increased significantly from 51 to 229 enrolments (P < 0.001). Our novel MDOSC designed to devise an individually tailored cancer risk management strategy had a high uptake amongst our BRCA1/2 carriers. Attendance resulted in improved breast and ovarian cancer risk management.

  10. 1.5-Tesla Multiparametric-Magnetic Resonance Imaging for the detection of clinically significant prostate cancer

    PubMed Central

    POPITA, CRISTIAN; POPITA, ANCA RALUCA; SITAR-TAUT, ADELA; PETRUT, BOGDAN; FETICA, BOGDAN; COMAN, IOAN

    2017-01-01

    Background and aim Multiparametric-magnetic resonance imaging (mp-MRI) is the main imaging modality used for prostate cancer detection. The aim of this study is to evaluate the diagnostic performance of mp-MRI at 1.5-Tesla (1.5-T) for the detection of clinically significant prostate cancer. Methods In this ethical board approved prospective study, 39 patients with suspected prostate cancer were included. Patients with a history of positive prostate biopsy and patients treated for prostate cancer were excluded. All patients were examined at 1.5-T MRI, before standard transrectal ultrasonography–guided biopsy. Results The overall sensitivity, specificity, positive predictive value and negative predictive value for mp-MRI were 100%, 73.68%, 80% and 100%, respectively. Conclusion Our results showed that 1.5 T mp-MRI has a high sensitivity for detection of clinically significant prostate cancer and high negative predictive value in order to rule out significant disease. PMID:28246496

  11. Enumeration of bacteria in clinically significant blood cultures in neutropenic and non-neutropenic patients using a pour plate method.

    PubMed

    Rice, P; Spencer, R C

    1991-03-01

    A 3-year review of clinically significant positive blood cultures was undertaken to assess any differences in the blood bacterial count between haematological neutropenic and other non-neutropenic patients. The pour-plate method was used. In Gram-positive infections the pour plate contained colonies in 61% of haematological patients and in 41% of others. In Gram-negative infection the figures were 54% and 25% respectively. The mean numbers of bacteria per ml of blood were increased in haematological patients compared with the others for both groups of organisms.

  12. Low-shrink composite resins: a review of their history, strategies for managing shrinkage, and clinical significance.

    PubMed

    Pitel, Mark L

    2013-09-01

    Despite numerous advances in composite resin technology over the course of many decades, shrinkage behavior and the resultant stresses inherent to direct placed composite restorations continue to challenge clinicians. This overview of composite resins includes a review of their history and development along with a discussion of strategies for reducing polymerization shrinkage. An assessment of the clinical significance of these materials is also provided, including a discussion of the differences between polymerization shrinkage and stress, incremental layering versus bulk placement, and the emergence of lower shrinkage stress monomer chemistry.

  13. The significance of autoantibodies to DFS70/LEDGFp75 in health and disease: integrating basic science with clinical understanding.

    PubMed

    Ochs, Robert L; Mahler, Michael; Basu, Anamika; Rios-Colon, Leslimar; Sanchez, Tino W; Andrade, Luis E; Fritzler, Marvin J; Casiano, Carlos A

    2016-08-01

    Antinuclear autoantibodies (ANAs) displaying the nuclear dense fine speckled immunofluorescence (DFS-IIF) pattern in HEp-2 substrates are commonly observed in clinical laboratory referrals. They target the dense fine speckled autoantigen of 70 kD (DFS70), most commonly known as lens epithelium-derived growth factor p75 (LEDGFp75). Interesting features of these ANAs include their low frequency in patients with systemic autoimmune rheumatic diseases (SARD), elevated prevalence in apparently healthy individuals, IgG isotype, strong trend to occur as the only ANA specificity in serum, and occurrence in moderate to high titers. These autoantibodies have also been detected at varied frequencies in patients with diverse non-SARD inflammatory and malignant conditions such as atopic diseases, asthma, eye diseases, and prostate cancer. These observations have recently stimulated vigorous research on their clinical and biological significance. Some studies have suggested that they are natural, protective antibodies that could serve as biomarkers to exclude a SARD diagnosis. Other studies suggest that they might be pathogenic in certain contexts. The emerging role of DFS70/LEDGFp75 as a stress protein relevant to human acquired immunodeficiency syndrome, cancer, and inflammation also points to the possibility that these autoantibodies could be sensors of cellular stress and inflammation associated with environmental factors. In this comprehensive review, we integrate our current knowledge of the biology of DFS70/LEDGFp75 with the clinical understanding of its autoantibodies in the contexts of health and disease.

