Molecular biology of breast cancer metastasis: Clinical implications of experimental studies on metastatic inefficiency

International Nuclear Information System (INIS)

Chambers, Ann F; Naumov, George N; Vantyghem, Sharon A; Tuck, Alan B

2000-01-01

Recent technological advances have led to an increasing ability to detect isolated tumour cells and groups of tumour cells in patients' blood, lymph nodes or bone marrow. However, the clinical significance of these cells is unclear. Should they be considered as evidence of metastasis, necessitating aggressive treatment, or are they in some cases unrelated to clinical outcome? Quantitative experimental studies on the basic biology of metastatic inefficiency are providing clues that may help in understanding the significance of these cells. This understanding will be of use in guiding clinical studies to assess the significance of isolated tumour cells and micrometastases in cancer patients

Biological, ecological and agronomic significance of plant phenolic ...

African Journals Online (AJOL)

Our understanding of some phenolic compounds in the last few decades has greatly improved. However, their biological, ecological and agronomical significance in the rhizosphere of most symbiotic legumes is much less clear. Further understanding of these biomolecules will increase our knowledge of their contribution in ...

Asymptomatic bacteriuria. Clinical significance and management.

Science.gov (United States)

Raz, Raul

2003-10-01

The clinical significance and management of asymptomatic bacteriuria (ASB) differs according to different groups of patients. ASB requires antibiotic treatment in pregnant women, children aged 5-6 years and prior to invasive genitourinary procedures. However, there is a consensus that ASB in the elderly, healthy school girls and young women, diabetic women and patients with indwelling catheters or intermittent catheterization has no clinical significance and antibiotic prescription is not indicated.

[Current clinical significance of anaerobic bacteremia].

Science.gov (United States)

Jirsa, Roman; Marešová, Veronika; Brož, Zdeněk

2010-10-01

to estimate tje current clinical significance of anaerobic bacteremia in a group of Czech hospitals. this retrospective analysis comprised 8 444 anaerobic blood cultures in patients admitted to four Czech hospitals between 2004 and 2007. in 16 patients, blood cultures yielded significant anaerobic bacteria. Thus, anaerobic bacteremia accounted for less than 2 % of clinically significant bacteremia. Four patients (18 %) died but none of the deaths could be clearly attributable to anaerobic bacteria in the bloodstream. The most common comorbidities predisposing to anaerobic bacteremia and the most frequent sources of infection were similar to those reported by other authors. The majority of anaerobic bacteremia cases were due to gram-negative bacteria, followed by Clostridium perfringens and, surprisingly, Eubacterium spp. (particularly Eubacterium lentum). anaerobic bacteremia remains rare. The comparison of our data with those by other authors suggests that (despite the reported high mortality) the actual clinical significance of anaerobic bacteremia is rather controversial and that the anaerobic bacteremia might not correspond to more serious pathogenic role of the anaerobic bacteria as the source of infection.

[Molecular Biology on the Mechanisms of Autism Spectrum Disorder for Clinical Psychiatrists].

Science.gov (United States)

Makinodan, Manabu

2015-01-01

While, in general, a certain number of clinical psychiatrists might not be familiar with molecular biology, the mechanisms of mental illnesses have been uncovered by molecular biology for decades. Among mental illnesses, even biological psychiatrists and neuroscientists have paid less attention to the biological treatment of autism spectrum disorder (ASD) than Alzheimer's disease and schizophrenia since ASD has been regarded as a developmental disorder that was seemingly untreatable. However, multifaceted methods of molecular biology have revealed the mechanisms that would lead to the medication of ASD. In this article, how molecular biology dissects the pathobiology of ASD is described in order to announce the possibilities of biological treatment for clinical psychiatrists.

Genetic and biological characterization of a Porcine Reproductive and Respiratory Syndrome Virus 2 (PRRSV-2)causing significant clinical disease in the field

DEFF Research Database (Denmark)

Kvisgaard, Lise Kirstine; Larsen, Lars Erik; Hjulsager, Charlotte Kristiane

2017-01-01

pathogenic or vaccine evading PRRSV strain had emerged in Denmark. The overall aim of the present study was to perform a genetic and biological characterization of the virus isolated from the diseased herd. Complete genome sequencing of isolates from this herd revealed that although the case strain had some...... in the Northern part of Denmark experienced an infection with PRRSV-2 with clinical signs that were much more severe than normally reported from current Danish PRRSV-2 affected herds. Due to the clinical observations of reproductive failure in sows and high mortality in piglets, it was speculated that a new, more...... unique genetic features including a deduced 3 amino acid deletion, it was in overall very similar to the other PRRS-2 viruses circulating in Denmark. In an experimental trial in growing pigs, no overt clinical signs or pathology were observed following intranasal inoculation with the new virus isolate...

Recommendations for designing and conducting veterinary clinical pathology biologic variation studies.

Science.gov (United States)

Freeman, Kathleen P; Baral, Randolph M; Dhand, Navneet K; Nielsen, Søren Saxmose; Jensen, Asger L

2017-06-01

The recent creation of a veterinary clinical pathology biologic variation website has highlighted the need to provide recommendations for future studies of biologic variation in animals in order to help standardize and improve the quality of published information and to facilitate review and selection of publications as standard references. The following recommendations are provided in the format and order commonly found in veterinary publications. A checklist is provided to aid in planning, implementing, and evaluating veterinary studies on biologic variation (Appendix S1). These recommendations provide a valuable resource for clinicians, laboratorians, and researchers interested in conducting studies of biologic variation and in determining the quality of studies of biologic variation in veterinary laboratory testing. © 2017 American Society for Veterinary Clinical Pathology.

Clinical significance of neonatal menstruation.

Science.gov (United States)

Brosens, Ivo; Benagiano, Giuseppe

2016-01-01

Past studies have clearly shown the existence of a spectrum of endometrial progesterone responses in neonatal endometrium, varying from proliferation to full decidualization with menstrual-like shedding. The bleedings represent, similar to what occurs in adult menstruation, a progesterone withdrawal bleeding. Today, the bleeding is completely neglected and considered an uneventful episode of no clinical significance. Yet clinical studies have linked the risk of bleeding to a series of events indicating fetal distress. The potential link between the progesterone response and major adolescent disorders requires to be investigated by prospective studies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Knowledge-fused differential dependency network models for detecting significant rewiring in biological networks.

Science.gov (United States)

Tian, Ye; Zhang, Bai; Hoffman, Eric P; Clarke, Robert; Zhang, Zhen; Shih, Ie-Ming; Xuan, Jianhua; Herrington, David M; Wang, Yue

2014-07-24

Modeling biological networks serves as both a major goal and an effective tool of systems biology in studying mechanisms that orchestrate the activities of gene products in cells. Biological networks are context-specific and dynamic in nature. To systematically characterize the selectively activated regulatory components and mechanisms, modeling tools must be able to effectively distinguish significant rewiring from random background fluctuations. While differential networks cannot be constructed by existing knowledge alone, novel incorporation of prior knowledge into data-driven approaches can improve the robustness and biological relevance of network inference. However, the major unresolved roadblocks include: big solution space but a small sample size; highly complex networks; imperfect prior knowledge; missing significance assessment; and heuristic structural parameter learning. To address these challenges, we formulated the inference of differential dependency networks that incorporate both conditional data and prior knowledge as a convex optimization problem, and developed an efficient learning algorithm to jointly infer the conserved biological network and the significant rewiring across different conditions. We used a novel sampling scheme to estimate the expected error rate due to "random" knowledge. Based on that scheme, we developed a strategy that fully exploits the benefit of this data-knowledge integrated approach. We demonstrated and validated the principle and performance of our method using synthetic datasets. We then applied our method to yeast cell line and breast cancer microarray data and obtained biologically plausible results. The open-source R software package and the experimental data are freely available at http://www.cbil.ece.vt.edu/software.htm. Experiments on both synthetic and real data demonstrate the effectiveness of the knowledge-fused differential dependency network in revealing the statistically significant rewiring in biological

Clinical significance of anismus in encopresis.

Science.gov (United States)

Catto-Smith, A G; Nolan, T M; Coffey, C M

1998-09-01

Treatments designed to relieve paradoxical contraction of the anal sphincters during defecation (anismus) have had limited success in children with encopresis. This has raised doubts as to the clinical relevance of this diagnosis in childhood as anorectal dysfunction. Our aim was to determine whether, in patients who had treatment-resistant encopresis, the presence of electromyographic anismus was associated with increased faecal retention. Sixty-eight children with soiling (mean age 8.7+/-2.06 years) were assessed by clinical examination, abdominal radiography and then with anorectal manometry. Patients with electromyographic anismus (n=32; 47%) had significantly increased radiographic rectal faecal retention and were significantly less likely to be able to defecate water-filled balloons. There were no significant differences in response to prior therapy, history of primary encopresis, behavioural adjustment or in sociodemographic data. Our results suggest that electromyographic anismus is associated with obstructed defecation and faecal retention.

Molecular Biology of Pancreatic Cancer: How Useful Is It in Clinical Practice?

OpenAIRE

George H Sakorafas; Vasileios Smyrniotis

2012-01-01

Context During the recent two decades dramatic advances of molecular biology allowed an in-depth understanding of pancreatic carcinogenesis. It is currently accepted that pancreatic cancer has a genetic component. The real challenge is now how these impressive advances could be used in clinical practice. Objective To critically present currently available data regarding clinical application of molecular biology in pancreatic cancer. Methods Reports about clinical implications of molecular bio...

The thresholds for statistical and clinical significance

DEFF Research Database (Denmark)

Jakobsen, Janus Christian; Gluud, Christian; Winkel, Per

2014-01-01

BACKGROUND: Thresholds for statistical significance are insufficiently demonstrated by 95% confidence intervals or P-values when assessing results from randomised clinical trials. First, a P-value only shows the probability of getting a result assuming that the null hypothesis is true and does...... not reflect the probability of getting a result assuming an alternative hypothesis to the null hypothesis is true. Second, a confidence interval or a P-value showing significance may be caused by multiplicity. Third, statistical significance does not necessarily result in clinical significance. Therefore...... of the probability that a given trial result is compatible with a 'null' effect (corresponding to the P-value) divided by the probability that the trial result is compatible with the intervention effect hypothesised in the sample size calculation; (3) adjust the confidence intervals and the statistical significance...

Melatonin: a chemical photoperiodic signal with clinical significance in humans.

Science.gov (United States)

Pang, S F; Pang, C S; Poon, A M; Lee, P P; Liu, Z M; Shiu, S Y

1998-03-01

Secretion of pineal melatonin exhibits a diumal rhythm and a seasonal rhythm in humans. Night-time melatonin is high at 3-5 year-old and decreases with age. Many drugs and pathological conditions also change melatonin levels in the circulation. Melatonin has a mild sedative effect and has been used effectively in synchronizing the sleep-wake cycle of patients with sleep disorders. Immunoenhancing, anti-cancer, anti-aging and anti-oxidant effects of melatonin have been proposed. Recent studies suggest that melatonin receptors are present in central and peripheral tissues. The importance of melatonin receptors on the nervous, reproductive, immune and renal functions is implicated. Studies on the molecular biology, physiology and pathology of melatonin receptors in different tissues are progressing rapidly. The physiological and pathological changes in melatonin secretion, multifarious melatonin actions, and diverse melatonin receptors reported suggest that melatonin is a photoperiodic signal with clinical significance in humans.

WE-FG-BRB-01: Clinical Significance of RBE Variations in Proton Therapy

Energy Technology Data Exchange (ETDEWEB)

Paganetti, H. [Massachusetts General Hospital (United States)

2016-06-15

The physical pattern of energy deposition and the enhanced relative biological effectiveness (RBE) of protons and carbon ions compared to photons offer unique and not fully understood or exploited opportunities to improve the efficacy of radiation therapy. Variations in RBE within a pristine or spread out Bragg peak and between particle types may be exploited to enhance cell killing in target regions without a corresponding increase in damage to normal tissue structures. In addition, the decreased sensitivity of hypoxic tumors to photon-based therapies may be partially overcome through the use of more densely ionizing radiations. These and other differences between particle and photon beams may be used to generate biologically optimized treatments that reduce normal tissue complications. In this symposium, speakers will examine the impact of the RBE of charged particles on measurable biological endpoints, treatment plan optimization, and the prediction or retrospective assessment of treatment outcomes. In particular, an AAPM task group was formed to critically examine the evidence for a spatially-variant RBE in proton therapy. Current knowledge of proton RBE variation with respect to dose, biological endpoint, and physics parameters will be reviewed. Further, the clinical relevance of these variations will be discussed. Recent work focused on improving simulations of radiation physics and biological response in proton and carbon ion therapy will also be presented. Finally, relevant biology research and areas of research needs will be highlighted, including the dependence of RBE on genetic factors including status of DNA repair pathways, the sensitivity of cancer stem-like cells to charged particles, the role of charged particles in hypoxic tumors, and the importance of fractionation effects. In addition to the physical advantages of protons and more massive ions over photons, the future application of biologically optimized treatment plans and their potential to

AID Biology: A pathological and clinical perspective.

Science.gov (United States)

Choudhary, Meenal; Tamrakar, Anubhav; Singh, Amit Kumar; Jain, Monika; Jaiswal, Ankit; Kodgire, Prashant

2018-01-02

Activation-induced cytidine deaminase (AID), primarily expressed in activated mature B lymphocytes in germinal centers, is the key factor in adaptive immune response against foreign antigens. AID is responsible for producing high-affinity and high-specificity antibodies against an infectious agent, through the physiological DNA alteration processes of antibody genes by somatic hypermutation (SHM) and class-switch recombination (CSR) and functions by deaminating deoxycytidines (dC) to deoxyuridines (dU), thereby introducing point mutations and double-stranded chromosomal breaks (DSBs). The beneficial physiological role of AID in antibody diversification is outweighed by its detrimental role in the genesis of several chronic immune diseases, under non-physiological conditions. This review offers a comprehensive and better understanding of AID biology and its pathological aspects, as well as addresses the challenges involved in AID-related cancer therapeutics, based on various recent advances and evidence available in the literature till date. In this article, we discuss ways through which our interpretation of AID biology may reflect upon novel clinical insights, which could be successfully translated into designing clinical trials and improving patient prognosis and disease management.

Clinical significance of the fabella

International Nuclear Information System (INIS)

Dodevski, A.; Lazarova-Tosovska, D.; Zhivadinovik, J.; Lazareska, M.

2012-01-01

Full text: Introduction: There is variable number of sesamoid bones in the human body; one of them is fabella, located in the tendon of the gastrocnemius muscle. Aim of this study was to investigate the frequency of occurrence of fabella in the Macedonian population and to discuss about clinical importance of this bone. Materials and methods: We retrospectively examined radiographs of 53 patients who had knee exams undertaken for a variety of clinical reasons, performed as a part of their medical treatment. Over a time span of six months, 53 patients (38 males and 15 females, age range 19-60 years, mean age of 36.7±12.3 years) were examined. Results: In seven (13.2%) patients of 53 analyzed reports, fabella was found in the lateral tendon of gastrocnemius muscle. We did not find a significant gender or side difference in the appearance of fabella. Conclusion: Although anatomic studies emphasized a lack of significance of the fabella, this bone has been associated with a spectrum of pathology affecting the knee as fabellar syndrome, perineal nerve injury and fracture. We should think of this sesamoid bone while performing diagnostic and surgical procedures

Recommendations for designing and conducting veterinary clinical pathology biologic variation studies

DEFF Research Database (Denmark)

Freeman, Kathleen P; Baral, Randolph M; Dhand, Navneet K

2017-01-01

The recent creation of a veterinary clinical pathology biologic variation website has highlighted the need to provide recommendations for future studies of biologic variation in animals in order to help standardize and improve the quality of published information and to facilitate review......). These recommendations provide a valuable resource for clinicians, laboratorians, and researchers interested in conducting studies of biologic variation and in determining the quality of studies of biologic variation in veterinary laboratory testing....

Clinical significance of dental root canal microflora.

Science.gov (United States)

Gomes, B P; Lilley, J D; Drucker, D B

1996-01-01

Previous work by this group has shown that a significant association exists between pain and the presence of either Prevotella or Peptostreptococcus spp. in dental root canals. The aim of this study was to examine a more extensive series of canals microbiologically, to determine whether any other particular endodontic symptoms or clinical signs showed specific associations with individual bacterial species. Seventy root canals were examined microbiologically and clinical data collected to investigate in detail such associations. Of the canals studied, 37 were associated with pain, 49 with tenderness to percussion, 23 with swelling, six with purulent exudate and 57 presented with wet root canals. Anaerobes were isolated from 70.3% of painful canals and from 29.7% of pain-free canals. Significant associations were found between (a) pain and either Prevotella spp. or peptostreptococci, both with P spp. (P Eubacterium spp. (P spp. or Pstr. micros, both with P spp. (each P Eubacterium, Peptostreptococcus, Prevotella or Propionibacterium (each P < 0.05). It was concluded that several different endodontic clinical signs and symptoms are significantly associated with specific bacterial species.

Biologics for Targeting Inflammatory Cytokines, Clinical Uses, and Limitations

Directory of Open Access Journals (Sweden)

Peleg Rider

2016-01-01

Full Text Available Proinflammatory cytokines are potent mediators of numerous biological processes and are tightly regulated in the body. Chronic uncontrolled levels of such cytokines can initiate and derive many pathologies, including incidences of autoimmunity and cancer. Therefore, therapies that regulate the activity of inflammatory cytokines, either by supplementation of anti-inflammatory recombinant cytokines or by neutralizing them by using blocking antibodies, have been extensively used over the past decades. Over the past few years, new innovative biological agents for blocking and regulating cytokine activities have emerged. Here, we review some of the most recent approaches of cytokine targeting, focusing on anti-TNF antibodies or recombinant TNF decoy receptor, recombinant IL-1 receptor antagonist (IL-1Ra and anti-IL-1 antibodies, anti-IL-6 receptor antibodies, and TH17 targeting antibodies. We discuss their effects as biologic drugs, as evaluated in numerous clinical trials, and highlight their therapeutic potential as well as emphasize their inherent limitations and clinical risks. We suggest that while systemic blocking of proinflammatory cytokines using biological agents can ameliorate disease pathogenesis and progression, it may also abrogate the hosts defense against infections. Moreover, we outline the rational need to develop new therapies, which block inflammatory cytokines only at sites of inflammation, while enabling their function systemically.

Towards a Unified Understanding of Lithium Action in Basic Biology and its Significance for Applied Biology.

Science.gov (United States)

Jakobsson, Eric; Argüello-Miranda, Orlando; Chiu, See-Wing; Fazal, Zeeshan; Kruczek, James; Nunez-Corrales, Santiago; Pandit, Sagar; Pritchet, Laura

2017-12-01

Lithium has literally been everywhere forever, since it is one of the three elements created in the Big Bang. Lithium concentration in rocks, soil, and fresh water is highly variable from place to place, and has varied widely in specific regions over evolutionary and geologic time. The biological effects of lithium are many and varied. Based on experiments in which animals are deprived of lithium, lithium is an essential nutrient. At the other extreme, at lithium ingestion sufficient to raise blood concentration significantly over 1 mM/, lithium is acutely toxic. There is no consensus regarding optimum levels of lithium intake for populations or individuals-with the single exception that lithium is a generally accepted first-line therapy for bipolar disorder, and specific dosage guidelines for sufferers of that condition are generally agreed on. Epidemiological evidence correlating various markers of social dysfunction and disease vs. lithium level in drinking water suggest benefits of moderately elevated lithium compared to average levels of lithium intake. In contrast to other biologically significant ions, lithium is unusual in not having its concentration in fluids of multicellular animals closely regulated. For hydrogen ions, sodium ions, potassium ions, calcium ions, chloride ions, and magnesium ions, blood and extracellular fluid concentrations are closely and necessarily regulated by systems of highly selective channels, and primary and secondary active transporters. Lithium, while having strong biological activity, is tolerated over body fluid concentrations ranging over many orders of magnitude. The lack of biological regulation of lithium appears due to lack of lithium-specific binding sites and selectivity filters. Rather lithium exerts its myriad physiological and biochemical effects by competing for macromolecular sites that are relatively specific for other cations, most especially for sodium and magnesium. This review will consider what is known

Independent component analysis reveals new and biologically significant structures in micro array data

Directory of Open Access Journals (Sweden)

Veerla Srinivas

2006-06-01

Full Text Available Abstract Background An alternative to standard approaches to uncover biologically meaningful structures in micro array data is to treat the data as a blind source separation (BSS problem. BSS attempts to separate a mixture of signals into their different sources and refers to the problem of recovering signals from several observed linear mixtures. In the context of micro array data, "sources" may correspond to specific cellular responses or to co-regulated genes. Results We applied independent component analysis (ICA to three different microarray data sets; two tumor data sets and one time series experiment. To obtain reliable components we used iterated ICA to estimate component centrotypes. We found that many of the low ranking components indeed may show a strong biological coherence and hence be of biological significance. Generally ICA achieved a higher resolution when compared with results based on correlated expression and a larger number of gene clusters with significantly enriched for gene ontology (GO categories. In addition, components characteristic for molecular subtypes and for tumors with specific chromosomal translocations were identified. ICA also identified more than one gene clusters significant for the same GO categories and hence disclosed a higher level of biological heterogeneity, even within coherent groups of genes. Conclusion Although the ICA approach primarily detects hidden variables, these surfaced as highly correlated genes in time series data and in one instance in the tumor data. This further strengthens the biological relevance of latent variables detected by ICA.

Dietary Polyphenols and Their Biological Significance

Directory of Open Access Journals (Sweden)

Hongxiang Lou

2007-09-01

Full Text Available Dietary polyphenols represent a wide variety of compounds that occur in fruits,vegetables, wine, tea, extra virgin olive oil, chocolate and other cocoa products. They aremostly derivatives and/or isomers of flavones, isoflavones, flavonols, catechins andphenolic acids, and possess diverse biological properties such as antioxidant, antiapoptosis,anti-aging, anticarcinogen, anti-inflammation, anti-atherosclerosis, cardiovascularprotection, improvement of the endothelial function, as well as inhibition of angiogenesisand cell proliferation activity. Most of these biological actions have been attributed to theirintrinsic reducing capabilities. They may also offer indirect protection by activatingendogenous defense systems and by modulating cellular signaling processes such asnuclear factor-kappa B (NF-кB activation, activator protein-1(AP-1 DNA binding,glutathione biosynthesis, phosphoinositide 3 (PI3-kinase/protein kinase B (Akt pathway,mitogen-activated protein kinase (MAPK proteins [extracellular signal-regulated proteinkinase (ERK, c-jun N-terminal kinase (JNK and P38 ] activation, and the translocationinto the nucleus of nuclear factor erythroid 2 related factor 2 (Nrf2. This paper covers themost recent literature on the subject, and describes the biological mechanisms of action andprotective effects of dietary polyphenols.

Findings from NSABP Protocol No. B-04: comparison of radical mastectomy with alternative treatments. II. The clinical and biologic significance of medial-central breast cancers

International Nuclear Information System (INIS)

Fisher, B.; Wolmark, N.; Redmond, C.; Deutsch, M.; Fisher, E.R.

1981-01-01

Findings from 1665 women with primary breast cancer, treated at 34 NSABP institutions in Canada and the United States, have failed to demonstrate that patients with medial-central tumors had a greater probability of developing distant metastases or dying than did those with lateral tumors despite the greater incidence of internal mammary (IM) node involvement when tumors are medial-central in location. A comparison of patients with similar clinical nodal status and tumor location who were treated either by radical mastectomy (RM) or by total mastectomy plus radiation therapy (TM + RT) failed to indicate that radiation of IM nodes reduced the probability of distant treatment failure (TF) or mortality. When findings from patients having equivalent clinical nodal status and tumor location treated by TM alone or TM + RT were compared, it was found that the addition of RT failed to alter the probability of the occurrence of a distant TF or of death. This was despite the fact that in the nonradiated group two putative sources of further tumor spread, i.e., positive axillary and IM nodes, were left unremoved and untreated. The findings provide further insight into the biologic significance of the positive lymph node and confirm our prior contention that positive regional lymph nodes are indicators of a host-tumor relationship which permits the development of metastases and that they are not important investigators of distant disease

Analysis of Biological Interactions by Affinity Chromatography: Clinical and Pharmaceutical Applications.

Science.gov (United States)

Hage, David S

2017-06-01

The interactions between biochemical and chemical agents in the body are important in many clinical processes. Affinity chromatography and high-performance affinity chromatography (HPAC), in which a column contains an immobilized biologically related binding agent, are 2 methods that can be used to study these interactions. This review presents various approaches that can be used in affinity chromatography and HPAC to characterize the strength or rate of a biological interaction, the number and types of sites that are involved in this process, and the interactions between multiple solutes for the same binding agent. A number of applications for these methods are examined, with an emphasis on recent developments and high-performance affinity methods. These applications include the use of these techniques for fundamental studies of biological interactions, high-throughput screening of drugs, work with modified proteins, tools for personalized medicine, and studies of drug-drug competition for a common binding agent. The wide range of formats and detection methods that can be used with affinity chromatography and HPAC for examining biological interactions makes these tools attractive for various clinical and pharmaceutical applications. Future directions in the development of small-scale columns and the coupling of these methods with other techniques, such as mass spectrometry or other separation methods, should continue to increase the flexibility and ease with which these approaches can be used in work involving clinical or pharmaceutical samples. © 2016 American Association for Clinical Chemistry.

Early diagnosis of Alzheimer's disease. Clinical significance and future perspectives

International Nuclear Information System (INIS)

Buerger, K.; Teipel, S.J.; Hampel, H.

2000-01-01

Early diagnosis of Alzheimer's disease describes the recognition and diagnosis in patients with very mild dementia. Internationally accepted diagnostic criteria support the diagnosis based on clinical evaluation. Recent advances in structural and functional neuroimaging as well as studies on specific proteins in the cerebro-spinal fluid that are related to distinct pathophysiological disease processes are most promising approaches to defining biological markers of Alzheimer's disease. (orig.) [de

Biologic and Clinical Aspects of Rhabdomyosarcoma

Directory of Open Access Journals (Sweden)

Arya Emami

2017-03-01

Full Text Available Rhabdomyosarcoma (RMS is a muscle-derived tumor and is the most common pediatric soft tissue sarcoma representing 5% of all childhood cancers. Statistically, soft tissue sarcomas account for approximately 10% of all cancers in children, of which more than half of these tumors are RMS. Thus, RMS is a major clinical problem in pediatric oncology. RMS is caused by a disruption in the pathway of primitive mesenchymal stem cells directed towards myogenesis. In most cases of patients diagnosed with RMS there is a genetic or chromosomal alteration involved. In past few years there have been discoveries of more therapeutic approaches that has improved the quality of life in RMS patients and has resulted in a better survival rate in this population from 25% to 60%. However, Additional researches and clinical trials are needed in order to minimize the devastating consequences of the pediatric cancer including RMS. In the current mini review we will briefly discuss current knowledge in RMS focusing on most common biological and clinical aspects of the disease.

Network Expansion and Pathway Enrichment Analysis towards Biologically Significant Findings from Microarrays

Directory of Open Access Journals (Sweden)

Wu Xiaogang

2012-06-01

Full Text Available In many cases, crucial genes show relatively slight changes between groups of samples (e.g. normal vs. disease, and many genes selected from microarray differential analysis by measuring the expression level statistically are also poorly annotated and lack of biological significance. In this paper, we present an innovative approach - network expansion and pathway enrichment analysis (NEPEA for integrative microarray analysis. We assume that organized knowledge will help microarray data analysis in significant ways, and the organized knowledge could be represented as molecular interaction networks or biological pathways. Based on this hypothesis, we develop the NEPEA framework based on network expansion from the human annotated and predicted protein interaction (HAPPI database, and pathway enrichment from the human pathway database (HPD. We use a recently-published microarray dataset (GSE24215 related to insulin resistance and type 2 diabetes (T2D as case study, since this study provided a thorough experimental validation for both genes and pathways identified computationally from classical microarray analysis and pathway analysis. We perform our NEPEA analysis for this dataset based on the results from the classical microarray analysis to identify biologically significant genes and pathways. Our findings are not only consistent with the original findings mostly, but also obtained more supports from other literatures.

Clinical Significance: a Therapeutic Approach Topsychological Assessment in Treatment Planning

Directory of Open Access Journals (Sweden)

Afolabi Olusegun Emmanuel

2015-06-01

Full Text Available Psychological assessment has long been reported as a key component of clinical psychology. This paper examines the complexities surrounding the clinical significance of therapeutic approach to treatment planning. To achieve this objective, the paper searched and used the PsycINFO and PubMed databases and the reference sections of chapters and journal articles to analysed, 1 a strong basis for the usage of therapeutic approach to psychological assessment in treatment plans, 2 explained the conceptual meaning of clinical significant change in therapeutic assessment, 3 answered some of the questions regarding practicability and the clinical significance of therapeutic approach to treatment plans, particularly during or before treatment, 4 linked therapeutic assessment to change in clients’ clinical impression, functioning and therapeutic needs 5 analysed the empirically documenting clinically significant change in therapeutic assessment. Finally, the study suggested that though therapeutic assessment is not sufficient for the systematic study of psychotherapy outcome and process, it is still consistent with both the layman and professional expectations regarding treatment outcome and also provides a precise method for classifying clients as ‘changed’ or ‘unchanged’ on the basis of clinical significance criteria.

pancreatic steatosis: diagnosis and clinical significance

Directory of Open Access Journals (Sweden)

Murat Daðdeviren

2017-03-01

Full Text Available Pancreatic steatosis (PS, with increased use of abdominal imaging in recent years generally appears as incidental. But it is a condition that is often overlooked. The reason for this is not yet fully demonstrated the clinical significance of PS while. However, in recent years, there are some studies conducted on the relationship with ps and other disease such as diabetes, metabolic syndrome, acute and chronic pancreatitis and pancreatic cancer. In this review, the etiology, diagnosis, treatment and clinical characteristics of ps were evaluated in the light of recent literature and current approaches. [J Contemp Med 2017; 7(1.000: 107-112

[Clinical and biological prognostic factors in relapsed acute myeloid leukemia patients].

Science.gov (United States)

Yébenes-Ramírez, Manuel; Serrano, Josefina; Martínez-Losada, Carmen; Sánchez-García, Joaquín

2016-09-02

Acute myeloid leukemia (AML) is the most frequent type of acute leukemia in adults. Despite recent advances in the characterization of pathogenesis of AML, the cure rates are under 40%, being leukemia relapse the most common cause of treatment failure. Leukaemia relapse occurs due to clonal evolution or clonal escape. In this study, we aimed to analyze the clinical and biological factors influencing outcomes in patients with AML relapse. We included a total of 75 AML patients who experienced leukaemia relapse after achieving complete remission. We performed complete immunophenotyping and conventional karyotyping in bone marrow aspirates obtained at diagnosis and at leukemia relapse. Overall survival (OS) of the series was 3.7%±2.3, leukaemia progression being the most common cause of death. Patients relapsing before 12 months and those with adverse cytogenetic-molecular risk had statistically significant worse outcomes. A percentage of 52.5 of patients showed phenotypic changes and 50% cytogenetic changes at relapse. We did not find significant clinical factors predicting clonal evolution. The presence of clonal evolution at relapse did not have a significant impact on outcome. Patients with relapsed AML have a dismal prognosis, especially those with early relapse and adverse cytogenetic-molecular risk. Clonal evolution with phenotypic and cytogenetic changes occurred in half of the patients without predictive clinical factors or impact on outcome. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

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

Science.gov (United States)

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

2013-12-01

Standard clinical significance classifications are based on movement between the "dysfunctional" and "functional" distributions; however, this dichotomy ignores heterogeneity within the "dysfunctional" population. Based on the methodology described by Tingey, Lambert, Burlingame, and Hansen (1996), the present study sought to present a 3-distribution clinical significance model for the 21-item version of the Depression Anxiety Stress Scales (DASS-21; P. F. Lovibond & Lovibond, 1995) using data from a normative sample (n = 2,914), an outpatient sample (n = 1,000), and an inpatient sample (n = 3,964). DASS-21 scores were collected at pre- and post-treatment for both clinical samples, and patients were classified into 1 of 5 categories based on whether they had made a reliable change and whether they had moved into a different functional range. Evidence supported the validity of the 3-distribution model for the DASS-21, since inpatients who were classified as making a clinically significant change showed lower symptom severity, higher perceived quality of life, and higher clinician-rated functioning than those who did not make a clinically significant change. Importantly, results suggest that the new category of recovering is an intermediate point between recovered and making no clinically significant change. Inpatients and outpatients have different treatment goals and therefore use of the concept of clinical significance needs to acknowledge differences in what constitutes a meaningful change. (c) 2013 APA, all rights reserved.

The biology, pathogenesis and clinical aspects of acute lymphoblastic leukemia in children with Down syndrome.

Science.gov (United States)

Lee, P; Bhansali, R; Izraeli, S; Hijiya, N; Crispino, J D

2016-09-01

Children with Down syndrome (DS) are at a 20-fold increased risk for acute lymphoblastic leukemia (DS-ALL). Although the etiology of this higher risk of developing leukemia remains largely unclear, the recent identification of CRLF2 (cytokine receptor like factor 2) and JAK2 mutations and study of the effect of trisomy of Hmgn1 and Dyrk1a (dual-specificity tyrosine phosphorylation-regulated kinase 1A) on B-cell development have shed significant new light on the disease process. Here we focus on the clinical features, biology and genetics of ALL in children with DS. We review the unique characteristics of DS-ALL on both the clinical and molecular levels and discuss the differences in treatments and outcomes in ALL in children with DS compared with those without DS. The identification of new biological insights is expected to pave the way for novel targeted therapies.

The clinical significance and biological function of lncRNA RGMB-AS1 in hepatocellular carcinoma.

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Sheng, Nan; Li, Yannan; Qian, Ruikun; Li, Yichun

2018-02-01

LncRNA RGMB-AS1 has been suggested to play significant roles in lung cancer progression. However, it remains unknown whether lncRNA RGMB-AS1 is involved in the development and progression of hepatocellular carcinoma. In our results, lncRNA RGMB-AS1 was low-expressed in hepatocellular carcinoma tissues and cell lines, and associated with clinical stage, tumor size and metastasis. Survival analysis indicated that lncRNA RGMB-AS1 high was an independent favorable prognostic factor for hepatocellular carcinoma patients. Gain-of-function studies showed up-regulated lncRNA RGMB-AS1 expression suppressed hepatocellular carcinoma cells proliferation, migration and invasion, and promoted cells apoptosis. There was a positively association between lncRNA RGMB-AS1 and RGMB in hepatocellular carcinoma tissues, and up-regulated lncRNA RGMB-AS1 expression increased RGMB mRNA and protein expressions in hepatocellular carcinoma cells. In conclusion, lncRNA RGMB-AS1 serves an anti-oncogenic role in hepatocellular carcinoma. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Piezosurgery applied to implant dentistry: clinical and biological aspects.

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Pereira, Cassiano Costa Silva; Gealh, Walter Cristiano; Meorin-Nogueira, Lamis; Garcia-Júnior, Idelmo Rangel; Okamoto, Roberta

2014-07-01

Piezosurgery is a new and modern technique of bone surgery in implantology. Selective cutting is possible for different ultrasonic frequencies acting only in hard tissues (mineralized), saving vital anatomical structures. With the piezoelectric osteotomy technique, receptor site preparation for implants, autogenous bone graft acquistition (particles and blocks), osteotomy for alveolar bone crest expansion, maxillary sinus lifting, and dental implant removal can be performed accurately and safely, providing excellent clinical and biological results, especially for osteocyte viability. The aim of this review was, through literature review, to present clinical applications of piezosurgery in implant dentistry and outline their advantages and disadvantages over conventional surgical systems. Moreover, this study addressed the biological aspects related to piezosurgery that differentiate it from those of bone tissue approaches. Overall, piezosurgery enables critical operations in simple and fully executable procedures; and effectively, areas that are difficult to access have less risk of soft tissue and neurovascular tissue damage via piezosurgery.

Sonographic ally Detected Architectural Distortion: Clinical Significance

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Kim, Shin Kee; Seo, Bo Kyoung; Yi, Ann; Cha, Sang Hoon; Kim, Baek Hyun; Cho, Kyu Ran; Kim, Young Sik; Son, Gil Soo; Kim, Young Soo; Kim, Hee Young [Korea University Ansan Hospital, Ansan (Korea, Republic of)

2008-12-15

Architectural distortion is a suspicious abnormality for the diagnosis of breast cancer. The aim of this study was to investigate the clinical significance of sonographic ally detected architectural distortion. From January 2006 to June 2008, 20 patients were identified who had sonographic ally detected architectural distortions without a history of trauma or surgery and abnormal mammographic findings related to an architectural distortion. All of the lesions were pathologically verified. We evaluated the clinical and pathological findings and then assessed the clinical significance of the sonographic ally detected architectural distortions. Based on the clinical findings, one (5%) of the 20 patients had a palpable lump and the remaining 19 patients had no symptoms. No patient had a family history of breast cancer. Based on the pathological findings, three (15%) patients had malignancies. The malignant lesions included invasive ductal carcinomas (n = 2) and ductal carcinoma in situ (n = 1). Four (20%) patients had high-risk lesions: atypical ductal hyperplasia (n = 3) and lobular carcinoma in situ (n = 1). The remaining 13 (65%) patients had benign lesions, however, seven (35%) out of 13 patients had mild-risk lesions (three intraductal papillomas, three moderate or florid epithelial hyperplasia and one sclerosing adenosis). Of the sonographic ally detected architectural distortions, 35% were breast cancers or high-risk lesions and 35% were mild-risk lesions. Thus, a biopsy might be needed for an architectural distortion without an associated mass as depicted on breast ultrasound, even though the mammographic findings are normal

Sonographic ally Detected Architectural Distortion: Clinical Significance

International Nuclear Information System (INIS)

Kim, Shin Kee; Seo, Bo Kyoung; Yi, Ann; Cha, Sang Hoon; Kim, Baek Hyun; Cho, Kyu Ran; Kim, Young Sik; Son, Gil Soo; Kim, Young Soo; Kim, Hee Young

2008-01-01

Architectural distortion is a suspicious abnormality for the diagnosis of breast cancer. The aim of this study was to investigate the clinical significance of sonographic ally detected architectural distortion. From January 2006 to June 2008, 20 patients were identified who had sonographic ally detected architectural distortions without a history of trauma or surgery and abnormal mammographic findings related to an architectural distortion. All of the lesions were pathologically verified. We evaluated the clinical and pathological findings and then assessed the clinical significance of the sonographic ally detected architectural distortions. Based on the clinical findings, one (5%) of the 20 patients had a palpable lump and the remaining 19 patients had no symptoms. No patient had a family history of breast cancer. Based on the pathological findings, three (15%) patients had malignancies. The malignant lesions included invasive ductal carcinomas (n = 2) and ductal carcinoma in situ (n = 1). Four (20%) patients had high-risk lesions: atypical ductal hyperplasia (n = 3) and lobular carcinoma in situ (n = 1). The remaining 13 (65%) patients had benign lesions, however, seven (35%) out of 13 patients had mild-risk lesions (three intraductal papillomas, three moderate or florid epithelial hyperplasia and one sclerosing adenosis). Of the sonographic ally detected architectural distortions, 35% were breast cancers or high-risk lesions and 35% were mild-risk lesions. Thus, a biopsy might be needed for an architectural distortion without an associated mass as depicted on breast ultrasound, even though the mammographic findings are normal

Clinical Significance of Immuno phenotypic Markers in Pediatric T-cell Acute Lymphoblastic Leukemia

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SIDHOM, I.; SHAABAN, Kh.; SOLIMAN, S.; HAMDY, N.; YASSIN, D.; SALEM, Sh.; HASSANEIN, H.; MANSOUR, M.T.; EZZAT, S.; EL-ANWAR, W.

2008-01-01

Background: Cell-marker profiling has led to conflicting conclusions about its prognostic significance in T-ALL. Aim: To investigate the prevalence of the expression of CD34, CD10 and myeloid associated antigens (CD13/ CD33) in childhood T-ALL and to relate their presence to initial clinical and biologic features and early response to therapy. Patients and Methods: This study included 67 consecutive patients with newly diagnosed T-ALL recruited from the Children's Cancer Hospital in Egypt during the time period from July 2007 to June 2008. Immuno phenotypic markers and minimal residual disease (MRD) were studied by five-color flow cytometry. Results: The frequency of CD34 was 34.9%, CD10 33.3%, while CD13/CD33 was 18.8%. No significant association was encountered between CD34, CD10 or myeloid antigen positivity and the presenting clinical features as age, sex, TLC and CNS leukemia. Only CD10+ expression had significant association with initial CNS involvement (p=0.039). CD34 and CD13/CD33 expression was significantly associated with T-cell maturation stages (p<0.05). No relationship was observed for age, TLC, gender, NCI risk or CNS involvement with early response to therapy illustrated by BM as well as MRD day 15 and day 42. CD34+, CD13/CD33+ and early T-cell stage had high MRD levels on day 15 that was statistically highly significant (p<0.01), but CD10+ had statistically significant lower MRD level on day 15 (p=0.049). However, only CD34 retained its significance at an MRD cut-off level of 0.01%. Conclusion: CD34, CD10, CD13/CD33 expression, as well as T-cell maturation stages, may have prognostic significance in pediatric T-ALL as they have a significant impact on early clearance of leukemic cells detected by MRD day 15.

Synthetic Biology and the Moral Significance of Artificial Life: A Reply to Douglas, Powell and Savulescu.

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Christiansen, Andreas

2016-06-01

I discuss the moral significance of artificial life within synthetic biology via a discussion of Douglas, Powell and Savulescu's paper 'Is the creation of artificial life morally significant'. I argue that the definitions of 'artificial life' and of 'moral significance' are too narrow. Douglas, Powell and Savulescu's definition of artificial life does not capture all core projects of synthetic biology or the ethical concerns that have been voiced, and their definition of moral significance fails to take into account the possibility that creating artificial life is conditionally acceptable. Finally, I show how several important objections to synthetic biology are plausibly understood as arguing that creating artificial life in a wide sense is only conditionally acceptable. © 2016 John Wiley & Sons Ltd.

Biological and clinical meaning of myeloid antigen expression in the acute lymphocytic leukemia in children

International Nuclear Information System (INIS)

Marsan Suarez, Vianed; Sanchez Segura, Miriam; Socarras Ferrer, Bertha B; Valle Perez, Lazaro O del

2009-01-01

In 238 children presenting with acute lymphoid leukemia (ALL) authors studied the possible association between the myeloid antigens expression with determined biologic and clinic features at disease onset. The cellular immunophenotyping was performed by ultraimmunocytochemical method. From the total of diagnosed ALLs, the 21,8% were LLA-Mi+. There was a lymphadenopathies predominance (71,2%), splenomegaly (65,4%) and hepatomegaly (57,7%) in patients with LLA-Mi+ and very significant differences (p =0,003, p = 0,0068, and p = 0,000, respectively. There was also alight predominance of mediastinum adenopathies, CNS infiltration and hemorrahagic manifestations in patients with LLA-Mi+, no statistically significant. Results showed that in our patients the myeloid antigen expression on the lymphoid blasts influenced on appearance of determined presentation of morphologic and clinical features in children

Growth factors: biological and clinical aspects

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Ruifrok, A.C.C.; McBride, W.H.

1999-01-01

Purpose: The purpose of this meeting summary is to provide an overview of cytokine research and its role in radiation oncology. Methods and Materials: The sixth annual Radiation Workshop was held at the International Festival Institute at Round Top, TX. Results: Presentations of seventeen speakers provided the framework for discussions on the biological and clinical aspects of cytokine research. Conclusion: Orchestration of coordinated cellular responses over the time course of radiation effects requires the interaction of many growth factors with their receptors as well as cell-cell and cell-matrix interactions. Cytokine networks and integrated systems are important in tumor development, cancer treatment, and normal and tumor response to cancer treatment

Toward a biologically significant and usable standard for ozone that will also protect plants

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Paoletti, Elena; Manning, William J.