  14. [Clinical studies in working populations: value and significance of anamnestic findings, clinical tests and instrumental tests for the diagnosis of musculoskeletal disorders of the upper extremities].

    PubMed

    De Marco, F; Menoni, O; Ricci, M G; Bonaiuti, D; Colombini, D; Occhipinti, E

    1996-01-01

    The authors discuss the value and significance of symptoms in WMSDs, considering that the anamnestic threshold proposed in epidemiological investigations cannot be used as clinical and diagnosing criteria. Some useful clinical procedures are suggested for cases where there is a suspicion of musculo-skeletal disorders of the cervical spine and upper limbs, bearing in mind that they are to be applied within the framework of health surveillance programmes undertaken by health care practitioners who are not specialists in orthopaedics, physiatrics or neurology. The recommendations for instrumental tests and specialist referrals are also discussed for the various disorders. The authors also provide flow charts for the diagnostic procedures pertaining to WMSDs. The Appendix shows a sample patient chart illustrating the proposed procedures; it also permits the findings to be encoded so that they can be stored in a dedicated database. The codes for diagnosing WMSDs are also reported for the same epidemiological purposes.

  15. A clinically significant drug interaction between warfarin and amoxicillin resulting in persistent postoperative bleeding in a dental patient.

    PubMed

    Goodchild, Jason H; Donaldson, Mark

    2013-07-01

    One of the few cases reported in the literature, this article reviews the case of a 66-year-old man who developed an elevated international normalized ratio and sustained clinically significant bleeding as a result of a drug-drug interaction between warfarin and amoxicillin. Given the popularity of these medications, it is surprising that these reports are not more commonplace, and there is a concern that the lack of reports may result in practitioners overlooking the significance of this possible complication. Although the mechanism for this interaction is not fully known, it is suspected that a decrease in vitamin K-producing gut flora, with resulting vitamin K deficiency, is the most likely contributing factor. An objective causality assessment revealed that this adverse drug event, secondary to the warfarin and amoxicillin interaction, was probable.

  16. Clinical significance and predictors of treatment response to cognitive-behavior therapy for insomnia secondary to chronic pain.

    PubMed

    Currie, Shawn R; Wilson, Keith G; Curran, Dorothyann

    2002-04-01

    We examined individual responses to cognitive-behavior therapy for insomnia in 51 persons with chronic pain to determine the rate of clinically significant change and to identify predictors of successful treatment response. Outcome measures consisted of the Pittsburgh Sleep Quality Index (PSQI) and diary measures of sleep latency and sleep continuity. Using reliable change indices, 57% of participants were statistically improved on the PSQI after 7 weeks of treatment, but only 18% were considered fully recovered from their sleep problems. No demographic variables predicted treatment response but persons who reliably improved on the PSQI had a lower sleep self-efficacy at baseline. Improvers showed a significant increase in sleep self-efficacy ratings and a decrease in self-reported levels of distress and pain-related disability. These results suggest that patients with insomnia secondary to chronic medical conditions can be helped with cognitive-behavior therapy, although most individuals continue to have mild or subthreshold sleep problems at posttreatment.

  17. The clinical significance of K-Cl cotransport activity in red cells of patients with HbSC disease.

    PubMed

    Rees, David C; Thein, Swee Lay; Osei, Anna; Drasar, Emma; Tewari, Sanjay; Hannemann, Anke; Gibson, John S

    2015-05-01

    HbSC disease is the second commonest form of sickle cell disease, with poorly understood pathophysiology and few treatments. We studied the role of K-Cl cotransport activity in determining clinical and laboratory features, and investigated its potential role as a biomarker. Samples were collected from 110 patients with HbSC disease and 41 with sickle cell anemia (HbSS). K-Cl cotransport activity was measured in the oxygenated (K-Cl cotransport(100)) and deoxygenated (K-Cl cotransport(0)) states, using radioactive tracer studies. K-Cl cotransport activity was high in HbSC and decreased significantly on deoxygenation. K-Cl cotransport activity correlated significantly and positively with the formation of sickle cells. On multiple regression analysis, K-Cl cotransport increased significantly and independently with increasing reticulocyte count and age. K-Cl cotransport activity was increased in patients who attended hospital with acute pain in 2011 compared to those who did not (K-Cl cotransport(100): mean 3.87 versus 3.20, P=0.009, independent samples T-test; K-Cl cotransport(0): mean 0.96 versus 0.68, P=0.037). On logistic regression only K-Cl cotransport was associated with hospital attendance. Increased K-Cl cotransport activity was associated with the presence of retinopathy, but this effect was confounded by age. This study links variability in a fundamental aspect of cellular pathology with a clinical outcome, suggesting that K-Cl cotransport is central to the pathology of HbSC disease. Increased K-Cl cotransport activity is associated with increasing age, which may be of pathophysiological significance. Effective inhibition of K-Cl cotransport activity is likely to be of therapeutic benefit.

  18. Clinical characteristics and significance of Streptococcus salivarius bacteremia and Streptococcus bovis bacteremia: a prospective 16-year study.

    PubMed

    Corredoira, J C; Alonso, M P; García, J F; Casariego, E; Coira, A; Rodriguez, A; Pita, J; Louzao, C; Pombo, B; López, M J; Varela, J

    2005-04-01

    The aim of this study was to determine the clinical significance of Streptococcus salivarius isolates recovered from blood cultures and compare them with isolates of Streptococcus bovis biotypes I and II. Seventeen of the 52 (32%) S. salivarius isolates recovered were considered clinically significant, compared with 62 of the 64 (97%) S. bovis isolates (p<0.0001). Bacteremia caused by S. salivarius occurred mostly in patients who showed relevant disruption of the mucous membranes and/or serious underlying diseases. Patients with S. salivarius bacteremia were younger than those with S. bovis bacteremia (57 vs. 67 years; p<0.01). Patients with S. salivarius bacteremia and patients with S. bovis II bacteremia had similar rates of endocarditis, colon tumors, and non-colon cancer. On the other hand, when compared with S. bovis I bacteremia, S. salivarius bacteremia was associated with lower rates of endocarditis (18% vs. 74%, respectively) (p<0.01) and colon tumors (0% vs. 57%, respectively) (p<0.005) and higher rates of non-colon cancer (53% vs. 9.5%, respectively) (p<0.01). Bacteremia caused by S. bovis II had a hepatobiliary origin in 50% of the patients, while, in contrast, that due to S. salivarius or S. bovis I was less frequently associated with a hepatobiliary origin (12% and 5%, respectively) (p<0.00001). The rate of penicillin resistance was 31% among S. salivarius isolates and 0% among S. bovis isolates (p<0.0001). In conclusion, the clinical characteristics of S. salivarius bacteremia and S. bovis II bacteremia are similar, and the isolation of S. salivarius in blood should not be systematically regarded as contamination.