2007-01-01

Ozone remains an important phytotoxic air pollutant and is also recognized as a significant greenhouse gas. In North America, Europe, and Asia, incidence of high concentrations is decreasing, but background levels are steadily rising. There is a need to develop a biologically significant and usable standard for ozone. We compare the strengths and weaknesses of concentration-based, exposure-based and threshold-based indices, such as SUM60 and AOT40, and examine the O 3 flux concept. We also present major challenges to the development of an air quality standard for ozone that has both biological significance and practicality in usage. - Current standards do not protect vegetation from ozone, but progress is being made

Lycopene metabolism and its biological significance12345

Science.gov (United States)

2012-01-01

The beneficial effects of a high intake of tomatoes and tomato products on the risk of certain chronic diseases have been presented in many epidemiologic studies, with the suggestion that lycopene (a major carotenoid in tomatoes) is a micronutrient with important health benefits. Within the past few years, we have gained greater knowledge of the metabolism of lycopene and the biological effects of lycopene derivatives. In particular, the characterization and study of β-carotene 9′,10′-oxygenase has shown that this enzyme can catalyze the excentric cleavage of both provitamin and non–provitamin A carotenoids to form apo-10′-carotenoids, including apo-10′-lycopenoids from lycopene. This raised an important question of whether the effect of lycopene on various cellular functions and signaling pathways is a result of the direct actions of intact lycopene or its derivatives. Several reports, including our own, support the notion that the biological activities of lycopene can be mediated by apo-10′-lycopenoids. More research is clearly needed to identify and characterize additional lycopene metabolites and their biological activities, which will potentially provide invaluable insights into the mechanisms underlying the effects of lycopene in humans. PMID:23053559

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

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Pistelli, Mirco, E-mail: mirco.pistelli@alice.it; Caramanti, Miriam [Clinica di Oncologia Medica, AO Ospedali Riuniti-Ancona, Università Politecnica delle Marche, Ancona 60020 (Italy); Biscotti, Tommasina; Santinelli, Alfredo [Anatomia Patologica, AO Ospedali Riuniti-Ancona, Università Politecnica delle Marche, Ancona 60020 (Italy); Pagliacci, Alessandra; De Lisa, Mariagrazia; Ballatore, Zelmira; Ridolfi, Francesca; Maccaroni, Elena; Bracci, Raffaella; Berardi, Rossana; Battelli, Nicola; Cascinu, Stefano [Clinica di Oncologia Medica, AO Ospedali Riuniti-Ancona, Università Politecnica delle Marche, Ancona 60020 (Italy)

2014-06-27

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.

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

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Mirco Pistelli

2014-06-01

Full Text Available 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.

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

International Nuclear Information System (INIS)

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

Respiratory neuroplasticity - Overview, significance and future directions.

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Fuller, David D; Mitchell, Gordon S

2017-01-01

Neuroplasticity is an important property of the neural system controlling breathing. However, our appreciation for its importance is still relatively new, and we have much to learn concerning different forms of plasticity, their underlying mechanisms, and their biological and clinical significance. In this brief review, we discuss several well-studied models of respiratory plasticity, including plasticity initiated by inactivity in the respiratory system, intermittent and sustained hypoxia, and traumatic injury to the spinal cord. Other aspects of respiratory plasticity are considered in other contributions to this special edition of Experimental Neurology on respiratory plasticity. Finally, we conclude with discussions concerning the biological and clinical significance of respiratory motor plasticity, and areas in need of future research effort. Copyright © 2016. Published by Elsevier Inc.

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

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Joshua G X Wong

Full Text Available 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.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.On admission, female gender (p38°C (p38°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.Clinical risk factors associated with clinically significant bleeding were identified. This model may be useful to complement clinical judgement in triaging adult dengue patients given the dynamic nature of acute dengue, particularly in pre-identifying those less likely to develop clinically significant bleeding.

Nanomaterial-Based Electrochemical Immunosensors for Clinically Significant Biomarkers

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Niina J. Ronkainen

2014-06-01

Full Text Available Nanotechnology has played a crucial role in the development of biosensors over the past decade. The development, testing, optimization, and validation of new biosensors has become a highly interdisciplinary effort involving experts in chemistry, biology, physics, engineering, and medicine. The sensitivity, the specificity and the reproducibility of biosensors have improved tremendously as a result of incorporating nanomaterials in their design. In general, nanomaterials-based electrochemical immunosensors amplify the sensitivity by facilitating greater loading of the larger sensing surface with biorecognition molecules as well as improving the electrochemical properties of the transducer. The most common types of nanomaterials and their properties will be described. In addition, the utilization of nanomaterials in immunosensors for biomarker detection will be discussed since these biosensors have enormous potential for a myriad of clinical uses. Electrochemical immunosensors provide a specific and simple analytical alternative as evidenced by their brief analysis times, inexpensive instrumentation, lower assay cost as well as good portability and amenability to miniaturization. The role nanomaterials play in biosensors, their ability to improve detection capabilities in low concentration analytes yielding clinically useful data and their impact on other biosensor performance properties will be discussed. Finally, the most common types of electroanalytical detection methods will be briefly touched upon.

Biological variability in biomechanical engineering research: Significance and meta-analysis of current modeling practices.

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Cook, Douglas; Julias, Margaret; Nauman, Eric

2014-04-11

Biological systems are characterized by high levels of variability, which can affect the results of biomechanical analyses. As a review of this topic, we first surveyed levels of variation in materials relevant to biomechanics, and compared these values to standard engineered materials. As expected, we found significantly higher levels of variation in biological materials. A meta-analysis was then performed based on thorough reviews of 60 research studies from the field of biomechanics to assess the methods and manner in which biological variation is currently handled in our field. The results of our meta-analysis revealed interesting trends in modeling practices, and suggest a need for more biomechanical studies that fully incorporate biological variation in biomechanical models and analyses. Finally, we provide some case study example of how biological variability may provide valuable insights or lead to surprising results. The purpose of this study is to promote the advancement of biomechanics research by encouraging broader treatment of biological variability in biomechanical modeling. Copyright © 2014 Elsevier Ltd. All rights reserved.

Clinical and Biological Predictors of Plasma Levels of Soluble RAGE in Critically Ill Patients: Secondary Analysis of a Prospective Multicenter Observational Study

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Thibaut Pranal

2018-01-01

Full Text Available Rationale. Although soluble forms of the receptor for advanced glycation end products (RAGE have been recently proposed as biomarkers in multiple acute or chronic diseases, few studies evaluated the influence of usual clinical and biological parameters, or of patient characteristics and comorbidities, on circulating levels of soluble RAGE in the intensive care unit (ICU setting. Objectives. To determine, among clinical and biological parameters that are usually recorded upon ICU admission, which variables, if any, could be associated with plasma levels of soluble RAGE. Methods. Data for this ancillary study were prospectively obtained from adult patients with at least one ARDS risk factor upon ICU admission enrolled in a large multicenter observational study. At ICU admission, plasma levels of total soluble RAGE (sRAGE and endogenous secretory (esRAGE were measured by duplicate ELISA and baseline patient characteristics, comorbidities, and usual clinical and biological indices were recorded. After univariate analyses, significant variables were used in multivariate, multidimensional analyses. Measurements and Main Results. 294 patients were included in this ancillary study, among whom 62% were admitted for medical reasons, including septic shock (11%, coma (11%, and pneumonia (6%. Although some variables were associated with plasma levels of RAGE soluble forms in univariate analysis, multidimensional analyses showed no significant association between admission parameters and baseline plasma sRAGE or esRAGE. Conclusions. We found no obvious association between circulating levels of soluble RAGE and clinical and biological indices that are usually recorded upon ICU admission. This trial is registered with NCT02070536.

76 FR 8708 - Availability of an Environmental Assessment and Finding of No Significant Impact for a Biological...

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2011-02-15

...] Availability of an Environmental Assessment and Finding of No Significant Impact for a Biological Control Agent... have been prepared by the Animal and Plant Health Inspection Service relative to a proposed biological... review and analysis of environmental impacts associated with the proposed biological control program...

76 FR 13597 - Availability of an Environmental Assessment and Finding of No Significant Impact for a Biological...

Science.gov (United States)

2011-03-14

... Significant Impact for a Biological Control Agent for Hawkweeds AGENCY: Animal and Plant Health Inspection... States as a biological control agent to reduce the severity of infestations of hawkweeds (Hieracium spp..., into the continental United States for the biological control of hawkweeds (Hieracium pilosella, H...

Variability in anatomical features of human clavicle: Its forensic anthropological and clinical significance

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Jagmahender Singh Sehrawat

2016-06-01

Full Text Available Bones can reflect the basic framework of human body and may provide valuable information about the biological identity of the deceased. They, often, survive the morphological alterations, taphonomic destructions, decay/mutilation and decomposition insults. In-depth knowledge of variations in clavicular shape, size and its dimensions is very important from both clinical (fixation of clavicular fractures using external or inter-medullary devices, designing orthopedic fixation devices as well as forensic anthropological perspectives. Human clavicle is the most frequently fractured bone of human skeleton, possessing high degree of variability in its anatomical, biomechanical and morphological features. Extended period of skeletal growth (up to third decade in clavicle imparts it an additional advantage for forensic identification purposes. In present study, five categories of clavicular features like lengths, diameters, angles, indices and robustness were examined to explore the suitability of collarbone for forensic and clinical purposes. For this purpose, 263 pairs of adult clavicles (195 Males and 68 Females were collected from autopsied cadavers and were studied for 13 anatomical features. Gender and occupational affiliations of cadavers were found to have significant influences on anatomical dimensions of their clavicles. Product index, weight and circumference of collarbone were found the best univariate variables, discriminating sex of more than 80% individuals. The best multivariate Function-I (DF: -17.315 + 0.054 CL-L+0.196 CC-R+0.184 DM-L could identify sex and occupation of 89.4% (89.2% Male and 89.7% Female and 65.4% individuals, respectively. All clavicular variables were found bilaterally asymmetric; left clavicles being significantly longer in length, lighter in weight, smooth in texture and less curved than the right side bones. Among non-metric traits, sub-clavian groove, nutrient foramina and ‘type’ of clavicle exhibited

A Meta-analysis for the Diagnostic Performance of Transient Elastography for Clinically Significant Portal Hypertension.

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You, Myung-Won; Kim, Kyung Won; Pyo, Junhee; Huh, Jimi; Kim, Hyoung Jung; Lee, So Jung; Park, Seong Ho

2017-01-01

We aimed to evaluate the correlation between liver stiffness measurement using transient elastography (TE-LSM) and hepatic venous pressure gradient and the diagnostic performance of TE-LSM in assessing clinically significant portal hypertension through meta-analysis. Eleven studies were included from thorough literature research and selection processes. The summary correlation coefficient was 0.783 (95% confidence interval [CI], 0.737-0.823). Summary sensitivity, specificity and area under the hierarchical summary receiver operating characteristic curve (AUC) were 87.5% (95% CI, 75.8-93.9%), 85.3 % (95% CI, 76.9-90.9%) and 0.9, respectively. The subgroup with low cut-off values of 13.6-18 kPa had better summary estimates (sensitivity 91.2%, specificity 81.3% and partial AUC 0.921) than the subgroup with high cut-off values of 21-25 kPa (sensitivity 71.2%, specificity 90.9% and partial AUC 0.769). In summary, TE-LSM correlated well with hepatic venous pressure gradient and represented good diagnostic performance in diagnosing clinically significant portal hypertension. For use as a sensitive screening tool, we propose using low cut-off values of 13.6-18 kPa in TE-LSM. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Expression and biological-clinical significance of hTR, hTERT and CKS2 in washing fluids of patients with bladder cancer

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Talesa Vincenzo N

2010-10-01

Full Text Available Abstract Background at present, pathogenesis of bladder cancer (BC has not been fully elucidated. Aim of this study is to investigate the role of human telomerase RNA (hTR, human telomerase reverse transcriptase (hTERT and CDC28 protein kinase regulatory subunit 2 (CKS2 in bladder carcinogenesis and their possible clinical significance; Methods the transcript levels of hTR, hTERT and CKS2 were quantified by Real time reverse transcriptase chain reaction in exfoliated cells from bladder washings of 36 patients with BC and 58 controls. The statistical significance of differences between BC bearing patients and control groups, in the general as well as in the stratified analysis (superficial or invasive BC, was assessed by Student's t test. Non parametric Receiver Operating Characteristics analysis (ROC was performed to ascertain the accuracy of study variables to discriminate between BC and controls. The clinical value of concomitant examination of hTR, hTERT and CKS2 was evaluated by logistic regression analysis; Results a significant decrease in hTR and a significant increase in hTERT or CKS2 gene expression were found between BC bearing patients and controls, as well as in the subgroups analysis. The area under the curve (AUC indicated an average discrimination power for the three genes, both in the general and subgroups analysis, when singularly considered. The ability to significantly discriminate between superficial and invasive BC was observed only for hTR transcript levels. A combined model including hTR and CKS2 was the best one in BC diagnosis; Conclusions our results, obtained from a sample set particularly rich of exfoliated cells, provide further molecular evidence on the involvement of hTR, hTERT and CKS2 gene expression in BC carcinogenesis. In particular, while hTERT and CKS2 gene expression seems to have a major involvement in the early stages of the disease, hTR gene expression, seems to be more involved in progression. In

Energy deposition and the formation of biologically significant lesions by accelerated ions

International Nuclear Information System (INIS)

Kiefer, J.

1985-01-01

The assumption that the number of biologically significant lesions depends only on the amount of of energy absorbed in a critical cellular site is not able to explain the increase of RBE with LET and leads to large discrepancies between predicted and measured inactivation cross sections in the LET range between 20 and 200 keV.μm -1 . It has, therefore, to be concluded that not only the amount of energy absorbed but also the spatial pattern of this deposition plays a decisive role. In the model presented it is postulated that two or more energy deposition events in nanometre sites are required for the formation of biologically significant lesions. This cooperative action has to take place in very short times so that only interactions within a single particle track contribute. The mathematical treatment will be outlined and qualitatively shown that the model is able to predict RBE-LET relationships. The calculations use a track structure model based on classical collision mechanics. It is compared with existing experimental results showing good agreement at least for higher particle energies. (author)

Aberrations of chromosome 8 in myelodysplastic syndromes: Clinical and biological significance

Directory of Open Access Journals (Sweden)

Marisavljević Dragomir

2006-01-01

Full Text Available Introduction: Rearrangements of any single chromosome in human karyotype have been reported in patients with pMDS. Objective: To examine the role of aberrations of chromosome 8 in pathogenesis, clinical presentation and progression of myelodysplastic syndromes. Method: Cytogenetic analysis of bone marrow cells was carried out by direct method and by means of 24- and/or 48-hour unstimulated cell culture. Chromosomes were obtained by modified method of HG-bands. Results: On presentation, 109 out of 271 successfully karyotyped patients (40,2% had abnormal karyotypes. Among them, 22 patients (10.9% had aberrations of chromosome 8. Ten patients had trisomy 8 as "simple" aberration whilst additional three cases had trisomy 8 included in "complex" karyotypes (≥3 chromosomes. Cases with constitutional trisomy 8 mosaicism (CT8M were excluded using the chromosome analyses of PHA-stimulated blood cultures. On the contrary, monosomy (seven patients or deletion of chromosome 8 (two patients were exclusively found in "complex" karyotypes. During prolonged cytogenetic follow-up, trisomy 8 was not recorded in evolving karyotypes. In contrast, trisomy 8 disappeared in two cases during subsequent cytogenetic studies, i.e. 23 and 72 months from diagnosis, accompanied in one patient with complete hematological remission. No difference regarding age, sex, cytopenia, blood and marrow blast count or response to treatment was found between patients with trisomy 8 as the sole aberration compared to those with normal cytogenetics. Median survival of patients with trisomy 8 as the sole aberration was 27 months, as compared to 32 months in patients with normal cytogenetics (p=0.468, whilst median survival of patients with aberrations of chromosome 8 included in "complex" karyotypes was only 4 months. Conclusion: Aberrations of chromosome 8 are common in patients with pMDS. The presence of a clone with trisomy 8 is not always the sign of disease progression or poor

Biological significance of sperm whale responses to sonar: Comparison with anti-predator responses

NARCIS (Netherlands)

Curé, C.; Isojunno, S.; Visser, F.; Wensveen, P.J.; Sivle, L.D.; Kvadsheim, P.H.; Lam, F.A.; Miller, P.J.O.

2016-01-01

A key issue when investigating effects of anthropogenic noise on cetacean behavior is to identify the biological significance of the responses. Predator presence can be considered a natural high-level disturbance stimulus to which prey animals have evolved adaptive response strategies to reduce

Clinical impact of concomitant immunomodulators on biologic therapy: Pharmacokinetics, immunogenicity, efficacy and safety.

Science.gov (United States)

Xu, Zhenhua; Davis, Hugh M; Zhou, Honghui

2015-03-01

Immune-mediated inflammatory diseases encompass a variety of different clinical syndromes, manifesting as either common diseases such as rheumatoid arthritis (RA), inflammatory bowel disease (IBD) and psoriasis, or rare diseases such as cryopyrin-associated periodic syndromes. The therapy for these diseases often involves the use of a wide range of drugs including nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, immunomodulators, and biologic therapies. Due to the abundance of relevant clinical data, this article provides a general overview on the clinical impact of the concomitant use of immunomodulators and biologic therapies, with a focus on anti-tumor necrosis factor-α agents (anti-TNFα), for the treatment of RA and Crohn's disease (CD). Compared to biologic monotherapy, concomitant use of immunomodulators (methotrexate, azathioprine, and 6-mercaptopurine) often increases the systemic exposure of the anti-TNFα agent and decreases the formation of antibodies to the anti-TNFα agent, consequently enhancing clinical efficacy. Nevertheless, long-term combination therapy with immunomodulators and anti-TNFα agents may be associated with increased risks of serious infections and malignancies. Therefore, the determination whether combination therapy is suitable for a patient should always be based on an individualized benefit-risk evaluation. More research should be undertaken to identify and validate prognostic markers for predicting patients who would benefit the most and those who are at greater risk from combination therapy with immunomodulators and anti-TNFα agents. © 2015, The American College of Clinical Pharmacology.

Orbitofrontal lesions eliminate signalling of biological significance in cue-responsive ventral striatal neurons.

Science.gov (United States)

Cooch, Nisha K; Stalnaker, Thomas A; Wied, Heather M; Bali-Chaudhary, Sheena; McDannald, Michael A; Liu, Tzu-Lan; Schoenbaum, Geoffrey

2015-05-21

The ventral striatum has long been proposed as an integrator of biologically significant associative information to drive actions. Although inputs from the amygdala and hippocampus have been much studied, the role of prominent inputs from orbitofrontal cortex (OFC) are less well understood. Here, we recorded single-unit activity from ventral striatum core in rats with sham or ipsilateral neurotoxic lesions of lateral OFC, as they performed an odour-guided spatial choice task. Consistent with prior reports, we found that spiking activity recorded in sham rats during cue sampling was related to both reward magnitude and reward identity, with higher firing rates observed for cues that predicted more reward. Lesioned rats also showed differential activity to the cues, but this activity was unbiased towards larger rewards. These data support a role for OFC in shaping activity in the ventral striatum to represent the biological significance of associative information in the environment.

Selenium: environmental significance, pollution, and biological treatment technologies.

Science.gov (United States)

Tan, Lea Chua; Nancharaiah, Yarlagadda V; van Hullebusch, Eric D; Lens, Piet N L

2016-01-01

Selenium is an essential trace element needed for all living organisms. Despite its essentiality, selenium is a potential toxic element to natural ecosystems due to its bioaccumulation potential. Though selenium is found naturally in the earth's crust, especially in carbonate rocks and volcanic and sedimentary soils, about 40% of the selenium emissions to atmospheric and aquatic environments are caused by various industrial activities such as mining-related operations. In recent years, advances in water quality and pollution monitoring have shown that selenium is a contaminant of potential environmental concern. This has practical implications on industry to achieve the stringent selenium regulatory discharge limit of 5μgSeL(-1) for selenium containing wastewaters set by the United States Environmental Protection Agency. Over the last few decades, various technologies have been developed for the treatment of selenium-containing wastewaters. Biological selenium reduction has emerged as the leading technology for removing selenium from wastewaters since it offers a cheaper alternative compared to physico-chemical treatments and is suitable for treating dilute and variable selenium-laden wastewaters. Moreover, biological treatment has the advantage of forming elemental selenium nanospheres which exhibit unique optical and spectral properties for various industrial applications, i.e. medical, electrical, and manufacturing processes. However, despite the advances in biotechnology employing selenium reduction, there are still several challenges, particularly in achieving stringent discharge limits, the long-term stability of biogenic selenium and predicting the fate of bioreduced selenium in the environment. This review highlights the significance of selenium in the environment, health, and industry and biotechnological advances made in the treatment of selenium contaminated wastewaters. The challenges and future perspectives are overviewed considering recent

Correlation of microdosimetric measurements with relative biological effectiveness from clinical experience for two neutron therapy beams

International Nuclear Information System (INIS)

Stinchcomb, T.G.; Kuchnir, F.T.; Myrianthopoulos, L.C.; Horton, J.L. Jr.; Roberts, W.K.

1986-01-01

Microdosimetric measurements were made for the neutron therapy beams at the University of Chicago and at the Cleveland Clinic with the same geometry and phantom material using the same tissue-equivalent spherical proportional counter and standard techniques. The energy deposition spectra (dose distributions in lineal energy) are compared for these beams and for their scattered components (direct beam blocked). The model of dual radiation action (DRA) of Kellerer and Rossi is employed to interpret these data in terms of biological effectiveness over this limited range of radiation qualities. The site-diameter parameter of the DRA theory is determined for the Cleveland beam by setting the biological effectiveness (relative to 60 Co gamma radiation) equal to the relative biological effectiveness value deduced from radiobiology experiments and clinical experience. The resulting value of this site-diameter parameter is then used to predict the biological effectiveness of the Chicago beam. The prediction agrees with the value deduced from radiobiology and clinical experience. The biological effectiveness of the scattered components of both beams is also estimated using the model

Clinical and biological significance of isolated Y chromosome loss in myelodysplastic syndromes and chronic myelomonocytic leukemia. A report from the Spanish MDS Group.

Science.gov (United States)

Nomdedeu, Meritxell; Pereira, Arturo; Calvo, Xavier; Colomer, Joan; Sole, Francesc; Arias, Amparo; Gomez, Candida; Luño, Elisa; Cervera, Jose; Arnan, Montserrat; Pomares, Helena; Ramos, Fernando; Oiartzabal, Itziar; Espinet, Blanca; Pedro, Carme; Arrizabalaga, Beatriz; Blanco, María Laura; Tormo, Mar; Hernandez-Rivas, Jesus Maria; Díez-Campelo, María; Ortega, Margarita; Valcárcel, David; Cedena, Maria-Teresa; Collado, Rosa; Grau, Javier; Granada, Isabel; Sanz, Guillermo; Campo, Elias; Esteve, Jordi; Costa, Dolors

2017-12-01

Isolate loss of chromosome Y (-Y) in myelodysplastic syndromes (MDS) is associated to a better outcome but it is also well described as an age-related phenomenon. In this study we aimed to analyze the prognostic impact of -Y in the context of the IPSS-R cytogenetic classification, evaluate the clinical significance of the percentage of metaphases with isolated -Y, and test whether finding -Y may predispose to over-diagnose MDS in patients with borderline morphological features. We evaluated 3581 male patients from the Spanish MDS Registry with a diagnosis of MDS or chronic myelomonocytic leukemia (CMML). -Y was identified in 177 patients (4.9%). Compared with the 2246 male patients with normal karyotype, -Y group showed a reduced risk of leukemic transformation that did not translate into a survival advantage. The overall survival and the risk of leukemic transformation were not influenced by the percentage of metaphases with -Y. The -Y group was not enriched in patients with minor morphologic traits of dysplasia, suggesting that the better outcome in the -Y group cannot be explained by enrichment in cases misdiagnosed as MDS. In conclusion, our results support the current recommendation of classifying patients with -Y within the very good risk category of the IPSS-R for MDS and rule out a selection bias as a possible explanation of this better outcome. An analysis of the molecular basis of MDS with isolated -Y would be of interest as it may provide a biological basis of protection against progression to acute leukemia. Copyright © 2017 Elsevier Ltd. All rights reserved.

Multiple daily fractionation in radiotherapy: biological rationale and preliminary clinical experiences

Energy Technology Data Exchange (ETDEWEB)

Arcangeli, G [Instituto Medico Scientifico, Rome (Italy). Dept. of Oncology; Mauro, F; Morelli, D; Nervi, C

1979-09-01

The biological bases of radiation dose fractionation are reviewed and discussed with special emphasis on reassortment. Experimental data on animal model systems are presented to clarify that reassortment has to be added to sublethal damage repair and reoxygenation in the rationale for an optimized radiotherapy course according to tumor cell kinetics. Clinical results on several human tumors treated with twice or thrice daily fractions are described. These results show that some clinically radioresistant tumors (especially if not characterized by a relatively long clinical doubling line) can be satisfactorily dealt with using multiple daily fractionation. Clinical observations indicate that a relatively high cumulative daily dose (200 + 150 + 150 rad) can be safely administered.

Quantifying the Clinical Significance of Cannabis Withdrawal

Science.gov (United States)

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

Quantifying the clinical significance of cannabis withdrawal.

Directory of Open Access Journals (Sweden)

David J Allsop

Full Text Available 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.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.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.

Biological characteristics and clinical outcome of triple negative primary breast cancer in older women - comparison with their younger counterparts.

Directory of Open Access Journals (Sweden)

Binafsha M Syed

Full Text Available Triple negative (ER, PgR and HER2 negative breast cancers (TNBCs are often considered as a poor prognostic phenotype. There is dearth of evidence showing the prevalence and biological behaviour of TNBCs in older women. This study aimed to analyse their biological characteristics in comparison with a well characterised younger series from a single centre with long term clinical follow-up. Over 37 years (1973-2010, 1,758 older (≥70 years women with early operable (<5 cm primary breast cancer were managed in a dedicated clinic and have complete clinical information available. Of these 813 patients underwent primary surgery and 575 had good quality tumour samples available for tissue microarray analysis using indirect immunohistochemistry. A total of 127 patients (22.1% had TNBCs and full biological analysis of 15 biomarkers was performed. The results were compared with those of their younger (<70 years counterparts 342 (18.9% from a previously characterised, consecutive series of primary breast cancer treated in the same unit (1986-1998. The 127 older patients with TNBCs showed lower rates of Ki67 and CK 7/8 positivity and high rates of bcl2 and CK18 positivity when compared with their younger counterparts (p<0.05. There was no significant difference in the long term clinical outcome between the two age groups, despite the fact that 47% of the younger patients had adjuvant chemotherapy, while none in the older cohort received such treatment. EGFR, axillary stage and pathological size showed prognostic significance in older women with TNBCs on univariate analysis. Despite not having received adjuvant chemotherapy, the older series had clinical outcome similar to the younger patients almost half of whom had chemotherapy. This appears to be related to other biomarkers (in addition to ER/PgR/HER2 eg Ki67, bcl2 and cytokeratins which have different expression patterns influencing prognosis.

[Clinical treatment adherence of health care workers and students exposed to potentially infectious biological material].

Science.gov (United States)

Almeida, Maria Cristina Mendes de; Canini, Silvia Rita Marin da Silva; Reis, Renata Karina; Toffano, Silmara Elaine Malaguti; Pereira, Fernanda Maria Vieira; Gir, Elucir

2015-04-01

To assess adherence to clinical appointments by health care workers (HCW) and students who suffered accidents with potentially infectious biological material. A retrospective cross-sectional study that assessed clinical records of accidents involving biological material between 2005 and 2010 in a specialized unit. A total of 461 individuals exposed to biological material were treated, of which 389 (84.4%) were HCWs and 72 (15.6%) students. Of the 461 exposed individuals, 307 (66.6%) attended a follow-up appointment. Individuals who had suffered an accident with a known source patient were 29 times more likely to show up to their scheduled follow-up appointments (OR: 29.98; CI95%: 16.09-55.83). The predictor in both univariate and multivariate analyses for adherence to clinical follow-up appointment was having a known source patient with nonreactive serology for the human immunodeficiency virus and/or hepatitis B and C.

Concordant bone marrow involvement of diffuse large B-cell lymphoma represents a distinct clinical and biological entity in the era of immunotherapy

DEFF Research Database (Denmark)

Yao, Zhilei; Deng, Lijuan; Xu-Monette, Z Y

2018-01-01

In diffuse large B-cell lymphoma (DLBCL), the clinical and biological significance of concordant and discordant bone marrow (BM) involvement have not been well investigated. We evaluated 712 de novo DLBCL patients with front-line rituximab-containing treatment, including 263 patients with positiv...

Biological significance of soluble IL-2 receptor

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Calogero Caruso

1993-01-01

Full Text Available A NUMBER of receptors for growth factors and differentiation antigens have been found to be secreted or released by cells. Following mononuclear cell (MNC activation and interleukin-2 receptor (IL-2R expression, a soluble form of the Alpha;-chain of IL-2R (sIL-2R is released. The sIL-2R has been shown to be present in the culture supernatants of activated MNCs as well as in normal sera and, in higher amounts, in sera from subjects affected by several diseases including neoplastic, infectious and autoimmune ones, and in sera from transplanted patients suffering allograft rejection. The blood sIL-2R levels depend on the number of producing cells and the number of molecules per cell, so that sIL-2R blood values may represent an index of the number and the functional state of producing cells, both normal and neoplastic. Thus, monitoring of the immune system, mostly T-cells and haematological malignancies might be targets for the measurement of sIL-2R. Since many conditions may influence sIL-2R production, little diagnostic use may result from these measurements. However, since blood sIL-2R levels may correlate with disease progression and/or response to therapy, their measurement may be a useful index of activity and extent of disease. The precise biological role of the soluble form of the IL-2R is still a matter of debate. However, we know that increased sIL-2R levels may be observed in association with several immunological abnormalities and that sIL-2R is able to bind IL-2. It is conceivable then that in these conditions the excess sIL-2R released in vivo by activated lymphoid cells or by neoplastic cells may somehow regulate IL-2-dependent processes. On the other hand, it cannot exclude that sIL-2R is a by-product without biological significance. Finally, it is puzzling that in many conditions in which an increase of blood sIL-2R values has been observed, MNCs display a decreased in vitro capacity to produce sIL-2R. These seemingly contrasting

Biologically effective dose distribution based on the linear quadratic model and its clinical relevance

International Nuclear Information System (INIS)

Lee, Steve P.; Leu, Min Y.; Smathers, James B.; McBride, William H.; Parker, Robert G.; Withers, H. Rodney

1995-01-01

Purpose: Radiotherapy plans based on physical dose distributions do not necessarily entirely reflect the biological effects under various fractionation schemes. Over the past decade, the linear-quadratic (LQ) model has emerged as a convenient tool to quantify biological effects for radiotherapy. In this work, we set out to construct a mechanism to display biologically oriented dose distribution based on the LQ model. Methods and Materials: A computer program that converts a physical dose distribution calculated by a commercially available treatment planning system to a biologically effective dose (BED) distribution has been developed and verified against theoretical calculations. This software accepts a user's input of biological parameters for each structure of interest (linear and quadratic dose-response and repopulation kinetic parameters), as well as treatment scheme factors (number of fractions, fractional dose, and treatment time). It then presents a two-dimensional BED display in conjunction with anatomical structures. Furthermore, to facilitate clinicians' intuitive comparison with conventional fractionation regimen, a conversion of BED to normalized isoeffective dose (NID) is also allowed. Results: Two sample cases serve to illustrate the application of our tool in clinical practice. (a) For an orthogonal wedged pair of x-ray beams treating a maxillary sinus tumor, the biological effect at the ipsilateral mandible can be quantified, thus illustrates the so-called 'double-trouble' effects very well. (b) For a typical four-field, evenly weighted prostate treatment using 10 MV x-rays, physical dosimetry predicts a comparable dose at the femoral necks between an alternate two-fields/day and four-fields/day schups. However, our BED display reveals an approximate 21% higher BED for the two-fields/day scheme. This excessive dose to the femoral necks can be eliminated if the treatment is delivered with a 3:2 (anterio-posterior/posterio-anterior (AP

The clinical features of alcohol use disorders in biological and step-fathers that predict risk for alcohol use disorders in offspring.

Science.gov (United States)

Kendler, Kenneth S; Ohlsson, Henrik; Edwards, Alexis; Sundquist, Jan; Sundquist, Kristina

2017-12-01

Given that Alcohol Use Disorder (AUD) is clinically heterogeneous, can we, in a large epidemiological sample using public registries, identify clinical features of AUD cases in biological and step-fathers that index, respectively, genetic and familial-environmental risk for AUD in their offspring? From all father-offspring pairs where the father had AUD and the offspring was born 1960-1990, we identified not-lived-with (NLW) biological fathers (n = 38,376) and step-father pairs (n = 9,711). The relationship between clinical and historical features of the father's AUD and risk for AUD in offspring was assessed by linear hazard regression. Age at first registration for AUD and recurrence of AUD registration were significantly stronger predictors of risk for AUD in the offspring of NLW fathers than in step-fathers. By contrast, number of AUD registrations in NLW fathers and step-fathers were equally predictive of risk for AUD in offspring. However, while the number of step-father AUD registrations that occurred when he was living them with significantly predicted risk for AUD in his step-children, the number of registrations that occurred when not residing with his step-children was unassociated with their AUD risk. In an epidemiological sample, we could meaningfully differentiate between features of AUD in fathers that indexed genetic risk which was transmitted to biological offspring (early age at onset and recurrence) versus indexed environmental risk (registrations while rearing) which increased risk in step-children. © 2017 Wiley Periodicals, Inc.

Biological and chemical weapons of mass destruction: updated clinical therapeutic countermeasures since 2003.

Science.gov (United States)

Pettineo, Christopher; Aitchison, Robert; Leikin, Scott M; Vogel, Stephen N; Leikin, Jerrold B

2009-01-01

The objective of this article is to provide updated treatment options for bioterrorism agents. This updated synopsis includes recent clinical cases and treatment recommendations that have arisen in the last 5 years. The decontamination, treatment, and disposition of these biologic and chemical agents are presented alphabetically by agent type: biologic, chemical, and radiologic/nuclear. The information provided outlines only new treatment options since 2003.

Confidence intervals for effect sizes: compliance and clinical significance in the Journal of Consulting and clinical Psychology.

Science.gov (United States)

Odgaard, Eric C; Fowler, Robert L

2010-06-01

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 editorial effort to improve statistical reporting practices in any APA journal in at least a decade, in this article we investigate the efficacy of that change. All intervention studies published in JCCP in 2003, 2004, 2007, and 2008 were reviewed. Each article was coded for method of clinical significance, type of ES, and type of associated CI, broken down by statistical test (F, t, chi-square, r/R(2), and multivariate modeling). By 2008, clinical significance compliance was 75% (up from 31%), with 94% of studies reporting some measure of ES (reporting improved for individual statistical tests ranging from eta(2) = .05 to .17, with reasonable CIs). Reporting of CIs for ESs also improved, although only to 40%. Also, the vast majority of reported CIs used approximations, which become progressively less accurate for smaller sample sizes and larger ESs (cf. Algina & Kessleman, 2003). Changes are near asymptote for ESs and clinical significance, but CIs lag behind. As CIs for ESs are required for primary outcomes, we show how to compute CIs for the vast majority of ESs reported in JCCP, with an example of how to use CIs for ESs as a method to assess clinical significance.

Biological and clinical dosimetry, July 1, 1964 to December 31, 1984. Final report

International Nuclear Information System (INIS)

Laughlin, J.S.; Zeitz, L.

1986-01-01

The goal was to develop systems for the determination of absorbed dose in biological research and clinical applications. The primary method under study is the local absorbed dose calorimeter. In addition, secondary dosimetric systems such as ionization chambers, chemical dosimeters and thermoluminescent dosimeters (TLD) are being developed and applied to provide an absolute basis for the evaluation and comparison of experiments, treatments and other procedures using radiation. In keeping with these objectives this project has accomplished significant advances in the following areas: (1) local absorbed dose calorimetry; (2) neutron dosimetry; (3) dosimetry of ultra-high intensity radiation sources; (4) solid state detector and germanium gamma camera program; (5) dosimetry for brachytherapy; and (6) ''non-isolated sensor'' calorimeters

Identification of clinically significant drug-drug interactions in cardiac ...

African Journals Online (AJOL)

Purpose: To identify clinically significant potential drug-drug interactions in cardiac intensive care units of two tertiary care ... hypertension, hyperlipidemia, diabetes or other diseases .... May result in digoxin toxicity (nausea, vomiting, cardiac.

Biology panel: coming to a clinic near you. Translational research in radiation biology

International Nuclear Information System (INIS)

Travis, Elizabeth L.; Thames, Howard D.

1996-01-01

The explosion of knowledge in molecular biology coupled with the rapid and continuing development of molecular techniques allow a new level of research in radiation biology aimed at understanding the processes that govern radiation damage and response in both tumors and normal tissues. The challenge to radiation biologists and radiation oncologists is to use this knowledge to improve the therapeutic ratio in the management of human tumors by rapidly translating these new findings into clinical practice. This panel will focus on both sides of the therapeutic ratio coin, the manipulation of tumor control by manipulating the processes that control cell cycle regulation and apoptosis, and the reduction of normal tissue morbidity by applying the emerging information on the genetic basis of radiosensitivity. Apoptosis is a form of cell death believed to represent a minor component of the clinical effects of radiation. However, if apoptosis is regulated by anti-apoptotic mechanisms, then it may be possible to produce a pro-apoptotic phenotype in the tumor cell population by modulating the balance between pro- and anti-apoptotic mechanisms by pharmacological intervention. Thus signaling-based apoptosis therapy, designed to overcome the relative resistance to radiation-induced apoptosis, may improve the therapeutic ratio in the management of human tumors. The explosion of information concerning cell cycle regulation in both normal and tumor cells has provided the opportunity for insights into the mechanism of action of chemotherapeutic agents that can act as radiosensitizers. The second talk will explore the hypothesis that the dysregulation of cell cycle checkpoints in some cancers can be exploited to improve the therapeutic index of radiation sensitizers, specifically the fluoropyrimidines which appear to act at the G1/S transition. Finally, efforts to increase tumor control will be translated into clinical practice only if such treatments do not increase the complication

The prevalence and clinical significance of maxillary sinus mucous retention cysts in a general clinic population.

Science.gov (United States)

Rhodus, N L

1990-02-01

Previous studies have documented the occurrence and potential clinical significance of MSMR cysts. Studies also have alluded to a relationship between the MSMR cyst and certain signs or symptoms of disease. We determined the prevalence of MSMR cysts in a general clinic population and identified some important correlations with clinical signs and symptoms.

Clinical treatment adherence of health care workers and students exposed to potentially infectious biological material

Directory of Open Access Journals (Sweden)

Maria Cristina Mendes de Almeida

2015-04-01

Full Text Available OBJECTIVE To assess adherence to clinical appointments by health care workers (HCW and students who suffered accidents with potentially infectious biological material. METHOD A retrospective cross-sectional study that assessed clinical records of accidents involving biological material between 2005 and 2010 in a specialized unit. RESULTS A total of 461 individuals exposed to biological material were treated, of which 389 (84.4% were HCWs and 72 (15.6% students. Of the 461 exposed individuals, 307 (66.6% attended a follow-up appointment. Individuals who had suffered an accident with a known source patient were 29 times more likely to show up to their scheduled follow-up appointments (OR: 29.98; CI95%: 16.09-55.83. CONCLUSION The predictor in both univariate and multivariate analyses for adherence to clinical follow-up appointment was having a known source patient with nonreactive serology for the human immunodeficiency virus and/or hepatitis B and C.

[Knowledge and adherence to bio-safety measures and biological accidents by nursing students during their clinical practice].

Science.gov (United States)

Merino-de la Hoz, Felicitas; Durá-Ros, María Jesús; Rodríguez-Martín, Elías; González-Gómez, Silvia; Mariano López-López, Luis; Abajas-Bustillo, Rebeca; de la Horra-Gutiérrez, Inmaculada

2010-01-01

To identify the degree of knowledge and performance of bio-safety measures by nursing students and knowing the type of biological accidents suffered during their clinical practice. A cross-sectional study was conducted on the students of three Nursing courses held in May of 2008. Data was collected by an anonymous self-administered questionnaire, with a return of 54%. A total of 97% of students seemed to know the standard biosafety measures, and all of them (100%) stated that those measures must be applied to every patient. However, the reality of clinical practice shows that biosafety measures are only partially applied. An average of 60.2% implement the personal hygiene measures, 66.1% use physical barriers, and 44% use sharp materials safely. Around 32.25% of the students have suffered some biological accident, with a greater incidence in the second year: administering injections (24%), drawing blood samples with Venojet needles (18%) and recapping used needles (17%). The high level of knowledge shown by the students on standard precautions is not always shown in clinical practice. There are significant deficiencies in student safety practices: recapping of used needles continues to be one of the most common risk practices carried out. Copyright (c) 2009 Elsevier España, S.L. All rights reserved.

Clinical relevance and biology of circulating tumor cells

Science.gov (United States)

2011-01-01

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

Correction of technical bias in clinical microarray data improves concordance with known biological information

DEFF Research Database (Denmark)

Eklund, Aron Charles; Szallasi, Zoltan Imre

2008-01-01

The performance of gene expression microarrays has been well characterized using controlled reference samples, but the performance on clinical samples remains less clear. We identified sources of technical bias affecting many genes in concert, thus causing spurious correlations in clinical data...... sets and false associations between genes and clinical variables. We developed a method to correct for technical bias in clinical microarray data, which increased concordance with known biological relationships in multiple data sets....

Assessing the clinical significance of tumor markers in common neoplasms.

Science.gov (United States)

Beketic-Oreskovic, Lidija; Maric, Petra; Ozretic, Petar; Oreskovic, Darko; Ajdukovic, Mia; Levanat, Sonja

2012-06-01

The term tumor markers include a spectrum of molecules and substances with widely divergent characteristics whose presence in the significant amount can be related to the malignant disease. An ideal tumor marker should have high specificity and sensitivity, which would allow its use in early diagnosis and prognosis of malignant disease, as well as in prediction of therapeutic response and follow-up of the patients. Numerous biochemical entities have emerged as potentially valuable tumor markers so far, but only few markers showed to be of considerable clinical reliability and have been accepted into standard clinical practice. Recent development of genomics and proteomics has enabled the examination of many new potential tumor markers. Scientific studies on discovery, development, and application of tumor markers have been proceeding quite rapidly providing great opportunities for improving the management of cancer patients. This review is focusing on the clinical usefulness of various tumor markers already in clinical practice as well as certain potential markers, giving a brief description of their prognostic and predictive significance in most common malignancies.

Clinically significant anti M antibodies--a report of two cases.

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Kaur, Gagandeep; Basu, Sabita; Kaur, Paramjit; Kaur, Ravneet

2012-12-01

Most anti-M antibodies are not active at 37°C and are thus of no clinical significance. Occasionally these antibodies have a wide thermal range and can lead to hemolytic transfusion reactions or hemolytic disease of the new born. We describe two cases of anti-M antibodies, both of which were clinically significant. The first case was detected due to crossmatch incompatibility and the second presented as a blood group discrepancy. When the antibody is active at 37°C, M antigen negative red cell units should be issued. Copyright © 2012 Elsevier Ltd. All rights reserved.