  19. Clinical analysis and prognostic significance of L-asparaginase containing multidrug chemotherapy regimen in incipient peripheral T-cell lymphoma

    PubMed Central

    Yao, Guoli; Zhou, De; Zhou, Meng; Bao, Changqian; He, Donghua; Li, Li; Zhu, Jingjing; He, Jinsong; Shi, Jimin; Zheng, Weiyan; Cai, Zhen; Huang, He; Ye, Xiujin; Xie, Wanzhuo

    2015-01-01

    Objective: To observe the clinical effects and adverse reactions, and analyze the clinical significance of L-asparaginase (L-ASP) containing multidrug chemotherapy regimen in incipient peripheral T-cell lymphoma (PTCL). Methods: A retrospective analysis was conducted of 102 patients with incipient PTCL who received L-ASP containing multidrug chemotherapy regimens or not in our hospital from January 2010 to December 2013. Complete remission (CR) rate, partial remission (PR) rate, overall remission (OR) rate, progression free survival (PFS), overall survival (OS) and adverse reactions were compared. Results: Patients who received L-ASP containing multidrug chemotherapy (L-ASP group) had higher OR rate than those who received L-ASP-free ones (non L-ASP group) (83.3% vs 61.7%, P=0.016), particularly those at phase III/IV (82.4% vs 54.0%, P=0.007) and with an international prognostic index (IPI) score of ≥2 (82.1% vs 50.0%, P=0.006). The median survival time (OS) was 10.5 months (range, 1-47months) in L-ASP group, while 13 months (range, 0.3-68 months) in non L-ASP group, and they had no statistically significance (P=0.754). Similarly, the progression free survival time(PFS)was 10 months (range, 1-47 months) in L-ASP group,while 11 months (range, 0.3-68 months) in non L-ASP group, also had no statistically significance (P=0.414). The 3-year OS rate of L-ASP group and non L-ASP group were 48.9% and 65.0% , respectively (P=0.974) and the 3-year PFS rate of L-ASP group and non L-ASP group were 40.8% and 61.0%, respectively (P=0.479). They all had no statistically significance. The L-ASP group had more adverse reactions than the non L-ASP group, though most of them were mild and could be improved by symptomatic and supportive care. Conclusion: L-ASP containing multidrug chemotherapy regimen in incipient PTCL showed a better short-term effect and controllable adverse reactions. A large prospective clinical trial of use L-ASP in first-line treatment of PTCL is worthy of

  20. Clinical significance of cell population data (CPD) on Sysmex XN-9000 in septic patients with our without liver impairment

    PubMed Central

    Seghezzi, Michela; Vavassori, Mauro; Dominoni, Paola; Apassiti Esposito, Sara; Manenti, Barbara; Mecca, Tommaso; Marchesi, Gianmariano; Castellucci, Enrico; Azzarà, Giovanna; Ottomano, Cosimo; Lippi, Giuseppe

    2016-01-01

    Background This study evaluated the clinical significance of cell population data (CPD) parameters obtained on Sysmex XN-9000 in septic patients admitted to intensive care unit (ICU) and stratified according to liver function. Methods The study population consisted in 84 patients, 44 of whom did not develop sepsis (NS), whereas the remaining 40 developed sepsis (SE) (n=24) or septic shock (SS) (n=16). Two hundred ostensibly healthy blood donors [healthy subjects (HS)], undergoing routine blood testing before a regular blood donation, were studied. Results Except for neutrophils and lymphocytes cell size (NE-FCS and LY-Z), all other CPD values were significantly different in ICU patients compared to HS. Neutrophils and monocytes fluorescence intensity (NE-SFL and MO-X) values were significantly higher in SS compared to sepsis and not develop sepsis patients. The value of many parameters was also different according to liver function. Overall, MO-X and neutrophils fluorescence intensity (NE-SFL) exhibited the best performance for diagnosing sepsis in all patients (AUC, 0.75 and 0.72), as well as in those with (AUC, 0.95 and 0.89) or without (AUC, 0.72 for both) liver impairment. These parameters were also significantly correlated with Sequential Organ Failure Assessment (SOFA) score. Conclusions This study suggested that some novel CPD parameters (namely NE-SFL and MO-X) may provide useful information for diagnosis and management of sepsis. PMID:27942509

  1. Clinical significance of immunogenic cell death biomarker rage and early growth response 1 in human primary gastric adenocarcinoma.

    PubMed

    Xu, X-C; Gao, H; Zhang, W-B; Abuduhadeer, X; Wang, Y-H

    2013-01-01

    The receptor for advanced glycation end products (RAGE), a pattern recognition receptor that binds multiple ligands derived from a damaged cell environment, contributes to multiple pathologies including cancer. Early growth response 1 (EGR1) is a tumor suppressor gene or a tumor promoter involved in tumorigenesis and progression of some cancers. However, there is some lack of knowledge about the expression and clinical significance of RAGE and EGR1 in human primary gastric adenocarcinoma (GAC). The present study was aimed to investigate the expression and clinical significance of RAGE and EGR1 in human GAC. One hundred and twenty cases of GAC tissues, adjacent non-cancer tissues (ANCT) and metastatic lymph node (MLN) tissues were collected. The expression of RAGE and EGR1 was assessed using immunohistochemistry (IHC) through tissue microarray procedure. The clinicopathologic characteristics of all patients were analyzed. As a result, the expression of RAGE in GAC and MLN tissues showed the positive staining mainly in the cytoplasm, with lower reactivity rate compared with the ANCT (P less than 0.001), while EGR1 expression had no significant difference between GAC, MLN tissues and ANCT (P=0.565). Moreover, the positive expression of RAGE was closely associated with the N stage of GAC patients, but did not correlate with their age, gender, tumor size, tumor sites, T stage, and metastatic lymph node (each P>0.05). In addition, Spearman Rank correlation analysis showed the positive correlation of RAGE expression with EGR1 in GAC tissues (r=0.658). Taken together, the expression of RAGE is decreased in GAC and MLN tissues, and is associated with the N stage of GAC patients, suggesting that RAGE may represent a potential therapeutic target for the treatment of GAC.

  2. Prevalence and Clinical Correlators of Undiagnosed Significant Depressive Symptoms Among Individuals with Type 2 Diabetes In A Mediterranean Population.

    PubMed

    Nicolau, J; Simó, R; Sanchís, P; Ayala, L; Fortuny, R; Rivera, R; Masmiquel, L

    2016-11-01

    Objective: To determine the frequency and clinical parameters, of clinically significant depressive symptoms among a type 2 diabetes (T2DM) sample from a Mediterranean area without an established diagnosis of depressive disorder (DD). Methods: 320 subjects with T2DM were recruited randomly from Primary-Care settings and the Endocrine Department from a tertiary center in Mallorca (Spain). 91 healthy individuals matched by age, gender and BMI were used as controls. All participating patients graded by the presence of DD by using the "Beck Depression Inventory" (BDI), considering pathological a cut-off score equal or greater than 16. Results: 27.2% T2DM subjects had significant symptoms of DD compared with 12.1% in the control group (p<0.01). BDI score was higher among T2DM when compared with controls (12±9.6 vs. 7.4±5, p<0.0001). The proportion of females (68% vs. 37%, p<0.0001), subjects without an active job (68% vs. 45%, p=0.01) and singles (38% vs. 18%, p=0.007) was greater among T2DM with a BDI≥16. Subjects with criteria for DD had a higher BMI (31.99±5.96 vs. 30.53±5.62, p=0.03). Fasting plasma glucose was higher among T2DM with a BDI≥16 (162±70 vs. 147±45 mg/dl, p=0.02) as well as HbA1c levels (7.9±1.8% vs. 7.4±1.4%, p=0.01), triglycerides (203±183 vs. 161±103 mg/dl; p=0.03) and LDL-cholesterol (112±31 vs. 104±35 mg/dl; p=0.03). Gender, marital status, BMI and triglycerides were independently related to the presence of DD after a logistic regression model. Conclusions: Relevant depressive symptoms are more prevalent among Mediterranean T2DM subjects than in general population. Main clinical correlators of significant depressive symptoms are gender, marital status and BMI.

  3. Combined steam-ultrasound treatment of 2 seconds achieves significant high aerobic count and Enterobacteriaceae reduction on naturally contaminated food boxes, crates, conveyor belts, and meat knives.