The influence of psychoeducation on regulating biological rhythm in a sample of patients with bipolar II disorder: a randomized clinical trial

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Faria AD

2014-06-01

Full Text Available Augusto Duarte Faria,1 Luciano Dias de Mattos Souza,2 Taiane de Azevedo Cardoso,2 Karen Amaral Tavares Pinheiro,2 Ricardo Tavares Pinheiro,2 Ricardo Azevedo da Silva,2 Karen Jansen21Department of Clinical and Health Psychology, Universidade Federal do Rio Grande – FURG, Rio Grande, RS, Brazil; 2Health and Behavior Postgraduate Program, Universidade Católica de Pelotas – UCPEL, Pelotas, RS, BrazilIntroduction: Changes in biological rhythm are among the various characteristics of bipolar disorder, and have long been associated with the functional impairment of the disease. There are only a few viable options of psychosocial interventions that deal with this specific topic; one of them is psychoeducation, a model that, although it has been used by practitioners for some time, only recently have studies shown its efficacy in clinical practice.Aim: To assess if patients undergoing psychosocial intervention in addition to a pharmacological treatment have better regulation of their biological rhythm than those only using medication.Method: This study is a randomized clinical trial that compares a standard medication intervention to an intervention combined with drugs and psychoeducation. The evaluation of the biological rhythm was made using the Biological Rhythm Interview of Assessment in Neuropsychiatry, an 18-item scale divided in four areas (sleep, activity, social rhythm, and eating pattern. The combined intervention consisted of medication and a short-term psychoeducation model summarized in a protocol of six individual sessions of 1 hour each.Results: The sample consisted of 61 patients with bipolar II disorder, but during the study, there were 14 losses to follow-up. Therefore, the final sample consisted of 45 individuals (26 for standard intervention and 19 for combined. The results showed that, in this sample and time period evaluated, the combined treatment of medication and psychoeducation had no statistically significant impact on the

Biological wound dressings sterilized with gamma radiation: Mexican clinical experience

Science.gov (United States)

Martínez-Pardo, M. E.; Ley-Chávez, E.; Reyes-Frías, M. L.; Rodríguez-Ferreyra, P.; Vázquez-Maya, L.; Salazar, M. A.

2007-11-01

Biological wound dressings sterilized with gamma radiation, such as amnion and pig skin, are a reality in Mexico. These tissues are currently processed in the tissue bank and sterilized in the Gamma Industrial Irradiation Plant; both facilities belong to the Instituto Nacional de Investigaciones Nucleares (ININ) (National Institute of Nuclear Research). With the strong support of the International Atomic Energy Agency, the bank was established at the ININ and the Mexican Ministry of Health issued its sanitary license on July 7, 1999. The Quality Management System of the bank was certified by ISO 9001:2000 on August 1, 2003; the scope of the system is "Research, Development and Processing of Biological Tissues Sterilized with Gamma Radiation". At present, more than 150 patients from 16 hospitals have been successfully treated with these tissues. This paper presents a brief description of the tissue processing, as well as the present Mexican clinical experience with children and adult patients who underwent medical treatment with radiosterilized amnion and pig skin, used as biological wound dressings on burns and ocular surface disorders.

Biological wound dressings sterilized with gamma radiation: Mexican clinical experience

Energy Technology Data Exchange (ETDEWEB)

Martinez-Pardo, M.E. [Instituto Nacional de Investigaciones Nucleares, Apdo. postal 18-1027, Col. Escandon 11801 Mexico DF (Mexico)], E-mail: memp@nuclear.inin.mx; Ley-Chavez, E. [ISSEMYM Toluca, Mexico DF (Mexico); Reyes-Frias, M.L. [Instituto Nacional de Investigaciones Nucleares, Apdo. postal 18-1027, Col. Escandon 11801 Mexico DF (Mexico); Rodriguez-Ferreyra, P. [Hospital ' Dr. Nicolas San Juan' , Toluca, Mexico DF (Mexico); Vazquez-Maya, L.; Salazar, M.A. [Hospital General de Mexico, Mexico DF (Mexico)

2007-11-15

Biological wound dressings sterilized with gamma radiation, such as amnion and pig skin, are a reality in Mexico. These tissues are currently processed in the tissue bank and sterilized in the Gamma Industrial Irradiation Plant; both facilities belong to the Instituto Nacional de Investigaciones Nucleares (ININ) (National Institute of Nuclear Research). With the strong support of the International Atomic Energy Agency, the bank was established at the ININ and the Mexican Ministry of Health issued its sanitary license on July 7, 1999. The Quality Management System of the bank was certified by ISO 9001:2000 on August 1, 2003; the scope of the system is 'Research, Development and Processing of Biological Tissues Sterilized with Gamma Radiation'. At present, more than 150 patients from 16 hospitals have been successfully treated with these tissues. This paper presents a brief description of the tissue processing, as well as the present Mexican clinical experience with children and adult patients who underwent medical treatment with radiosterilized amnion and pig skin, used as biological wound dressings on burns and ocular surface disorders.

Biological wound dressings sterilized with gamma radiation: Mexican clinical experience

International Nuclear Information System (INIS)

Martinez-Pardo, M.E.; Ley-Chavez, E.; Reyes-Frias, M.L.; Rodriguez-Ferreyra, P.; Vazquez-Maya, L.; Salazar, M.A.

2007-01-01

Biological wound dressings sterilized with gamma radiation, such as amnion and pig skin, are a reality in Mexico. These tissues are currently processed in the tissue bank and sterilized in the Gamma Industrial Irradiation Plant; both facilities belong to the Instituto Nacional de Investigaciones Nucleares (ININ) (National Institute of Nuclear Research). With the strong support of the International Atomic Energy Agency, the bank was established at the ININ and the Mexican Ministry of Health issued its sanitary license on July 7, 1999. The Quality Management System of the bank was certified by ISO 9001:2000 on August 1, 2003; the scope of the system is 'Research, Development and Processing of Biological Tissues Sterilized with Gamma Radiation'. At present, more than 150 patients from 16 hospitals have been successfully treated with these tissues. This paper presents a brief description of the tissue processing, as well as the present Mexican clinical experience with children and adult patients who underwent medical treatment with radiosterilized amnion and pig skin, used as biological wound dressings on burns and ocular surface disorders

Clinical significance of anaplasia in childhood rhabdomyosarcoma

International Nuclear Information System (INIS)

Sidhom, I.; El Nadi, E.; Taha, H.; Elkinaai, N.; Zaghloul, M.S.; Younes, A.; Labib, R.; Sabry, M.

2015-01-01

Background: The presence of anaplastic features has been known to correlate with poor clinical outcome in various pediatric malignancies, including Wilms tumor and medulloblastoma but not in rhabdomyosarcoma. Aim: Aim was to study the frequency of anaplasia at presentation in childhood rhabdomyosarcoma and its relationship to clinical and pathological characteristics as well as to outcome. Patients and Methods: Anaplasia was retrospectively assessed in 105 consecutive pediatric rhabdomyosarcoma patients who were registered at the Children’s Cancer Hospital in Egypt (CCHE) during the period from July 2007 till the end of May 2010. Results: Anaplasia was diagnosed in 18 patients (17.1%), focal in 10 (9.5%) and diffuse in 8 (7.6%). The distribution of anaplasia was found to be more common in older patients having age P 10 years. Also it was more likely to occur in the high risk group and in tumors with unfavorable histology (alveolar subtype), and stage IV. The 3-year failure free survival rates for patients with and without anaplasia were 27.8 ± 10.6% and 53.4 ± 5.8%, respectively (p = 0.014) and the 3-year overall survival rates were 35.3 ± 11.6% and 61 ± 6%, respectively (p = 0.019). Conclusions: The frequency of anaplasia in pediatric patients with rhabdomyosarcoma in our study was 17.1%. The presence of anaplasia had statistically significant worse clinical outcome

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

Science.gov (United States)

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

2013-01-01

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

Obesity Paradox in Lung Cancer Prognosis: Evolving Biological Insights and Clinical Implications.

Science.gov (United States)

Zhang, Xueli; Liu, Yamin; Shao, Hua; Zheng, Xiao

2017-10-01

The survival rate of lung cancer remains low despite the progress of surgery and chemotherapy. With the increasing comorbidity of obesity in patients with lung cancer, new challenges are emerging in the management of this patient population. A key issue of interest is the prognostic effect of obesity on surgical and chemotherapeutic outcomes in patients with lung cancer, which is fueled by the growing observation of survival benefits in overweight or obese patients. This unexpected inverse relationship between obesity and lung cancer mortality, called the obesity paradox, remains poorly understood. The evolving insights into the heterogeneity of obesity phenotypes and associated biological connections with lung cancer progression in recent years may help explain some of the seemingly paradoxical relationship, and well-designed clinical studies looking at the causal role of obesity-associated molecules are expected. Here, we examine potential biological mechanisms behind the protective effects of obesity in lung cancer. We highlight the need to clarify the clinical implications of this relationship toward an updated intervention strategy in the clinical care of patients with lung cancer and obesity. Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Clinical and Biological Features of Interval Colorectal Cancer

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Yu Mi Lee

2017-05-01

Full Text Available Interval colorectal cancer (I-CRC is defined as a CRC diagnosed within 60 months after a negative colonoscopy, taking into account that 5 years is the “mean sojourn time.” It is important to prevent the development of interval cancer. The development of interval colon cancer is associated with female sex, old age, family history of CRC, comorbidities, diverticulosis, and the skill of the endoscopist. During carcinogenesis, sessile serrated adenomas/polyps (SSA/Ps share many genomic and colonic site characteristics with I-CRCs. The clinical and biological features of I-CRC should be elucidated to prevent the development of interval colon cancer.

Short-term biological variation of clinical chemical values in dumeril's monitors (Varanus dumerili)

DEFF Research Database (Denmark)

Bertelsen, Mads Frost; Kjelgaard-Hansen, Mads Jens; Howell, Jennifer R.

2007-01-01

Plasma biochemical values are routinely used in the medical management of ill reptiles, and for monitoring the health of clinically normal animals. Laboratory tests, including clinical biochemical values, are subject to biological and analytical variation, the magnitude of which determines the ut...

Radiation damage and repair in cells and cell components. Part 2. Physical radiations and biological significance. Final report

International Nuclear Information System (INIS)

Fluke, D.J.

1984-08-01

The report comprises a teaching text, encompassing all physical radiations likely to be of biological interest, and the relevant biological effects and their significance. Topics include human radiobiology, delayed effects, radiation absorption in organisms, aqueous radiation chemistry, cell radiobiology, mutagenesis, and photobiology

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

Science.gov (United States)

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.

Clinical significance of anaplasia in childhood rhabdomyosarcoma.

Science.gov (United States)

Sidhom, Iman; El Nadi, Enas; Taha, Hala; Elkinaai, Naglaa; Zaghloul, Mohamed S; Younes, Alaa; Labib, Rania; Sabry, Mohamed

2015-06-01

The presence of anaplastic features has been known to correlate with poor clinical outcome in various pediatric malignancies, including Wilms tumor and medulloblastoma but not in rhabdomyosarcoma. Aim was to study the frequency of anaplasia at presentation in childhood rhabdomyosarcoma and its relationship to clinical and pathological characteristics as well as to outcome. Anaplasia was retrospectively assessed in 105 consecutive pediatric rhabdomyosarcoma patients who were registered at the Children's Cancer Hospital in Egypt (CCHE) during the period from July 2007 till the end of May 2010. Anaplasia was diagnosed in 18 patients (17.1%), focal in 10 (9.5%) and diffuse in 8 (7.6%). The distribution of anaplasia was found to be more common in older patients having age⩾10 years. Also it was more likely to occur in the high risk group and in tumors with unfavorable histology (alveolar subtype), and stage IV. The 3-year failure free survival rates for patients with and without anaplasia were 27.8±10.6% and 53.4±5.8%, respectively (p=0.014) and the 3-year overall survival rates were 35.3±11.6% and 61±6%, respectively (p=0.019). The frequency of anaplasia in pediatric patients with rhabdomyosarcoma in our study was 17.1%. The presence of anaplasia had statistically significant worse clinical outcome. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Prevalence and clinical significance of cathepsin G antibodies in systemic sclerosis

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M. Favaro

2011-09-01

Full Text Available Objectives: To evaluate the prevalence and clinical significance of cathepsin G antibodies in patients affected with systemic sclerosis (SSc, scleroderma. Methods: 115 patients affected by SSc, 55 (47,8% with diffuse scleroderma (dSSc and 60 (52,2% with limited scleroderma (lSSc, were tested for cathepsin G antibodies by ELISA method. Moreover these sera were evaluated by indirect immunofluorescence (IIF on ethanol and formalin fixed human neutrophils. Results: By means of the ELISA method 16 (13,9% patients were found to be sera positive for anti-cathepsin G, 2 (12.5% of which showed a perinuclear fluorescence pattern (P-ANCA and 4 (25% an atypical ANCA staining, while 10 (62,5% were negative on IIF. The IIF on scleroderma sera revealed 5 (4,3% P-ANCA and 18 (15,7% atypical ANCA patterns. The anti-cathepsin G antibodies significantly prevailed in scleroderma sera (p=0.02 when their frequency was compared with that of healthy controls; while they were not significantly associated to any clinical or serological features of SSc patients. Conclusions: The anti-cathepsin G antibodies were significantly frequent in scleroderma sera; however, no clinical correlations were found. Thus, the significance of their presence in SSc still needs to be clarified.

Application of molecular biology of differentiated thyroid cancer for clinical prognostication.

Science.gov (United States)

Marotta, Vincenzo; Sciammarella, Concetta; Colao, Annamaria; Faggiano, Antongiulio

2016-11-01

Although cancer outcome results from the interplay between genetics and environment, researchers are making a great effort for applying molecular biology in the prognostication of differentiated thyroid cancer (DTC). Nevertheless, role of molecular characterisation in the prognostic setting of DTC is still nebulous. Among the most common and well-characterised genetic alterations related to DTC, including mutations of BRAF and RAS and RET rearrangements, BRAF V600E is the only mutation showing unequivocal association with clinical outcome. Unfortunately, its accuracy is strongly limited by low specificity. Recently, the introduction of next-generation sequencing techniques led to the identification of TERT promoter and TP53 mutations in DTC. These genetic abnormalities may identify a small subgroup of tumours with highly aggressive behaviour, thus improving specificity of molecular prognostication. Although knowledge of prognostic significance of TP53 mutations is still anecdotal, mutations of the TERT promoter have showed clear association with clinical outcome. Nevertheless, this genetic marker needs to be analysed according to a multigenetic model, as its prognostic effect becomes negligible when present in isolation. Given that any genetic alteration has demonstrated, taken alone, enough specificity, the co-occurrence of driving mutations is emerging as an independent genetic signature of aggressiveness, with possible future application in clinical practice. DTC prognostication may be empowered in the near future by non-tissue molecular prognosticators, including circulating BRAF V600E and miRNAs. Although promising, use of these markers needs to be refined by the technical sight, and the actual prognostic value is still yet to be validated. © 2016 Society for Endocrinology.

Clinical Significance and Characteristic Clinical Differences of Cytolytic Vaginosis in Recurrent Vulvovaginitis.

Science.gov (United States)

Yang, Shuhua; Zhang, Yuexiang; Liu, Ying; Wang, Jianhong; Chen, Shuqin; Li, Shuxia

2017-01-01

The study aimed to evaluate whether cytolytic vaginosis (CV) has important clinical implications for recurrent vulvovaginitis and to identify clinical differences between CV and vulvovaginal candidosis (VVC). Medical histories, physical examinations and laboratory findings were used to diagnose and assess the prevalence rates of various vulvovaginal infections among 536 women with recurrent vulvovaginitis. Chi-square and Fisher exact tests were used to compare age, menstrual cycle phase at episode onset, symptoms/signs of infection and discharge characteristics between CV and VVC with single infection. Among the 484 women with a single-infection recurrent vulvovaginitis, the prevalence of CV (n = 143; 26.7%) was second only to VVC (n = 196; 36.6%). CV symptoms occurred predominantly during the ovulatory and luteal phases. Meanwhile, VVC episodes were not concentrated premenstrually, but rather occurred throughout the menstrual cycle. Significant differences were found in the vaginal pH, discharge characteristics and frequency of inflammatory symptoms between the 2 groups. CV is clinically important, because it is a common cause of recurrent vulvovaginitis. To distinguish CV from VVC, gynecologists should consider the patient's medical history, physical and laboratory findings, vaginal pH and vaginal discharge characteristics. © 2016 S. Karger AG, Basel.

Induction, regulation, degradation, and biological significance of mammalian metallothioneins.

Science.gov (United States)

Miles, A T; Hawksworth, G M; Beattie, J H; Rodilla, V

2000-01-01

MTs are small cysteine-rich metal-binding proteins found in many species and, although there are differences between them, it is of note that they have a great deal of sequence and structural homology. Mammalian MTs are 61 or 62 amino acid polypeptides containing 20 conserved cysteine residues that underpin the binding of metals. The existence of MT across species is indicative of its biological demand, while the conservation of cysteines indicates that these are undoubtedly central to the function of this protein. Four MT isoforms have been found so far, MT-1, MT-2, MT-3, and MT-4, but these also have subtypes with 17 MT genes identified in man, of which 10 are known to be functional. Different cells express different MT isoforms with varying levels of expression perhaps as a result of the different function of each isoform. Even different metals induce and bind to MTs to different extents. Over 40 years of research into MT have yielded much information on this protein, but have failed to assign to it a definitive biological role. The fact that multiple MT isoforms exist, and the great variety of substances and agents that act as inducers, further complicates the search for the biological role of MTs. This article reviews the current knowledge on the biochemistry, induction, regulation, and degradation of this protein in mammals, with a particular emphasis on human MTs. It also considers the possible biological roles of this protein, which include participation in cell proliferation and apoptosis, homeostasis of essential metals, cellular free radical scavenging, and metal detoxification.

Clinical Significance of CK19 Negative Breast Cancer

Energy Technology Data Exchange (ETDEWEB)

Fujisue, Mamiko, E-mail: nishimura.reiki@cityhosp-kumamoto.jp; Nishimura, Reiki; Okumura, Yasuhiro [Department of Breast and Endocrine Surgery, Kumamoto City Hospital, 1-1-60 Kotoh, Kumamoto City, Kumamoto 862-8505 (Japan); Tashima, Rumiko [Department of Surgery, Kumamoto City Hospital, 1-1-60 Kotoh, Kumamoto City, Kumamoto 862-8505 (Japan); Nishiyama, Yasuyuki; Osako, Tomofumi [Department of Breast and Endocrine Surgery, Kumamoto City Hospital, 1-1-60 Kotoh, Kumamoto City, Kumamoto 862-8505 (Japan); Toyozumi, Yasuo; Arima, Nobuyuki [Department of Pathology, Kumamoto City Hospital, 1-1-60 Kotoh, Kumamoto City, Kumamoto 862-8505 (Japan)

2012-12-21

Analysis of sentinel lymph nodes (SLNs) by means of One-Step Nucleic Acid Amplification (OSNA) is gaining widespread use as a quick and accurate method. This assay detects the expression level of cytokeratin 19 (CK19) which is present in some but not all breast tumors. In this study, the clinical significance of negative CK19 was investigated in 219 cases of primary breast cancer. In 179 patients with clinically negative nodes, OSNA and imprint smear cytology of SLN were performed simultaneously. The OSNA revealed a node-positive rate of 24.6%. Negative CK19 correlated significantly with negative ER/PgR and higher Ki-67 values, and marginally with higher nuclear grade and p53 overexpression. The triple negative subtype showed lower CK19 expression. OSNA revealed that one of the negative CK19 cases was actually a false negative but this was corrected with the use of the imprint smear cytology. In conclusion, CK19 negativity reflected the aggressiveness of primary breast cancer. OSNA assay used to analyze SLN was useful, but there is a possibility that it will mistakenly detect false negatives in CK19 negative tumors. Therefore, in tumors with negative CK19, the imprint smear cytology may be more useful in cases with macrometastasis.

Clinical Significance of CK19 Negative Breast Cancer

Directory of Open Access Journals (Sweden)

Nobuyuki Arima

2012-12-01

Full Text Available Analysis of sentinel lymph nodes (SLNs by means of One-Step Nucleic Acid Amplification (OSNA is gaining widespread use as a quick and accurate method. This assay detects the expression level of cytokeratin 19 (CK19 which is present in some but not all breast tumors. In this study, the clinical significance of negative CK19 was investigated in 219 cases of primary breast cancer. In 179 patients with clinically negative nodes, OSNA and imprint smear cytology of SLN were performed simultaneously. The OSNA revealed a node-positive rate of 24.6%. Negative CK19 correlated significantly with negative ER/PgR and higher Ki-67 values, and marginally with higher nuclear grade and p53 overexpression. The triple negative subtype showed lower CK19 expression. OSNA revealed that one of the negative CK19 cases was actually a false negative but this was corrected with the use of the imprint smear cytology. In conclusion, CK19 negativity reflected the aggressiveness of primary breast cancer. OSNA assay used to analyze SLN was useful, but there is a possibility that it will mistakenly detect false negatives in CK19 negative tumors. Therefore, in tumors with negative CK19, the imprint smear cytology may be more useful in cases with macrometastasis.

Clinical Significance of CK19 Negative Breast Cancer

International Nuclear Information System (INIS)

Fujisue, Mamiko; Nishimura, Reiki; Okumura, Yasuhiro; Tashima, Rumiko; Nishiyama, Yasuyuki; Osako, Tomofumi; Toyozumi, Yasuo; Arima, Nobuyuki

2012-01-01

Analysis of sentinel lymph nodes (SLNs) by means of One-Step Nucleic Acid Amplification (OSNA) is gaining widespread use as a quick and accurate method. This assay detects the expression level of cytokeratin 19 (CK19) which is present in some but not all breast tumors. In this study, the clinical significance of negative CK19 was investigated in 219 cases of primary breast cancer. In 179 patients with clinically negative nodes, OSNA and imprint smear cytology of SLN were performed simultaneously. The OSNA revealed a node-positive rate of 24.6%. Negative CK19 correlated significantly with negative ER/PgR and higher Ki-67 values, and marginally with higher nuclear grade and p53 overexpression. The triple negative subtype showed lower CK19 expression. OSNA revealed that one of the negative CK19 cases was actually a false negative but this was corrected with the use of the imprint smear cytology. In conclusion, CK19 negativity reflected the aggressiveness of primary breast cancer. OSNA assay used to analyze SLN was useful, but there is a possibility that it will mistakenly detect false negatives in CK19 negative tumors. Therefore, in tumors with negative CK19, the imprint smear cytology may be more useful in cases with macrometastasis

Results of efforts by the Convention on Biological Diversity to describe ecologically or biologically significant marine areas.

Science.gov (United States)

Bax, Nicholas J; Cleary, Jesse; Donnelly, Ben; Dunn, Daniel C; Dunstan, Piers K; Fuller, Mike; Halpin, Patrick N

2016-06-01

In 2004, Parties to the Convention on Biological Diversity (CBD) addressed a United Nations (UN) call for area-based planning, including for marine-protected areas that resulted in a global effort to describe ecologically or biologically significant marine areas (EBSAs). We summarized the results, assessed their consistency, and evaluated the process developed by the Secretariat of the CBD to engage countries and experts in 9 regional workshops held from 2011 to 2014. Experts from 92 countries and 79 regional or international bodies participated. They considered 250 million km(2) of the world's ocean area (two-thirds of the total). The 204 areas they examined in detail differed widely in area (from 5.5 km(2) to 11.1 million km(2) ). Despite the initial focus of the CBD process on areas outside national jurisdiction, only 31 of the areas examined were solely outside national jurisdiction. Thirty-five extended into national jurisdictions, 137 were solely within national jurisdictions, and 28 included the jurisdictions of more than 1 country (1 area lacked precise boundaries). Data were sufficient to rank 88-99% of the areas relative to each of the 7 criteria for EBSAs agreed to previously by Parties to the CBD. The naturalness criterion ranked high for a smaller percentage of the EBSAs (31%) than other criteria (51-70%), indicating the difficulty in finding relatively undisturbed areas in the ocean. The highly participatory nature of the workshops, including easy and consistent access to the relevant information facilitated by 2 technical teams, contributed to the workshop participants success in identifying areas that could be ranked relative to most criteria and areas that extend across jurisdictional boundaries. The formal recognition of workshop results by the Conference of Parties to the CBD resulted in these 204 areas being identified as EBSAs by the 196 Parties. They represent the only suite of marine areas recognized by the international community for their

Clinical, biological, histological features and treatment of oral mucositis induced by radiation therapy: a literature review

International Nuclear Information System (INIS)

Bonan, Paulo Rogerio Ferreti; Lopes, Marcio Ajudarte; Almeida, Oslei Paes de; Alves, Fabio de Abreu

2005-01-01

The oral mucositis is a main side effect of radiotherapy on head and neck, initiating two weeks after the beginning of the treatment. It is characterized by sensation of local burning to intense pain, leading in several cases, to the interruption of the treatment. The purpose of this work is to review the main published studies that discuss the clinical, biological and histopathological features of oral mucositis induced by radiation therapy and to describe the main approaches recommended to prevent or to treat it. Although the clinical features of mucositis are intensively described in the literature, few studies address the histopathological alterations in oral mucositis and only recently, its biological processes have been investigated. The biological mechanisms involved in the radiation tissue damage have been only recently discussed and there is no consensus among treatment modalities. Yet, the progressive knowledge in the histopathology and biological characteristics of oral mucositis probably will lead to more effective in prevention and control strategies. (author)

The diagnosis and management of pre-invasive breast disease: Flat epithelial atypia – classification, pathologic features and clinical significance

International Nuclear Information System (INIS)

Schnitt, Stuart J

2003-01-01

Flat epithelial atypia is a descriptive term that encompasses lesions of the breast terminal duct lobular units in which variably dilated acini are lined by one to several layers of epithelial cells, which are usually columnar in shape and which display low-grade cytologic atypia. Observational studies have suggested that at least some of these lesions may represent either a precursor of ductal carcinoma in situ (DCIS) or the earliest morphological manifestation of DCIS. In contrast, the limited available clinical follow-up data suggest that the risk of both local recurrence and progression of these lesions to invasive cancer is extremely low, supporting the notion that categorizing such lesions as 'clinging carcinoma' and managing them as if they were fully developed DCIS will result in overtreatment of many patients. Additional studies are needed to better understand the biological nature and clinical significance of these lesions

Immunoregulation by Mesenchymal Stem Cells: Biological Aspects and Clinical Applications

Science.gov (United States)

Castro-Manrreza, Marta E.; Montesinos, Juan J.

2015-01-01

Mesenchymal stem cells (MSCs) are multipotent cells capable of differentiation into mesenchymal lineages and that can be isolated from various tissues and easily cultivated in vitro. Currently, MSCs are of considerable interest because of the biological characteristics that confer high potential applicability in the clinical treatment of many diseases. Specifically, because of their high immunoregulatory capacity, MSCs are used as tools in cellular therapies for clinical protocols involving immune system alterations. In this review, we discuss the current knowledge about the capacity of MSCs for the immunoregulation of immunocompetent cells and emphasize the effects of MSCs on T cells, principal effectors of the immune response, and the immunosuppressive effects mediated by the secretion of soluble factors and membrane molecules. We also describe the mechanisms of MSC immunoregulatory modulation and the participation of MSCs as immune response regulators in several autoimmune diseases, and we emphasize the clinical application in graft versus host disease (GVHD). PMID:25961059

Periodic Table Target: A Game that Introduces the Biological Significance of Chemical Element Periodicity

Science.gov (United States)

Sevcik, Richard S.; McGinty, Ragan L.; Schultz, Linda D.; Alexander, Susan V.

2008-01-01

Periodic Table Target, a game for middle school or high school students, familiarizes students with the form of the periodic table and the biological significance of different elements. The Periodic Table Target game board is constructed as a class project, and the game is played to reinforce the content. Students are assigned several elements…

Bridging cancer biology with the clinic: relative expression of a GRHL2-mediated gene-set pair predicts breast cancer metastasis.

Directory of Open Access Journals (Sweden)

Xinan Yang

Full Text Available Identification and characterization of crucial gene target(s that will allow focused therapeutics development remains a challenge. We have interrogated the putative therapeutic targets associated with the transcription factor Grainy head-like 2 (GRHL2, a critical epithelial regulatory factor. We demonstrate the possibility to define the molecular functions of critical genes in terms of their personalized expression profiles, allowing appropriate functional conclusions to be derived. A novel methodology, relative expression analysis with gene-set pairs (RXA-GSP, is designed to explore the potential clinical utility of cancer-biology discovery. Observing that Grhl2-overexpression leads to increased metastatic potential in vitro, we established a model assuming Grhl2-induced or -inhibited genes confer poor or favorable prognosis respectively for cancer metastasis. Training on public gene expression profiles of 995 breast cancer patients, this method prioritized one gene-set pair (GRHL2, CDH2, FN1, CITED2, MKI67 versus CTNNB1 and CTNNA3 from all 2717 possible gene-set pairs (GSPs. The identified GSP significantly dichotomized 295 independent patients for metastasis-free survival (log-rank tested p = 0.002; severe empirical p = 0.035. It also showed evidence of clinical prognostication in another independent 388 patients collected from three studies (log-rank tested p = 3.3e-6. This GSP is independent of most traditional prognostic indicators, and is only significantly associated with the histological grade of breast cancer (p = 0.0017, a GRHL2-associated clinical character (p = 6.8e-6, Spearman correlation, suggesting that this GSP is reflective of GRHL2-mediated events. Furthermore, a literature review indicates the therapeutic potential of the identified genes. This research demonstrates a novel strategy to integrate both biological experiments and clinical gene expression profiles for extracting and elucidating the genomic

Models to Study NK Cell Biology and Possible Clinical Application.

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Zamora, Anthony E; Grossenbacher, Steven K; Aguilar, Ethan G; Murphy, William J

2015-08-03

Natural killer (NK) cells are large granular lymphocytes of the innate immune system, responsible for direct targeting and killing of both virally infected and transformed cells. NK cells rapidly recognize and respond to abnormal cells in the absence of prior sensitization due to their wide array of germline-encoded inhibitory and activating receptors, which differs from the receptor diversity found in B and T lymphocytes that is due to the use of recombination-activation gene (RAG) enzymes. Although NK cells have traditionally been described as natural killers that provide a first line of defense prior to the induction of adaptive immunity, a more complex view of NK cells is beginning to emerge, indicating they may also function in various immunoregulatory roles and have the capacity to shape adaptive immune responses. With the growing appreciation for the diverse functions of NK cells, and recent technological advancements that allow for a more in-depth understanding of NK cell biology, we can now begin to explore new ways to manipulate NK cells to increase their clinical utility. In this overview unit, we introduce the reader to various aspects of NK cell biology by reviewing topics ranging from NK cell diversity and function, mouse models, and the roles of NK cells in health and disease, to potential clinical applications. © 2015 by John Wiley & Sons, Inc. Copyright © 2015 John Wiley & Sons, Inc.

OCCUPATIONAL ACCIDENTS WITH BIOLOGICAL MATERIALS IN CLINICAL ANALYSIS LABORATORY: CAUSES AND CONSEQUENCES

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T. M. Azevedo

2014-07-01

Full Text Available Accidents involving biological material can cause diseases to the professional healthcare and also bring psychosocial effects. The aim of this study was to characterize the accidents occurring with biological material with professional of clinical laboratories of Sinop-MT. Data were collected by a questionnaire consisting of sociodemographic and health variables. 21 (87.5% of respondents stated that they never suffered any kind of accident. One of the injured workers reported that there was involvement in your emotional life. It is observed underreporting of occupational accidents by employees affected, making it difficult to increase research on the subject and actions about the problem.

Redefining Perineural Invasion: Integration of Biology With Clinical Outcome.

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Schmitd, Ligia B; Beesley, Lauren J; Russo, Nickole; Bellile, Emily L; Inglehart, Ronald C; Liu, Min; Romanowicz, Genevieve; Wolf, Gregory T; Taylor, Jeremy M G; D'Silva, Nisha J

2018-05-22

A diagnosis of perineural invasion (PNI), defined as cancer within or surrounding at least 33% of the nerve, leads to selection of aggressive treatment in squamous cell carcinoma (SCC). Recent mechanistic studies show that cancer and nerves interact prior to physical contact. The purpose of this study was to explore cancer-nerve interactions relative to clinical outcome. Biopsy specimens from 71 patients with oral cavity SCC were stained with hematoxylin and eosin and immunohistochemical (IHC; cytokeratin, S100, GAP43, Tuj1) stains. Using current criteria, PNI detection was increased with IHC. Overall survival (OS) tended to be poor for patients with PNI (P = .098). OS was significantly lower for patients with minimum tumor-nerve distance smaller than 5 μm (P = .011). The estimated relative death rate decreased as the nerve-tumor distance increased; there was a gradual drop off in death rate from distance equal to zero that stabilized around 500 μm. In PNI-negative patients, nerve diameter was significantly related to OS (HR 2.88, 95%CI[1.11,7.49]). Among PNI-negative nerves, larger nerve-tumor distance and smaller nerve diameter were significantly related to better OS, even when adjusting for T-stage and age (HR 0.82, 95% CI[0.72,0.92]; HR 1.27, 95% CI[1.00,1.62], respectively). GAP43, a marker for neuronal outgrowth, stained less than Tuj1 in nerves at greater distances from tumor (OR 0.76, 95% CI[0.73,0.79]); more GAP43 staining was associated with PNI. Findings from a small group of patients suggest that nerve parameters other than presence of PNI can influence outcome and that current criteria of PNI need to be re-evaluated to integrate recent biological discoveries. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Heat shock protein 72: release and biological significance during exercise.

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Whitham, Martin; Fortes, Matthew Benjamin

2008-01-01

The cumulative stressors of exercise manifest themselves at a cellular level by threatening the protein homeostasis of the cell. In these conditions, Heat Shock Proteins (HSP) are synthesised to chaperone mis-folded and denatured proteins. As such, the intracellular HSP response is thought to aid cell survival in the face of otherwise lethal cellular stress. Recently, the inducible isoform of the 70 Kda heat shock protein family, Hsp72 has been detected in the extracellular environment. Furthermore, the release of this protein into the circulation has been shown to occur in response to a range of exercise bouts. The present review summarises the current research on the exercise Hsp72 response, the possible mediators and mechanisms of extracellular (e)Hsp72 release, and the possible biological significance of this systemic response. In particular, the possible role of eHsp72 in the modulation of immunity during exercise is discussed.

Prevalence and clinical significance of extravascular incidental findings in patients undergoing CT cervico-cerebral angiography

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Crockett, Matthew Thomas; Murphy, Blathnaid; Smith, Jennifer; Kavanagh, Eoin Carl

2015-01-01

Highlights: • CT cervico-cerebral angiography (CTCCA) is a commonly performed study for assessment of vascular pathologies of head and neck. • This study assessed the prevalence, clinical significance and management of extravascular incidental findings detected on CTCCA. • This study demonstrated the presence of clinically significant incidental findings in 14% of patients undergoing CTCCA with 8% of these findings deemed to be highly significant. 19% of patients with highly clinically significant findings did not receive appropriate follow up. • A standardised method of reporting incidental findings, such as that used in this paper is suggested to aid radiologists and referring physicians in recording and communicating these findings. - Abstract: Introduction: CT cervico-cerebral angiography (CTCCA) is now the first line diagnostic imaging modality for the majority of vascular pathologies of the head and neck with diagnostic value comparable to or better than traditional angiographic techniques. The aim of this study was to assess the prevalence, clinical significance and management of extravascular incidental findings detected on CTCCA. Materials and methods: A retrospective review of the CTCCA reports of 302 consecutive patients from 2009 to 2013 was undertaken. Extravascular incidental findings were classified, according to an adaptation of the CT colonography data and reporting system (CRADS), as EV1–EV4. EV1 = no incidental findings, EV2 = clinically insignificant incidental finding, EV3 = incidental finding of intermediate clinical significance, EV4 = highly clinically significant finding. Follow up of the electronic medical records of patients with EV3 or EV4 findings was undertaken to determine subsequent management. Results: Potentially clinically significant findings were demonstrated in 14.2% of patients with 8.6% of patients having a highly clinically significant finding. 4 incidental findings were confirmed to be malignant lesions and 5

Clinical analysis and prognostic significance of haemophagocytic lymphohistiocytosis-associated anaplastic large cell lymphoma in children.

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Pasqualini, Claudia; Minard-Colin, Veronique; Saada, Veronique; Lamant, Laurence; Delsol, Georges; Patte, Catherine; Le Deley, Marie-Cécile; Valteau-Couanet, Dominique; Brugières, Laurence

2014-04-01

Haemophagocytic lymphohistiocytosis (HLH) has been rarely described in children treated for an anaplastic large-cell lymphoma (ALCL). We evaluated the incidence, the clinical and histological characteristics and the prognosis of HLH associated-ALCL. The medical, biological, cytological and histological data of patients treated for ALK-positive ALCL in the paediatric department of a single institution between 1975 and 2008 were analysed and assessed for HLH according to diagnosis criteria of the Histiocyte Society. Data concerning a series of 50 consecutive children with ALCL were reviewed. HLH-associated ALCL was observed in 12% of the patients. Lung involvement was significantly more frequent in HLH-associated ALCL patients than in the group without HLH (P = 0·004), as well as central nervous system (CNS) and bone marrow involvement (P = 0·001 and P = 0·007 respectively). The histological subtype in children with HLH-associated ALCL did not differ from that of the group without HLH. There was no significant difference between the two groups in 5-year EFS and OS (P = 0·91 and P > 0·99 respectively). In conclusion, HLH is not rare in paediatric ALCL. Despite a high incidence of visceral, CNS and bone marrow involvement, HLH does not seem to exert a significant impact on outcome in children treated for ALCL. © 2014 John Wiley & Sons Ltd.

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

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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…

Computational Approach to Annotating Variants of Unknown Significance in Clinical Next Generation Sequencing.

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Schulz, Wade L; Tormey, Christopher A; Torres, Richard

2015-01-01

Next generation sequencing (NGS) has become a common technology in the clinical laboratory, particularly for the analysis of malignant neoplasms. However, most mutations identified by NGS are variants of unknown clinical significance (VOUS). Although the approach to define these variants differs by institution, software algorithms that predict variant effect on protein function may be used. However, these algorithms commonly generate conflicting results, potentially adding uncertainty to interpretation. In this review, we examine several computational tools used to predict whether a variant has clinical significance. In addition to describing the role of these tools in clinical diagnostics, we assess their efficacy in analyzing known pathogenic and benign variants in hematologic malignancies. Copyright© by the American Society for Clinical Pathology (ASCP).

The Biological and Clinical Significance of Androgen Receptor Variants

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2014-04-01

of AR-V7 in low- grade PCa might be associated with development of high-grade Pea . Aim 3 was to evaluate the role of AR-V7 in mediating primary... protein expression of AR-V7 in CRPC vs. hormone nai’ve prostate cancer (PCa).2 In addition, AR-V7 mRNA expression in bone metastases of men with CRPC...ISH method is compatible with IHC to enable the detection of RNA and protein markers in the same tissue section for colocalization and functional

Biologics or tofacitinib for people with rheumatoid arthritis unsuccessfully treated with biologics: a systematic review and network meta-analysis.

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Singh, Jasvinder A; Hossain, Alomgir; Tanjong Ghogomu, Elizabeth; Mudano, Amy S; Maxwell, Lara J; Buchbinder, Rachelle; Lopez-Olivo, Maria Angeles; Suarez-Almazor, Maria E; Tugwell, Peter; Wells, George A

2017-03-10

of bias for major baseline imbalance. We downgraded the quality of the evidence for most outcomes to moderate or low due to study limitations, heterogeneity, or rarity of direct comparator trials. Biologic monotherapy versus placeboCompared to placebo, biologics were associated with clinically meaningful and statistically significant improvement in RA as demonstrated by higher ACR50 and RA remission rates. RR was 4.10 for ACR50 (95% CI 1.97 to 8.55; moderate-quality evidence); absolute benefit RD 14% (95% CI 6% to 21%); and NNTB = 8 (95% CI 4 to 23). RR for RA remission was 13.51 (95% CI 1.85 to 98.45, one study available; moderate-quality evidence); absolute benefit RD 9% (95% CI 5% to 13%); and NNTB = 11 (95% CI 3 to 136). Results for withdrawals due to adverse events and serious adverse events did not show any statistically significant or clinically meaningful differences. There were no studies available for analysis for function measured by HAQ, radiographic progression, or cancer outcomes. There were not enough data for any of the outcomes to look at subgroups. Biologic + MTX versus active comparator (MTX/other traditional DMARDs)Compared to MTX/other traditional DMARDs, biologic + MTX was associated with a clinically meaningful and statistically significant improvement in ACR50, function measured by HAQ, and RA remission rates in direct comparisons. RR for ACR50 was 4.07 (95% CI 2.76 to 5.99; high-quality evidence); absolute benefit RD 16% (10% to 21%); NNTB = 7 (95% CI 5 to 11). HAQ scores showed an improvement with a mean difference (MD) of 0.29 (95% CI 0.21 to 0.36; high-quality evidence); absolute benefit RD 9.7% improvement (95% CI 7% to 12%); and NNTB = 5 (95% CI 4 to 7). Remission rates showed an improved RR of 20.73 (95% CI 4.13 to 104.16; moderate-quality evidence); absolute benefit RD 10% (95% CI 8% to 13%); and NNTB = 17 (95% CI 4 to 96), among the biologic + MTX group compared to MTX/other DMARDs. There were no studies for radiographic progression

Significance of mammographic signs in clinically occult disease

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Waal, J.C. de; 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% hat 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.

Integrative approach to pre-operative determination of clinically significant prostate cancer

Directory of Open Access Journals (Sweden)

Shatylko T.V.

2015-09-01

Full Text Available Aim: improvement of early diagnostics of prostate cancer by developing a technique, which makes possible to predict its clinical significance in outpatient setting before initiation of invasive procedures. Material and Methods. Clinical data of 398 patients who underwent transrectal prostate biopsy in 2012-2014 in SSMU S. R. Mirotvortsev Clinical Hospital, was used to build an artificial neural network, while its output allowed to determine whether the tumour corresponds to Epstein criteria and which D'Amico risk group it belongs to. Internal validation was performed on 80 patients, who underwent prostate biopsy in September 2014 — December 2014. Sensitivity, specificity, positive and negative predictive value of artificial neural network were calculated. Results. Accuracy of predicting adenocarcinoma presence in biopsy specimen was 93,75%; accuracy of predicting whether the cancer meets active surveillance criteria was 90%. Accuracy of predicting T stage (T1c, T2a, T2b, T2cwas 57,1%. Prediction of D'Amico risk group was accurate in 70% of cases; for low-risk cancer accuracy was 81,2%. Conclusion. Artificial neural networks may be responsible for prostate cancer risk stratification and determination of its clinical significance prior to biopsy.

Expression and clinical significance of Pax6 gene in retinoblastoma

Directory of Open Access Journals (Sweden)

Hai-Dong Huang

2013-07-01

Full Text Available AIM: To discuss the expression and clinical significance of Pax6 gene in retinoblastoma(Rb. METHODS: Totally 15 cases of fresh Rb organizations were selected as observation group and 15 normal retinal organizations as control group. Western-Blot and reverse transcriptase polymerase chain reaction(RT-PCRmethods were used to detect Pax6 protein and Pax6 mRNA expressions of the normal retina organizations and Rb organizations. At the same time, Western Blot method was used to detect the Pax6 gene downstream MATH5 and BRN3b differentiation gene protein level expression. After the comparison between two groups, the expression and clinical significance of Pax6 gene in Rb were discussed. RESULTS: In the observation group, average value of mRNA expression of Pax6 gene was 0.99±0.03; average value of Pax6 gene protein expression was 2.07±0.15; average value of BRN3b protein expression was 0.195±0.016; average value of MATH5 protein expression was 0.190±0.031. They were significantly higher than the control group, and the differences were statistically significant(PCONCLUSION: Abnormal expression of Pax6 gene is likely to accelerate the occurrence of Rb.

Prognostic significance of clinical seizures after cardiac arrest and target temperature management

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Lybeck, Anna; Friberg, Hans; Aneman, Anders

2017-01-01

AIM: Clinical seizures are common after cardiac arrest and predictive of a poor neurological outcome. Seizures may be myoclonic, tonic-clonic or a combination of seizure types. This study reports the incidence and prognostic significance of clinical seizures in the target temperature management (...

Stress-related exhaustion disorder--clinical manifestation of burnout? A review of assessment methods, sleep impairments, cognitive disturbances, and neuro-biological and physiological changes in clinical burnout.

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Grossi, Giorgio; Perski, Aleksander; Osika, Walter; Savic, Ivanka

2015-12-01

The aim of this paper was to provide an overview of the literature on clinically significant burnout, focusing on its assessment, associations with sleep disturbances, cognitive impairments, as well as neurobiological and physiological correlates. Fifty-nine English language articles and six book chapters were included. The results indicate that exhaustion disorder (ED), as described in the Swedish version of the International Classification of Diseases, seems to be the most valid clinical equivalent of burnout. The data supports the notion that sleep impairments are causative and maintaining factors for this condition. Patients with clinical burnout/ED suffer from cognitive impairments in the areas of memory and executive functioning. The studies on neuro-biological mechanisms have reported functional uncoupling of networks relating the limbic system to the pre-frontal cortex, and decreased volumes of structures within the basal ganglia. Although there is a growing body of literature on the physiological correlates of clinical burnout/ED, there is to date no biomarker for this condition. More studies on the role of sleep disturbances, cognitive impairments, and neurobiological and physiological correlates in clinical burnout/ED are warranted. © 2015 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

A novel complete-case analysis to determine statistical significance between treatments in an intention-to-treat population of randomized clinical trials involving missing data.

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Liu, Wei; Ding, Jinhui

2018-04-01

The application of the principle of the intention-to-treat (ITT) to the analysis of clinical trials is challenged in the presence of missing outcome data. The consequences of stopping an assigned treatment in a withdrawn subject are unknown. It is difficult to make a single assumption about missing mechanisms for all clinical trials because there are complicated reactions in the human body to drugs due to the presence of complex biological networks, leading to data missing randomly or non-randomly. Currently there is no statistical method that can tell whether a difference between two treatments in the ITT population of a randomized clinical trial with missing data is significant at a pre-specified level. Making no assumptions about the missing mechanisms, we propose a generalized complete-case (GCC) analysis based on the data of completers. An evaluation of the impact of missing data on the ITT analysis reveals that a statistically significant GCC result implies a significant treatment effect in the ITT population at a pre-specified significance level unless, relative to the comparator, the test drug is poisonous to the non-completers as documented in their medical records. Applications of the GCC analysis are illustrated using literature data, and its properties and limits are discussed.

Clinically significant change in stroke volume in pulmonary hypertension.

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van Wolferen, Serge A; van de Veerdonk, Marielle C; Mauritz, Gert-Jan; Jacobs, Wouter; Marcus, J Tim; Marques, Koen M J; Bronzwaer, Jean G F; Heymans, Martijn W; Boonstra, Anco; Postmus, Pieter E; Westerhof, Nico; Vonk Noordegraaf, Anton

2011-05-01

Stroke volume is probably the best hemodynamic parameter because it reflects therapeutic changes and contains prognostic information in pulmonary hypertension (PH). Stroke volume directly reflects right ventricular function in response to its load, without the correction of compensatory increased heart rate as is the case for cardiac output. For this reason, stroke volume, which can be measured noninvasively, is an important hemodynamic parameter to monitor during treatment. However, the extent of change in stroke volume that constitutes a clinically significant change is unknown. The aim of this study was to determine the minimal important difference (MID) in stroke volume in PH. One hundred eleven patients were evaluated at baseline and after 1 year of follow-up with a 6-min walk test (6MWT) and cardiac MRI. Using the anchor-based method with 6MWT as the anchor, and the distribution-based method, the MID of stroke volume change could be determined. After 1 year of treatment, there was, on average, a significant increase in stroke volume and 6MWT. The change in stroke volume was related to the change in 6MWT. Using the anchor-based method, an MID of 10 mL in stroke volume was calculated. The distribution-based method resulted in an MID of 8 to 12 mL. Both methods showed that a 10-mL change in stroke volume during follow-up should be considered as clinically relevant. This value can be used to interpret changes in stroke volume during clinical follow-up in PH.

Comparison of 5 health care professionals’ratings of the clinical significance of drug related problems

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Villesen, Christine; Hojsted, Jette; Kjeldsen, Lene Juel

2014-01-01

to a mutual agreement on the level of clinical significance. However, to what degree does the panel agree?Purpose To compare the agreement between different health care professionals who have evaluated the clinical significance of DRPs.Materials and methods DRPs were identified in 30 comprehensive medicines...... reviews conducted by a clinical pharmacist. Two hospital pharmacists, a general practitioner and two specialists in pain management from hospital care (the Panel) evaluated each DRP considering the potential clinical outcome for the patient. The DRPs were rated either nil, low, minor, moderate or highly...... clinically significant. Agreement was analysed using Kappa statistics. A Kappa value of 0.8 to 1.0 indicated nearly perfect agreement between ratings of the Panel members.Results The Panel rated 45 percent of the total 162 DRPs as of moderate clinical significance. However, the overall kappa score was 0...

Association of MYCN copy number with clinical features, tumor biology, and outcomes in neuroblastoma: A report from the Children's Oncology Group.

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Campbell, Kevin; Gastier-Foster, Julie M; Mann, Meegan; Naranjo, Arlene H; Van Ryn, Collin; Bagatell, Rochelle; Matthay, Katherine K; London, Wendy B; Irwin, Meredith S; Shimada, Hiroyuki; Granger, M Meaghan; Hogarty, Michael D; Park, Julie R; DuBois, Steven G

2017-11-01

High-level MYCN amplification (MNA) is associated with poor outcome and unfavorable clinical and biological features in patients with neuroblastoma. To the authors' knowledge, less is known regarding these associations in patients with low-level MYCN copy number increases. In this retrospective study, the authors classified patients has having tumors with MYCN wild-type tumors, MYCN gain (2-4-fold increase in MYCN signal compared with the reference probe), or MNA (>4-fold increase). Tests of trend were used to investigate ordered associations between MYCN copy number category and features of interest. Log-rank tests and Cox models compared event-free survival and overall survival by subgroup. Among 4672 patients, 3694 (79.1%) had MYCN wild-type tumors, 133 (2.8%) had MYCN gain, and 845 (18.1%) had MNA. For each clinical/biological feature, the percentage of patients with an unfavorable feature was lowest in the MYCN wild-type category, intermediate in the MYCN gain category, and highest in the MNA category (PNeuroblastoma Staging System) and patients with non-high-risk disease with MYCN gain had a significantly increased risk for death, a finding confirmed on multivariable testing. Increasing MYCN copy number is associated with an increasingly higher rate of unfavorable clinical/biological features, with 11q aberration being an exception. Patients with MYCN gain appear to have inferior outcomes, especially in otherwise more favorable groups. Cancer 2017;123:4224-4235. © 2017 American Cancer Society. © 2017 American Cancer Society.

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

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

2016-05-01

This study evaluated the clinical significance as well as predictors of outcome for adolescents with severe anorexia nervosa (AN) treated in an inpatient setting. Body mass index (BMI), eating disorder (ED) symptoms [Eating Disorder Inventory-2 (EDI-2)], general psychopathology and depression were assessed in 238 patients at admission and discharge. BMI increased from 14.8 + 1.2 to 17.3 + 1.4 kg/m(2). Almost a fourth (23.6%) of the patients showed reliable changes, and 44.7% showed clinically significant changes (EDI-2). BMI change did not significantly differ between those with reliable or clinically significant change or no reliable change in EDI-2. Length of stay, depression and body dissatisfaction were negative predictors of a clinically significant change. Inpatient treatment is effective in about two thirds of adolescents with AN and should be considered when outpatient treatment fails. About one third of patients showed significant weight gain, but did not improve regarding overall ED symptomatology. Future studies should focus on treatment strategies for non-responders. Copyright © 2015 John Wiley & Sons, Ltd and Eating Disorders Association.

Radiation-induced DNA-protein cross-links: Mechanisms and biological significance.

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Nakano, Toshiaki; Xu, Xu; Salem, Amir M H; Shoulkamy, Mahmoud I; Ide, Hiroshi

2017-06-01

Ionizing radiation produces various DNA lesions such as base damage, DNA single-strand breaks (SSBs), DNA double-strand breaks (DSBs), and DNA-protein cross-links (DPCs). Of these, the biological significance of DPCs remains elusive. In this article, we focus on radiation-induced DPCs and review the current understanding of their induction, properties, repair, and biological consequences. When cells are irradiated, the formation of base damage, SSBs, and DSBs are promoted in the presence of oxygen. Conversely, that of DPCs is promoted in the absence of oxygen, suggesting their importance in hypoxic cells, such as those present in tumors. DNA and protein radicals generated by hydroxyl radicals (i.e., indirect effect) are responsible for DPC formation. In addition, DPCs can also be formed from guanine radical cations generated by the direct effect. Actin, histones, and other proteins have been identified as cross-linked proteins. Also, covalent linkages between DNA and protein constituents such as thymine-lysine and guanine-lysine have been identified and their structures are proposed. In irradiated cells and tissues, DPCs are repaired in a biphasic manner, consisting of fast and slow components. The half-time for the fast component is 20min-2h and that for the slow component is 2-70h. Notably, radiation-induced DPCs are repaired more slowly than DSBs. Homologous recombination plays a pivotal role in the repair of radiation-induced DPCs as well as DSBs. Recently, a novel mechanism of DPC repair mediated by a DPC protease was reported, wherein the resulting DNA-peptide cross-links were bypassed by translesion synthesis. The replication and transcription of DPC-bearing reporter plasmids are inhibited in cells, suggesting that DPCs are potentially lethal lesions. However, whether DPCs are mutagenic and induce gross chromosomal alterations remains to be determined. Copyright © 2017 Elsevier Inc. All rights reserved.

[Clinical Significance of HBV Detection in NHL Patients].

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Zhang, Tian-Ling; Zhang, Juan; Lv, Cheng-Xiu; Hu, Tian-Yu; Li, Qing

2018-04-01

To analyze the relation of HBV infection with clinical characteristics and prognosis in NHL patients, so as to explore the significance of HBV detection. Sixty-eight NHL patients from December 2013 to December 2016 were enrolled in NHL group and 136 patients with other malignancies were chosen in control group, the detectable rate of HBV was compared between 2 groups. The correlation of HBV infection with sex, age, stage, cell origin, expression of P53 and BCL-2 in NHL patients was analyzed. The prognosis-related factors in NHL patients were also analyzed. The infection rate of HBV in NHL group was 51.47%(35/68), that in control group was 15.44% (21/136), and the difference was statistically significant(χ 2 =27.768,PHBV infection correlated with cell origins and expression of BCL-2 in NHL patients(PHBV infection (P>0.05), while the prognosis was significantly related with stage, expression of P53 and BCL-2(PHBV infection correlates with BCL-2 expression level of NHL patients, and shows influence on the prognosis of patients.

Clinical significance of circumportal pancreas, a rare congenital anomaly, in pancreatectomy.

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Ohtsuka, Takao; Mori, Yasuhisa; Ishigami, Kousei; Fujimoto, Takaaki; Miyasaka, Yoshihiro; Nakata, Kohei; Ohuchida, Kenoki; Nagai, Eishi; Oda, Yoshinao; Shimizu, Shuji; Nakamura, Masafumi

2017-08-01

Circumportal pancreas is a rare congenital pancreatic anomaly. The aim of this study was to clarify the clinical characteristics of patients with circumportal pancreases undergoing pancreatectomy. The medical records of 508 patients who underwent pancreatectomy were retrospectively reviewed. The prevalence of circumportal pancreas and related anatomical variations were assessed. Surgical procedures and postoperative outcomes were compared in patients with and without circumportal pancreas. Circumportal pancreas was observed in 9 of the 508 patients (1.7%). In all nine patients, the portal vein was completely encircled by the pancreatic parenchyma above the level of the splenoportal junction, and the main pancreatic duct ran dorsal to the portal vein. The rate of variant hepatic artery did not differ significantly in patients with and without circumportal pancreas. Pancreatic fistula developed more frequently in patients with than without circumportal pancreas (44% vs. 14%, p = 0.03), but other clinical parameters did not differ significantly in these two groups. Despite being rare, circumportal pancreas may increase the risk of postoperative pancreatic fistula in patients undergoing pancreatectomy. However, a prospective, large-cohort study is necessary to determine the real incidence of relevant anatomical variations and the definitive clinical significance of this rare anomaly. Copyright © 2016 Elsevier Inc. All rights reserved.

Clinical significance of Phosphatidyl Inositol Synthase overexpression in oral cancer

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Kaur, Jatinder; Sawhney, Meenakshi; DattaGupta, Siddartha; Shukla, Nootan K; Srivastava, Anurag; Ralhan, Ranju

2010-01-01

We reported increased levels of Phosphatidyl Inositol synthase (PI synthase), (enzyme that catalyses phosphatidyl inositol (PI) synthesis-implicated in intracellular signaling and regulation of cell growth) in smokeless tobacco (ST) exposed oral cell cultures by differential display. This study determined the clinical significance of PI synthase overexpression in oral squamous cell carcinoma (OSCC) and premalignant lesions (leukoplakia), and identified the downstream signaling proteins in PI synthase pathway that are perturbed by smokeless tobacco (ST) exposure. Tissue microarray (TMA) Immunohistochemistry, Western blotting, Confocal laser scan microscopy, RT-PCR were performed to define the expression of PI synthase in clinical samples and in oral cell culture systems. Significant increase in PI synthase immunoreactivity was observed in premalignant lesions and OSCCs as compared to oral normal tissues (p = 0.000). Further, PI synthase expression was significantly associated with de-differentiation of OSCCs, (p = 0.005) and tobacco consumption (p = 0.03, OR = 9.0). Exposure of oral cell systems to smokeless tobacco (ST) in vitro confirmed increase in PI synthase, Phosphatidylinositol 3-kinase (PI3K) and cyclin D1 levels. Collectively, increased PI synthase expression was found to be an early event in oral cancer and a target for smokeless tobacco

Clinical significance of gamma camera renography in chronic renal insufficiency

International Nuclear Information System (INIS)

Dudczak, R.; Frischauf, H.; Kletter, K.

1980-01-01

Gamma camera renography allows, together with renal imaging, an evaluation of individual renal function. For these examinations, I 123 orthoiodohippurate is preferred and most widely used. The results on patients with chronic renal insufficiency, including urologic and posttransplantation patients, are reported. Whereas the method is of clinical significance in evaluating posttransplantation complications and in assessing individual kidney function preoperatively in urology, as well as in monitoring therapeutic effects in the early period of renal disease, it is of limited diagnostic value in chronic renal insufficiency. In this latter regard, clinical and laboratory examinations are of primary importance. (author)

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

NARCIS (Netherlands)

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

2007-01-01

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

Significance of clinical and biologic features in Stage 3 neuroblastoma: a report from the International Neuroblastoma Risk Group project.

Science.gov (United States)

Meany, Holly J; London, Wendy B; Ambros, Peter F; Matthay, Katherine K; Monclair, Tom; Simon, Thorsten; Garaventa, Alberto; Berthold, Frank; Nakagawara, Akira; Cohn, Susan L; Pearson, Andrew D J; Park, Julie R

2014-11-01

International Neuroblastoma Staging System (INSS) Stage 3 neuroblastoma is a heterogeneous disease. Data from the International Neuroblastoma Risk Group (INRG) database were analyzed to define patient and tumor characteristics predictive of outcome. Of 8,800 patients in the INRG database, 1,483 with INSS Stage 3 neuroblastoma and complete follow-up data were analyzed. Secondary analysis was performed in 1,013 patients (68%) with MYCN-non-amplified (NA) tumors. Significant prognostic factors were identified via log-rank test comparisons of survival curves. Multivariable Cox proportional hazards regression model was used to identify factors independently predictive of event-free survival (EFS). Age at diagnosis (P INSS Stage 3 neuroblastoma patients, age at diagnosis, MYCN status and histology predict outcome. Patients <547 days of age with MYCN-NA tumors that lack chromosome 11q aberrations or those with serum ferritin <96 ng/ml have excellent prognosis and should be considered for therapy reduction. Prospective clinical trials are needed to identify optimal therapy for those patients ≥ 547 days of age with undifferentiated histology or elevated serum ferritin. © 2014 Wiley Periodicals, Inc.

Re-evaluating concepts of biological function in clinical medicine: towards a new naturalistic theory of disease.

Science.gov (United States)

Chin-Yee, Benjamin; Upshur, Ross E G

2017-08-01

Naturalistic theories of disease appeal to concepts of biological function, and use the notion of dysfunction as the basis of their definitions. Debates in the philosophy of biology demonstrate how attributing functions in organisms and establishing the function-dysfunction distinction is by no means straightforward. This problematization of functional ascription has undermined naturalistic theories and led some authors to abandon the concept of dysfunction, favoring instead definitions based in normative criteria or phenomenological approaches. Although this work has enhanced our understanding of disease and illness, we need not necessarily abandon naturalistic concepts of function and dysfunction in the disease debate. This article attempts to move towards a new naturalistic theory of disease that overcomes the limitations of previous definitions and offers advantages in the clinical setting. Our approach involves a re-evaluation of concepts of biological function employed by naturalistic theories. Drawing on recent insights from the philosophy of biology, we develop a contextual and evaluative account of function that is better suited to clinical medicine and remains consistent with contemporary naturalism. We also show how an updated naturalistic view shares important affinities with normativist and phenomenological positions, suggesting a possibility for consilience in the disease debate.

Biology and clinical application of CAR T cells for B cell malignancies.

Science.gov (United States)

Davila, Marco L; Sadelain, Michel

2016-07-01

Chimeric antigen receptor (CAR)-modified T cells have generated broad interest in oncology following a series of dramatic clinical successes in patients with chemorefractory B cell malignancies. CAR therapy now appears to be on the cusp of regulatory approval as a cell-based immunotherapy. We review here the T cell biology and cell engineering research that led to the development of second generation CARs, the selection of CD19 as a CAR target, and the preclinical studies in animal models that laid the foundation for clinical trials targeting CD19+ malignancies. We further summarize the status of CD19 CAR clinical therapy for non-Hodgkin lymphoma and B cell acute lymphoblastic leukemia, including their efficacy, toxicities (cytokine release syndrome, neurotoxicity and B cell aplasia) and current management in humans. We conclude with an overview of recent pre-clinical advances in CAR design that argues favorably for the advancement of CAR therapy to tackle other hematological malignancies as well as solid tumors.

Subclassification of autoimmune pancreatitis: a histologic classification with clinical significance.

Science.gov (United States)

Deshpande, Vikram; Gupta, Rajib; Sainani, Nisha; Sahani, Dushyant V; Virk, Renu; Ferrone, Cristina; Khosroshahi, Arezou; Stone, John H; Lauwers, Gregory Y

2011-01-01

Autoimmune pancreatitis (AIP) is a chronic inflammatory disease of the pancreas. Examination of pancreatic resection specimens from patients with AIP has shown that there are 2 subclasses of this disease. However, there is no widely accepted pathologic classification scheme and the clinical significance of such a classification remains to be established. In this study, we revisited the subclassification of AIP and examine whether this provides clinically and prognostically meaningful information. We evaluated 29 pancreatic resection specimens from patients with AIP. Demographic, clinical, and imaging data were recorded, as was evidence of extrapancreatic manifestations. In addition to a detailed and semiquantitative histologic evaluation, immunohistochemistry for IgG4 was performed on pancreatic and extrapancreatic tissues. We also evaluated 48 consecutive cases of chronic pancreatitis, not otherwise specified. The resected specimens could readily be subclassified into 2 subtypes: type 1 (n=11) and type 2 (n=18). In comparison with patients with type 2 disease, patients with type 1 disease were significantly more likely to be males (P=0.09), older (P=0.02), and present with jaundice (P=0.01), and less likely to be associated with abdominal pain (P=0.04). On imaging, the pancreatic tail cut-off sign was exclusively seen in patients with type 2 disease (4 of 10 cases). Hypercellular inflamed interlobular stroma was unique to type 1 pattern (91%), whereas significant ductal injury in the form of microabscesses and ductal ulceration was almost exclusively seen in type 2 pattern (78%). Eight of 10 patients with a type 1 pattern had evidence of a systemic disease. Three patients with type 2 disease had recurrent episodes of pancreatitis after their pancreatic resection. In comparison with the cohort of chronic pancreatitis, not otherwise specified, type 2 AIP cases were less likely to be associated with a history of alcohol abuse, and showed significantly more foci of

Melatonin Distribution Reveals Clues to Its Biological Significance in Basal Metazoans

Science.gov (United States)

Roopin, Modi; Levy, Oren

2012-01-01

Although nearly ubiquitous in nature, the precise biological significance of endogenous melatonin is poorly understood in phylogenetically basal taxa. In the present work, we describe insights into the functional role of melatonin at the most “basal” level of metazoan evolution. Hitherto unknown morphological determinants of melatonin distribution were evaluated in Nematostella vectensis by detecting melatonin immunoreactivity and examining the spatial gene expression patterns of putative melatonin biosynthetic and receptor elements that are located at opposing ends of the melatonin signaling pathway. Immuno-melatonin profiling indicated an elaborate interaction with reproductive tissues, reinforcing previous conjectures of a melatonin-responsive component in anthozoan reproduction. In situ hybridization (ISH) to putative melatonin receptor elements highlighted the possibility that the bioregulatory effects of melatonin in anthozoan reproduction may be mediated by interactions with membrane receptors, as in higher vertebrates. Another intriguing finding of the present study pertains to the prevalence of melatonin in centralized nervous structures. This pattern may be of great significance given that it 1) identifies an ancestral association between melatonin and key neuronal components and 2) potentially implies that certain effects of melatonin in basal species may be spread widely by regionalized nerve centers. PMID:23300630

Yoga & Cancer Interventions: A Review of the Clinical Significance of Patient Reported Outcomes for Cancer Survivors

Directory of Open Access Journals (Sweden)

S. Nicole Culos-Reed

2012-01-01

Full Text Available Limited research suggests yoga may be a viable gentle physical activity option with a variety of health-related quality of life, psychosocial and symptom management benefits. The purpose of this review was to determine the clinical significance of patient-reported outcomes from yoga interventions conducted with cancer survivors. A total of 25 published yoga intervention studies for cancer survivors from 2004–2011 had patient-reported outcomes, including quality of life, psychosocial or symptom measures. Thirteen of these studies met the necessary criteria to assess clinical significance. Clinical significance for each of the outcomes of interest was examined based on 1 standard error of the measurement, 0.5 standard deviation, and relative comparative effect sizes and their respective confidence intervals. This review describes in detail these patient-reported outcomes, how they were obtained, their relative clinical significance and implications for both clinical and research settings. Overall, clinically significant changes in patient-reported outcomes suggest that yoga interventions hold promise for improving cancer survivors' well-being. This research overview provides new directions for examining how clinical significance can provide a unique context for describing changes in patient-reported outcomes from yoga interventions. Researchers are encouraged to employ indices of clinical significance in the interpretation and discussion of results from yoga studies.

Dual cusped protostylid: Case report and clinical significance

Directory of Open Access Journals (Sweden)

Preeti Bhattacharya

2016-01-01

Full Text Available Protostylids are superstructures on maxillary or mandibular molars, which have rarely been reported in literature, and the significance of their presence has also been underestimated. The dental practitioners may easily misdiagnose a tooth, with such conical tubercles as malformed tooth. Interestingly, this is neither a malformation nor an anomaly but rather an important morphological trait of an individual. Once in a while, one may come across such a distinct morphological trait without being able to diagnose. To the authors' best knowledge, only one similar case has been reported previously, and the second such case internationally. Bearing all such facts in mind, the authors attempt to educate the readers towards the existence of such a trait so that it can be identified and studied in larger numbers. Hence, it is the authors' endeavor to report an unusual case of dual cusped maxillary protostylid along with its clinical significance.

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

Science.gov (United States)

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

2005-01-01

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

Intensive inpatient treatment for bulimia nervosa: Statistical and clinical significance of symptom changes.

Science.gov (United States)

Diedrich, Alice; Schlegl, Sandra; Greetfeld, Martin; Fumi, Markus; Voderholzer, Ulrich

2018-03-01

This study examines the statistical and clinical significance of symptom changes during an intensive inpatient treatment program with a strong psychotherapeutic focus for individuals with severe bulimia nervosa. 295 consecutively admitted bulimic patients were administered the Structured Interview for Anorexic and Bulimic Syndromes-Self-Rating (SIAB-S), the Eating Disorder Inventory-2 (EDI-2), the Brief Symptom Inventory (BSI), and the Beck Depression Inventory-II (BDI-II) at treatment intake and discharge. Results indicated statistically significant symptom reductions with large effect sizes regarding severity of binge eating and compensatory behavior (SIAB-S), overall eating disorder symptom severity (EDI-2), overall psychopathology (BSI), and depressive symptom severity (BDI-II) even when controlling for antidepressant medication. The majority of patients showed either reliable (EDI-2: 33.7%, BSI: 34.8%, BDI-II: 18.1%) or even clinically significant symptom changes (EDI-2: 43.2%, BSI: 33.9%, BDI-II: 56.9%). Patients with clinically significant improvement were less distressed at intake and less likely to suffer from a comorbid borderline personality disorder when compared with those who did not improve to a clinically significant extent. Findings indicate that intensive psychotherapeutic inpatient treatment may be effective in about 75% of severely affected bulimic patients. For the remaining non-responding patients, inpatient treatment might be improved through an even stronger focus on the reduction of comorbid borderline personality traits.

A review of the biological and clinical aspects of radiation caries.

Science.gov (United States)

Aguiar, Gabrielle P; Jham, Bruno C; Magalhães, Cláudia S; Sensi, Luis Guilherme; Freire, Addah R

2009-07-01

The aim of this article is to review the clinical and biological features underlying the development and progression of radiation caries. Although radiotherapy (RT) plays an important role in the management of patients with head and neck cancer (HNC), it is also associated with several undesired side effects such as radiation caries which is a common, yet serious, complication. To review the condition, the Pubmed database was searched using the keywords "radiotherapy," "radiation," "caries," "hyposalivation," "prevention" and "management". Only studies published in the English language were selected. Cross-referencing identified additionally relevant studies. RT leads to alterations in the dentition, saliva, oral microflora, and diet of patients. Consequently, irradiated patients are at increased risk for the development of a rapid, rampant carious process known as radiation caries. Motivation of patients, adequate plaque control, stimulation of salivary flow, fluoride use, and nutritional orientation are essential to reduce the incidence of radiation caries and ultimately improve the quality of life for HNC patients. Radiation caries is an aggressive side effect of RT. Dentists play an important role in the prevention of the condition via comprehensive oral healthcare before, during, and after the active cancer therapy. Dentists should understand the clinical and biological aspects underlying radiation caries to prevent the development of lesions and provide optimal treatment when needed.

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

Science.gov (United States)

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.…

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

International Nuclear Information System (INIS)

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

2004-01-01

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

Pharmaceutical, biological, and clinical properties of botulinum neurotoxin type A products.

Science.gov (United States)

Frevert, Jürgen

2015-03-01

Botulinum neurotoxin injections are a valuable treatment modality for many therapeutic indications and have revolutionized the field of aesthetic medicine so that they are the leading cosmetic procedure performed worldwide. Studies show that onabotulinumtoxinA, abobotulinumtoxinA, and incobotulinumtoxinA are comparable in terms of clinical efficacy. Differences between the products relate to the botulinum neurotoxin complexes, specific biological potency, and their immunogenicity. Protein complex size and molecular weight have no effect on biological activity, stability, distribution, or side effect profile. Complexing proteins and inactive toxin (toxoid) content increase the risk of neutralizing antibody formation, which can cause secondary treatment failure, particularly in chronic disorders that require frequent injections and long-term treatment. These attributes could lead to differences in therapeutic outcomes, and, given the widespread aesthetic use of these three neurotoxin products, physicians should be aware of how they differ to ensure their safe and effective use.

Accurate coding in sepsis: clinical significance and financial implications.

Science.gov (United States)

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. Copyright © 2016 The Healthcare Infection Society. All rights reserved.

Clinical Significance of HER-2 Splice Variants in Breast Cancer Progression and Drug Resistance

Directory of Open Access Journals (Sweden)

Claire Jackson

2013-01-01

Full Text Available Overexpression of human epidermal growth factor receptor (HER-2 occurs in 20–30% of breast cancers and confers survival and proliferative advantages on the tumour cells making HER-2 an ideal therapeutic target for drugs like Herceptin. Continued delineation of tumour biology has identified splice variants of HER-2, with contrasting roles in tumour cell biology. For example, the splice variant 16HER-2 (results from exon 16 skipping increases transformation of cancer cells and is associated with treatment resistance; conversely, Herstatin (results from intron 8 retention and p100 (results from intron 15 retention inhibit tumour cell proliferation. This review focuses on the potential clinical implications of the expression and coexistence of HER-2 splice variants in cancer cells in relation to breast cancer progression and drug resistance. “Individualised” strategies currently guide breast cancer management; in accordance, HER-2 splice variants may prove valuable as future prognostic and predictive factors, as well as potential therapeutic targets.

The normal limits, subclinical significance, related metabolic derangements and distinct biological effects of body site-specific adiposity in relatively healthy population.

Directory of Open Access Journals (Sweden)

Chun-Ho Yun

Full Text Available BACKGROUND: The accumulation of visceral adipose tissue that occurs with normal aging is associated with increased cardiovascular risks. However, the clinical significance, biological effects, and related cardiometabolic derangements of body-site specific adiposity in a relatively healthy population have not been well characterized. MATERIALS AND METHODS: In this cross-sectional study, we consecutively enrolled 608 asymptomatic subjects (mean age: 47.3 years, 27% female from 2050 subjects undergoing an annual health survey in Taiwan. We measured pericardial (PCF and thoracic peri-aortic (TAT adipose tissue volumes by 16-slice multi-detector computed tomography (MDCT (Aquarius 3D Workstation, TeraRecon, San Mateo, CA, USA and related these to clinical characteristics, body fat composition (Tanita 305 Corporation, Tokyo, Japan, coronary calcium score (CCS, serum insulin, high-sensitivity C-reactive protein (Hs-CRP level and circulating leukocytes count. Metabolic risk was scored by Adult Treatment Panel III guidelines. RESULTS: TAT, PCF, and total body fat composition all increased with aging and higher metabolic scores (all p<0.05. Only TAT, however, was associated with higher circulating leukocyte counts (ß-coef.:0.24, p<0.05, serum insulin (ß-coef.:0.17, p<0.05 and high sensitivity C-reactive protein (ß-coef.:0.24, p<0.05. These relationships persisted after adjustment in multivariable models (all p<0.05. A TAT volume of 8.29 ml yielded the largest area under the receiver operating characteristic curve (AUROC: 0.79, 95%CI: 0.74-0.83 to identify metabolic syndrome. TAT but not PCF correlated with higher coronary calcium score after adjustment for clinical variables (all p<0.05. CONCLUSION: In our study, we observe that age-related body-site specific accumulation of adipose tissue may have distinct biological effects. Compared to other adiposity measures, peri-aortic adiposity is more tightly associated with cardiometabolic risk profiles and

Frequency and clinical significance of transient hyperechoic renal medulla in neonates

International Nuclear Information System (INIS)

Cho, Sung Shick; Kim, Jung Hoon; Hong, Hyun Sook; Shin, Ji Hoon; Hwang, Jung Hwa; Goo, Dong Erk; Kwon, Kui Hyang; Choi, Deuk Lin

2001-01-01

To evaluate the clinical significance of transient hyperechogenicity of the renal medulla in neonates by comparing the clinical features, urinalysis and follow-up ultrasonographic examination of the control group. One hundred ten neonates were divided into 2 groups, hyperechoic and normal renal medulla groups, and all of them underwent abdominal ultrasound with a 7.5 MHz linear transducer (Sonoace 8800MT, Medicine, Korea) from November 1999 to January 2000. Whether there was any difference in clinical features including birth weight, body surface area, gestational age, sex, date of examination and mode of delivery between two groups was evaluated. In addition, any difference in their urinary osmolarity, albumin, uric acid and calcium in 41 neonates who underwent urinalysis was evaluated. In ten neonates with hyperechoic renal medulla underwent follow-up study, the follow-up ultrasonographic findings were compared with the initial study. In 67 of 110 (61%) neonates, ultrasonography demonstrated hyperechoic renal medulla. There was no difference in clinical features between the hyperechoic renal medullary group and normal group. In 41 neonates, there was no significant difference in urinalysis between two groups. (Osmolarity=146.46 ± 68.4 mOsml/KgH 2 O in the hyperechoic renal medullary group vs. 149.8 ± 77.7 mOsml/KgH 2 O in the normal group; albumin=13.9 ± 10.2 mg/ml vs. 17.6 ± 13.6 mg/dl; uric acid=50.0 ± 23.3 mg/dl vs. 44.9 ± 34.1 mg/dl; calcium=1.38 ± 3.0 mg/ dl vs. 0.44 ± 0.07 mg/dl.) Ten neonates who underwent follow-up ultrasonography within 20 days after the initial study showed the normal medullary echogenicity. There were no significant difference between the hyperechoic renal medullary group and the normal echogenic group in their clinical features and urinalysis. Therefore, the hyperechoic renal medullar in neonate is considered as an usual and transient finding which disappears on follow-up study.

Thymomodulin: biological properties and clinical applications.

Science.gov (United States)

Kouttab, N M; Prada, M; Cazzola, P

1989-01-01

Thymomodulin (Ellem Industria Farmaceutica s.p.a., Milan, Italy) is a calf thymus acid lysate derivative, composed of several peptides with a molecular weight range of 1-10 kD. Thymomodulin did not exhibit any mutagenic effect. Furthermore, thymomodulin used in animal studies showed no toxicity even when used at high concentrations. Of major significance are the observations in murine and human systems that thymomodulin remains active when administered orally. In vitro and in vivo administered thymomodulin was able to induce the maturation of T-lymphocytes. Additionally, studies in vitro showed that this thymic derivative can enhance the functions of mature T-lymphocytes with cascading effects on B-cell and macrophage functions. Extensive human clinical trials with thymomodulin showed that this agent can improve the clinical symptoms observed with various disease processes, including infections, allergies and malignancies, and can improve immunological functions during ageing.

The clinical significance of detection of serum Pre-S1 antigen

International Nuclear Information System (INIS)

Jiang Xuehua; Huang Zhuqing; Han Yi; Gong Shoujun

2003-01-01

To study the clinical significance of detection of serum Pre-S 1 Ag, the serum Pre-S 1 Ag, HBV-marks and HBV-DNA were detected in 338 patients with hepatitis B. The positive rate and the relationship between them were analyzed and compared. In 338 patients, the positive rate of serum Pre-S 1 Ag, HBeAg, HBV-DNA was 63.02%, 48.52%, 68.05% respectively, and the co-positive rate of Pre-S 1 Ag with HBV-DNA, HBeAg was 78.56%, 81.17% respectively. There was a significant correlation between Pre-S 1 Ag, HBeAg and HBV-DNA (P 1 Ag could well reflect the reproductive status of hepatitis B virus, and so it could be used as the clinical marker of the reproductive status of hepatitis B virus

Significance and clinical value of the transitional zone volume (TZV ...

African Journals Online (AJOL)

M. El Ghoneimy

2017-01-12

Jan 12, 2017 ... Objective: The aim of this work was to evaluate the significance and clinical value of the TZI, which has been a point of ... Conclusion: Estimating the transition zone volume during TRUS is a reasonable way to obtain the required ... Besides the IPSS score, a complete medical and surgical history was also.

Polycystic ovarian syndrome: clinical and biological diagnosis.

Science.gov (United States)

Bachelot, Anne

2016-12-01

Polycystic ovary syndrome (PCOS) is the most common ovarian disorder associated with androgen excess in women, which justifies the growing interest of endocrinologists. This syndrome leads to clinical hyperandrogenism and/or a biological dysovulation and infertility. Its diagnosis is based on consensual diagnostic criteria, but which are likely to change in the near future with the rise of the interest of new markers such as AMH. Diagnostic tools of PCOS are also discussed, with emphasis on the laboratory evaluation of androgens and other potential biomarkers of ovarian and metabolic dysfunctions. The exact etiology of PCOS is unknown and is likely multifactorial. Many studies indicate that PCOS results from originally ovarian abnormalities. In some patients, secondary hyperinsulinemia with insulin resistance plays a role in the pathophysiology. In addition, the relevant impact of metabolic issues, specifically insulin resistance and obesity, on the pathogenesis of PCOS, and the susceptibility to develop earlier than expected glucose intolerance states, including type 2 diabetes, has supported the notion that these aspects should be considered when defining the PCOS phenotype and planning potential therapeutic strategies in an affected subject.

Clinical significance of inadequate endometrial biopsies prior to hysterectomy.

Science.gov (United States)

Turney, Emily H; Farghaly, Hanan; Eskew, Ashley M; Parker, Lynn P; Milam, Michael R

2012-01-01

To evaluate preoperative clinical risk factors associated with significant uterine histopathologic abnormalities in final hysterectomy specimens in patients with inadequate preoperative endometrial biopsies. This is an institutional review board-approved, retrospective cohort analysis of 469 consecutive patients who underwent preoperative endometrial biopsies with subsequent hysterectomy from January 1, 2005, to December 31, 2009, at the University of Louisville Medical Center. We analyzed risk factors for inadequate biopsy and for final diagnosis of endometrial pathology (defined as endometrial hyperplasia or uterine cancer). Of the 469 preoperative endometrial biopsies reviewed, 26.2% (123/469) were inadequate (IBx) and 73.8% (346/469) were adequate and benign. IBx on endometrial biopsies was associated with a greater risk of having significant uterine histopathologic abnormalities on final hysterectomy specimens (6.5% vs. 2.3%, RR 2.8 [95% CI 1.1-7.3], p = 0.04). Although inadequate endometrial biopsies are a common finding, they can be associated with significant uterine histopathologic abnormalities on final hysterectomy specimens.

Exploring rhizosphere bacteria of Eichhornia crassipes for metal tolerance and biological activity

Digital Repository Service at National Institute of Oceanography (India)

PrabhaDevi; Gomez, S.; Ribeiro, M.; Deshpande, S.A.; Singh, K.S.; DeSouza, L.

Cl₃, They were further screened for antibiotic sensitivity and biological activity according to Kirby-Bauer disc diffusion method The MTB under metal stress condition showed significant biological activity against clinical pathogens, fouling...

Pediatric High Grade Glioma: a Review and Update on Tumor Clinical Characteristics and Biology

Energy Technology Data Exchange (ETDEWEB)

Fangusaro, Jason, E-mail: jfangusaro@luriechildrens.org [Pediatric Neuro-Oncology, The Ann & Robert H. Lurie Children’s Hospital of Chicago, Feinberg School of Medicine, Northwestern University, Chicago, IL (United States)

2012-08-24

High grade gliomas (HGG) are one of the most common central nervous system (CNS) tumors encountered in adults, but they only represent approximately 8–12% of all pediatric CNS tumors. Historically, pediatric HGG were thought to be similar to adult HGG since they appear histologically identical; however, molecular, genetic, and biologic data reveal that they are distinct. Similar to adults, pediatric HGG are very aggressive and malignant lesions with few patients achieving long-term survival despite a variety of therapies. Initial treatment strategies typically consist of a gross total resection (GTR) when feasible followed by focal radiotherapy combined with chemotherapy. Over the last few decades, a wealth of data has emerged from basic science and pre-clinical animal models helping to better define the common biologic, genetic, and molecular make-up of these tumors. These data have not only provided a better understanding of tumor biology, but they have also provided new areas of research targeting molecular and genetic pathways with the potential for novel treatment strategies and improved patient outcomes. Here we provide a review of pediatric non-brainstem HGG, including epidemiology, presentation, histology, imaging characteristics, treatments, survival outcomes, and an overview of both basic and translational research. An understanding of all relevant pre-clinical tumor models, including their strengths and pitfalls is essential in realizing improved patient outcomes in this population.

Pediatric High Grade Glioma: a Review and Update on Tumor Clinical Characteristics and Biology

International Nuclear Information System (INIS)

Fangusaro, Jason

2012-01-01

High grade gliomas (HGG) are one of the most common central nervous system (CNS) tumors encountered in adults, but they only represent approximately 8–12% of all pediatric CNS tumors. Historically, pediatric HGG were thought to be similar to adult HGG since they appear histologically identical; however, molecular, genetic, and biologic data reveal that they are distinct. Similar to adults, pediatric HGG are very aggressive and malignant lesions with few patients achieving long-term survival despite a variety of therapies. Initial treatment strategies typically consist of a gross total resection (GTR) when feasible followed by focal radiotherapy combined with chemotherapy. Over the last few decades, a wealth of data has emerged from basic science and pre-clinical animal models helping to better define the common biologic, genetic, and molecular make-up of these tumors. These data have not only provided a better understanding of tumor biology, but they have also provided new areas of research targeting molecular and genetic pathways with the potential for novel treatment strategies and improved patient outcomes. Here we provide a review of pediatric non-brainstem HGG, including epidemiology, presentation, histology, imaging characteristics, treatments, survival outcomes, and an overview of both basic and translational research. An understanding of all relevant pre-clinical tumor models, including their strengths and pitfalls is essential in realizing improved patient outcomes in this population.

Gene variants of unknown clinical significance in Lynch syndrome. An introduction for clinicians

NARCIS (Netherlands)

Sijmons, Rolf H.; Greenblatt, Marc S.; Genuardi, Maurizio

Clinicians referring patients for genetic testing for Lynch syndrome will sooner or later receive results for DNA Mismatch Repair (MMR) genes reporting DNA changes that are unclear from a clinical point of view. These changes are referred to as variants of unknown, or unclear, clinical significance

Biological effects of proton radiation: an update

International Nuclear Information System (INIS)

Girdhani, S.; Hlatky, L.; Sachs, R.

2015-01-01

Proton radiation provides significant dosimetric advantages when compared with gamma radiation due to its superior energy deposition characteristics. Although the physical aspects of proton radiobiology are well understood, biological and clinical endpoints are understudied. The current practice to assume the relative biological effectiveness of low linear energy transfer (LET) protons to be a generic value of about 1.1 relative to photons likely obscures important unrecognised differentials in biological response between these radiation qualities. A deeper understanding of the biological properties induced by proton radiation would have both radiobiological and clinical impact. This article briefly points to some of the literature pertinent to the effects of protons on tissue-level processes that modify disease progression, such as angiogenesis, cell invasion and cancer metastasis. Recent findings hint that proton radiation may, in addition to offering improved radio-therapeutic targeting, be a means to provide a new dimension for increasing therapeutic benefits for patients by manipulating these tissue-level processes. (authors)

Clinical significance of nerve root enhancement in contrast-enhanced MR imaging of the postoperative lumbar spine

International Nuclear Information System (INIS)

Lee, Yeon Soo; Lee, Eun Ja; Kang, Si Won; Choi, Eun Seok; Song, Chang June; Kim, Jong Chul

2001-01-01

To determine the significance of nerve root contrast enhancement in patients with residual or recurrent symptomatic postoperative lumbar spine. Eighty-eight patients with 116 postoperative lumbar disc lesions causing radiating back pain underwent enhanced MR imaging. Intradural nerve root enhancement was quantified by pixel measurement, and affected nerve roots were compared before and after contrast administration. Extradural nerve root enhancement was assessed visually, and nerve root enhancement and clinical symptoms were correlated. Associated lesions such as recurrent disc herniation, scar tissue, nerve root thickening and nerve root displacement were also evaluated. Of 26 cases (22.4%) involving intradural nerve root enhancement, 22 (84.6%) showed significant clinical symptoms (p=0.002). and of 59 (50.9%) demonstrating extradural enhancement, clinical symptoms showed significant correlation in 47 (79.7%) (p=0.001). Nerve root enhancement, including eleven cases where this was both intra-and extradural, showed highly significant association with clinical symptoms in 74 of the 116 cases (63.8%) (p=0.000). Among 33 cases (28.4%) of recurrent disc herniation, nerve root enhancement was observed in 28 (84.8%) and in 24 of these 28 (85.7%), significant correlation with clinical symptoms was observed (p=0.000). Where epidural fibrosis was present, correlation between nerve root enhancement and clinical symptoms was not significant (p>0.05). Nerve root thickening and displaced nerve root were, however, significantly associated with symptoms (87.2% and 88.6%, respectively). In patients with postoperative lumbar spine, the association between nerve root enhancement revealed by MRI and clinical symptoms was highly significant

[Care and specialized clinical follow-up of nursing professionals who have been victims of accidents with biological material].