    PubMed

    Musavian, Hanieh S; Butt, Tariq M; Larsen, Annette Baltzer; Krebs, Niels

    2015-02-01

    Food contact surfaces require rigorous sanitation procedures for decontamination, although these methods very often fail to efficiently clean and disinfect surfaces that are visibly contaminated with food residues and possible biofilms. In this study, the results of a short treatment (1 to 2 s) of combined steam (95°C) and ultrasound (SonoSteam) of industrial fish and meat transportation boxes and live-chicken transportation crates naturally contaminated with food and fecal residues were investigated. Aerobic counts of 5.0 to 6.0 log CFU/24 cm(2) and an Enterobacteriaceae spp. level of 2.0 CFU/24 cm(2) were found on the surfaces prior to the treatment. After 1 s of treatment, the aerobic counts were significantly (P < 0.0001) reduced, and within 2 s, reductions below the detection limit (<10 CFU) were reached. Enterobacteriaceae spp. were reduced to a level below the detection limit with only 1 s of treatment. Two seconds of steam-ultrasound treatment was also applied on two different types of plastic modular conveyor belts with hinge pins and one type of flat flexible rubber belt, all visibly contaminated with food residues. The aerobic counts of 3.0 to 5.0 CFU/50 cm(2) were significantly (P < 0.05) reduced, while Enterobacteriaceae spp. were reduced to a level below the detection limit. Industrial meat knives were contaminated with aerobic counts of 6.0 log CFU/5 cm(2) on the handle and 5.2 log CFU/14 cm(2) on the steel. The level of Enterobacteriaceae spp. contamination was approximately 2.5 log CFU on the handle and steel. Two seconds of steam-ultrasound treatment reduced the aerobic counts and Enterobacteriaceae spp. to levels below the detection limit on both handle and steel. This study shows that the steam-ultrasound treatment may be an effective replacement for disinfection processes and that it can be used for continuous disinfection at fast process lines. However, the treatment may not be able to replace efficient cleaning processes used to remove high

  4. Clinical significance of respiratory bronchiolitis on open lung biopsy and its relationship to smoking related interstitial lung disease

    PubMed Central

    Moon, J.; du Bois, R. M; Colby, T.; Hansell, D.; Nicholson, A.

    1999-01-01

    BACKGROUND—Respiratory bronchiolitis-associated interstitial lung disease (RBILD) is a rare form of interstitial lung disease which may present in similar fashion to other types of chronic interstitial pneumonia. The purpose of this study was to undertake a clinicopathological review of 10 patients with RBILD and to examine the clinical and imaging data related to its histopathological pattern, in particular the relationship of RBILD to smoking.
METHODS—Thirteen out of 168 retrospectively reviewed patients, from whom biopsy specimens were taken for suspected diffuse lung disease, were identified with a histopathological pattern of RBILD. Three cases were rejected as follow up data were unavailable. The 10remaining cases constituted the study group and both clinical and imaging data were collected from patients' notes and referring physicians.
RESULTS—Histopathologically, four cases of RBILD overlapped with the pattern of desquamative interstitial pneumonitis (DIP) and nine also had microscopic evidence of centrilobular emphysema. Nine patients were smokers, ranging from 3 to 80 pack years. The one non-smoker had an occupational exposure to the fumes of solder flux. The sex distribution was equal with an age range of 32-65 years. Two patients were clubbed. Lung function tests showed both restrictive and obstructive patterns together with severe reductions in carbon monoxide transfer factor in seven patients. Chest radiographs showed reticular or reticulonodular infiltrates in five patients and a ground glass pattern in two. CT scans were consistent with either DIP or RBILD in six of eight patients. Although seven patients remained stable or improved, either with or without treatment, three patients deteriorated.
CONCLUSIONS—This study adds weight to the hypothesis that smoking can cause clinically significant interstitial lung disease, with deterioration in pulmonary function despite treatment. Given the overlapping histopa