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Pimenta, Flaviana Regina; Ferreira, Milene Dias; Gir, Elucir; Hayashida, Miyeko; Canini, Silvia Rita Marin da Silva

2013-02-01

This cross-sectional study aimed to evaluate the conduct of nursing professionals who had been victims of accidents with biological material in a teaching hospital in the interior of the state of São Paulo, Brazil, regarding their care and specialized clinical follow-up. The study population consisted of 1,215 nursing professionals, who were interviewed individually between 2010 and 2011. Of the 1,215 nursing professionals interviewed, 636 (52.3%) reported having experienced accidents with biological material; of this population, 182 (28.6%) didn't sought specialized care. The most frequent reason reported for not seeking care was believing that it was a low-risk accident. The reasons professionals do not seek care and do not complete treatment and the clinical follow-up can contribute to strategies to increase professionals' adherence to prophylaxis measures after occupational exposure to biological material.

Evaluating Study Withdrawal Among Biologics and Immunomodulators in Treating Ulcerative Colitis: A Meta-analysis of Controlled Clinical Trials.

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Shah, Eric D; Siegel, Corey A; Chong, Kelly; Melmed, Gil Y

2016-04-01

We conducted a systematic review and meta-analysis to evaluate the efficacy and adverse event (AE)-associated tolerability of treatment with immunomodulators and biologics in ulcerative colitis clinical trials. We performed a literature search of PubMed and the Cochrane databases to identify randomized placebo-controlled trials of immunomodulators and biologics. Tolerability was defined through study withdrawal due to AEs and efficacy through clinical response in induction trials and clinical remission in maintenance trials. We performed meta-analyses using a random-effects model to determine relative risks (RRs) of efficacy and study withdrawal. Number needed to treat (NNT) and number needed to stop (NNS) were determined. The ratio of NNS/NNT was calculated, with a higher ratio indicating a greater number of patients in remission for every AE study discontinuation. We examined 13 single-agent trials representing biologics (infliximab, adalimumab, golimumab, and vedolizumab) and immunomodulators (tacrolimus and azathioprine). Induction therapy did not result in excess study withdrawal with immunomodulators (RR = 0.9, 95% CI 0.1-12.0) or biologics (RR = 0.7, 95% CI 0.3-1.8), therefore the NNS/NNT ratio could not be assessed because of high tolerability. Maintenance immunomodulator therapy resulted in a NNS of 14 (RR = 2.8, 95% CI 0.7-10.5) and NNS/NNT ratio of 2.4 in 2 trials. Biologics did not result in excess study withdrawal in maintenance (RR = 0.7, 95% CI 0.3-1.7) or combined induction-and-maintenance (RR = 0.6, 95% CI 0.4-1.0) trials. Biologics were not associated with a higher RR of study withdrawal due to AE than placebo. There were insufficient data to compare these results with immunomodulators.

Chromosomal Aberrations Associated with Clonal Evolution and Leukemic Transformation in Fanconi Anemia: Clinical and Biological Implications

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Stefan Meyer

2012-01-01

Full Text Available Fanconi anaemia (FA is an inherited disease with congenital and developmental abnormalities, bone marrow failure, and extreme risk of leukemic transformation. Bone marrow surveillance is an important part of the clinical management of FA and often reveals cytogenetic aberrations. Here, we review bone marrow findings in FA and discuss the clinical and biological implications of chromosomal aberrations associated with leukemic transformation.

Assessment of radiation damage - the need for a multi-parametric and integrative approach with the help of both clinical and biological dosimetry

International Nuclear Information System (INIS)

Meineke, Viktor

2008-01-01

Full text: Accidental exposure to ionising radiation leads to a damage on different levels of the biological organization of the organism. Depending on exposure conditions, such as nature of radiation, time and affected organs and organ systems, the clinical endpoint of radiation damage and the resulting acute and chronic radiation syndromes may vary to a great extent. Exposure situations range from pure localised radiation scenarios and partial body exposures up to whole body exposures. Therefore clinical pictures vary from localized radiation injuries up to the extreme situation of a radiation-induced multi-organ involvement and failure requiring immediate, intensive and interdisciplinary medical treatment. These total different and complex clinical situations not only show up most different clinical diagnostic and therapeutic aspects but necessarily due to different levels of the underlying biological damage, biological indicators of effects may vary to a wide extent. This fact means that an exact assessment of the extent of radiation damage within individual patients can only be performed when taking into consideration both clinical signs and symptoms as well as different biological indicators. Among the clinical indicators, routine laboratory parameters such as blood counts and the documentation of clinical signs and symptoms (such as the METREPOL system) are the key parameters, whereas the dicentric assay, the gold standard for biological dosimetry, but also methods under development such as the gamma-H2Ax focus assay or the estimation of variations of gene expression have to be taken into account. Each method provides best results in different situations, or in other words, there are methods that work better in a specific exposure condition or at a given time of examination (e.g. time after exposure) than others. Some methods show up results immediately, others require days to weeks until results are available for clinical decision making. Therefore to

Clinical significance of the corpus callosum in cerebral palsy

International Nuclear Information System (INIS)

Lee, Eun Ja; Kim, Ji Chang; Kim, Jong Chul; And Others

2000-01-01

To evaluate, using magnetic resonance (MR) imaging, the clinal significance of the corpus callosum by measuring the size of various portions of the corpus callosum in children with cerebral palsy, and in paired controls. Fifty-two children (30 boys and 22 girls aged between six and 96 (median, 19) months) in whom cerebral palsy was clinically diagnosed underwent MR imaging. There were 23 term patients and 29 preterm, and the control group was selected by age and sex matching. Clinal subtypes of cerebral palsy were classified as hemiplegia (n=14), spastic diplegia (n=22), or spastic quadriplegia (n=16), and according to the severity of motor palsy, the condition was also classified as mild (n=26), moderate (n=13), or severe (n=13). In addition to the length and height of the corpus callosum, the thickness of its genu, body, transitional zone and splenium, as seen on midsagittal T1-weighted MR images, were also measured. Differences in the measured values of the two groups were statistically analysed and differences in the size of the corpus callosum according to the clinical severity and subtypes of cerebral palsy, and gestational age, were also assessed. Except for height, the measured values of the corpus callosum in patients with cerebral palsy were significantly less than those of the control group (p less than 0.05). Its size decreased according to the severity of motor palsy. Compared with term patients, the corpus callosum in preterm patients was considerably smaller (p less than 0.05). There was statistically significant correlation between the severity of motor palsy and the size of the corpus callosum. Quantitative evaluation of the corpus callosum might be a good indicator of neurologic prognosis, and a sensitive marker for assessing the extent of brain injury

Clinical significance of the corpus callosum in cerebral palsy

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Lee, Eun Ja; Kim, Ji Chang [The Catholic University of Korea, Seoul (Korea, Republic of); Kim, Jong Chul [School of Medicine, Chungnam National University, Taejon (Korea, Republic of); And Others

2000-10-01

To evaluate, using magnetic resonance (MR) imaging, the clinal significance of the corpus callosum by measuring the size of various portions of the corpus callosum in children with cerebral palsy, and in paired controls. Fifty-two children (30 boys and 22 girls aged between six and 96 (median, 19) months) in whom cerebral palsy was clinically diagnosed underwent MR imaging. There were 23 term patients and 29 preterm, and the control group was selected by age and sex matching. Clinal subtypes of cerebral palsy were classified as hemiplegia (n=14), spastic diplegia (n=22), or spastic quadriplegia (n=16), and according to the severity of motor palsy, the condition was also classified as mild (n=26), moderate (n=13), or severe (n=13). In addition to the length and height of the corpus callosum, the thickness of its genu, body, transitional zone and splenium, as seen on midsagittal T1-weighted MR images, were also measured. Differences in the measured values of the two groups were statistically analysed and differences in the size of the corpus callosum according to the clinical severity and subtypes of cerebral palsy, and gestational age, were also assessed. Except for height, the measured values of the corpus callosum in patients with cerebral palsy were significantly less than those of the control group (p less than 0.05). Its size decreased according to the severity of motor palsy. Compared with term patients, the corpus callosum in preterm patients was considerably smaller (p less than 0.05). There was statistically significant correlation between the severity of motor palsy and the size of the corpus callosum. Quantitative evaluation of the corpus callosum might be a good indicator of neurologic prognosis, and a sensitive marker for assessing the extent of brain injury.

[Sarcoptic mange of dogs: biology of the organism, epidemiology, pathogenesis, clinical aspect, diagnosis and treatment].

Science.gov (United States)

Kraiss, A; Kraft, W; Gothe, R

1987-01-01

A review is presented on the biology of the causative agent, epidemiology, pathogenesis, clinical features, diagnosis and therapy of canine Sarcoptes scabiei infestation. This survey includes also clinical data of the period 1978-1986 in the Small Animal Hospital, Munich Veterinary Faculty. Several skin scrapings are usually necessary for diagnosis. For therapy application of acaricides once a week, altogether at least three times is sufficient. Simultaneously a decontamination of the dog's surroundings should be carried out.

Clinical Significance of A Waves in Acute Inflammatory Demyelinating Polyradiculoneuropathy.

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Lakshminarasimhan, Sindhuja; Venkatraman, Chandramouleeswaran; Vellaichamy, Kannan; Ranganathan, Lakshminarasimhan

2018-05-25

A wave is a late response recognized during recording of F waves. Though they might be seen in healthy subjects, their presence assumes significance in a patient presenting with polyradiculoneuropathy. In this prospective study, 75 patients with acute inflammatory demyelinating polyradiculoneuropathy (AIDP) were enrolled. They were divided into two groups based on the presence or absence of A waves. Clinical features, electrophysiological parameters and extent of clinical recovery in short-term follow-up were analyzed. A waves were present in 49 out of 75 patients (65%). Most common pattern observed was multiple A waves. Prevalence of A waves was more in lower limb nerves than upper limb nerves. Occurrence of A waves correlated with the presence of conduction block. Patients with A waves had higher Hughes grade (P = 0.003) and lower Medical Research Council sum score at 6 weeks of follow-up (P = 0.04) as compared to patients without A waves. A waves are common in acute inflammatory demyelinating polyradiculoneuropathy form of Guillain Barre syndrome and are considered as a marker of demyelination. Long-term follow-up studies are required to ascertain their significance in prognostication and assessing recovery.

Clinical significance of pretreatment FDG PET/CT IN MOBG-avid pediatric neuroblastoma

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Kang, Seo Young; Kim, Yong Il; Cheon, Gi Jeong; Kang, Keon Wook; Chung, June Key; Lee, Dong Soo; Kang, Hyoung Jin; Shin, Hee Young [Seoul National University Hospital, Seoul (Korea, Republic of); Kim, E. Edmund [Seoul National University, Seoul (Korea, Republic of); Rahim, Muhammad Kashif [Nishtar Medical College and Hospital, Multan (Pakistan)

2017-06-15

{sup 18}F-fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging is well known to have clinical significance in the initial staging and response evaluation of the many kinds of neoplasms. However, its role in the pediatric neuroblastoma is not clearly defined. In the present study, the clinical significance of FDG-PET/computed tomography (CT) in 123I- or 131I-metaiodobenzylguanidine (MIBG)-avid pediatric neuroblastoma was investigated. Twenty patients with neuroblastoma who undertook pretreatment FDG PET/CT at our institute between 2008 and 2015 and showed MIBG avidity were retrospectively enrolled in the present study. Clinical information—including histopathology, and serum markers—and several PET parameters—including SUVmax of the primary lesion (Psuv), target-to-background ratio (TBR), metabolic tumor volume (MTV), and coefficient of variation (CV)—were analyzed. The prognostic effect of PET parameters was evaluated in terms of progression-free survival (PFS). Total 20 patients (4.5 ± 3.5 years) were divided as two groups by disease progression. Six patients (30.0 %) experienced disease progression and one patient (5.0 %) died during follow-up period. There were not statistically significant in age, stage, MYCN status, primary tumor size, serum lactate dehydrogenase (LDH), neuron-specific enolase (NSE), and ferritin level between two groups with progression or no progression. However, Psuv (p = 0.017), TBR (p = 0.09), MTV (p = 0.02), and CV (p = 0.036) showed significant differences between two groups. In univariate analysis, PFS was significantly associated with Psuv (p = 0.021) and TBR (p = 0.023). FDG-PET parameters were significantly related with progression of neuroblastoma. FDG-PET/CT may have the potential as a valuable modality for evaluating prognosis in the patients with MIBG-avid pediatric neuroblastoma.

Differential expression of OPN, VEGF-A, and HIF-1α and its clinical significance in hepatocellular carcinoma

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ZHENG Yan

2013-01-01

Full Text Available ObjectiveTo investigate the expression patterns of osteopontin (OPN, vascular endothelial growth factor-A (VEGF-A, and hypoxia-inducible factor-1α(HIF-1α in primary hepatocellular carcinoma (HCC and determine the clinical significance of this differential expression profile. MethodsImmunohistochemical staining of OPN, VEGF-A, and HIF-1α was carried out on primary HCC tissues from 90 patients, HCC-adjacent cirrhosis tissues from 20 of those patients, and normal liver tissues from 15 healthy controls. Correlations between expression levels and HCC clinicopathological characteristics were assessed by Spearman's correlation coefficient. ResultsThe majority of HCC tissues showed positive immunostaining for OPN (69/90, 76.67%, VEGF-A (64/90, 71.11%, and HIF-1α (66/90, 73.33%. OPN- and VEGF-A-positivity were significantly higher than the results from the cirrhosis tissues and normal tissues. HIF-1α-positivity was similar between the HCC and cirrhosis tissues, but both were significantly different from the normal tissues. The differential expressions of OPN, VEGF-A, and HIF-1α were significantly correlated with tumor thrombus, capsular integrity, tumor differentiation and stage, and metastasis (P＜0.05. ConclusionHCC tissues overexpress OPN, VEGF-A, and HIF-1α and this differential profile may be related to HCC progression. Future investigations of this triad of factors may provide novel insights into the biological characteristics of HCC and reveal important targets of molecular therapy.

Genetic variation and significance of hepatitis B surface antigen

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ZHANG Zhenhua

2013-11-01

Full Text Available Hepatitis B virus (HBV is prone to genetic variation because there is reverse transcription in the process of HBV replication. The gene mutation of hepatitis B surface antigen may affect clinical diagnosis of HBV infection, viral replication, and vaccine effect. The current research and existing problems are discussed from the following aspects: the mechanism and biological and clinical significance of S gene mutation. Most previous studies focused on S gene alone, so S gene should be considered as part of HBV DNA in the future research on S gene mutation.

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

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Kelly, Peter James

2010-01-01

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

Clinical, Radiologic, and Legal Significance of "Extensor Response" in Posttraumatic Coma.

Science.gov (United States)

Firsching, Raimund; Woischneck, Dieter; Langejürgen, Alexander; Parreidt, Andreas; Bondar, Imre; Skalej, Martin; Röhl, Friedrich; Voellger, Benjamin

2015-11-01

The timely detection of neurologic deterioration can be critical for the survival of a neurosurgical patient following head injury. Because little reliable evidence is available on the prognostic value of the clinical sign "extensor response" in comatose posttraumatic patients, we investigated the correlation of this clinical sign with outcome and with early radiologic findings from magnetic resonance imaging (MRI). This retrospective analysis of prospectively obtained data included 157 patients who had remained in a coma for a minimum of 24 hours after traumatic brain injury. All patients received a 1.5-T MRI within 10 days (median: 2 days) of the injury. The correlations between clinical findings 12 and 24 hours after the injury-in particular, extensor response and pupillary function, MRI findings, and outcome after 1 year-were investigated. Statistical analysis included contingency tables, Fisher exact test, odds ratios (ORs) with confidence intervals (CIs), and weighted κ values. There were 48 patients with extensor response within the first 24 hours after the injury. Patients with extensor response (World Federation of Neurosurgical Societies coma grade III) statistically were significantly more likely to harbor MRI lesions in the brainstem when compared with patients in a coma who had no further deficiencies (coma grade I; p = 0.0004 by Fisher exact test, OR 10.8 with 95% CI, 2.7-42.5) and patients with unilateral loss of pupil function (coma grade II; p = 0.0187, OR 2.8 with 95% CI, 1.2-6.5). The correlation of brainstem lesions as found by MRI and outcome according to the Glasgow Outcome Scale after 1 year was also highly significant (p ≤ 0.016). The correlation of extensor response and loss of pupil function with an unfavorable outcome and with brainstem lesions revealed by MRI is highly significant. Their sudden onset may be associated with the sudden onset of brainstem dysfunction and should therefore be regarded as one of the most

Asymptomatic proteinuria. Clinical significance.

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Papper, S

1977-09-01

Patients with asymptomatic proteinuria have varied reasons for the proteinuria and travel diverse courses. In the individual with normal renal function and no systemic cause, ie, idiopathic asymptomatic proteinuria, the outlook is generally favorable. Microscopic hematuria probably raises some degree of question about prognosis. The kidney shows normal glomeruli, subtle changes, or an identifiable lesion. The initial approach includes a clinical and laboratory search for systemic disease, repeated urinalyses, quantitative measurements of proteinuria, determination of creatinine clearance, protein electrophoresis where indicated, and intravenous pyelography. The need for regularly scheduled follow-up evaluation is emphasized. Although the initial approach need not include renal biopsy, a decline in creatinine clearance, an increase in proteinuria, or both are indications for biopsy and consideration of drug therapy.

Clinical significance of combined measurement of serum sex hormones in secondary amenorrhea

International Nuclear Information System (INIS)

Chen Boxun; Chen Yue; Gan Xilun

2004-01-01

Objective: To study the clinical significance of changes of levels of serum sex hormones in the diagnosis of the types of secondary amenorrhea. Methods: Serum sex hormones levels were measured with chemiluminescence in 100 patients with secondary amenorrhea and 42 controls. The serum hormones determined were: estradiol (E 2 )-, progesterone (PROG), follicle stimulating hormone (FSH)-, luteinizing hormone (LH), prolactin (PRL), testosterone (TSTO). Results: Patients with secondary amenorrhea had significantly higher levels of serum FSH, LH and PRL ( P 2 (P<0.05) than those in the controls. Serum levels of PROG and TSTO were about the same in the patients and controls. Conclusion: Determination of serum hormones levels with chemiluminescence is clinically useful for diagnosis of the types of secondary amenorrhea. (authors)

Spontaneous pneumomediastinum on CT : related condition and its clinical significance

International Nuclear Information System (INIS)

Kim, Sung Hyun; Im, Jung Gi; Seo, Joon Beom; Park, Jae Hyung; Yeon, Kyung Mo; Han, Man Chung

1998-01-01

The purpose of this paper is to tabulate underlying disease and to assess the clinical significance of CT-diagnosed spontaneous pneumomediastinum. We retrospectively reviewed CT scans and medical records of 11 consecutive patients with spontaneous pneumomediastinum, and analyzed their clinical history and course, and in five cases, pulmonary function. CT scans of 126 patients with idiopathic pulmonary fibrosis (IPE) collected while the 11 consecutive patients were being treated were analyzed for the prevalence of pneumomediastinum. We analyzed CT findings with respect to the amount and distribution of air in the mediastinum, and the presence of absence of air outside the mediastinum. Spontaneous pneumomediastinum might be associated with idiopathic pulmonary fibrosis and might be a poor prognostic factor in patients with IPE or BOOP. (author). 18 refs., 2 figs

Spontaneous pneumomediastinum on CT : related condition and its clinical significance

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Kim, Sung Hyun; Im, Jung Gi; Seo, Joon Beom; Park, Jae Hyung; Yeon, Kyung Mo; Han, Man Chung [Seoul National Univ. (Korea, Republic of). Coll. of Medicine

1998-03-01

The purpose of this paper is to tabulate underlying disease and to assess the clinical significance of CT-diagnosed spontaneous pneumomediastinum. We retrospectively reviewed CT scans and medical records of 11 consecutive patients with spontaneous pneumomediastinum, and analyzed their clinical history and course, and in five cases, pulmonary function. CT scans of 126 patients with idiopathic pulmonary fibrosis (IPE) collected while the 11 consecutive patients were being treated were analyzed for the prevalence of pneumomediastinum. We analyzed CT findings with respect to the amount and distribution of air in the mediastinum, and the presence of absence of air outside the mediastinum. Spontaneous pneumomediastinum might be associated with idiopathic pulmonary fibrosis and might be a poor prognostic factor in patients with IPE or BOOP. (author). 18 refs., 2 figs.

Leptospirosis in Franche-Comté (FRANCE): clinical, biological, and therapeutic data.

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Estavoyer, J M; Chirouze, C; Faucher, J F; Floret, N; Couetdic, G; Leroy, J; Hoen, B

2013-09-01

We report the patient data in 77 cases of leptospirosis confirmed by PCR and/or serology (micro-agglutination), observed between 1994 and 2008 at the Besançon teaching hospital. Our aim was to compare the epidemiological, clinical, biological, and therapeutic characteristics of leptospirosis in the Franche-Comté region, to those reported in other regions. The median age was 42years and 95% were male patients. Leptospirosis acquisition was likely related to aquatic leisure activities (50.6%), professional exposure (28.6%), building maintenance works (11.7%), or unknown (9.1%). Forty-eight cases were uncomplicated and 29 were severe presentations of leptospirosis. Among severe cases, eight patients had to be managed in an intensive care unit, and one patient died. L. grippotyphosa and L. icterohaemorrhagiae were the main serogroups involved. Age above 50years and serogroup L. icterohaemorrhagiae were positively associated with clinical severity. The outcome was favorable for 15 patients treated with ceftriaxone for less than 7days. We recommended conducting clinical trials aiming at validating short courses of ceftriaxone to treat leptospirosis. Copyright © 2013. Published by Elsevier SAS.

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

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Simon Roh

2016-04-01

Full Text Available 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.

Clinical significance of abnormal nonosseous soft tissue uptake of bone tracer

International Nuclear Information System (INIS)

Zhu Bao; Shang Yukun; Li Jiannan; Bai Jing; Cai Liang

2006-01-01

Objective: To evaluate the clinical significance of abnormal soft tissue uptake of bone tracer. Methods: Thirty patients with abnormal soft tissue uptake of bone tracer on 99 Tc m -methylene diphosphonic acid (MDP) skeletal imaging were analyzed. Radioactivity of soft tissue accumulated equal to or greater than the ribs were considered as abnormal. The result was compared with pathology, MRI, CT, X-ray, ultrasound, findings for evaluating its clinical significance. Results: In 7 patients with diffuse liver uptake of 99 Tc m -MDP, 6 were massive and 1 nodular liver cancer. In 2 patients with local liver uptake, one was metastatic and the other primary liver cancer. In 5 local lung uptake cases 4 were primary lung cancer and one metastatic. In 5 cases with colonic uptake 1 was schistosomiasis while the other 4 unexplainable. Subcutaneous tissue uptake was observed in 4 patients, symmetrical uptake in 2 patients with metastatic calcification microfoci in multiple myeloma, unsymmetrical uptake in 2 patients with hemangioma and abscess. Pleural uptake in 3 patients all was metastatic cancer. Abdominal uptake in 3 patients was omentum, paravertebral soft tissue metastasis and unknown cause. Breast uptake in one patient was due to breast cancer. Conclusions: There are many causes resulting in abnormal nonosseous soft tissue uptake of 99 Tc m -MDP. The final diagnosis should correlate with clinical data and other examinations. (authors)

Biological dysrhythm in remitted bipolar I disorder.

Science.gov (United States)

Iyer, Aishwarya; Palaniappan, Pradeep

2017-12-01

Recent treatment guidelines support treatment of biological rhythm abnormalities as a part of treatment of bipolar disorder, but still, literature examining various domains (Sleep, Activity, Social, and Eating) of biological rhythm and its clinical predictors are less. The main aim of our study is to compare various domains of biological rhythm among remitted bipolar I subjects and healthy controls. We also explored for any association between clinical variables and biological rhythm among bipolar subjects. 40 subjects with Bipolar I disorder and 40 healthy controls who met inclusion and exclusion criteria were recruited for the study. Diagnoses were ascertained by a qualified psychiatrist using MINI 5.0. Sociodemographic details, biological rhythm (BRIAN-Biological Rhythm Interview of assessment in Neuropsychiatry) and Sleep functioning (PSQI- Pittsburgh Sleep Quality Index) were assessed in all subjects. Mean age of the Bipolar subjects and controls were 41.25±11.84years and 38.25±11.25 years respectively. Bipolar subjects experienced more biological rhythm disturbance when compared to healthy controls (total BRIAN score being 34.25±9.36 vs 28.2±6.53) (p=0.002). Subsyndromal depressive symptoms (HDRS) had significant positive correlation with BRIAN global scores(r=0.368, p=0.02). Linear regression analysis showed that number of episodes which required hospitalization (β=0.601, t=3.106, P=0.004), PSQI (β=0.394, t=2.609, p=0.014), HDRS (β=0.376, t=2.34, t=0.036) explained 31% of variance in BRIAN scores in remitted bipolar subjects. Biological rhythm disturbances seem to persist even after clinical remission of bipolar illness. More studies to look into the impact of subsyndromal depressive symptoms on biological rhythm are needed. Copyright © 2017 Elsevier B.V. All rights reserved.

[Expression and clinical significance of 5hmC in bladder urothelial carcinoma].

Science.gov (United States)

Li, Jie; Xu, Yuqiao; Zhang, Zhiwen; Zhang, Ming; Zhang, Zhekai; Zhang, Feng; Li, Qing

2016-02-01

To investigate the expression of 5-hydroxymethylcytosine (5hmC) in bladder urothelial carcinoma (UC) and its clinical significance. The expression of 5hmC in 21 cases of UC tissues and pericarcinous urinary tract epithelium was detected by immunohistochemical staining. Then the expression of 5hmC in the surgical resection of UC tissues in 92 cases was also surveyed. Non parametric U Mann-Whitney test was used to analyze the correlation between 5hmC expression and clinical data. Single factor survival analysis was performed by Kaplan-Meier test. The expression of 5hmC in normal urinary tract epithelium and UC tissues was significantly different, but there was no significant difference in the expression of 5hmC between low and high grades of UC tissues as well as between different TNM grades. Kaplan-Meier single factor survival analysis showed that there was no significant correlation between the 5hmC expression level and the survival rate or the recurrence-free survival of UC patients. The expression level of 5hmC in UC tissues is significantly lower than that in pericarcinous urinary tract epithelium. There is no correlation between the 5hmC expression and the progression, prognosis and recurrence of UC.

Clinical significance of determination of serum C-peptide levels

International Nuclear Information System (INIS)

Wang Guohong; Xu Ruiji; Zhang Zhongshu; Wang Xiaoji

2006-01-01

Objective: To study the clinical meanings of changes of serum C-peptide levels and insulin/C-peptide ratio. Methods: Serum insulin and C-peptide levels were determined with RIA in 171 patients with DM-2 of all ages (31-50, n= 50, 51-60, n=60, over 60, n=61) and 50 patients with renal insufficiency. The insulin/C-peptide ratio were calculated. Results: The serum C-peptide and insulin levels in patients with renal insufficiency were significantly higher than those in diabetics of all age groups and the insulin/C-peptide ratio were significantly lower than those in diabetics (P 0.05), but the serum C-peptide levels increased as the age of patients increased with decrease of insulin/C-peptide ratio (P<0.01). Conclusion: Abnormal changes of C-peptide levels and insulin/C-peptide ratio in diabetics (the age-factor corrected) might reflect renal dysfunction. (authors)

Expression and clinical significance of MMP-2, MVD, MEK-2 in endometriosis

Directory of Open Access Journals (Sweden)

Wei Zhang

2016-03-01

Full Text Available Objective: To investigate the expression and clinical significance of MMP-2, MVD, MEK-2in the endometriosis. Methods: A total of 42 endometrial endometriosis patients with surgery were selected in our hospital obstetrics and gynecology from September 1, 2008 to December 18, 2014. Endometriosis were removed during surgery and served as ectopic group. A total of 42 examples of the above-described patients with endometriosis eutopic were taken out as the eutopic group. Another 34 patients with uterine fibroids were selected in our hospital obstetrics and gynecology during the same period. Normal endometrium were taken as the normal endometrium group. Clinical expression of MMP-2, MVD, MEK-2 of three groups were analyzed. Results: MVD in ectopic endometrium group were significantly higher than those in eutopic and normal endometrium (P<0.05. MEK-2 expression in normal endometrial tissue mainly was negative and weakly positive. The expression was positive in ectopic endometrium and eutopic. The expression of ectopic endometrium MEK-2and MMP-2 were the highest, followed by the reign of endometrium, and the expression of normal endometrium were the lowest. Conclusions: MMP-2, MVD, MEK-2 in ectopic endometrium show high expression, detection of MMP-2, MVD, MEK-2-clinical expression in endometriosis can help in pathogenesis, clinical diagnosis and treatment.

Occult pneumomediastinum in blunt chest trauma: clinical significance.

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Rezende-Neto, J B; Hoffmann, J; Al Mahroos, M; Tien, H; Hsee, L C; Spencer Netto, F; Speers, V; Rizoli, S B

2010-01-01

Thoracic injuries are potentially responsible for 25% of all trauma deaths. Chest X-ray is commonly used to screen patients with chest injury. However, the use of computed tomography (CT) scan for primary screening is increasing, particularly for blunt trauma. CT scans are more sensitive than chest X-ray in detecting intra-thoracic abnormalities such as pneumothoraces and pneumomediastinums. Pneumomediastinum detected by chest X-ray or "overt pneumomediastinum", raises the concern of possible aerodigestive tract injuries. In contrast, there is scarce information on the clinical significance of pneumomediastinum diagnosed by CT scan only or "occult pneumomediastinum". Therefore we investigated the clinical consequences of occult pneumomediastinum in our blunt trauma population. A 2-year retrospective chart review of all blunt chest trauma patients with initial chest CT scan admitted to a level I trauma centre. Data extracted from the medical records include; demographics, occult, overt, or no pneumomediastinum, the presence of intra-thoracic aerodigestive tract injuries (trachea, bronchus, and/or esophagus), mechanism and severity of injury, endotracheal intubation, chest thoracostomy, operations and radiological reports by an attending radiologist. All patients with intra-thoracic aerodigestive tract injuries from 1994 to 2004 were also investigated. Of 897 patients who met the inclusion criteria 839 (93.5%) had no pneumomediastinum. Five patients (0.6%) had overt pneumomediastinum and 53 patients (5.9%) had occult pneumomediastinum. Patients with occult pneumomediastinum had significantly higher ISS and AIS chest (pchest thoracostomy tube was more common (ppneumothorax. None of the patients with occult pneumomediastinum had aerodigestive tract injuries (95%CI 0-0.06). Follow up CT scan of patients with occult pneumomediastinum showed complete resolution in all cases, in average 3 h after the initial exam. Occult pneumomediastinum occurred in approximately 6% of

Clinical history and biologic age predicted falls better than objective functional tests.

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Gerdhem, Paul; Ringsberg, Karin A M; Akesson, Kristina; Obrant, Karl J

2005-03-01

Fall risk assessment is important because the consequences, such as a fracture, may be devastating. The objective of this study was to find the test or tests that best predicted falls in a population-based sample of elderly women. The fall-predictive ability of a questionnaire, a subjective estimate of biologic age and objective functional tests (gait, balance [Romberg and sway test], thigh muscle strength, and visual acuity) were compared in 984 randomly selected women, all 75 years of age. A recalled fall was the most important predictor for future falls. Only recalled falls and intake of psycho-active drugs independently predicted future falls. Women with at least five of the most important fall predictors (previous falls, conditions affecting the balance, tendency to fall, intake of psychoactive medication, inability to stand on one leg, high biologic age) had an odds ratio of 11.27 (95% confidence interval 4.61-27.60) for a fall (sensitivity 70%, specificity 79%). The more time-consuming objective functional tests were of limited importance for fall prediction. A simple clinical history, the inability to stand on one leg, and a subjective estimate of biologic age were more important as part of the fall risk assessment.

NK cell-based cancer immunotherapy: from basic biology to clinical application.

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Li, Yang; Yin, Jie; Li, Ting; Huang, Shan; Yan, Han; Leavenworth, JianMei; Wang, Xi

2015-12-01

Natural killer (NK) cells, which recognize and kill target cells independent of antigen specificity and major histocompatibility complex (MHC) matching, play pivotal roles in immune defence against tumors. However, tumor cells often acquire the ability to escape NK cell-mediated immune surveillance. Thus, understanding mechanisms underlying regulation of NK cell phenotype and function within the tumor environment is instrumental for designing new approaches to improve the current cell-based immunotherapy. In this review, we elaborate the main biological features and molecular mechanisms of NK cells that pertain to regulation of NK cell-mediated anti-tumor activity. We further overview current clinical approaches regarding NK cell-based cancer therapy, including cytokine infusion, adoptive transfer of autologous or allogeneic NK cells, applications of chimeric antigen receptor (CAR)-expressing NK cells and adoptive transfer of memory-like NK cells. With these promising clinical outcomes and fuller understanding the basic questions raised in this review, we foresee that NK cell-based approaches may hold great potential for future cancer immunotherapy.

Clinical and Biologic Significance of MYC Genetic Mutations in De Novo Diffuse Large B-cell Lymphoma

DEFF Research Database (Denmark)

Xu-Monette, Zijun Y; Deng, Qipan; Manyam, Ganiraju C

2016-01-01

.1% at the protein level (nonsynonymous mutations). Most of the nonsynonymous mutations correlated with better survival outcomes; in contrast, T58 and F138 mutations (which were associated with MYC rearrangements), as well as several mutations occurred at the 3' untranslated region, correlated with significantly...... worse survival outcomes. However, these mutations occurred infrequently (only in approximately 2% of DLBCL). A germline SNP encoding the Myc-N11S variant (observed in 6.5% of the study cohort) was associated with significantly better patient survival, and resulted in reduced tumorigenecity in mouse...

Selenium-Doped Hydroxyapatite Nanocrystals–Synthesis, Physicochemical Properties and Biological Significance

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Kamil Pajor

2018-04-01

Full Text Available Hydroxyapatites (HAs, as materials with a similar structure to bone minerals, play a key role in biomaterials engineering. They have been applied as bone substitute materials and as coatings for metallic implants, which facilitates their osseointegration. One of the beneficial characteristics of HA, when used to create biocompatible materials with improved physicochemical or biological properties, is its capacity for ionic substitution. The aim of the study was to present the current state of knowledge about HAs containing selenate ions IV or VI. The enrichment of HAs with selenium aims to create a material with advantageous effects on bone tissue metabolism, as well as having anticancer and antibacterial activity. The work is devoted to both methods of obtaining Se-HA and an evaluation of its chemical structure and physicochemical properties. In addition, the biological activity of such materials in vitro and in vivo is discussed.

Multiparametric MRI in the detection of clinically significant prostate cancer

Energy Technology Data Exchange (ETDEWEB)

Futterer, Jurgen J. [Dept. of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen (Netherlands)

2017-08-01

Prostate cancer is the most common cancer among men aged 50 years and older in developed countries and the third leading cause of cancer-related death in men. Multiparametric prostate MR imaging is currently the most accurate imaging modality to detect, localize, and stage prostate cancer. The role of multi-parametric MR imaging in the detection of clinically significant prostate cancer are discussed. In addition, insights are provided in imaging techniques, protocol, and interpretation.

[Acute lymphoblastic leukemia of T progenitors: from biology to clinics].

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Genescà, Eulàlia; Ribera, Jordi; Ribera, Josep-Maria

2015-03-09

Acute lymphoblastic leukemia (ALL) is the most common cancer in children and the main cause of morbidity among childhood blood disorders. There are 2 subtypes according to the affected lymphoid progenitor: B-ALL and T-ALL. The T-ALL is the less common and, although historically was associated with poor prognosis in both adults and children, at present, treatment outcomes do not differ significantly between the 2 types of ALL. The T-ALL subtype is the most complex and heterogeneous at the genetic level and currently the one with less new therapeutic alternatives available. This trend is changing thanks to the remarkable progress upon understanding its biology. This review summarizes the most recent and important biological findings in T-ALL and their possible therapeutic implications. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

Biological and clinical dosimetry. Progress report July 1, 1964-June 30, 1979

International Nuclear Information System (INIS)

Laughlin, J.S.; McDonald, J.C.

1979-01-01

The dosimetric studies at this laboratory were initiated with the primary goal of developing systems for the determination of absorbed dose in biological research and clinical applications. The primary method under study is the local absorbed dose calorimeter, a concept initiated and developed by J. S. Laughlin. In addition, secondary dosimetric systems such as ionization chambers, chemical dosimeters and thermoluminescent dosimeters (TLD) are being developed and applied to provide an absolute basis for the evaluation and comparison of experiments, treatments, and other procedures using radiation

Towards multidimensional radiotherapy (MD-CRT): biological imaging and biological conformality

International Nuclear Information System (INIS)

Ling, C. Clifton; Humm, John; Larson, Steven; Amols, Howard; Fuks, Zvi; Leibel, Steven; Koutcher, Jason A.

2000-01-01

Purpose: The goals of this study were to survey and summarize the advances in imaging that have potential applications in radiation oncology, and to explore the concept of integrating physical and biological conformality in multidimensional conformal radiotherapy (MD-CRT). Methods and Materials: The advances in three-dimensional conformal radiotherapy (3D-CRT) have greatly improved the physical conformality of treatment planning and delivery. The development of intensity-modulated radiotherapy (IMRT) has provided the 'dose painting' or 'dose sculpting' ability to further customize the delivered dose distribution. The improved capabilities of nuclear magnetic resonance imaging and spectroscopy, and of positron emission tomography, are beginning to provide physiological and functional information about the tumor and its surroundings. In addition, molecular imaging promises to reveal tumor biology at the genotype and phenotype level. These developments converge to provide significant opportunities for enhancing the success of radiotherapy. Results: The ability of IMRT to deliver nonuniform dose patterns by design brings to fore the question of how to 'dose paint' and 'dose sculpt', leading to the suggestion that 'biological' images may be of assistance. In contrast to the conventional radiological images that primarily provide anatomical information, biological images reveal metabolic, functional, physiological, genotypic, and phenotypic data. Important for radiotherapy, the new and noninvasive imaging methods may yield three-dimensional radiobiological information. Studies are urgently needed to identify genotypes and phenotypes that affect radiosensitivity, and to devise methods to image them noninvasively. Incremental to the concept of gross, clinical, and planning target volumes (GTV, CTV, and PTV), we propose the concept of 'biological target volume' (BTV) and hypothesize that BTV can be derived from biological images and that their use may incrementally improve

Occult pneumothoraces in Chinese patients with significant blunt chest trauma: radiological classification and proposed clinical significance.

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Lee, Ryan K L; Graham, Colin A; Yeung, Janice H H; Ahuja, Anil T; Rainer, Timothy H

2012-12-01

An occult pneumothorax (OP) is a pneumothorax not seen on a supine chest X-ray (CXR) but detected on abdominal or thoracic computed tomography (CT) scanning. With the increasing use of CT in the management of significantly injured trauma patients, more OPs are being detected. The aim of this study was to classify OPs diagnosed on thoracic CT (TCT) and correlate them with their clinical significance. Retrospective analysis of prospectively collected trauma registry data. Total 36 (N=36) consecutive significantly injured trauma patients admitted through the emergency department (ED) who sustained blunt chest trauma and underwent TCT between 1 January 2007 and 31 December 2008 were included. OP was defined as the identification (by a consultant radiologist) of a pneumothorax on TCT that had not been detected on supine CXR. OPs were classified by laterality (unilateral/bilateral) and location (apical, basal, non apical/basal). The size of pneumothoraces, severity of injury [including number of associated thoracic injuries and injury severity score (ISS)], length of hospital stay and mortality were compared between groups. The need for tube thoracostomy and clinical outcome were also analysed. Patients with bilateral OPs (N=8) had significantly more associated thoracic injuries (median: 2 vs. 1, p=0.01), higher ISS (median: 35 vs. 23, p=0.02) and longer hospital stay (median: 20 days vs. 11 days, p=0.01) than those with a unilateral OP (N=28). Basal OPs (N=7) were significantly larger than apical (N=10) and non-apical/basal Ops (N=11). Basal OPs were associated with significantly more associated thoracic injuries (median: 2 vs. 1, p=0.01), higher ISS (median: 35 vs. 25, p=0.04) and longer hospital stays (median: 23 days vs. 17 days, p=0.02) than apical Ops, which had higher ISS (median: 35 vs. 25, p=0.04) and longer hospital stays (median: 23 days vs. 15 days, p=0.02) than non-apical/basal OPs. Non-apical/basal OPs were associated with more related injuries (median: 2

Integrated DNA methylation and copy-number profiling identify three clinically and biologically relevant groups of anaplastic glioma.

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Wiestler, Benedikt; Capper, David; Sill, Martin; Jones, David T W; Hovestadt, Volker; Sturm, Dominik; Koelsche, Christian; Bertoni, Anna; Schweizer, Leonille; Korshunov, Andrey; Weiß, Elisa K; Schliesser, Maximilian G; Radbruch, Alexander; Herold-Mende, Christel; Roth, Patrick; Unterberg, Andreas; Hartmann, Christian; Pietsch, Torsten; Reifenberger, Guido; Lichter, Peter; Radlwimmer, Bernhard; Platten, Michael; Pfister, Stefan M; von Deimling, Andreas; Weller, Michael; Wick, Wolfgang

2014-10-01

The outcome of patients with anaplastic gliomas varies considerably. Whether a molecular classification of anaplastic gliomas based on large-scale genomic or epigenomic analyses is superior to histopathology for reflecting distinct biological groups, predicting outcomes and guiding therapy decisions has yet to be determined. Epigenome-wide DNA methylation analysis, using a platform which also allows the detection of copy-number aberrations, was performed in a cohort of 228 patients with anaplastic gliomas (astrocytomas, oligoastrocytomas, and oligodendrogliomas), including 115 patients of the NOA-04 trial. We further compared these tumors with a group of 55 glioblastomas. Unsupervised clustering of DNA methylation patterns revealed two main groups correlated with IDH status: CpG island methylator phenotype (CIMP) positive (77.5 %) or negative (22.5 %). CIMP(pos) (IDH mutant) tumors showed a further separation based on copy-number status of chromosome arms 1p and 19q. CIMP(neg) (IDH wild type) tumors showed hallmark copy-number alterations of glioblastomas, and clustered together with CIMP(neg) glioblastomas without forming separate groups based on WHO grade. Notably, there was no molecular evidence for a distinct biological entity representing anaplastic oligoastrocytoma. Tumor classification based on CIMP and 1p/19q status was significantly associated with survival, allowing a better prediction of outcome than the current histopathological classification: patients with CIMP(pos) tumors with 1p/19q codeletion (CIMP-codel) had the best prognosis, followed by patients with CIMP(pos) tumors but intact 1p/19q status (CIMP-non-codel). Patients with CIMP(neg) anaplastic gliomas (GBM-like) had the worst prognosis. Collectively, our data suggest that anaplastic gliomas can be grouped by IDH and 1p/19q status into three molecular groups that show clear links to underlying biology and a significant association with clinical outcome in a prospective trial cohort.

Thyroid Incidentalomas on 18F-FDG PET/CT: Clinical Significance and Controversies

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William Makis

2017-10-01

Full Text Available Objective: The purpose of the current study is to examine the incidence and clinical significance of unexpected focal uptake of 18F-fluorodeoxyglucose (18F-FDG on positron emission tomography/computed tomography (PET/CT in the thyroid gland of oncology patients, the maximum standardized uptake value (SUVmax of benign and malignant thyroid incidentalomas in these patients, and review the literature. Methods: Seven thousand two hundred fifty-two 18F-FDG PET/CT studies performed over four years, were retrospectively reviewed. Studies with incidental focal 18F-FDG uptake in the thyroid gland were further analyzed. Results: Incidental focal thyroid 18F-FDG uptake was identified in 157 of 7252 patients (2.2%. Sufficient follow-up data (≥12 months were available in 128 patients, of whom 57 (45% had a biopsy performed and 71 had clinical follow-up. Malignancy was diagnosed in 14 of 128 patients (10.9%. There was a statistically significant difference between the median SUVmax of benign thyroid incidentalomas (SUVmax 4.8 vs malignant (SUVmax 6.3, but the wide range of overlap between the two groups yielded no clinically useful SUVmax threshold value to determine malignancy. Conclusion: 18F-FDG positive focal thyroid incidentalomas occurred in 2.2% of oncologic PET/CT scans, and were malignant in 10.9% of 128 patients. This is the lowest reported malignancy rate in a North American study to date, and significantly lower than the average malignancy rate (35% reported in the literature. Invasive biopsy of all 18F-FDG positive thyroid incidentalomas, as recommended by some studies, is unwarranted and further research to determine optimal management is needed. There was no clinically useful SUVmax cut-off value to determine malignancy and PET/CT may not be a useful imaging modality to follow these patients conservatively.

Anaerobic bacteraemia in patients admitted to Auckland City Hospital: its clinical significance.

Science.gov (United States)

Muttaiyah, Sharmini; Paviour, Sue; Buckwell, Leanne; Roberts, Sally A

2007-11-09

To determine the clinical significance and outcomes for patients with anaerobic bacteraemia at our institution over a 2-year period. The isolates were identified from the laboratory database and patient information obtained from clinical records. Anaerobes were isolated from 140 blood culture sets taken from 114 patients. For 59 patients, the isolates were considered to be contaminants. Of note, all Propionibacterium spp. were considered contaminants. For the patients with true bacteraemias, the most likely source of infection was intra-abdominal, 26 (50%), mucositis associated with neutropaenia contributed to by cytotoxic therapy, 11 (19%), skin and soft tissue, 4 (8%), pelvic, 5 (9%) and oropharyngeal, 4 (8%). Thirty-five patients were on appropriate therapy prior to the availability culture results. Five patients died but only one death was directly attributable to anaerobic bacteraemia. At our institution, anaerobes accounted for 2.3% of all positive blood cultures. Excluding Propionibacterium spp., most isolates were considered clinically significant. The most common source for the bacteraemia was intra-abdominal infection, followed by mucositis in neutropaenic patients. Empiric antimicrobial therapy provided appropriate cover for two-thirds of the patients. One death was directly attributable to anaerobic bacteraemia.

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

Science.gov (United States)

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

2013-01-01

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

The clinical significance of quality of life assessments in oncology: a summary for clinicians

NARCIS (Netherlands)

Sloan, Jeff A.; Frost, Marlene H.; Berzon, Rick; Dueck, Amylou; Guyatt, Gordon; Moinpour, Carol; Sprangers, Mirjam; Ferrans, Carol; Cella, David

2006-01-01

BACKGROUND: A series of six manuscripts with an introduction appeared in the Mayo Clinic Proceedings, based upon the collective effort of 30 individuals with an interest and expertise in assessing the clinical significance of quality of life (QOL) assessments. The series of manuscripts described the

[Side effects of biologic therapies in psoriasis].

Science.gov (United States)

Altenburg, A; Augustin, M; Zouboulis, C C

2018-04-01

The introduction of biologics has revolutionized the treatment of moderate to severe plaque psoriasis. Due to the continuous expansion of biological therapies for psoriasis, it is particularly important to acknowledge efficacy and safety of the compounds not only in clinical trials but also in long-term registry-based observational studies. Typical side effects and significant risks of antipsoriatic biologic therapies considering psoriatic control groups are presented. A selective literature search was conducted in PubMed and long-term safety studies of the psoriasis registries PsoBest, PSOLAR and BADBIR were evaluated. To assess the long-term safety of biologics, the evaluation of the course of large patient cohorts in long-term registries is of particular medical importance. Newer biologic drugs seem to exhibit a better safety profile than older ones.

Clinically significant discrepancies between sleep problems assessed by standard clinical tools and actigraphy

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Kjersti Marie Blytt

2017-10-01

Full Text Available Abstract Background Sleep disturbances are widespread among nursing home (NH patients and associated with numerous negative consequences. Identifying and treating them should therefore be of high clinical priority. No prior studies have investigated the degree to which sleep disturbances as detected by actigraphy and by the sleep-related items in the Cornell Scale for Depression in Dementia (CSDD and the Neuropsychiatric Inventory – Nursing Home version (NPI-NH provide comparable results. Such knowledge is highly needed, since both questionnaires are used in clinical settings and studies use the NPI-NH sleep item to measure sleep disturbances. For this reason, insight into their relative (disadvantages is valuable. Method Cross-sectional study of 83 NH patients. Sleep was objectively measured with actigraphy for 7 days, and rated by NH staff with the sleep items in the CSDD and the NPI-NH, and results were compared. McNemar's tests were conducted to investigate whether there were significant differences between the pairs of relevant measures. Cohen's Kappa tests were used to investigate the degree of agreement between the pairs of relevant actigraphy, NPI-NH and CSDD measures. Sensitivity and specificity analyses were conducted for each of the pairs, and receiver operating characteristics (ROC curves were designed as a plot of the true positive rate against the false positive rate for the diagnostic test. Results Proxy-raters reported sleep disturbances in 20.5% of patients assessed with NPI-NH and 18.1% (difficulty falling asleep, 43.4% (multiple awakenings and 3.6% (early morning awakenings of patients had sleep disturbances assessed with CSDD. Our results showed significant differences (p<0.001 between actigraphy measures and proxy-rated sleep by the NPI-NH and CSDD. Sensitivity and specificity analyses supported these results. Conclusions Compared to actigraphy, proxy-raters clearly underreported NH patients' sleep disturbances as assessed

FACE Analysis as a Fast and Reliable Methodology to Monitor the Sulfation and Total Amount of Chondroitin Sulfate in Biological Samples of Clinical Importance

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Evgenia Karousou

2014-06-01

Full Text Available Glycosaminoglycans (GAGs due to their hydrophilic character and high anionic charge densities play important roles in various (pathophysiological processes. The identification and quantification of GAGs in biological samples and tissues could be useful prognostic and diagnostic tools in pathological conditions. Despite the noteworthy progress in the development of sensitive and accurate methodologies for the determination of GAGs, there is a significant lack in methodologies regarding sample preparation and reliable fast analysis methods enabling the simultaneous analysis of several biological samples. In this report, developed protocols for the isolation of GAGs in biological samples were applied to analyze various sulfated chondroitin sulfate- and hyaluronan-derived disaccharides using fluorophore-assisted carbohydrate electrophoresis (FACE. Applications to biologic samples of clinical importance include blood serum, lens capsule tissue and urine. The sample preparation protocol followed by FACE analysis allows quantification with an optimal linearity over the concentration range 1.0–220.0 µg/mL, affording a limit of quantitation of 50 ng of disaccharides. Validation of FACE results was performed by capillary electrophoresis and high performance liquid chromatography techniques.

[Clinical and biological predictors of ketamine response in treatment-resistant major depression: Review].

Science.gov (United States)

Romeo, B; Choucha, W; Fossati, P; Rotge, J-Y

2017-08-01

The aim of this review was to determine the clinical and biological predictors of the ketamine response. A systematic research on PubMed and PsycINFO database was performed without limits on year of publication. The main predictive factors of ketamine response, which were found in different studies, were (i) a family history of alcohol dependence, (ii) unipolar depressive disorder, and (iii) neurocognitive impairments, especially a slower processing speed. Many other predictive factors were identified, but not replicated, such as personal history of alcohol dependence, no antecedent of suicide attempt, anxiety symptoms. Some biological factors were also found such as markers of neural plasticity (slow wave activity, brain-derived neurotrophic factor Val66Met polymorphism, expression of Shank 3 protein), other neurologic factors (anterior cingulate activity, concentration of glutamine/glutamate), inflammatory factors (IL-6 concentration) or metabolic factors (concentration of B12 vitamin, D- and L-serine, alterations in the mitochondrial β-oxidation of fatty acids). This review had several limits: (i) patients had exclusively resistant major depressive episodes which represent a sub-type of depression and not all depression, (ii) response criteria were more frequently assessed than remission criteria, it was therefore difficult to conclude that these predictors were similar, and finally (iii) many studies used a very small number of patients. In conclusion, this review found that some predictors of ketamine response, like basal activity of anterior cingulate or vitamin B12 concentration, were identical to other therapeutics used in major depressive episode. These factors could be more specific to the major depressive episode and not to the ketamine response. Others, like family history of alcohol dependence, body mass index, or D- and L-serine were different from the other therapeutics. Neurocognitive impairments like slower speed processing or alterations in

PRAME Gene Expression in Acute Leukemia and Its Clinical Significance

International Nuclear Information System (INIS)

Ding, Kai; Wang, Xiao-ming; Fu, Rong; Ruan, Er-bao; Liu, Hui; Shao, Zong-hong

2012-01-01

To investigate the expression of the preferentially expressed antigen of melanoma (PRAME) gene in acute leukemia and its clinical significance. The level of expressed PRAME mRNA in bone marrow mononuclear cells from 34 patients with acute leukemia (AL) and in 12 bone marrow samples from healthy volunteers was measured via RT-PCR. Correlation analyses between PRAME gene expression and the clinical characteristics (gender, age, white blood count, immunophenotype of leukemia, percentage of blast cells, and karyotype) of the patients were performed. The PRAME gene was expressed in 38.2% of all 34 patients, in 40.7% of the patients with acute myelogenous leukemia (AML, n=27), and in 28.6% of the patients with acute lymphoblastic leukemia (ALL, n=7), but was not expressed in the healthy volunteers. The difference in the expression levels between AML and ALL patients was statistically significant. The rate of gene expression was 80% in M 3 , 33.3% in M 2 , and 28.6% in M 5 . Gene expression was also found to be correlated with CD15 and CD33 expression and abnormal karyotype, but not with age, gender, white blood count or percentage of blast cells. The PRAME gene is highly expressed in acute leukemia and could be a useful marker to monitor minimal residual disease. This gene is also a candidate target for the immunotherapy of acute leukemia

Specific determination of clinical and toxicological important substances in biological samples by LC-MS

International Nuclear Information System (INIS)

Mitulovic, G.

2001-02-01

This thesis of this dissertation is the specific determination of clinical and toxicological important substances in biological samples by LC-MS. Nicotine was determined in serum after application of nicotine plaster and nicotine nasal spray with HPLC-ESI-MS. Cotinine was determined direct in urine with HPLC-ESI-MS. Short time anesthetics were determined in blood and cytostatics were determined in liquor with HPLC-ESI-MS. (botek)

Novel perspectives on diagnosis and clinical significance of the post-thrombotic syndrome in children.

Science.gov (United States)

Jones, Sophie; Newall, Fiona; Monagle, Paul

2016-10-01

Given the increase in venous thromboembolic events (VTE) in children, the incidence, diagnosis and management of post thrombotic syndrome (PTS) in children is of increasing interest. Current challenges facing clinicians caring for children with VTE is the limited evidence of the long-term outcomes for this cohort; specifically the significance and potential functional impairment associated with PTS. This paper reviews the current evidence to elucidate the risk factors for PTS in children, methods for diagnosis and management of PTS in children (aged less than 18 years). Medline, Cinahl and PsycINFO database searches were undertaken using key search terms. Priority areas in need of further research are highlighted. Expert commentary: The two paediatric PTS assessment tools currently in use have been acknowledged to overcall the incidence of mild PTS in children. A PTS tool's ability to distinguish between clinically significant PTS and mild PTS is crucial. Variation in how PTS has been reported in children across the literature suggests that the real incidence of moderate and /or clinically significant PTS in children is unknown. Furthermore, evidence is lacking about the functional impairment experienced by children with clinically significant PTS and what this means for their long-term health.

Tick-Tock Chimes the Kidney Clock – from Biology of Renal Ageing to Clinical Applications

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Joshua Rowland

2018-01-01

Full Text Available Ageing of the kidney is a multi-dimensional process that occurs simultaneously at the molecular, cellular, histological, anatomical and physiological level. Nephron number and renal cortical volume decline, renal tubules become atrophic and glomeruli become sclerotic with age. These structural changes are accompanied by a decline in glomerular filtration rate, decreased sodium reabsorption and potassium excretion, reduced urinary concentrating capacity and alterations in the endocrine activity of the kidney. However, the pace of progression of these changes is not identical in everyone - individuals of the same age and seemingly similar clinical profile often exhibit stark differences in the age-related decline in renal health. Thus, chronological age poorly reflects the time-dependent changes that occur in the kidney. An ideal measure of renal vitality is biological kidney age – a measure of the age-related changes in physiological function. Replacing chronological age with biological age could provide numerous clinical benefits including improved prognostic accuracy in renal transplantation, better stratification of risk and identification of those who are on a fast trajectory to an age-related drop in kidney health.

Sex as a Biological Variable in Emergency Medicine Research and Clinical Practice: A Brief Narrative Review

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Alyson J. McGregor

2017-10-01

Full Text Available The National Institutes of Health recently highlighted the significant role of sex as a biological variable (SABV in research design, outcome and reproducibility, mandating that this variable be accounted for in all its funded research studies. This move has resulted in a rapidly increasing body of literature on SABV with important implications for changing the clinical practice of emergency medicine (EM. Translation of this new knowledge to the bedside requires an understanding of how sex-based research will ultimately impact patient care. We use three case-based scenarios in acute myocardial infarction, acute ischemic stroke and important considerations in pharmacologic therapy administration to highlight available data on SABV in evidence-based research to provide the EM community with an important foundation for future integration of patient sex in the delivery of emergency care as gaps in research are filled.

Clinical significance of anaplasia in childhood rhabdomyosarcoma

OpenAIRE

Sidhom, Iman; El Nadi, Enas; Taha, Hala; Elkinaai, Naglaa; Zaghloul, Mohamed S.; Younes, Alaa; Labib, Rania; Sabry, Mohamed

2015-01-01

Background: The presence of anaplastic features has been known to correlate with poor clinical outcome in various pediatric malignancies, including Wilms tumor and medulloblastoma but not in rhabdomyosarcoma. Aim: Aim was to study the frequency of anaplasia at presentation in childhood rhabdomyosarcoma and its relationship to clinical and pathological characteristics as well as to outcome. Patients and Methods: Anaplasia was retrospectively assessed in 105 consecutive pediatric rhabdomy...

Brief Group Psychoeducation for Bulimia Nervosa: Assessing the Clinical Significance of Change.

Science.gov (United States)

Davis, Ron; And Others

1990-01-01

Brief intervention designed to promote symptom management was completed by 41 women with bulimia nervosa. Findings revealed diversity of outcomes that individuals reported following participation in intervention. Found differential reporting of clinically significant change in favor of specific eating psychopathology relative to personality…

The clinical significance of gastrointestinal decontamination in the occurrence of endogenous infections.

Science.gov (United States)

Ozawa, A; Nagao, T; Sawamura, S; Ikigai, H

1984-12-01

No significant difference was seen in the incidence of infections between subjects receiving complete, selective and no decontamination aimed at the intestinal microflora in studies evaluating the preventative potential against endogenous infections in the compromised host maintained under protective isolation. This finding is reported together with a report of Serratia marcescens septicemia in a patient with leukemia who was given antibiotics systemically and kept under protective isolation. The establishment of opportunistic infections in relation to these results is discussed in terms of the biological phenomena of the interaction between the intestinal flora and the host, and between the species comprising the intestinal flora.

Clinical significance and taxonomy of Actinobacillus hominis

DEFF Research Database (Denmark)

Friis-Møller, Alice; Christensen, J J; Fussing, V

2001-01-01

Clinical findings in 36 immunosuppressed patients with lower respiratory tract infection or bacteremia with Actinobacillus hominis are described. Animal contact was only recorded for three patients; nine patients died despite appropriate antimicrobial treatment. Although infections with this micr......Clinical findings in 36 immunosuppressed patients with lower respiratory tract infection or bacteremia with Actinobacillus hominis are described. Animal contact was only recorded for three patients; nine patients died despite appropriate antimicrobial treatment. Although infections...

Engineering Therapeutic T Cells: From Synthetic Biology to Clinical Trials.

Science.gov (United States)

Esensten, Jonathan H; Bluestone, Jeffrey A; Lim, Wendell A

2017-01-24

Engineered T cells are currently in clinical trials to treat patients with cancer, solid organ transplants, and autoimmune diseases. However, the field is still in its infancy. The design, and manufacturing, of T cell therapies is not standardized and is performed mostly in academic settings by competing groups. Reliable methods to define dose and pharmacokinetics of T cell therapies need to be developed. As of mid-2016, there are no US Food and Drug Administration (FDA)-approved T cell therapeutics on the market, and FDA regulations are only slowly adapting to the new technologies. Further development of engineered T cell therapies requires advances in immunology, synthetic biology, manufacturing processes, and government regulation. In this review, we outline some of these challenges and discuss the contributions that pathologists can make to this emerging field.

Introduction to economic modeling for clinical rheumatologists: application to biologic agents in rheumatoid arthritis.

Science.gov (United States)

Marra, Carlo A; Bansback, Nick; Anis, Aslam H; Shojania, Kamran

2011-03-01

Rheumatoid arthritis (RA) is a chronic, debilitating inflammatory, progressive musculoskeletal disease that affects 0.5-1.0% of the adult population in Western countries. The joint destruction and progressive functional disability associated with uncontrolled RA result in tremendous impacts on health-related quality of life, ability to work, and mortality. In addition, the treatment of the disease and associated complications exact a substantial economic burden to the patients, their families, and society. In the last decade, several biological agents (biologics) have been approved for use in RA, revolutionizing treatment. These biologics, which target cytokines such as tumor necrosis factor or lymphocytes such as B or T cells, reduce functional disability and substantially slow the progression of joint damage. However, because these agents typically cost ten to 100 times more than existing available older drug therapies, there has been worldwide concern regarding their impact on healthcare budgets. As such, there has been increased attention towards economic evaluation as a means to determine whether, and in which subgroup of patients, these newer, more expensive agents confer appropriate value for their additional cost. Indeed, evaluations have guided coverage decisions for both private and public health insurance agencies such as the National Institute for Health and Clinical Excellence in the UK. The use of economic evaluations to determine value for money for these agents has attracted both debate and controversy. Some of the controversy is related to the appropriateness of the structure of, and assumptions underlying, the decision models employed to estimate the long-term costs and benefits of these agents over existing therapies. To fully appreciate the debate, one must first understand the basic principles of economic evaluation and the necessity for using decision models to evaluate cost effectiveness. To understand the basic principles of economic

Prostate atypia: does repeat biopsy detect clinically significant prostate cancer?

Science.gov (United States)

Dorin, Ryan P; Wiener, Scott; Harris, Cory D; Wagner, Joseph R

2015-05-01

While the treatment pathway in response to benign or malignant prostate biopsies is well established, there is uncertainty regarding the risk of subsequently diagnosing prostate cancer when an initial diagnosis of prostate atypia is made. As such, we investigated the likelihood of a repeat biopsy diagnosing prostate cancer (PCa) in patients in which an initial biopsy diagnosed prostate atypia. We reviewed our prospectively maintained prostate biopsy database to identify patients who underwent a repeat prostate biopsy within one year of atypia (atypical small acinar proliferation; ASAP) diagnosis between November 1987 and March 2011. Patients with a history of PCa were excluded. Chart review identified patients who underwent radical prostatectomy (RP), radiotherapy (RT), or active surveillance (AS). For some analyses, patients were divided into two subgroups based on their date of service. Ten thousand seven hundred and twenty patients underwent 13,595 biopsies during November 1987-March 2011. Five hundred and sixty seven patients (5.3%) had ASAP on initial biopsy, and 287 (50.1%) of these patients underwent a repeat biopsy within one year. Of these, 122 (42.5%) were negative, 44 (15.3%) had atypia, 19 (6.6%) had prostatic intraepithelial neoplasia, and 102 (35.6%) contained PCa. Using modified Epstein's criteria, 27/53 (51%) patients with PCa on repeat biopsy were determined to have clinically significant tumors. 37 (36.3%) proceeded to RP, 25 (24.5%) underwent RT, and 40 (39.2%) received no immediate treatment. In patients who underwent surgery, Gleason grade on final pathology was upgraded in 11 (35.5%), and downgraded 1 (3.2%) patient. ASAP on initial biopsy was associated with a significant risk of PCa on repeat biopsy in patients who subsequently underwent definitive local therapy. Patients with ASAP should be counseled on the probability of harboring both clinically significant and insignificant prostate cancer. © 2015 Wiley Periodicals, Inc.

Clinical significance of MUC13 in pancreatic ductal adenocarcinoma.

Science.gov (United States)

Khan, Sheema; Zafar, Nadeem; Khan, Shabia S; Setua, Saini; Behrman, Stephen W; Stiles, Zachary E; Yallapu, Murali M; Sahay, Peeyush; Ghimire, Hemendra; Ise, Tomoko; Nagata, Satoshi; Wang, Lei; Wan, Jim Y; Pradhan, Prabhakar; Jaggi, Meena; Chauhan, Subhash C

2018-01-15

Poor prognosis of pancreatic cancer (PanCa) is associated with lack of an effective early diagnostic biomarker. This study elucidates significance of MUC13, as a diagnostic/prognostic marker of PanCa. MUC13 was assessed in tissues using our in-house generated anti-MUC13 mouse monoclonal antibody and analyzed for clinical correlation by immunohistochemistry, immunoblotting, RT-PCR, computational and submicron scale mass-density fluctuation analyses, ROC and Kaplan Meir curve analyses. MUC13 expression was detected in 100% pancreatic intraepithelial neoplasia (PanIN) lesions (Mean composite score: MCS = 5.8; AUC >0.8, P 0.8; P artificial intelligence based algorithm analyses also elucidated association of MUC13 with greater morphological disorder (P < 0.001) and nuclear MUC13 as strong predictor for cancer aggressiveness and poor patient survival. This study provides significant information regarding MUC13 expression/subcellular localization in PanCa samples and supporting the use anti-MUC13 MAb for the development of PanCa diagnostic/prognostic test. Copyright © 2018 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

The significance of reduced respiratory chain enzyme activities: clinical, biochemical and radiological associations.

Science.gov (United States)

Mordekar, S R; Guthrie, P; Bonham, J R; Olpin, S E; Hargreaves, I; Baxter, P S

2006-03-01

Mitochondrial diseases are an important group of neurometabolic disorders in children with varied clinical presentations and diagnosis that can be difficult to confirm. To report the significance of reduced respiratory chain enzyme (RCE) activity in muscle biopsy samples from children. Retrospective odds ratio was used to compare clinical and biochemical features, DNA studies, neuroimaging, and muscle biopsies in 18 children with and 48 without reduced RCE activity. Children with reduced RCE activity were significantly more likely to have consanguineous parents, to present with acute encephalopathy and lactic acidaemia and/or within the first year of life; to have an axonal neuropathy, CSF lactate >4 mmol/l; and/or to have signal change in the basal ganglia. There were positive associations with a maternal family history of possible mitochondrial cytopathy; a presentation with failure to thrive and lactic acidaemia, ragged red fibres, reduced fibroblast fatty acid oxidation and with an abnormal allopurinol loading test. There was no association with ophthalmic abnormalities, deafness, epilepsy or myopathy. The association of these clinical, biochemical and radiological features with reduced RCE activity suggests a possible causative link.

Clinically significant bleeding in incurable cancer patients: effectiveness of hemostatic radiotherapy

International Nuclear Information System (INIS)

Cihoric, Nikola; Crowe, Susanne; Eychmüller, Steffen; Aebersold, Daniel M; Ghadjar, Pirus

2012-01-01

This study was performed to evaluate the outcome after hemostatic radiotherapy (RT) of significant bleeding in incurable cancer patients. Patients treated by hemostatic RT between November 2006 and February 2010 were retrospectively analyzed. Bleeding was assessed according to the World Health Organization (WHO) scale (grade 0 = no bleeding, 1 = petechial bleeding, 2 = clinically significant bleeding, 3 = bleeding requiring transfusion, 4 = bleeding associated with fatality). The primary endpoint was bleeding at the end of RT. Key secondary endpoints included overall survival (OS) and acute toxicity. The bleeding score before and after RT were compared using the Wilcoxon signed rank test. Time to event endpoints were estimated using the Kaplan Meier method. Overall 62 patients were analyzed including 1 patient whose benign cause of bleeding was pseudomyxoma peritonei. Median age was 66 (range, 37–93) years. Before RT, bleeding was graded as 2 and 3 in 24 (39%) and 38 (61%) patients, respectively. A median dose of 20 (range, 5–45) Gy of hemostatic RT was applied to the bleeding site. At the end of RT, there was a statistically significant difference in bleeding (p < 0.001); it was graded as 0 (n = 39), 1 (n = 12), 2 (n = 6), 3 (n = 4) and 4 (n = 1). With a median follow-up of 19.3 (range, 0.3-19.3) months, the 6-month OS rate was 43%. Forty patients died (65%); 5 due to bleeding. No grade 3 or above acute toxicity was observed. Hemostatic RT seems to be a safe and effective treatment for clinically and statistically significantly reducing bleeding in incurable cancer patients

Endodontic radiology, practice, and knowledge of radiation biology, hazard, and protection among clinical dental students and interns

Directory of Open Access Journals (Sweden)

Joan Emien Enabulele

2015-01-01

Full Text Available Objective: To evaluate the practice and knowledge of endodontic radiology as well as assess the knowledge of radiation biology, hazard, and protection among clinical dental students and interns. Materials and Methods: Cross-sectional study of clinical dental students and interns at University of Benin and University of Benin Teaching hospital respectively. Data was collected using a questionnaire which covered practice and knowledge of endodontic radiography, knowledge of radiation biology, hazard, and protection. Data was analyzed using Statistical Package for Social Sciences (SPSS version 17.0. Result: Seventy participants were included in the study, 40% were final year students and 24.3% house officers. Majority (95.7% agreed that they exposed radiographs as part of endodontic treatment. Only 18.6% knew that the apices of teeth should be 3mm from the border of the X-ray film, while 24.3% knew that 3mm of periapical bone should be visible on X-ray. Less than half (31.4% knew that paralleling technique was the technique of choice for endodontic radiography and this was statistically Significant in relationship to the status of the of the respondents. A few (4.3% of the respondents had knowledge of new horizons in endodontic imaging. Half of the respondents knew that damage by X-rays is mainly due to formation of free radicals. The most frequently reported radiation hazards was reduced salivary flow, while the least reported was rampant caries. Most knew how to protect patients, themselves, and other persons while exposing radiographs. Conclusion: There is need for inclusion of endodontic radiography in the undergraduate curriculum to ensure proper and correct radiographs during endodontic procedure.

Small airway function changes and its clinical significance of asthma patients in different clinical phases

Directory of Open Access Journals (Sweden)

Yan-Hui Zhou

2016-11-01

Full Text Available Objective: To observe the small airways function changes of asthmatic patients in different clinical phases and to discuss its clinical significance. Methods: A total of 127 patients diagnosed as asthma were selected randomly and pulmonary function (PF of them was determined by conventional method. Then they were divided into A, B and C group based on PF results. All 34 patients in A group suffered from acute asthma attack for the first time. All 93 patients in B group had been diagnosed as asthma but in remission phase. C Group was regarded as Control group with 20 healthy volunteers. Then FEV1, FEF50%, FEF75% levels of patients in each group were analyzed, and ΔFEV1, ΔFEF75% and ΔFEF50% levels of patients in each group were compared after bronchial dilation test. Results: It was found that most patients in group A and B had abnormal small airways function, and their small airways function was significantly different compared with that of group C (P<0.01. In addition, except for group C, ΔFEF75%,ΔFEF50% levels in A and B group were improved more significantly than ΔFEV1 levels (P<0.01. Conclusions: Asthma patients in acute phase all have abnormal small airways function. Most asthma patients in remission phase also have abnormal small airways function. After bronchial dilation test, whether patients in acute phase or in remission phase, major and small airways function of them are improved, but improvement of small airways function is weaker than that of major airways. This indicates that asthma respiratory tract symptoms in different phases exists all the time and so therapeutic process is needed to perform step by step.

Selective biologics for ulcerative colitis and Crohn's disease – clinical utility of vedolizumab

Directory of Open Access Journals (Sweden)

Petkau JM

2016-03-01

Full Text Available Jill MV Petkau, Bertus Eksteen Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada Abstract: Inflammatory bowel disease (IBD encompasses a cluster of different disease phenotypes which are broadly classified into ulcerative colitis and Crohn's disease. Disease pathogenesis is driven by abnormal host immune responses to their resident gut microbiome in genetically susceptible individuals. Clinical disease features and outcomes are heterogenous and not unexpected as over 163 genetic loci are associated with disease susceptibility, and there are great variability in environmental exposures. Despite this variability, there has been relatively few efficacious therapies for particularly moderate-to-severe IBD. Treatment has been dominated by antitumor necrosis alpha agents with significant success but equally potentially serious adverse events. Therapeutic targeting of leucocyte trafficking has emerged as a viable alternative therapy, with vedolizumab being the lead compound. This review focuses primarily on its biological function as a selective gut immunotherapy, its safety and efficacy, and its emerging role as a mainstream therapy in managing IBD. Keywords: adhesion molecule antagonist, anti-α4β7 integrin, inflammatory bowel disease, leukocyte trafficking, monoclonal antibody, selective gut immunotherapy, tumor necrosis factor alpha

Photocoagulation treatment for clinically significant radiation macular oedema

Energy Technology Data Exchange (ETDEWEB)

Kinyoun, J.L.; Zamber, R.W.; Lawrence, B.S.; Barlow, W.E.; Arnold, A.M. [Washington Univ., Seattle, WA (United States)

1995-02-01

Macular oedema is a leading cause of vision loss in patients with radiation retinopathy. In an effort to find an effective treatment for this vision threatening complication, 12 eyes (eight patients) were treated with photocoagulation for clinically significant radiation macular oedema (CSRMO) defined as central macular thickening, exudates threatening the macular centre, or one disc area of thickening in the macula. Median visual acuity improved from 20/100 pre-operatively to 20/90 at the initial post-operative examination (mean follow up 5 months) and to 20/75 at the final post-operative examination (mean follow up 39 months). At the final post-operative examination, visual acuity had improved in eight (67%) eyes and six (50%) eyes had complete resolution of the CSRMO; two (17%) other eyes had improved anatomically in that fewer CSRMO criteria were present. These results suggest that macular photocoagulation is effective in decreasing macular oedema and improving vision in eyes with CSRMO. (author).

Photocoagulation treatment for clinically significant radiation macular oedema

International Nuclear Information System (INIS)

Kinyoun, J.L.; Zamber, R.W.; Lawrence, B.S.; Barlow, W.E.; Arnold, A.M.

1995-01-01

Macular oedema is a leading cause of vision loss in patients with radiation retinopathy. In an effort to find an effective treatment for this vision threatening complication, 12 eyes (eight patients) were treated with photocoagulation for clinically significant radiation macular oedema (CSRMO) defined as central macular thickening, exudates threatening the macular centre, or one disc area of thickening in the macula. Median visual acuity improved from 20/100 pre-operatively to 20/90 at the initial post-operative examination (mean follow up 5 months) and to 20/75 at the final post-operative examination (mean follow up 39 months). At the final post-operative examination, visual acuity had improved in eight (67%) eyes and six (50%) eyes had complete resolution of the CSRMO; two (17%) other eyes had improved anatomically in that fewer CSRMO criteria were present. These results suggest that macular photocoagulation is effective in decreasing macular oedema and improving vision in eyes with CSRMO. (author)

Clinical significance of isometric bite force versus electrical activity in temporal and masseter muscles

DEFF Research Database (Denmark)

Bakke, Merete; Michler, L; Han, K

1989-01-01

significant with respect to unilateral, but not to bilateral force measurements. Only in the masseter muscle was strength of dynamic contractions during chewing significantly correlated to bite force. With the present method it was demonstrated that unilateral bite force is a simple clinical indicator...

[The changes in vestibular function in patients with diabetes mellitus and its clinical significance].

Science.gov (United States)

Li, Juan; Zhang, Tianyu; Shen, Jianzhong; Gong, Jingrong; Wang, Hongli; Zhang, Jimin; Pang, Yufeng

2008-01-01

To study the changes of vestibular function in patients with diabetes mellitus and its clinical significance. Electronystagmography (ENG) was used to examine 76 patients with diabetes mellitus and 60 healthy adults subjects. After clinical detection of vestibular function including spontaneous nystagmus, positional test, head shaking nystagmus, neck torsion test, caloric test, and sensory organization tests which consist of gaze, saccade and smooth pursuit test, the results of these two groups were recorded for qualitative and quantitative statistical analysis. The rate of vestibular dysfunction in patients with diabetes mellitus were 68.4%. and that of the controls were 8.3%. There was significant difference between these two groups (chi2 = 15.472, P Vertigo or dizziness occurred in patients with diabetes mellitus might be related to vestibular dysfunction. ENG test could be used as one of the objective clinical examinations in patients with diabetes mellitus.

75 FR 8968 - Draft Guidance for Industry on Adaptive Design Clinical Trials for Drugs and Biologics; Availability

Science.gov (United States)

2010-02-26

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0090] Draft Guidance for Industry on Adaptive Design Clinical Trials for Drugs and Biologics; Availability... familiar and less familiar approaches. As more experience is obtained with the less familiar designs...

Clinical significance of conventional rib series in patients with minor thoracic trauma

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Hoffstetter, P.; Dornia, C. [Asklepios Medical Center, Bad Abbach (Germany). Radiology; University Medical Center Regensburg (Germany). Radiology; Wagner, M.; Niessen, C.; Dendl, L.M.; Stroszczynski, C.; Schreyer, A.G. [University Medical Center Regensburg (Germany). Radiology; Al Suwaidi, M.H. [Asklepios Medical Center, Bad Abbach (Germany). Rheumatology/Clinical Immmunology

2014-09-15

Background: Conventional rib series (RS) represent a dedicated radiographic technique to visualize the bony parts of the chest wall. The method is commonly used to evaluate minor thoracic trauma, frequently in combination with chest radiographs (CRs). The aim of this study is to asses the clinical relevance of rib fractures diagnosed by RS in minor thoracic trauma. Methods: Retrospective study of 669 patients who received RS for the evaluation of minor thoracic trauma. 405 of the 669 patients received an additional CR. Radiological reports were classified into fracture versus no fracture. Patients were divided into four groups depending on the clinical follow-up. The findings of RS and CR were analyzed using the McNemar test. The statistical significance between the results of the radiographic examinations and the clinical follow-up was analyzed by the Chi-Square test and the Kruskal-Wallis test. Results: We included 669 patients (61.4% men, 38.6% women, median age: 51 years, range: 13-92 years). Analyzing the reports of 669 patients who received RS, 157 (23.5%) patients were diagnosed with at least one fractured rib while no fracture was found in 512 (76.5%) patients. Considering the 157 patients with fractured ribs, 73 (46.8%) had a single fracture, 38 (24.4%) and two fractures and 45 (28.8%) had more than two fractures. When assessing the 405 CRs, we detected 69 (17%) fractures while the corresponding RS of the same patients revealed 87 (21.5%) fractures (p < 0.05). Concerning all patients with rib fractures, 63.1% received medical therapy, while 64.5% of those patients without a radiologically documented fracture also received therapy (p = 0.25). Conclusion: Our results suggest a limited clinical value of detected rib fractures based on RS. Despite being superior compared to CR in diagnosing rib fractures, the results from RS seem to have no significant influence on further clinical management and therapeutic measures. Minor thoracic trauma should be evaluated

Clinical significance of conventional rib series in patients with minor thoracic trauma

International Nuclear Information System (INIS)

Hoffstetter, P.; Dornia, C.; University Medical Center Regensburg; Wagner, M.; Niessen, C.; Dendl, L.M.; Stroszczynski, C.; Schreyer, A.G.; Al Suwaidi, M.H.

2014-01-01

Background: Conventional rib series (RS) represent a dedicated radiographic technique to visualize the bony parts of the chest wall. The method is commonly used to evaluate minor thoracic trauma, frequently in combination with chest radiographs (CRs). The aim of this study is to asses the clinical relevance of rib fractures diagnosed by RS in minor thoracic trauma. Methods: Retrospective study of 669 patients who received RS for the evaluation of minor thoracic trauma. 405 of the 669 patients received an additional CR. Radiological reports were classified into fracture versus no fracture. Patients were divided into four groups depending on the clinical follow-up. The findings of RS and CR were analyzed using the McNemar test. The statistical significance between the results of the radiographic examinations and the clinical follow-up was analyzed by the Chi-Square test and the Kruskal-Wallis test. Results: We included 669 patients (61.4% men, 38.6% women, median age: 51 years, range: 13-92 years). Analyzing the reports of 669 patients who received RS, 157 (23.5%) patients were diagnosed with at least one fractured rib while no fracture was found in 512 (76.5%) patients. Considering the 157 patients with fractured ribs, 73 (46.8%) had a single fracture, 38 (24.4%) and two fractures and 45 (28.8%) had more than two fractures. When assessing the 405 CRs, we detected 69 (17%) fractures while the corresponding RS of the same patients revealed 87 (21.5%) fractures (p < 0.05). Concerning all patients with rib fractures, 63.1% received medical therapy, while 64.5% of those patients without a radiologically documented fracture also received therapy (p = 0.25). Conclusion: Our results suggest a limited clinical value of detected rib fractures based on RS. Despite being superior compared to CR in diagnosing rib fractures, the results from RS seem to have no significant influence on further clinical management and therapeutic measures. Minor thoracic trauma should be evaluated

Studies on clinical significances of intracranial meningiomas in computerized tomography

International Nuclear Information System (INIS)

Kasamo, Shizuya

1986-01-01

Meningioma has been widely assumed to be a representative benign tumor among the primary intracranial tumors. However, many problems still remain in the clinical management of meningioma. The author had studied the clinical significance of meningiomas from the 104 cases he had experienced. CT was performed in 101 cases of them. In this paper, CT findings of meningioma were initially analyzed with reference to correlations of symptomatological and histopathological features. The mechanism of occurrence of the peritumoral low density (PTL) found on CT was discussed under an identification of cerebral edema. Secondly, the endocrinological environment was studied since certain hormonal changes might influence the growth and spread of the tumor. Estrogen receptor (ER) and progesterone receptor (PgR) in the tumor tissue were studied and discussed as to their clinical evaluation. Thirdly, fine structures in 12 cases of meningiomas were studied by transmission electron microscopy (TEM). And the correlation between the TEM findings and clinical and endocrinological findings were discussed. From these results, the author drew the following conclusions; 1) There was no correlation between the tumor and the hormonal environment, but there is a suggestive evidence that meningioma might be hormone-dependent. 2) The factors of occurrence of PTL were tumor size, location of tumor and histological subtype. And from the findings of TEM, one of the mechanisms of occurrence of PTL might be due to secretion of an edema factor from tumor tissue. 3) Close correlation between tumor size and period from onset to admission was found, and when the tumor size (xmm) was measured on CT, the time of occurrence of tumor (y months ago) could be roughly calculated from the following equation; y = 1.9x - 13.3 (r = 0.683, p < 0.01). (J.P.N.)

Biological imaging in radiation therapy: role of positron emission tomography

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Nestle, Ursula; Hentschel, Michael; Grosu, Anca-Ligia [Departments of Radiation Oncology, University of Freiburg, Robert Koch Str. 3, 79106 Freiburg (Germany); Weber, Wolfgang [Nuclear Medicine, University of Freiburg, Robert Koch Str. 3, 79106 Freiburg (Germany)], E-mail: ursula.nestle@uniklinik-freiburg.de

2009-01-07

In radiation therapy (RT), staging, treatment planning, monitoring and evaluation of response are traditionally based on computed tomography (CT) and magnetic resonance imaging (MRI). These radiological investigations have the significant advantage to show the anatomy with a high resolution, being also called anatomical imaging. In recent years, so called biological imaging methods which visualize metabolic pathways have been developed. These methods offer complementary imaging of various aspects of tumour biology. To date, the most prominent biological imaging system in use is positron emission tomography (PET), whose diagnostic properties have clinically been evaluated for years. The aim of this review is to discuss the valences and implications of PET in RT. We will focus our evaluation on the following topics: the role of biological imaging for tumour tissue detection/delineation of the gross tumour volume (GTV) and for the visualization of heterogeneous tumour biology. We will discuss the role of fluorodeoxyglucose-PET in lung and head and neck cancer and the impact of amino acids (AA)-PET in target volume delineation of brain gliomas. Furthermore, we summarize the data of the literature about tumour hypoxia and proliferation visualized by PET. We conclude that, regarding treatment planning in radiotherapy, PET offers advantages in terms of tumour delineation and the description of biological processes. However, to define the real impact of biological imaging on clinical outcome after radiotherapy, further experimental, clinical and cost/benefit analyses are required. (topical review)

Biological imaging in radiation therapy: role of positron emission tomography.

Science.gov (United States)

Nestle, Ursula; Weber, Wolfgang; Hentschel, Michael; Grosu, Anca-Ligia

2009-01-07

In radiation therapy (RT), staging, treatment planning, monitoring and evaluation of response are traditionally based on computed tomography (CT) and magnetic resonance imaging (MRI). These radiological investigations have the significant advantage to show the anatomy with a high resolution, being also called anatomical imaging. In recent years, so called biological imaging methods which visualize metabolic pathways have been developed. These methods offer complementary imaging of various aspects of tumour biology. To date, the most prominent biological imaging system in use is positron emission tomography (PET), whose diagnostic properties have clinically been evaluated for years. The aim of this review is to discuss the valences and implications of PET in RT. We will focus our evaluation on the following topics: the role of biological imaging for tumour tissue detection/delineation of the gross tumour volume (GTV) and for the visualization of heterogeneous tumour biology. We will discuss the role of fluorodeoxyglucose-PET in lung and head and neck cancer and the impact of amino acids (AA)-PET in target volume delineation of brain gliomas. Furthermore, we summarize the data of the literature about tumour hypoxia and proliferation visualized by PET. We conclude that, regarding treatment planning in radiotherapy, PET offers advantages in terms of tumour delineation and the description of biological processes. However, to define the real impact of biological imaging on clinical outcome after radiotherapy, further experimental, clinical and cost/benefit analyses are required.

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

Science.gov (United States)

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…

Molecular imaging of prostate cancer: translating molecular biology approaches into the clinical realm.

Science.gov (United States)

Vargas, Hebert Alberto; Grimm, Jan; F Donati, Olivio; Sala, Evis; Hricak, Hedvig

2015-05-01

The epidemiology of prostate cancer has dramatically changed since the introduction of prostate-specific antigen (PSA) screening in the 1980's. Most prostate cancers today are detected at early stages of the disease and are considered 'indolent'; however, some patients' prostate cancers demonstrate a more aggressive behaviour which leads to rapid progression and death. Increasing understanding of the biology underlying the heterogeneity that characterises this disease has led to a continuously evolving role of imaging in the management of prostate cancer. Functional and metabolic imaging techniques are gaining importance as the impact on the therapeutic paradigm has shifted from structural tumour detection alone to distinguishing patients with indolent tumours that can be managed conservatively (e.g., by active surveillance) from patients with more aggressive tumours that may require definitive treatment with surgery or radiation. In this review, we discuss advanced imaging techniques that allow direct visualisation of molecular interactions relevant to prostate cancer and their potential for translation to the clinical setting in the near future. The potential use of imaging to follow molecular events during drug therapy as well as the use of imaging agents for therapeutic purposes will also be discussed. • Advanced imaging techniques allow direct visualisation of molecular interactions in prostate cancer. • MRI/PET, optical and Cerenkov imaging facilitate the translation of molecular biology. • Multiple compounds targeting PSMA expression are currently undergoing clinical translation. • Other targets (e.g., PSA, prostate-stem cell antigen, GRPR) are in development.

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

Science.gov (United States)

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

2012-05-15

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

Biological impact of geometric uncertainties: what margin is needed for intra-hepatic tumors?

International Nuclear Information System (INIS)

Kuo, Hsiang-Chi; Liu, Wen-Shan; Wu, Andrew; Mah, Dennis; Chuang, Keh-Shih; Hong, Linda; Yaparpalvi, Ravi; Guha, Chandan; Kalnicki, Shalom

2010-01-01

To evaluate and compare the biological impact on different proposed margin recipes for the same geometric uncertainties for intra-hepatic tumors with different tumor cell types or clinical stages. Three different margin recipes based on tumor motion were applied to sixteen IMRT plans with a total of twenty two intra-hepatic tumors. One recipe used the full amplitude of motion measured from patients to generate margins. A second used 70% of the full amplitude of motion, while the third had no margin for motion. The biological effects of geometric uncertainty in these three situations were evaluated with Equivalent Uniform Doses (EUD) for various survival fractions at 2 Gy (SF 2 ). There was no significant difference in the biological impact between the full motion margin and the 70% motion margin. Also, there was no significant difference between different tumor cell types. When the margin for motion was eliminated, the difference of the biological impact was significant among different cell types due to geometric uncertainties. Elimination of the motion margin requires dose escalation to compensate for the biological dose reduction due to the geometric misses during treatment. Both patient-based margins of full motion and of 70% motion are sufficient to prevent serious dosimetric error. Clinical implementation of margin reduction should consider the tumor sensitivity to radiation

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

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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.

Clinical and prognostic significance of plasma fibrinogen in lung cancer

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Chen YS

2014-01-01

Full Text Available Objectives: Hyperfibrinogenemia is a common problem associated with various carcinomas. The recent studies have shown that high plasma fibrinogen concentration is associated with invasion, growth and metastases of cancer. Furthermore, the recent studies focus on the prognostic significance of fibrinogen in the patients with advanced NSCLC (stage IIIB -IV. However, the prognostic significance of the plasma fibrinogen levels in early stage NSCLC patients (stage I -IIIA still remains unclear. In addition, it remains unclear whether or not chemotherapy-induced changes in fibrinogen level relate to the prognosis. The aims of this study were to 1 further explore the relationship between the plasma fibrinogen concentration and the stage and metastases of lung cancer 2 evaluate the prognostic significance of the basal plasma fibrinogen level in patients with lung cancer 3 explore the prognostic value of the change in fibrinogen levels between pre and post-chemotherapy. Methods: In this retrospective study, the data from 370 patients with lung cancer were enrolled into this study. The plasma fibrinogen levels were compared with the clinical and prognostic significance of lung cancer. The association between the plasma fibrinogen level and clinical-prognostic characteristics were analyzed using SPSS 17.0 software. Results: 1 The median pre-treatment plasma fibrinogen levels were 4.20g/L. Pre-treatment plasma fibrinogen levels correlated significantly with gender (p = 0.013. A higher plasma fibrinogen concentration was associated with squamous cell carcinoma versus adenocarcinoma (4.83±1.50 g/L versus 4.15±1.30 g/L; P<0.001, there was a significant association between plasma fibrinogen level and metastases of lung cancer, pointing a higher plasma fibrinogen level in lymph nodes or distant organ metastases (p < 0.001. 2 Patients with low plasma fibrinogen concentration demonstrates higher overall survival compared with those with high plasma fibrinogen

Dog and cat respiratory capilariasis - clinical, parasitological and epidemiological significance

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Ilić Tamara

2015-01-01

Full Text Available Respiratory capillariasis is a disease of domestic and wild carnivores as well as of people, caused by nematode Eucoleus aerophilus syn. Capillaria aerophila, which lives as a parasite in mucosa of trachea, bronchi and bronchioles, rarely in nasal and frontal sinuses of the host. This parasite has either direct or indirect development cycle which includes optional transition hosts - earthworms. Clinical picture is manifested in the form of a very severe respiratory disease, which is accompanied by an increased bronchovesicular sound, sneezing, gasping and chronic dry cough. Despite the fact that this nematode is widespread in all the parts of the world, that it causes a disease followed by a severe clinical picture and has a zoonotic potential as well, it has been insufficiently investigated and moreover from clinical and parasitological aspect it has not been given enough attention so far. The reason for this is the fact that C. aerophila had been considered to be a strain of very low level of pathogenicity causing only sporadic respiratory infections in dogs and cats. The interest of scientific community for this parasitosis increased the moment when its causative agent spread outside the endemic areas. From the standpoint of monitoring and health protection of both carnivores and peorle, knowledge of basic epizootiological and epidemiological characteristics of these nematodes is of crucial importance, having in mind that its prevalence has significantly increased in dogs and cats in the last ten years, both in Europe and worldwide.

[Expression of IMP3 in osteosarcoma and its clinical significance].

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Li, Kang-hua; Huang, Yue-ping; Zhang, Jun; Li, Guo-jun; Li, Si-hong

2009-05-01

To analyze the expressional variability of IMP3 between osteosarcoma and osteochondroma and explore its clinical significance. Paraffin sections from 68 patients with osteosarcoma and 20 patients with osteochondroma were examined for the expression of IMP3 by SP immunohistochemistry. The negative, weak positive, moderate positive and strong positive expression rates of IMP3 in 68 patients with osteosarcoma were 4.41% (3/68), 22.06% (15/68), 22.74% (19/68), 45.59% (31/68), respectively, which were significantly higher than those in 20 cases of osteochondroma tissues (P<0.01). The positive expression of IMP3 in osteosarcoma was negative correlation with the 3-year survival rate of osteosarcoma patients after the operation (P<0.01). The results suggest that IMP3 plays important roles in the tumorigenesis, progress and prognosis of osteosarcoma, and the expression of IMP3 may be an important feature of osteosarcoma.

Expression and Clinical Significance of the Autophagy Proteins BECLIN 1 and LC3 in Ovarian Cancer

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Guido Valente

2014-01-01

Full Text Available Autophagy is dysregulated in cancer and might be involved in ovarian carcinogenesis. BECLIN-1, a protein that interacts with either BCL-2 or PI3k class III, plays a critical role in the regulation of both autophagy and cell death. Induction of autophagy is associated with the presence of vacuoles characteristically labelled with the protein LC3. We have studied the biological and clinical significance of BECLIN 1 and LC3 in ovary tumours of different histological types. The positive expression of BECLIN 1 was well correlated with the presence of LC3-positive autophagic vacuoles and was inversely correlated with the expression of BCL-2. The latter inhibits the autophagy function of BECLIN 1. We found that type I tumours, which are less aggressive than type II, were more frequently expressing high level of BECLIN 1. Of note, tumours of histologic grade III expressed low level of BECLIN 1. Consistently, high level of expression of BECLIN 1 and LC3 in tumours is well correlated with the overall survival of the patients. The present data are compatible with the hypotheses that a low level of autophagy favours cancer progression and that ovary cancer with upregulated autophagy has a less aggressive behaviour and is more responsive to chemotherapy.

Creating biological nanomaterials using synthetic biology

International Nuclear Information System (INIS)

Rice, MaryJoe K; Ruder, Warren C

2014-01-01

Synthetic biology is a new discipline that combines science and engineering approaches to precisely control biological networks. These signaling networks are especially important in fields such as biomedicine and biochemical engineering. Additionally, biological networks can also be critical to the production of naturally occurring biological nanomaterials, and as a result, synthetic biology holds tremendous potential in creating new materials. This review introduces the field of synthetic biology, discusses how biological systems naturally produce materials, and then presents examples and strategies for incorporating synthetic biology approaches in the development of new materials. In particular, strategies for using synthetic biology to produce both organic and inorganic nanomaterials are discussed. Ultimately, synthetic biology holds the potential to dramatically impact biological materials science with significant potential applications in medical systems. (review)

Creating biological nanomaterials using synthetic biology.

Science.gov (United States)

Rice, MaryJoe K; Ruder, Warren C

2014-02-01

Synthetic biology is a new discipline that combines science and engineering approaches to precisely control biological networks. These signaling networks are especially important in fields such as biomedicine and biochemical engineering. Additionally, biological networks can also be critical to the production of naturally occurring biological nanomaterials, and as a result, synthetic biology holds tremendous potential in creating new materials. This review introduces the field of synthetic biology, discusses how biological systems naturally produce materials, and then presents examples and strategies for incorporating synthetic biology approaches in the development of new materials. In particular, strategies for using synthetic biology to produce both organic and inorganic nanomaterials are discussed. Ultimately, synthetic biology holds the potential to dramatically impact biological materials science with significant potential applications in medical systems.

Do glycine-extended hormone precursors have clinical significance?

DEFF Research Database (Denmark)

Rehfeld, Jens Frederik

2014-01-01

Half of the known peptide hormones are C-terminally amidated. Subsequent biogenesis studies have shown that the immediate precursor is a glycine-extended peptide. The clinical interest in glycine-extended hormones began in 1994, when it was suggested that glycine-extended gastrin stimulated cancer...... and clinical effects of glycine-extended precursors for most other amidated hormones than gastrin and cholecystokinin (CCK). The idea of glycine-extended peptides as independent messengers was interesting. But clinical science has to move ahead from ideas that cannot be supported at key points after decades...

Change and clinical significance of serum PG in patients with chronic gastritis

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Wei-Hua Huan

2017-06-01

Full Text Available Objective: To observe the change and clinical significance of serum PG in patients with chronic atrophic gastritis (CAG. Methods: ELISA was used to detect the peripheral blood PG level in patients confirmed with CAG, gastric polyps, and gastric cancer who were admitted in our hospital from January, 2015 to January, 2016. The normal individuals who came for physical examinations were served as the control group. The peripheral blood PG level in patients with various gastric diseases was observed. Results: The serum PG Ⅰ expression and PG I/PG Ⅱ in the gastritis group were significantly lower than those in the gastric polyps group and control group, but were significantly higher than those in the gastric cancer group; while PG Ⅱ expression was significantly higher than that in the gastric polyps group and control group, but was significantly lower than those in the gastric cancer group. PG Ⅰ expression and PG I/ PG Ⅱ in the gastric polyps group were significantly higher than those in the gastritis group and gastric cancer group, while PG Ⅱ expression was significantly lower than that in the gastritis group and gastric cancer group. PG Ⅰ expression and PG I/ PG Ⅱ in the gastric cancer group were significantly lower than those in the other three groups, while PG Ⅱ expression was significantly higher than that in the other three groups. The serum PG Ⅰ expression in patients with positive HP infection in the gastritis group and gastric cancer group was significantly higher than that in patients with negative HP infection, but the comparison of PG I/ PG Ⅱ was not statistically significant. The serum PG Ⅰ expression and PG I/ PG Ⅱ in patients with negative and positive HP infection in the gastritis group were significantly higher than those in patients with negative and positive HP infection in the gastric cancer group; while PG Ⅱ expression was significantly was significantly lower than that in the gastric cancer group

Shear-wave elastography of the liver and spleen identifies clinically significant portal hypertension

DEFF Research Database (Denmark)

Jansen, Christian; Bogs, Christopher; Verlinden, Wim

2017-01-01

BACKGROUND & AIMS: Clinically significant portal hypertension (CSPH) is associated with severe complications and decompensation of cirrhosis. Liver stiffness measured either by transient elastography (TE) or Shear-wave elastography (SWE) and spleen stiffness by TE might be helpful in the diagnosis...... correlate with portal pressure and can both be used as a non-invasive method to investigate CSPH. Even though external validation is still missing, these algorithms to rule-out and rule-in CSPH using sequential SWE of liver and spleen might change the clinical practice....

[Aortic elastic properties and its clinical significance in intracranial aneurysms].

Science.gov (United States)

Pu, Zhao-xia; You, Xiang-dong; Weng, Wen-chao; Wang, Jian-an; Shi, Jian

2011-09-01

To investigate the aortic elastic properties and its clinical significance in intracranial aneurysms (IAs). One hundred and seven IAs patients (57 with hypertension) and 108 healthy subjects were recruited. The internal aortic diameters in systole and diastole were measured by the M-mode echocardiography, the aortic elasticity indexes were calculated and compared. The aortic distensibility (DIS) was lower and the aortic stiffness index (SI) was higher in IAs patients than those in controls (both P IAs patients with hypertension (IAs-HP) than those in IAs with no hypertension (P IAs patients and hypertension is closely related to the severity of aortic elasticity.

Clinical and biological characteristics of cervical neoplasias with FGFR3 mutation

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Thiery Jean

2005-05-01

Full Text Available Abstract Background We have previously reported activating mutations of the gene coding for the fibroblast growth factor receptor 3 (FGFR3 in invasive cervical carcinoma. To further analyze the role of FGFR3 in cervical tumor progression, we extended our study to screen a total of 75 invasive tumors and 80 cervical intraepithelial neoplasias (40 low-grade and 40 high-grade lesions. Results Using single strand conformation polymorphism (SSCP followed by DNA sequencing, we found FGFR3 mutation (S249C in all cases in 5% of invasive cervical carcinomas and no mutation in intraepithelial lesions. These results suggest that, unlike in bladder carcinoma, FGFR3 mutation does not or rarely occur in non invasive lesions. Compared to patients with wildtype FGFR3 tumor, patients with S249C FGFR3 mutated tumors were older (mean age 64 vs. 49.4 years, P = 0.02, and were more likely to be associated with a non-16/18 HPV type in their tumor. Gene expression analysis demonstrated that FGFR3 mutated tumors were associated with higher FGFR3b mRNA expression levels compared to wildtype FGFR3 tumors. Supervised analysis of Affymetrix expression data identified a significant number of genes specifically differentially expressed in tumors with respect to FGFR3 mutation status. Conclusion This study suggest that tumors with FGFR3 mutation appear to have distinctive clinical and biological characteristics that may help in defining a population of patients for FGFR3 mutation screening.

Clinical significance of posteroanterior and its cephalometry in adults with facial asymmetry

International Nuclear Information System (INIS)

Sun Xinhua; Feng Qinghui; Jiao Jian

2004-01-01

Objective: To study the clinical significance of posteroanterior (PA) radiographs and cephalometries for diagnosis of facial asymmetry of adults. Methods: PA radiographs in 16 cases of facial asymmetry patients (experiment group, 8 males and 8 females) and 16 normal adults with facial symmetry (control group, 8 males and 8 females) were taken and analyzed. The data was analyzed with Student T test. Results: There were significant differences of DifManM-Y, DifMaxM-Y, DifGo-Y, Me-Y and LI-Y between experiment group and control group by PA radiographs and cephalometries (P<0.01, P<0.05). Conclusion: PA radiographs and cephalometries have a specific significance of diagnosis for facial asymmetry in adults

Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM): novel biological insights and development of early treatment strategies.

Science.gov (United States)

Korde, Neha; Kristinsson, Sigurdur Y; Landgren, Ola

2011-05-26

Monoclonal gammopathy of unknown significance (MGUS) and smoldering multiple myeloma (SMM) are asymptomatic plasma cell dyscrasias, with a propensity to progress to symptomatic MM. In recent years there have been improvements in risk stratification models (involving molecular markers) of both disorders, which have led to better understanding of the biology and probability of progression of MGUS and SMM. In the context of numerous molecular events and heterogeneous risk of progression, developing individualized risk profiles for patients with MGUS and SMM represents an ongoing challenge that has to be addressed by prospective clinical monitoring and extensive correlative science. In this review we discuss the current standard of care of patients with MGUS and SMM, the use of risk models, including flow cytometry and free-light chain analyses, for predicting risk of progression. Emerging evidence from molecular studies on MGUS and SMM, involving cytogenetics, gene-expression profiling, and microRNA as well as molecular imaging is described. Finally, future directions for improving individualized management of MGUS and SMM patients, as well as the potential for developing early treatment strategies designed to delay and prevent development of MM are discussed.

Clinical significance of determination serum sex hormones levels in patients with secondary amenorrhea

International Nuclear Information System (INIS)

Jiang Hua

2007-01-01

Objective: To explore the clinical significance of changes of serum sex hormones levels in patients with secondary amenorrhea. Methods: Serum levels of E 2 , FSH, LH, PRL and P were detected with RIA in 33 patients with secondary amenorrhea and 30 controls. Results: In the patients, the serum E 2 levels were significantly lower and FSH, LH, PRL and P levels were significantly higher than those in controls (P 2 , FSH, LH, PRL and P levels is of help for assessment of severity of secondary amenorrhea as well as outcome prediction. (authors)

How Cognitive Neuroscience could be more biological – and what it might learn from Clinical Neuropsychology

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Stefan eFrisch

2014-07-01

Full Text Available Three widespread assumptions of Cognitive-affective Neuroscience are discussed: First, mental functions are assumed to be localized in circumscribed brain areas which can be exactly determined, at least in principle (localizationism. Second, this assumption is associated with the more general claim that these functions (and dysfunctions, such as in neurological or mental diseases are somehow generated inside the brain (internalism. Third, these functions are seen to be biological in the sense that they can be decomposed and finally explained on the basis of elementary biological causes (i. e. genetic, molecular, neurophysiological etc., causes that can be identified by experimental methods as the gold standard (isolationism. Clinical neuropsychology is widely assumed to support these tenets. However, by making reference to the ideas of Kurt Goldstein, one of its most important founders, I argue that none of these assumptions is sufficiently supported. From the perspective of a clinical-neuropsychological practitioner, assessing and treating brain damage sequelae reveals a quite different picture of the brain as well as of us brain carriers, making the organism (or person in its specific environment the crucial reference point. This conclusion can be further elaborated: All experimental and clinical research on humans presupposes the notion of a situated, reflecting, and interacting subject, which precedes all kinds of scientific decomposition, however useful. These implications support the core assumptions of the embodiment approach to brain and mind, and, as I argue, Goldstein and his clinical-neuropsychological observations are part of its very origin, for both theoretical and historical reasons.

CT classification and clinical significance of rupture globe

International Nuclear Information System (INIS)

Diao Jinzhong; Zhang Guixiang

1998-01-01

Purpose: To discuss CT appearances of the rupture globe, and CT classifications and their clinical significance. Materials and methods: Forty-nine rupture globes were verified; 79% patents were scanned within 24 hours. Axial plane scanning were done with 3 mm slice and 256 x 256 matrix. Bone and soft tissue conditions were adjusted to analyse the bone and globe structures. Results: CT showed that globe circle rupture in one point of 32%, two points of 20%, and multiple points of 28%. Thickening of globe circle was as follows: 5 mm in 10 globes, 6 mm in 24, and 7 mm in 9.20% injured globes were enlarged and 32% were contracted. 14 anterior chambers deepened more than 4 mm. 83% rupture globes also had intraglobe hemorrhage and 48% foreign bodies. 28% injured globes had exophthalmus, and 75% had injured parasinuses or orbits, or brain trauma. Conclusion: The authors classified the rupture globe into three types. Type III showed unrepaired that should ablate the injured globes, whereas type I and II had to repair and to debride

Clinical significance of quantitative analysis of facial nerve enhancement on MRI in Bell's palsy.

Science.gov (United States)

Song, Mee Hyun; Kim, Jinna; Jeon, Ju Hyun; Cho, Chang Il; Yoo, Eun Hye; Lee, Won-Sang; Lee, Ho-Ki

2008-11-01

Quantitative analysis of the facial nerve on the lesion side as well as the normal side, which allowed for more accurate measurement of facial nerve enhancement in patients with facial palsy, showed statistically significant correlation with the initial severity of facial nerve inflammation, although little prognostic significance was shown. This study investigated the clinical significance of quantitative measurement of facial nerve enhancement in patients with Bell's palsy by analyzing the enhancement pattern and correlating MRI findings with initial severity of facial palsy and clinical outcome. Facial nerve enhancement was measured quantitatively by using the region of interest on pre- and postcontrast T1-weighted images in 44 patients diagnosed with Bell's palsy. The signal intensity increase on the lesion side was first compared with that of the contralateral side and then correlated with the initial degree of facial palsy and prognosis. The lesion side showed significantly higher signal intensity increase compared with the normal side in all of the segments except for the mastoid segment. Signal intensity increase at the internal auditory canal and labyrinthine segments showed correlation with the initial degree of facial palsy but no significant difference was found between different prognostic groups.

Urtica dioica pollen allergy: Clinical, biological, and allergomics analysis.

Science.gov (United States)

Tiotiu, Angelica; Brazdova, Andrea; Longé, Cyril; Gallet, Patrice; Morisset, Martine; Leduc, Virginie; Hilger, Christiane; Broussard, Cédric; Couderc, Rémy; Sutra, Jean-Pierre; Sénéchal, Hélène; Poncet, Pascal

2016-11-01

The most emblematic members of Urticaceae at allergic risk level are wall pellitories (Parietaria), whereas nettle (Urtica) pollen is considered as poorly allergenic. No allergen from nettle pollen has yet been characterized, whereas 4 are listed for Parietaria pollen by the International Union of Immunological Societies. Clinical and biological profiles of 2 adult men who developed symptoms against nettle pollen and/or leaves were studied. To characterize the allergic reaction and identify the potential nettle pollen sensitizing allergens. IgE-mediated reaction to nettle pollen extract was evaluated by skin prick test, immunoassay, nasal provocation, and basophil activation test. To characterize specific nettle pollen allergens, an allergomic (IgE immunoproteomic) analysis was performed combining 1- and 2-dimensional electrophoresis, IgE immunoblots of nettle pollen extract, identification of allergens by mass spectrometry, and database queries. The results of biological and immunochemical analyses revealed that the allergic rhinitis was due to Urtica dioica pollen in both patients. The allergomic analysis of nettle pollen extract allowed the characterization of 4 basic protein allergens: a thaumatin-like protein (osmotin) with a relative molecular mass of 27 to 29 kDa, a pectinesterase (relative molecular mass, 40 kDa), and 2 other basic proteins with relative molecular masses of 14 to 16 kDa and 43 kDa. There is no or only very weak allergen associations between pellitory and nettle pollen. Exposure to nettle pollen can be responsible of allergic symptoms, and several allergens were characterized. Unravelling the allergens of this underestimated allergy might help to improve diagnosis and care for patients, to predict cross-reactivities and design adapted specific immunotherapy. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Low-molecular-weight cyclin E: the missing link between biology and clinical outcome

International Nuclear Information System (INIS)

Akli, Said; Keyomarsi, Khandan

2004-01-01

Cyclin E, a key mediator of transition during the G 1 /S cellular division phase, is deregulated in a wide variety of human cancers. Our group recently reported that overexpression and generation of low-molecular-weight (LMW) isoforms of cyclin E were associated with poor clinical outcome among breast cancer patients. However, the link between LMW cyclin E biology in mediating a tumorigenic phenotype and clinical outcome is unknown. To address this gap in knowledge, we assessed the role of LMW isoforms in breast cancer cells; we found that these forms of cyclin E induced genomic instability and resistance to p21, p27, and antiestrogens in breast cancer. These findings suggest that high levels of LMW isoforms of cyclin E not only can predict failure to endocrine therapy but also are true prognostic indicators because of their influence on cell proliferation and genetic instability

Clinical significance of serum thymosin α1 assay in tumor patients

International Nuclear Information System (INIS)

Wang Jiamin; Lv Ming'en; Zhao Xiaojuan; Gao Weiqiang; Bai Xia; Wang Zhaoyue

2003-01-01

Objective: To investigate the clinical significance of thymosin α1(Tα1) measurement in evaluating clinical status of patients with solid malignant tumors. Methods: Tα1 levels in serum of 50 normal adults, 20 patients with benign tumors and 63 patients with malignant tumors were measured by enzyme linked immunosorbent assay (ELISA). The association of Tα1 level with tumor invasion, metastasis and its alteration after different treatment in patients with malignant tumors were also studied. Results: The serum Tα1 level was 0.69±0.35 μg/L in normal adults, 0.96±0.37 μg/L in patients with benign tumors and 1.46±0.90 μg/L in patients with malignant tumors. In comparison it was both increased between patients with benign and malignant tumors and the normal adults (P<0.01 and P<0.001). And its increasing extent in malignant tumors was much greater than that in benign tumors (P<0.05). The serum Tα1 level in patients with malignant tumors was correlated with tumor invasion, metastasis and different treatment intervention. Conclusions: Our findings suggest that the serum Tα1 level be increased in tumor patients, and that it may be used as a new tumor marker in clinic

The future of research in craniofacial biology and what this will mean for oral health professional education and clinical practice.

Science.gov (United States)

Slavkin, H C

2014-06-01

Today, and looking to the future, scientific discoveries from cellular, developmental and molecular biology inform our understanding of cell, tissue and organ morphogenesis as exemplified in skin, bone, cartilage, dentine, enamel, muscle, nerve and many organs such as salivary glands and teeth. Present day biomedical science yields principles for the biomimetic design and fabrication of cells, tissues and organs. Bioengineering has become a strategy that can 'mimic' biological processes, and inform clinical procedures for tissue and organ replacements. The future of regenerative craniofacial biology holds enormous promise for the diagnosis and treatment of congenital birth defects, traumatic injuries, degenerative chronic diseases as well as for Mendelian single gene and complex multigene diseases and disorders. The past 50 years have heralded the completion of the human genome and the introduction of 'personalized medicine and dentistry', the utilization of stem cell therapy for an array of diseases and disorders, the 'proof of principle' to reverse select inherited diseases such as anhidrotic ectodermal dysplasia (ED), and the fruits from interdisciplinary research drawn from the diverse biomedical sciences. Looking to the future, we can readily anticipate as major goals to emphasize the clinician's role in identifying clinical phenotypes that can lead to differential diagnosis, and rejuvenate missing or damaged tissues by establishing processes for the utilization of gene, cell and/or protein therapies. The future is replete with remarkable opportunities to enhance clinical outcomes for congenital as well as acquired craniofacial malformations. Clinicians play a pivotal role because critical thinking and sound clinical acumen substantially improve diagnostic precision and thereby clinical health outcomes. © 2014 Australian Dental Association.

The clinical significance of axillary sentinel lymph node biopsy in different clinical stages breast cancer patients after neoadjuvant chemotherapy

Institute of Scientific and Technical Information of China (English)

Juan Xu; Xinhong Wu; Yaojun Feng; Feng Yuan; Wei Fan

2013-01-01

Objective:We aimed to study the success and false negative rate of sentinel lymph node biopsy (SLNB) in dif-ferent clinical stages breast cancer patients being carried out with neoadjuvant chemotherapy (NAC), and the clinical signifi-cance of SLNB, we conducting this trial. Methods:One hunderd and thirty-seven cases were enrol ed in this clinical research from March 2003 to March 2007. Al of the patients’ sentinel lymph nodes were detected with 99mTc-Dx and methylene blue. There were 61 patients with stage T1-2N0M0 carried SLNB without NAC (group A), 76 cases were carried out NAC 3-4 cycles before SLNB, including 39 T2-4N0-1M0 cases (group B) and 27 T2-4N2-3M0 cases (group C). The success and false negative rate of SLNB were analysed with chi-square test. Results:In group A, the successful and false negative rate of SLNB were 92.31%(36/39), 8.57%(3/35), and in group B and C were 92.31%(36/39), 8.57%(3/35) and 74.07%(20/27), 18.52%(5/27), respectively. The successful rate of group C decreased and false negative rate increased significantly compared with group A and B (P0.05). Conclusion:The SLNB can accurately predict lymph node status of axil ary lymph node in N0-1 stage patients with NAC, but in N2-3 stage patients the success rate decreased and false rate increased negative significantly.

Clinical significance of cumulative biological effective dose and overall treatment time in the treatment of carcinoma cervix

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Mandal Abhijit

2007-01-01

Full Text Available The purpose of this retrospective study is to report the radiotherapy treatment response of, and complications in, patients with cervical cancer on the basis of cumulative biologic effective dose (BED and overall treatment time (OTT. Sixty-four (stage II - 35/64; stage III - 29/64 patients of cervical cancer were treated with combination of external beam radiotherapy (EBRT and low dose rate intracavitary brachytherapy (ICBT. The cumulative BED was calculated at Point A (BED 10 ; and bladder, rectal reference points (BED 2.5 using the linear-quadratic BED equations. The local control (LC rate and 5-year disease-free survival (DFS rate in patients of stage II were comparable for BED 10 < 84.5 and BED 10 > 84.5 but were much higher for BED 10 > 84.5 than BED 10 < 84.5 ( P < 0.01 in stage III patients. In the stage II patients, The LC rate and 5-year DFS rate were comparable for OTT < 50 days and for OTT> 50 days but were much higher in stage III patients with OTT < 50 than OTT> 50 days ( P < 0.001. It was also observed that patients who received BED 2.5 < 105 had lesser rectal ( P < 0.001 and bladder complications than BED 2.5 > 105. Higher rectal complication-free survival (CFS R rate, bladder complication-free survival (CFS B rate and all-type late complication-free survival rate were observed in patients who received BED 2.5 < 105 than BED 2.5 > 105. A balanced, optimal and justified radiotherapy treatment schedule to deliver higher BED 10 (>84.5 and lower BED 2.5 (< 105 in lesser OTT (< 50 days is essential in carcinoma cervix to expect a better treatment outcome in all respects.

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

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Sebben, Juliana Canedo; Cambruzzi, Eduardo; Avena, Luisa Martins; Gazeta, Cristina do Amaral; Gottschall, Carlos Antonio Mascia; Quadros, Alexandre Schaan de, E-mail: quadros.pesquisa@gmail.com [Instituto de Cardiologia / Fundação Universitária de Cardiologia - IC/FUC, Porto Alegre, RS (Brazil)

2013-12-15

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

[Biological agents].

Science.gov (United States)

Amano, Koichi

2009-03-01

There are two types of biological agents for the treatment of rheumatoid arthritis (RA); monoclonal antibodies and recombinant proteins. Among the latter, etanercept, a recombinant fusion protein of soluble TNF receptor and IgG was approved in 2005 in Japan. The post-marketing surveillance of 13,894 RA patients revealed the efficacy and safety profiles of etanercept in the Japanese population, as well as overseas studies. Abatacept, a recombinant fusion protein of CTLA4 and IgG, is another biological agent for RA. Two clinical trials disclosed the efficacy of abatacept for difficult-to-treat patients: the AIM for MTX-resistant cases and the ATTAIN for patients who are resistant to anti-TNF. The ATTEST trial suggested abatacept might have more acceptable safety profile than infliximab. These biologics are also promising for the treatment of RA for not only relieving clinical symptoms and signs but retarding structural damage.

Clinical significance of pneumatosis intestinalis - correlation of MDCT-findings with treatment and outcome

Energy Technology Data Exchange (ETDEWEB)

Treyaud, Marc-Olivier; Duran, Rafael; Knebel, Jean-Francois; Meuli, Reto A.; Schmidt, Sabine [Lausanne University Hospital, Department of Diagnostic and Interventional Radiology, Lausanne (Switzerland); Zins, Marc [Fondation Hopital St Joseph, Department of Radiology, Paris (France)

2017-01-15

To evaluate the clinical significance of pneumatosis intestinalis (PI) including the influence on treatment and outcome. Two radiologists jointly reviewed MDCT-examinations of 149 consecutive emergency patients (53 women, mean age 64, range 21-95) with PI of the stomach (n = 4), small (n = 68) and/or large bowel (n = 96). PI extension, distribution and possibly associated porto-mesenteric venous gas (PMVG) were correlated with other MDCT-findings, risk factors, clinical management, laboratory, histopathology, final diagnosis and outcome. The most frequent cause of PI was intestinal ischemia (n = 80,53.7 %), followed by infection (n = 18,12.1 %), obstructive (n = 12,8.1 %) and non-obstructive (n = 10,6.7 %) bowel dilatation, unknown aetiologies (n = 8,5.4 %), drugs (n = 8,5.4 %), inflammation (n = 7,4.7 %), and others (n = 6,4 %). Neither PI distribution nor extension significantly correlated with underlying ischemia. Overall mortality was 41.6 % (n = 62), mostly related to intestinal ischemia (p = 0.003). Associated PMVG significantly correlated with underlying ischemia (p = 0.009), as did the anatomical distribution of PMVG (p = 0.015). Decreased mural contrast-enhancement was the only other MDCT-feature significantly associated with ischemia (p p < 0.001). Elevated white blood count significantly correlated with ischemia (p = 0.03). In emergency patients, ischemia remains the most common aetiology of PI, showing the highest mortality. PI with associated PMVG is an alerting sign. PI together with decreased mural contrast-enhancement indicates underlying ischemia. (orig.)

Systematic Review with Network Meta-Analysis: Comparative Efficacy of Biologics in the Treatment of Moderately to Severely Active Ulcerative Colitis.

Directory of Open Access Journals (Sweden)

Adrian D Vickers

Full Text Available Biological therapies are increasingly used to treat ulcerative colitis (UC.To compare the efficacy of biologics in adults with moderately-to-severely active UC, stratified by prior exposure to anti-tumour necrosis factor (anti-TNF therapy.A systematic literature review was undertaken to identify studies of biologics approved for UC. Network meta-analysis was conducted for endpoints at induction and maintenance.Seven studies were included in the meta-analysis of induction treatment for anti-TNF therapy-naïve patients. All biologics were more effective than placebo in inducing clinical response, clinical remission, and mucosal healing. Infliximab demonstrated a statistically significant improvement over adalimumab in clinical response (odds ratio [OR] [95% credible interval (CrI]: 2.19 [1.35-3.55], clinical remission (OR [95% CrI]: 2.81 [1.49-5.49], and mucosal healing (OR [95% CrI]: 2.23 [1.21-4.14]; there were no other significant differences between biologics for induction efficacy. Five studies were included in the meta-analysis of maintenance treatment, two studies rerandomised responder patients at end of induction, and three followed the same patients 'straight through'. To account for design differences, the number of responders at end of induction was assumed to be equivalent to the number rerandomised. Vedolizumab showed significantly different durable clinical response from comparators (OR [95% CrI] infliximab 3.18 [1.14-9.20], golimumab 2.33 [1.04-5.41], and adalimumab 3.96 [1.67-9.84]. In anti-TNF therapy-experienced patients, only vedolizumab and adalimumab could be compared. At induction, no significant differences in efficacy were seen. During maintenance, vedolizumab showed significantly improved rates of mucosal healing versus adalimumab (OR [95% CrI]: 6.72 [1.36-41.0].This study expands the understanding of comparative efficacies of biologic treatments for UC, encompassing outcomes and populations not previously studied. All

Assessing clinical significance in measuring oncology patient quality of life: Introduction to the symposium, content overview, and definition of terms

NARCIS (Netherlands)

Sloan, Jeff A.; Cella, David; Frost, Marlene; Guyatt, Gordon H.; Sprangers, Mirjam; Symonds, Tara

2002-01-01

The Clinical Significance Consensus Meeting Group of the Symposium on the Clinical Significance of Quality-of-Life Measures in Cancer Patients produced 6 articles regarding the clinical significance of quality of life (QOL) assessments in oncology. The 6 articles deal with the methods used to date:

Sonographic Evaluation of Clinically Significant Perigraft Hematomas in Kidney Transplant Recipients.

Science.gov (United States)

Fananapazir, Ghaneh; Rao, Rajiv; Corwin, Michael T; Naderi, Sima; Santhanakrishnan, Chandrasekar; Troppmann, Christoph

2015-10-01

The purpose of this study was to assess the sensitivity of ultrasound in evaluating peritransplant hematomas that require surgical evacuation in recipients of kidney transplants. Thirty-four patients who underwent 37 hematoma evacuations underwent ultrasound examinations in the 24 hours before surgical evacuation. The operative reports were evaluated for presence and size of collection, presence of active bleeding at operation, and composition of the hematoma. The clinical findings leading to the ultrasound examination were recorded. Ultrasound examinations were evaluated in consensus by two board-certified and fellowship-trained abdominal radiologists for the presence, size, and echogenicity of the collection; subjective perfusion visualized with color and power Doppler ultrasound; velocities of the renal arteries; and arcuate artery resistive indexes. Ten of the 37 imaged hematomas (27%) had either no or small (hematomas. Our results suggest that gray-scale sonography alone appears to have limited sensitivity in detecting clinically significant peritransplant hematomas and that its use may result in overall underestimates of hematomas.

Toward a unified theory of childhood trauma and psychosis: A comprehensive review of epidemiological, clinical, neuropsychological and biological findings.

Science.gov (United States)

Misiak, Błażej; Krefft, Maja; Bielawski, Tomasz; Moustafa, Ahmed A; Sąsiadek, Maria M; Frydecka, Dorota

2017-04-01

There is a growing body of research focused on the relationship between childhood trauma and the risk of developing psychosis. Numerous studies, including many large-scale population-based studies, controlling for possible mediating variables, provide persuasive evidence of a dose-response association and are indicative of a causal relationship. Existing evidence supports the specificity model, showing differential associations between particular adversities and clinical symptoms, with cumulative adversity causing less favorable clinical and functional outcomes in psychotic patients. To date, several psychological and biological models have been proposed to search for underlying developmental trajectories leading to the onset of psychosis, influencing psychopathological manifestation and negative functional outcomes due to a history of childhood trauma. In this article, we provide a unified review on the relationship between childhood trauma and psychosis by integrating results of epidemiological, clinical, neuropsychological and biological studies. The question whether psychosis with a positive history of childhood trauma should be considered as a new psychotic phenotype, requiring specific therapeutic interventions, warrants further investigation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Clinical significance of pulmonary nodules detected on abdominal CT in pediatric patients

International Nuclear Information System (INIS)

Breen, Micheal; Lee, Edward Y.; Zurakowski, David

2015-01-01

The clinical significance of a pulmonary nodule that is detected incidentally on CT studies in children is unknown. In addition, there is limited information regarding the management of incidentally detected pulmonary nodules discovered on abdominal CT studies in children. The purpose of this study was to investigate the clinical significance of incidental pulmonary nodules detected on abdominal CT studies in children. This was a retrospective study performed following institutional review board approval. Abdominal CT reports in patients younger than 18 years of age from July 2004 to June 2011 were reviewed for the terms ''nodule,'' ''nodular'' or ''mass'' in reference to the lung bases. The study population included those pediatric patients in whom pulmonary nodules were initially detected on abdominal CT studies. The largest pulmonary nodules detected on CT studies were evaluated for their features (size, shape, margin, attenuation, location, and presence of calcification and cavitation). Follow-up CT studies and clinical records were reviewed for demographic information, history of underlying malignancies and the clinical outcome of the incidental pulmonary nodules. Comparison of malignant versus benign pulmonary nodules was performed with respect to the size of the nodule, imaging features on CT, and patient history of malignancy using the Student's t-test and Fisher exact test. Youden J-index in receiver operating characteristic (ROC) analysis was used to determine the optimal cut-off size for suggesting a high risk of malignancy of incidentally detected pulmonary nodules. Pulmonary nodules meeting inclusion criteria were detected in 62 (1.2%) of 5,234 patients. The mean age of patients with nodules was 11.2 years (range: 5 months-18 years). Thirty-one patients (50%) had follow-up CT studies and two of these patients (6%) were subsequently found to have malignant pulmonary nodules. Both of these

Clinical significance of pulmonary nodules detected on abdominal CT in pediatric patients

Energy Technology Data Exchange (ETDEWEB)

Breen, Micheal; Lee, Edward Y. [Boston Children' s Hospital and Harvard Medical School, Department of Radiology, Boston, MA (United States); Zurakowski, David [Boston Children' s Hospital and Harvard Medical School, Departments of Anesthesiology and Surgery, Boston, MA (United States)

2015-11-15

The clinical significance of a pulmonary nodule that is detected incidentally on CT studies in children is unknown. In addition, there is limited information regarding the management of incidentally detected pulmonary nodules discovered on abdominal CT studies in children. The purpose of this study was to investigate the clinical significance of incidental pulmonary nodules detected on abdominal CT studies in children. This was a retrospective study performed following institutional review board approval. Abdominal CT reports in patients younger than 18 years of age from July 2004 to June 2011 were reviewed for the terms ''nodule,'' ''nodular'' or ''mass'' in reference to the lung bases. The study population included those pediatric patients in whom pulmonary nodules were initially detected on abdominal CT studies. The largest pulmonary nodules detected on CT studies were evaluated for their features (size, shape, margin, attenuation, location, and presence of calcification and cavitation). Follow-up CT studies and clinical records were reviewed for demographic information, history of underlying malignancies and the clinical outcome of the incidental pulmonary nodules. Comparison of malignant versus benign pulmonary nodules was performed with respect to the size of the nodule, imaging features on CT, and patient history of malignancy using the Student's t-test and Fisher exact test. Youden J-index in receiver operating characteristic (ROC) analysis was used to determine the optimal cut-off size for suggesting a high risk of malignancy of incidentally detected pulmonary nodules. Pulmonary nodules meeting inclusion criteria were detected in 62 (1.2%) of 5,234 patients. The mean age of patients with nodules was 11.2 years (range: 5 months-18 years). Thirty-one patients (50%) had follow-up CT studies and two of these patients (6%) were subsequently found to have malignant pulmonary nodules. Both of these

Biflorin: an o-naphthoquinone of clinical significance.

Science.gov (United States)

Wisintainer, Gabrielle G N S; Simões, Evelyne R B; Lemos, Telma L G; Moura, Sidnei; Souza, Luciana G S; Fonseca, Aluisio M; Moraes, Manoel Odorico; Pessoa, Claudia; Roesch-Ely, Mariana; Henriques, João A P

2014-10-14

Biflorin is an o-naphthoquinone with proven cytotoxic effects on tumor cells showing antimicrobial, antitumor and antimutagenic activities. Biflorin is an isolated compound taken from the roots of the plant Capraria biflora L. (Schrophulariaceae), indigenous of the West Indies and South America, which is located in temperate or tropical areas. This compound has shown to be strongly active against grampositive and alcohol-acid-resistant bacteria. It has been efficient in inhibiting the proliferation tumor cell lines CEM, HL-60, B16, HCT-8 and MCF-7. Recently, SK-Br3 cell line was treated with biflorin showing important cytotoxic effects. In this article, information related to the first structural characterization studies are presented, as well as the latest reports concerning the biological activity of this molecule.

Radiation biology and radiation therapy

International Nuclear Information System (INIS)

Wideroee, R.

1975-01-01

Radiation biology and radiation therapy can be compared with investigations in different layers of earth. Radiation biology works upwards from the elementary foundations, therapy works downwards with roots to secure and improve the clinical 'surface work'. The Ellis formula (Strandquist), which is a collection of clinical experience, is suited to form connections with radiobiology in the middle layers, and cooperation can give impulses for research. The structure and conditions of tumours and the complicated problems met with are discussed, based on the Carmel symposium of 1969. The oxygen problem in anoxic tumours is not yet solved. Experimental investigations of the effect itself give partly contradictory results. From a clinical viewpoint reoxygenation is of the utmost significance for obtaining control over the primary tumour, and advanced irradiation programmes will here give better results than the traditional ones. New chemicals, e.g. R 0 -07-0582, appear to reduce the OER value to 1.5, thereby making neutron therapy superfluous. Finally a problem from fundamental research is dealt with, wherein two hypotheses explaining the β-effect are described. The repair hypothesis gives a simple explanation but leaves many questions unanswered. The other hypothesis explains the β-effect as two neighbouring single breaks of the DNA molecule. It still presents difficulties, and is scarcely the correct explanation. (JIW)

Clinically Applicable Monte Carlo–based Biological Dose Optimization for the Treatment of Head and Neck Cancers With Spot-Scanning Proton Therapy

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Wan Chan Tseung, Hok Seum, E-mail: wanchantseung.hok@mayo.edu; Ma, Jiasen; Kreofsky, Cole R.; Ma, Daniel J.; Beltran, Chris

2016-08-01

Purpose: Our aim is to demonstrate the feasibility of fast Monte Carlo (MC)–based inverse biological planning for the treatment of head and neck tumors in spot-scanning proton therapy. Methods and Materials: Recently, a fast and accurate graphics processor unit (GPU)–based MC simulation of proton transport was developed and used as the dose-calculation engine in a GPU-accelerated intensity modulated proton therapy (IMPT) optimizer. Besides dose, the MC can simultaneously score the dose-averaged linear energy transfer (LET{sub d}), which makes biological dose (BD) optimization possible. To convert from LET{sub d} to BD, a simple linear relation was assumed. By use of this novel optimizer, inverse biological planning was applied to 4 patients, including 2 small and 1 large thyroid tumor targets, as well as 1 glioma case. To create these plans, constraints were placed to maintain the physical dose (PD) within 1.25 times the prescription while maximizing target BD. For comparison, conventional intensity modulated radiation therapy (IMRT) and IMPT plans were also created using Eclipse (Varian Medical Systems) in each case. The same critical-structure PD constraints were used for the IMRT, IMPT, and biologically optimized plans. The BD distributions for the IMPT plans were obtained through MC recalculations. Results: Compared with standard IMPT, the biologically optimal plans for patients with small tumor targets displayed a BD escalation that was around twice the PD increase. Dose sparing to critical structures was improved compared with both IMRT and IMPT. No significant BD increase could be achieved for the large thyroid tumor case and when the presence of critical structures mitigated the contribution of additional fields. The calculation of the biologically optimized plans can be completed in a clinically viable time (<30 minutes) on a small 24-GPU system. Conclusions: By exploiting GPU acceleration, MC-based, biologically optimized plans were created for

Measuring Biological Age via Metabonomics: The Metabolic Age Score.

Science.gov (United States)

Hertel, Johannes; Friedrich, Nele; Wittfeld, Katharina; Pietzner, Maik; Budde, Kathrin; Van der Auwera, Sandra; Lohmann, Tobias; Teumer, Alexander; Völzke, Henry; Nauck, Matthias; Grabe, Hans Jörgen

2016-02-05

Chronological age is one of the most important risk factors for adverse clinical outcome. Still, two individuals at the same chronological age could have different biological aging states, leading to different individual risk profiles. Capturing this individual variance could constitute an even more powerful predictor enhancing prediction in age-related morbidity. Applying a nonlinear regression technique, we constructed a metabonomic measurement for biological age, the metabolic age score, based on urine data measured via (1)H NMR spectroscopy. We validated the score in two large independent population-based samples by revealing its significant associations with chronological age and age-related clinical phenotypes as well as its independent predictive value for survival over approximately 13 years of follow-up. Furthermore, the metabolic age score was prognostic for weight loss in a sample of individuals who underwent bariatric surgery. We conclude that the metabolic age score is an informative measurement of biological age with possible applications in personalized medicine.

Glioma CpG island methylator phenotype (G-CIMP): biological and clinical implications.

Science.gov (United States)

Malta, Tathiane M; de Souza, Camila F; Sabedot, Thais S; Silva, Tiago C; Mosella, Maritza S; Kalkanis, Steven N; Snyder, James; Castro, Ana Valeria B; Noushmehr, Houtan

2018-04-09

Gliomas are a heterogeneous group of brain tumors with distinct biological and clinical properties. Despite advances in surgical techniques and clinical regimens, treatment of high-grade glioma remains challenging and carries dismal rates of therapeutic success and overall survival. Challenges include the molecular complexity of gliomas, as well as inconsistencies in histopathological grading, resulting in an inaccurate prediction of disease progression and failure in the use of standard therapy. The updated 2016 World Health Organization (WHO) classification of tumors of the central nervous system reflects a refinement of tumor diagnostics by integrating the genotypic and phenotypic features, thereby narrowing the defined subgroups. The new classification recommends molecular diagnosis of isocitrate dehydrogenase (IDH) mutational status in gliomas. IDH-mutant gliomas manifest the cytosine-phosphate-guanine (CpG) island methylator phenotype (G-CIMP). Notably, the recent identification of clinically relevant subsets of G-CIMP tumors (G-CIMP-high and G-CIMP-low) provides a further refinement in glioma classification that is independent of grade and histology. This scheme may be useful for predicting patient outcome and may be translated into effective therapeutic strategies tailored to each patient. In this review, we highlight the evolution of our understanding of the G-CIMP subsets and how recent advances in characterizing the genome and epigenome of gliomas may influence future basic and translational research.

Change in expression of cyclin G2 in kidney cancer cell and its significance.

Science.gov (United States)

Cui, D W; Sun, G G; Cheng, Y J

2014-04-01

This study aims to analyze the expression and clinical significance of cyclin G2 (CCNG2) in kidney carcinoma, and the biological effect in its cell line by CCNG2 overexpression. Immunohistochemistry and western blot were used to analyze CCNG2 protein expression in 63 cases of kidney cancer and normal tissues to study the relationship between CCNG2 expression and clinical factors. CCNG2 lentiviral vector and empty vector were respectively transfected into kidney ACHN cell line. During immunohistochemistry, the level of CCNG2 protein expression was found to be significantly lower in kidney cancer tissue than normal tissues (P kidney cancer tissue was respectively found to be significantly lower than in normal tissues (P 0.05), but it was correlated with lymph node metastasis, clinic stage, and histological grade (P kidney cancer and correlated significantly with lymph node metastasis, clinical stage, histological grade, and poor overall survival, suggesting that CCNG2 may play important roles as a negative regulator to kidney cancer ACHN cell by promoting degradation of CDK2.

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

Science.gov (United States)

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.

Posttranslational modifications of proopiomelanocortin in vertebrates and their biological significance

Directory of Open Access Journals (Sweden)

Akiyoshi eTakahashi

2013-10-01

Full Text Available Proopiomelanocortin (POMC is the precursor of several peptide hormones generated in the pituitary gland. After biosynthesis, POMC undergoes several posttranslational modifications, including proteolytic cleavage, acetylation, amidation, phosphorylation, glycosylation, and disulfide linkage formation, which generate mature POMC-derived peptides. Therefore, POMC is a useful model for the investigation of posttranslational modifications. These processes have been extensively investigated in mammals, primarily in rodents. In addition, over the last decade, much information has been obtained about the posttranslational processing of POMC in non-mammalian animals such as fish, amphibians, reptiles, and birds through sequencing and peptide identification by mass spectrometry. One POMC modification, acetylation, is known to modulate the biological activities of POMC-derived alpha-melanocyte-stimulating hormone (alpha-MSH having an acetyl group at N-terminal through potentiation or inhibition. This bidirectional regulation depends on its intrinsic roles in the tissue or cell; for example, alpha-MSH, as well as desacety-alpha-MSH, stimulates pigment dispersion in the xanthophores of a flounder. In contrast, alpha-MSH does not stimulate pigment dispersion in the melanophores of the same species, whereas desacetyl-alpha-MSH does. Regulation of pigment-dispersing activities may be associated with the subtle balance in the expression of receptor genes. In this review, we consider the posttranslational modifications of POMC in vertebrates from an evolutionary aspect, with a focus on the relationship between acetylation and the biological activities of alpha-MSH as an important consequence of posttranslational modification.

External Beam Radiotherapy for Clinically Localized Hormone-Refractory Prostate Cancer: Clinical Significance of Nadir Prostate-Specific Antigen Value Within 12 Months

International Nuclear Information System (INIS)

Ogawa, Kazuhiko; Nakamura, Katsumasa; Sasaki, Tomonari; Onishi, Hiroshi; Koizumi, Masahiko; Shioyama, Yoshiyuki; Araya, Masayuki; Mukumoto, Nobutaka M.S.; Mitsumori, Michihide; Teshima, Teruki

2009-01-01

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.

Candiduria: A review of clinical significance and management

International Nuclear Information System (INIS)

Bukhary, Z.A.

2008-01-01

Candiduria is a common nosocomial infection afflicting the urinary tract. This review is aimed at providing an updated summary of the problem in hospitalized adult patients. A review of English Medline literature published between January 1970 until June 2007 was performed. Reviews, clinical trials and case-controlled studies in adult patients were included. Risk factors for candiduria included urinary indwelling catheters, use of antibiotics, elderly age, underlying genitourinary tract abnormality, previous surgery and presence of diabetes mellitus. Presence of candiduria may represent only colonization and there are no consistent diagnostic criteria to define significant infection. Candiduria may not be associated with candidemia and most cases are asymptomatic. Asymptomatic canididuria is usually benign, and does not require local or systemic antifungal therapy. Physicians need to confirm the infection by a second sterile urine sample, adopt non-pharmacologic interventions and modify risk factors. Mortality rate can be high particularly in debilitated patients and awareness to validate candiduria is necessary to stratify treatment according to patient status. Appropriate use of antifungal drugs, when indicated, should not replace correction of the underlying risk factors. Treatment of symptomatic candiduria is less controversial and easier. (author)

[Expression and clinical significance of CD147 in parathyroid carcinoma].

Science.gov (United States)

Du, X M; Wang, L L; Chang, H; Meng, W; Zhang, J Y; Shen, B

2016-06-08

To study the expression and clinical significance of CD147 in the patients of parathyroid carcinoma. Fourteen cases of parathyroid carcinoma encountered during the period from 2012 to 2015 were enrolled. Thirty three cases of parathyroid adenoma encountered during the same period were enrolled. The expression of CD147 in parathyroid carcinoma and parathyroid adenoma was studied by means of immunohistochemistry (EnVision method). CD147 positive color was brown and yellow, and positive position was located mainly in the cytomembrane, and a small amount of cytoplasm was appeared. Among 14 cases of parathyroid carcinoma, 11 cases of CD147 positive score was 3+ , 3 cases of CD147 positive score was 2+ ; Among 33 cases of parathyroid adenoma , 8 cases of CD147 positive score was 2+ , 15 cases of it was 1+ , 10 cases of it was negative. CD147 was highly expressed in parathyroid carcinoma tissues, and the expression of CD147 was significantly different from the expression of parathyroid adenoma(PCD147 immunohistochemical staining can help to diagnose parathyroid carcinoma.

[Expression and clinical significance of KIAA1199 in primary hepatocellular carcinoma].

Science.gov (United States)

Gu, C J; Ni, Q C; Ni, K; Zhang, S; Qian, H X

2018-05-29

Objective: To investigate the expression and clinical significance of KIAA1199 in primary hepatocellular carcinoma. Methods: A total of 136 cases of primary hepatocellular carcinoma tissues and paired adjacent tissues were collected. Immunohistochemistry and Western blot were used to detect the expression of KIAA1199 in primary hepatocellular carcinoma tissues and paired adjacent tissues. The relationship between KIAA1199 and clinicopathological parameter of primary hepatocellular carcinoma was analyzed. Results: The positive rate of KIAA1199 in primary hepatocellular carcinoma was 82.3% (112/136), which was higher than that in paired para-cancerous tissues (14.7%, 20/136). High expression of KIAA1199 was significantly correlated with age, cirrhosis history, tumor size, tumor number, degree of differentiation, TNM staging and microvenous invasion (MVI) ( P 0.05). The Kaplan-Meier survival curves indicated that high KIAA1199 expression was associated with poor survival ( P hepatocellular carcinoma, which is significantly correlated with the clinicopathological features and prognosis, high expression of KIAA1199 increased the risk of death in patients with primary hepatocellular carcinoma.

Extensive next-generation sequencing analysis in chronic lymphocytic leukemia at diagnosis: clinical and biological correlations

Directory of Open Access Journals (Sweden)

Gian Matteo Rigolin

2016-09-01

Full Text Available Abstract Background In chronic lymphocytic leukemia (CLL, next-generation sequencing (NGS analysis represents a sensitive, reproducible, and resource-efficient technique for routine screening of gene mutations. Methods We performed an extensive biologic characterization of newly diagnosed CLL, including NGS analysis of 20 genes frequently mutated in CLL and karyotype analysis to assess whether NGS and karyotype results could be of clinical relevance in the refinement of prognosis and assessment of risk of progression. The genomic DNA from peripheral blood samples of 200 consecutive CLL patients was analyzed using Ion Torrent Personal Genome Machine, a NGS platform that uses semiconductor sequencing technology. Karyotype analysis was performed using efficient mitogens. Results Mutations were detected in 42.0 % of cases with 42.8 % of mutated patients presenting 2 or more mutations. The presence of mutations by NGS was associated with unmutated IGHV gene (p = 0.009, CD38 positivity (p = 0.010, risk stratification by fluorescence in situ hybridization (FISH (p < 0.001, and the complex karyotype (p = 0.003. A high risk as assessed by FISH analysis was associated with mutations affecting TP53 (p = 0.012, BIRC3 (p = 0.003, and FBXW7 (p = 0.003 while the complex karyotype was significantly associated with TP53, ATM, and MYD88 mutations (p = 0.003, 0.018, and 0.001, respectively. By multivariate analysis, the multi-hit profile (≥2 mutations by NGS was independently associated with a shorter time to first treatment (p = 0.004 along with TP53 disruption (p = 0.040, IGHV unmutated status (p < 0.001, and advanced stage (p < 0.001. Advanced stage (p = 0.010, TP53 disruption (p < 0.001, IGHV unmutated status (p = 0.020, and the complex karyotype (p = 0.007 were independently associated with a shorter overall survival. Conclusions At diagnosis, an extensive biologic characterization including

Biflorin: an o-naphthoquinone of clinical significance

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GABRIELLE G.N.S. WISINTAINER

2014-12-01

Full Text Available Biflorin is an o-naphthoquinone with proven cytotoxic effects on tumor cells showing antimicrobial, antitumor and antimutagenic activities. Biflorin is an isolated compound taken from the roots of the plant Capraria biflora L. (Schrophulariaceae, indigenous of the West Indies and South America, which is located in temperate or tropical areas. This compound has shown to be strongly active against grampositive and alcohol-acid-resistant bacteria. It has been efficient in inhibiting the proliferation tumor cell lines CEM, HL-60, B16, HCT-8 and MCF-7. Recently, SK-Br3 cell line was treated with biflorin showing important cytotoxic effects. In this article, information related to the first structural characterization studies are presented, as well as the latest reports concerning the biological activity of this molecule.

A novel melittin nano-liposome exerted excellent anti-hepatocellular carcinoma efficacy with better biological safety

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Jie Mao

2017-03-01

Full Text Available Abstract Melittin is the main effective component of bee venom and has extensive biological functions; however, serious side effects have restricted its clinical application. Preclinical and clinical studies showed that the main adverse events were allergic reaction and pain at the administration site. To decrease the toxicity, we prepared melittin nano-liposomes by encapsulating melittin with poloxamer 188 and explored the inhibitory activities on liver cancer together with biological safety. Here, we showed that melittin nano-liposomes significantly inhibited the survival of hepatocellular carcinoma (HCC cells in vitro and prominently suppressed the growth of subcutaneous and orthotopic HCC transplantation tumors in vivo. It was important that it induced less inflammation and allergy in mice compared with melittin. Overall, melittin nano-liposomes would have a better application in HCC therapy due to its significant anti-tumor activity and better biological safety.

A novel melittin nano-liposome exerted excellent anti-hepatocellular carcinoma efficacy with better biological safety.

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Mao, Jie; Liu, Shujun; Ai, Min; Wang, Zhuo; Wang, Duowei; Li, Xianjing; Hu, Kaiyong; Gao, Xinghua; Yang, Yong

2017-03-20

Melittin is the main effective component of bee venom and has extensive biological functions; however, serious side effects have restricted its clinical application. Preclinical and clinical studies showed that the main adverse events were allergic reaction and pain at the administration site. To decrease the toxicity, we prepared melittin nano-liposomes by encapsulating melittin with poloxamer 188 and explored the inhibitory activities on liver cancer together with biological safety. Here, we showed that melittin nano-liposomes significantly inhibited the survival of hepatocellular carcinoma (HCC) cells in vitro and prominently suppressed the growth of subcutaneous and orthotopic HCC transplantation tumors in vivo. It was important that it induced less inflammation and allergy in mice compared with melittin. Overall, melittin nano-liposomes would have a better application in HCC therapy due to its significant anti-tumor activity and better biological safety.

Characterization of relative biological effectiveness for conventional radiation therapy: a comparison of clinical 6 MV X-rays and 137Cs.

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Howard, Michelle; Beltran, Chris; Sarkaria, Jann; Herman, Michael G

2017-09-01

Various types of radiation are utilized in the treatment of cancer. Equal physical doses of different radiation types do not always result in the same amount of biological damage. In order to account for these differences, a scaling factor known as the relative biological effectiveness (RBE) can be used. 137Cesium (137Cs) has been used as a source of radiation in a significant body of radiation therapy research. However, high-energy X-rays, such as 6 MV X-rays, are currently used clinically to treat patients. To date, there is a gap in the literature regarding the RBE comparison of these two types of radiation. Therefore, the purpose of this study was to investigate the RBE of 137Cs relative to that of 6 MV X-rays. To determine the RBE, five cell lines were irradiated [Chinese hamster ovary (CHO); human lung adenocarcinoma (A549); human glioma (U251); human glioma (T98); and human osteosarcoma (U2OS)] by both types of radiation and assessed for cell survival using a clonogenic assay. Three of the five cell lines resulted in RBE values of ~1.00 to within 11% for all survival fractions, showing the physical and biological dose for these two types of radiation were equivalent. The other two cell lines gave RBE values differing from 1.00 by up to 36%. In conclusion, the results show the range in biological effect seen between cell lines, and therefore cell type must be considered when characterizing RBE. © The Author 2017. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Exogenous near-infrared fluorophores and their applications in cancer diagnosis: biological and clinical perspectives.

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Zhang, Hua; Uselman, Ryan R; Yee, Douglas

2011-05-01

Near-infrared fluorescent (NIRF) imaging is a rapidly growing research field which has the potential to be an important imaging modality in cancer diagnosis. Various exogenous NIR fluorophores have been developed for the technique, including small molecule fluorophores and nanoparticles. NIRF imaging has been used in animal models for the detection of cancer overthe last twenty years and has in recent years been used in human clinical trials. This article describes the types and characteristics of exogenous fluorophores available for in vivo fluorescent cancer imaging. The article also discusses the progression of NIRF cancer imaging over recent years and its future challenges, from both a biological and clinical perspective. in The review also looks at its application for lymph node mapping, tumor targeting and characterization, and tumor margin definition for surgical guidance. NIRF imaging is not in routine clinical cancer practice; yet, the authors predict that techniques using NIR fluorophores for tumor margin definition and lymph node mapping will enter clinical practice in the near future. The authors also anticipate that NIRF imaging research will lead to the development of flurophores with 'high brightness' that will overcome the limited penetration of this modality and be better suited for non invasive tumor targeting.

Risk management of biologicals: a regulatory and clinical perspective

NARCIS (Netherlands)

Giezen, T.J.|info:eu-repo/dai/nl/304823112

2011-01-01

Biologicals are a relatively new class of drugs and are important treatment options for a variety of chronic and/or serious conditions. Biologicals have different characteristics as compared to the traditional chemically synthesised drugs, which may result in different risk profiles and the need for

Expression and clinical significance of fibroblast growth factor 1 in gastric adenocarcinoma

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Liu NQ

2015-03-01

Full Text Available Naiqing Liu,1,2,* Jingyu Zhang,2,* Shuxiang Sun,2 Liguang Yang,2 Zhongjin Zhou,2 Qinli Sun,2 Jun Niu11Department of General Surgery, Qilu Hospital Affiliated to Shandong University, Jinan, People’s Republic of China; 2Department of General Surgery, Yishui Central Hospital, Linyi, People’s Republic of China*These authors contributed equally to this workBackground: The clinical significance of fibroblast growth factor 1 (FGF1 has been revealed in several cancers, including ovarian cancer, breast cancer, and bladder cancer. However, the clinical significance of FGF1 in gastric adenocarcinoma has not been explored.Patients and methods: In our experiments, we systematically evaluated FGF1 expression in 178 cases of gastric adenocarcinoma with immunohistochemistry, and subsequently analyzed the correlation between FGF1 expression and clinicopathologic features. Moreover, FGF1 expression in tumor tissue and corresponding adjacent tissue was detected and compared by real-time polymerase chain reaction. The Kaplan–Meier method and the Cox-regression model were used with univariate and multivariate analysis, respectively, to evaluate the prognostic value of FGF1 in gastric adenocarcinoma.Results: Higher FGF1 expression rate is 56.7% (101/178 in gastric adenocarcinoma. FGF1 expression in gastric adenocarcinoma was significantly higher than adjacent tissue (P<0.0001. Expression of FGF1 is significantly associated with lymph node invasion (P<0.001, distant metastasis (P=0.013, and differentiation (P=0.015. Moreover, FGF1 overexpression was closely related to unfavorable overall survival rate (P=0.021, and can be identified to be an independent unfavorable prognostic factor (P=0.004.Conclusion: FGF1 is an independent prognostic factor, indicating that FGF1 could be a potential molecular drug target in gastric adenocarcinoma.Keywords: fibroblast growth factor 1, gastric adenocarcinoma, prognosis, biomarker, lymph node, gene fusion

Childhood exposure to violence and lifelong health: clinical intervention science and stress-biology research join forces.

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Moffitt, Terrie E

2013-11-01

Many young people who are mistreated by an adult, victimized by bullies, criminally assaulted, or who witness domestic violence react to this violence exposure by developing behavioral, emotional, or learning problems. What is less well known is that adverse experiences like violence exposure can lead to hidden physical alterations inside a child's body, alterations that may have adverse effects on life-long health. We discuss why this is important for the field of developmental psychopathology and for society, and we recommend that stress-biology research and intervention science join forces to tackle the problem. We examine the evidence base in relation to stress-sensitive measures for the body (inflammatory reactions, telomere erosion, epigenetic methylation, and gene expression) and brain (mental disorders, neuroimaging, and neuropsychological testing). We also review promising interventions for families, couples, and children that have been designed to reduce the effects of childhood violence exposure. We invite intervention scientists and stress-biology researchers to collaborate in adding stress-biology measures to randomized clinical trials of interventions intended to reduce effects of violence exposure and other traumas on young people.

Radiation-induced secretory protein, clusterin. Its inductive mechanism and biological significance

International Nuclear Information System (INIS)

Suzuki, Masatoshi; Boothman, D.A.

2007-01-01

This paper describes biochemistry of secretory clusterin (C), its radiation-inductive mechanism and biological significance. C is a glycoprotein found to be secreted from cells given various stresses like radiation and ultraviolet (UV)-ray, and participates to red cell clustering. Human C gene locates on the chromosome 8p21-p12, C has MW of 60 kDa, its precursor undergoes the degrading processing to α- and β-chains to form their heterodimer before glycosylation, and the C is finally secreted. So many other names have been given to C due to its numerous functions which have been discovered in other fields, such as apolipoprotein J. C is abundant in plasma, milk, urine, cerebrospinal fluid, semen, etc. Within 24 hr after X-ray irradiation, extracellular insulin-like growth factor-1 (IGF-1) level is elevated, and through its binding to the receptor, Src/MAPK signaling participates to C expression. Nuclear C, also induced by radiation, is a splicing variant of C and not secreted from cells. C is induced by radiation with as low dose as 2 cGy, which is different from induction of nuclear C. Secreted C is incorporated in cells by endocytosis and promotes the intracellular survival reaction through IGF-1 receptor/MAPK/Egr-1 pathway, whereas nuclear C induces cell apoptosis via unknown mechanism. Further studies are required for elucidation of the roles of secretory and nuclear C in cellular radiation responses. (R.T.)

Study to determine the clinical significance of HEmolysis During Orbital AtheRectomy (CLEAR study).

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Staniloae, Cezar S; Korabathina, Ravikiran; Lane, Thomas A; Dattilo, Raymond; Church, Kevin J; Mody, Kanika P; Mayeda, Guy S

2011-02-01

To evaluate the incidence of clinically evident hemolysis associated with orbital atherectomy used to treat severe peripheral artery disease. The observational CLEAR study enrolled 31 subjects (16 men; mean age 71 ± 10 years, range 44-92) with claudication (58.1%) or critical limb ischemia (38.7%) who underwent orbital atherectomy with the Diamondback 360 system at 4 US centers. The 42 lesions in 31 limbs were located in the superficial femoral (n = 19, 45.2%), popliteal (n = 8, 19.0%), and tibial arteries (n = 15, 35.8%). The majority of lesions (34, 81.0%) were de novo; moderate or severe calcification was identified in 90.5% of cases. Lesion and procedural parameters were analyzed at a core laboratory. Blood samples were collected during and post procedure and analyzed for markers of hemolysis. The primary endpoint was the occurrence of clinically significant hemolysis. The secondary endpoints included the occurrence of any clinical symptoms/signs potentially related to hemolysis. Statistical analysis was performed to identify predictors for hemolysis. Laboratory evidence of hemolysis was seen in 11 (35.5%) subjects. No one met the clinical event criteria, and so the primary endpoint of the study was not reached. The secondary endpoints were hypertensive crisis (1, 3.2%) and transient hemoglobinuria (3, 9.7%). Lower glomerular filtration rates, calcified plaque, long atherectomy runs, and solid crown selection were independent predictors of hemolysis. There was no clinically significant hemolysis after orbital atherectomy. The results of this study will enable users to predict conditions that predispose to high levels of red cell hemolysis following orbital atherectomy and to take appropriate measures to limit its occurrence.

Clinical significance of methicillin-resistant Staphylococcus aureus colonization on hospital admission: one-year infection risk.

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Jessica P Ridgway

Full Text Available BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA nasal colonization among inpatients is a well-established risk factor for MRSA infection during the same hospitalization, but the long-term risk of MRSA infection is uncertain. We performed a retrospective cohort study to determine the one-year risk of MRSA infection among inpatients with MRSA-positive nasal polymerase chain reaction (PCR tests confirmed by positive nasal culture (Group 1, patients with positive nasal PCR but negative nasal culture (Group 2, and patients with negative nasal PCR (Group 3. METHODOLOGY/PRINCIPAL FINDINGS: Subjects were adults admitted to a four-hospital system between November 1, 2006 and March 31, 2011, comprising 195,255 admissions. Patients underwent nasal swab for MRSA PCR upon admission; if positive, nasal culture for MRSA was performed; if recovered, MRSA was tested for Panton-Valentine Leukocidin (PVL. Outcomes included MRSA-positive clinical culture and skin and soft tissue infection (SSTI. Group 1 patients had a one-year risk of MRSA-positive clinical culture of 8.0% compared with 3.0% for Group 2 patients, and 0.6% for Group 3 patients (p<0.001. In a multivariable model, the hazard ratios for future MRSA-positive clinical culture were 6.52 (95% CI, 5.57 to 7.64 for Group 1 and 3.40 (95% CI, 2.70 to 4.27 for Group 2, compared with Group 3 (p<0.0001. History of MRSA and concurrent MRSA-positive clinical culture were significant risk factors for future MRSA-positive clinical culture. Group 1 patients colonized with PVL-positive MRSA had a one-year risk of MRSA-positive clinical culture of 10.1%, and a one-year risk of MRSA-positive clinical culture or SSTI diagnosis of 21.7%, compared with risks of 7.1% and 12.5%, respectively, for patients colonized with PVL-negative MRSA (p = 0.04, p = 0.005, respectively. CONCLUSIONS/SIGNIFICANCE: MRSA nasal colonization is a significant risk factor for future MRSA infection; more so if detected by

Clinical significance of autoantibodies in autoimmune hepatitis.

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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. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

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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.

The clinical significance of brain microbleeds in patients with Alzheimer′s disease: Preliminary study

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Jae-Hyeok Heo

2016-01-01

Full Text Available 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.

Expression of transcription factor Pokemon in non-small cell lung cancer and its clinical significance.

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Zhao, Zhi-hong; Wang, Sheng-fa; Yu, Liang; Wang, Ju; Chang, Hao; Yan, Wei-li; Fu, Kai; Zhang, Jian

2008-03-05

Transcription factor Pokemon, a central regulation gene of the important tumor suppressor ARF gene, exerted its activity by acting upstream of many tumor-suppressing genes and proto-oncogenes. Its expression in non-small cell lung cancer (NSCLC) and its clinical significance remains unclear. The aim of this study was to investigate the expression of Pokemon in NSCLC and to explore its correlation with the clinical pathological characteristics and its influence on patients' prognosis. Fifty-five cases of NSCLC were involved in this study. The expression of Pokemon in the tumor tissue, the corresponding tumor adjacent tissue and the surrounding tissue was detected via reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, with the aim of investigating the correlation between the expression of Pokemon in tumor tissue of NSCLC and its clinical pathological characteristics. Moreover, a prognostic analysis was carried out based upon the immunohistochemical (IHC) detection of the expression of Pokemon gene in archival tumor specimens (5 years ago) of 62 cases of NSCLC. Statistical significance of the expression of Pokemon mRNA and protein was determined in the tumor tissue, the tumor adjacent tissue and the surrounding tissue (PPokemon was determined not to be associated with the patients' sex, age, smoking condition, tumor differentiation degree, histology and lymph node metastasis condition. However, its relationship with TNM staging was established (PPokemon expression was significantly higher than that of those with positive Pokemon expression (P=0.004), therefore, the expression of Pokemon is believed to be an independent factor affecting prognosis (P=0.034). Pokemon was over-expressed in NSCLC tissue and the expression of Pokemon might be of clinical significance in non-small cell lung cancer prognostic evaluation.

Prevalence, characterization and clinical significance of Klebsiella pneumoniae carbapenemase (KPC producing Klebsiella pneumoniae

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: Sarita Nayak, Suman Singh, Soeb Jankhwala, Riddhi Pradhan

2014-11-01

Full Text Available Klebsiella peumoniae, a capsulated gram negative bacillus is responsible for causing life threatening infections in humans. Carbapenems are the drug of choice for serious infection caused by multidrug resistant Klebsiella pneumoniae. The emergence of carbapenem resistance has made it extremely difficult to treat such infections resulting in significant morbidity and mortality. Aims: To study the prevalence of carbapenem resistance using ertapenem as a marker and to detect Klebsiella pneumoniae Carbapenemase (KPC producing Klebsiella pneumoniae as a mechanism of resistance. Material and Methods: The study included 102 patients from which Klebsiella pneumoniae isolated. Identification and antibiotic susceptibility testing of Klebsiella pneumoniae was performed on miniAPI (Analytical Profile Index, Semiautomated bacterial identification system according to Clinical and Laboratory Standards Institute (CLSI guidelines of 2011. The modified Hodge test was performed for detection of Carbapenemase production. Patient’s clinical and demographic details along with risk factors and co-morbid conditions, type of response to antimicrobial therapy and mortality were collected. Results: The prevalence of carbapenem resistance was found to be 30.41% with 16.6% KPC producing Klebsiella pneumoniae. The co-morbid conditions like immunocompromised state (p =0.042, prior antibiotics therapy (p=0.047, previous hospitalization (p =0.021, intensive care unit stay (p=0.047 and use of indwelling devices (p =0.013 were found to be significantly associated with carbapenem resistance. Adverse clinical outcomes (death or worsening among patients infected with ertapenem resistant patients was found to be statistically significant than ertapenem sensitive strains (p =0.008. Conclusions: A high degree of carbapenem resistance in present study is alarming and poses therapeutic dilemmas for clinicians. Initiating timely and appropriate infection control measures along with a

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

DEFF Research Database (Denmark)

Stensvold, Christen Rune; Nielsen, Susanne Dam; Badsberg, Jens Henrik

2011-01-01

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 e...

Clinical significance of serum neuropeptide Y levels changes in chronic obstructive pulmonary diseases

International Nuclear Information System (INIS)

Jin Yuanhong; Pan Jiongwei; Cao Zhuo; Ji Naijun

2004-01-01

Objective: To study the clinical significance of serum neuropeptide Y level changes in patients with chronic obstructive pulmonary diseases (COPD). Methods: The serum neuropeptide Y levels were determined by radioimmunoassay in 40 patients with chronic obstructive pulmonary diseases (COPD) and 30 patients without COPD. Results: Mean serum neuropeptide Y level in patients with COPD was significantly higher than that in patients without COPD (130.36 ± 20.58 pg/ml vs 86.62 ± 13.02 pg/ml; t=10.201, p<0.01). Moreover, the levels in patients of the different stages (I, II, III) of COPD were significantly different from one another (F=20.334, p<0.01). Conclusion: the serum neuropeptide Y levels increased significantly in patients with COPD and were correlated to the different disease stages

Magnetic resonance: safety measures and biological effects

International Nuclear Information System (INIS)

Gordillo, I.; Lafuente, J.; Fernandez, C.; Barbero, M.J.; Cascon, E.

1997-01-01

The biological effects of electromagnetic fields is currently a subject of great controversy. For this reason, magnetic resonance imaging (MRI) and spectroscopy are constantly under investigation. The source of the risk in MRI is associated with the three types of electromagnetic radiation to which the patient is exposed: the static magnetic field, variable (gradient) magnetic fields and radiofrequency fields. Each is capable of producing significant biological effects when employed at sufficient intensity. Patients exposed to risk sources are those situated within the lines of force of the magnetic field, ellipsoid lines that are arranged around the magnet, representing the strength of the surrounding field. To date, at the intensity normally utilized in MRI(<2T) and respecting the field limit recommendations established by the US Food and Drug Administration (FDA) for clinical use of this technique no adverse secondary biological effects have been reported. The known biological effects and other possible secondary effects are reviewed, and the recommended safety measures are discussed. (Author)

Effect of postmortem sampling technique on the clinical significance of autopsy blood cultures.

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Hove, M; Pencil, S D

1998-02-01

Our objective was to investigate the value of postmortem autopsy blood cultures performed with an iodine-subclavian technique relative to the classical method of atrial heat searing and antemortem blood cultures. The study consisted of a prospective autopsy series with each case serving as its own control relative to subsequent testing, and a retrospective survey of patients coming to autopsy who had both autopsy blood cultures and premortem blood cultures. A busy academic autopsy service (600 cases per year) at University of Texas Medical Branch Hospitals, Galveston, Texas, served as the setting for this work. The incidence of non-clinically relevant (false-positive) culture results were compared using different methods for collecting blood samples in a prospective series of 38 adult autopsy specimens. One hundred eleven adult autopsy specimens in which both postmortem and antemortem blood cultures were obtained were studied retrospectively. For both studies, positive culture results were scored as either clinically relevant or false positives based on analysis of the autopsy findings and the clinical summary. The rate of false-positive culture results obtained by an iodine-subclavian technique from blood drawn soon after death were statistically significantly lower (13%) than using the classical method of obtaining blood through the atrium after heat searing at the time of the autopsy (34%) in the same set of autopsy subjects. When autopsy results were compared with subjects' antemortem blood culture results, there was no significant difference in the rate of non-clinically relevant culture results in a paired retrospective series of antemortem blood cultures and postmortem blood cultures using the iodine-subclavian postmortem method (11.7% v 13.5%). The results indicate that autopsy blood cultures obtained using the iodine-subclavian technique have reliability equivalent to that of antemortem blood cultures.

Antenatal Sonographic Diagnosis and Clinical Significance of Placenta Previa Accreta after Cesarean Section.

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Liu, Zhen-Zhen; Wei, Yao; Wang, Ruo-Jiao; Xu, Wen; Shi, Zhi-Min; Dai, Qing

2017-10-30

Objective To investigate the clinical and antenatal sonographic characteristics of placenta previa accreta after cesarean section. Methods The data of 21 inpatients diagnosed as placenta previa accreta after cesarean section in PUMC Hospital from 2006 to 2016 were retrospectively reviewed. The clinical and ultrasound features were recorded and compared among three placental accreta groups,including placenta accrete group(n=5),increta group(n=12),and percreta group(n=4). The relationship between the placental thickness at the uterine anterior lower segment level and the blood loss of the following cesarean section was tested. Results Of 21 patients,placenta previa was diagnosed by ultrasound in 20 cases(95.2%) and placenta previa accreta was diagnosed in 9 cases(42.9%). Antenatal ultrasound findings included following signs:loss of "clear zone"(15/18,83.3%),myometrial thinning(12/18,66.7%),abnormal placental lacunae(12/19,63.2%),bladder wall interruption(2/18,11.1%),and uterovesical hypervascularity(4/9,44.4%). Myometrial thinning(J-T=64.000,P=0.036),abnormal placental lacunae(J-T=74.500,P=0.032) and the placental thickness at the uterine anterior lower segment level(U=83.000,P=0.010) showed significant difference among different placenta accreta groups. Placental thickness at the uterine anterior lower segment level showed linear correlation with the blood loss of the following cesarean section(r=0.669,P=0.002). The blood loss of the following cesarean section showed significant difference among different placenta accreta groups(U=118.500,P=0.000). Conclusions The clinical and sonographic manifestations of placenta previa accreta after cesarean section show a spectrum of demographic characteristics. The measurement of thickness of placenta at the anterior lower segment may help the evaluation of the clinical prognosis of this special pathology.

Stereotactic Body Radiotherapy for Oligometastasis: Opportunities for Biology to Guide Clinical Management.

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Correa, Rohann J M; Salama, Joseph K; Milano, Michael T; Palma, David A

2016-01-01

Oligometastasis refers to a state of limited metastatic disease burden, in which surgical or ablative treatment to all known visible metastases holds promise to extend survival or even effect cure. Stereotactic body radiotherapy is a form of radiation treatment capable of delivering a high biologically effective dose of radiation in a highly conformal manner, with a favorable toxicity profile. Enthusiasm for oligometastasis ablation, however, should be counterbalanced against the limited supporting evidence. It remains unknown to what extent (if any) ablation influences survival or quality of life. Rising clinical equipoise necessitates the completion of randomized controlled trials to assess this, several of which are underway. However, a lack of clear identification criteria or biomarkers to define the oligometastatic state hampers optimal patient selection.This narrative review explores the evolutionary origins of oligometastasis, the steps of the metastatic process at which oligometastases may arise, and the biomolecular mediators of this state. It discusses clinical outcomes with treatment of oligometastases, ongoing trials, and areas of basic and translational research that may lead to novel biomarkers. These efforts should provide a clearer, biomolecular definition of oligometastatic disease and aid in the accurate selection of patients for ablative therapies.

The clinical significance of neutrophilic pleocytosis in cerebrospinal fluid in patients with viral central nervous system infections

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Siraya Jaijakul

2017-06-01

Conclusions: The results of a study exploring the association between CSF neutrophilic pleocytosis and clinical and prognostic significance are presented here. This study suggests that CSF neutrophilic pleocytosis is not associated with higher adverse clinical outcomes.

Phospholipids in Milk Fat: Composition, Biological and Technological Significance, and Analytical Strategies

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Giovanna Contarini

2013-01-01

Full Text Available Glycerophospholipids and sphingolipids are quantitatively the most important phospholipids (PLs in milk. They are located on the milk fat globule membrane (MFGM and in other membranous material of the skim milk phase. They include principally phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol and phosphatidylserine, while sphingomyelin is the dominant species of sphingolipids There is considerable evidence that PLs have beneficial health effects, such as regulation of the inflammatory reactions, chemopreventive and chemotherapeutic activity on some types of cancer, and inhibition of the cholesterol absorption. PLs show good emulsifying properties and can be used as a delivery system for liposoluble constituents. Due to the amphiphilic characteristics of these molecules, their extraction, separation and detection are critical points in the analytical approach. The extraction by using chloroform and methanol, followed by the determination by high pressure liquid chromatography (HPLC, coupled with evaporative light scattering (ELSD or mass detector (MS, are the most applied procedures for the PL evaluation. More recently, nuclear magnetic resonance spectrometry (NMR was also used, but despite it demonstrating high sensitivity, it requires more studies to obtain accurate results. This review is focused on milk fat phospholipids; their composition, biological activity, technological properties, and significance in the structure of milk fat. Different analytical methodologies are also discussed.

MIBG avidity correlates with clinical features, tumor biology, and outcomes in neuroblastoma: A report from the Children's Oncology Group.

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DuBois, Steven G; Mody, Rajen; Naranjo, Arlene; Van Ryn, Collin; Russ, Douglas; Oldridge, Derek; Kreissman, Susan; Baker, David L; Parisi, Marguerite; Shulkin, Barry L; Bai, Harrison; Diskin, Sharon J; Batra, Vandana; Maris, John M; Park, Julie R; Matthay, Katherine K; Yanik, Gregory

2017-11-01

Prior studies suggest that neuroblastomas that do not accumulate metaiodobenzylguanidine (MIBG) on diagnostic imaging (MIBG non-avid) may have more favorable features compared with MIBG avid tumors. We compared clinical features, biologic features, and clinical outcomes between patients with MIBG nonavid and MIBG avid neuroblastoma. Patients had metastatic high- or intermediate-risk neuroblastoma and were treated on Children's Oncology Group protocols A3973 or A3961. Comparisons of clinical and biologic features according to MIBG avidity were made with chi-squared or Fisher exact tests. Event-free (EFS) and overall (OS) survival compared using log-rank tests and modeled using Cox models. Thirty of 343 patients (8.7%) had MIBG nonavid disease. Patients with nonavid tumors were less likely to have adrenal primary tumors (34.5 vs. 57.2%; P = 0.019), bone metastases (36.7 vs. 61.7%; P = 0.008), or positive urine catecholamines (66.7 vs. 91.0%; P neuroblastoma have lower rates of adrenal primary tumors, bone metastasis, and catecholamine secretion. Despite being more likely to have MYCN-amplified tumors, these patients have superior outcomes compared with patients with MIBG avid disease. © 2017 Wiley Periodicals, Inc.

The clinical significance of perivalvular pannus in prosthetic mitral valves: Can cardiac CT be helpful?

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Chang, Suyon; Suh, Young Joo; Han, Kyunghwa; Kim, Jin Young; Kim, Young Jin; Chang, Byung-Chul; Choi, Byoung Wook

2017-12-15

The clinical significance of pannus in the prosthetic mitral valve (MV) is not well documented. To investigate the clinical significance of pannus on cardiac computed tomography (CT) in patients with a prosthetic MV. A total of 130 patients with previous MV replacement who underwent cardiac CT were retrospectively included in this study. The presence of pannus, paravalvular leak (PVL) around the prosthetic MV and limitation of motion (LOM) of the MV were analyzed using CT. Between patients with MV pannus and those without pannus, CT, echocardiographic, and redo-surgery findings were compared. The diagnostic performance of CT and transesophageal echocardiography (TEE) for the detection of MV pannus was also compared, using surgical findings as a standard reference. MV pannus was observed on cardiac CT in 32.3% of the study population. Patients with MV pannus detected on CT more commonly had LOM (28.2% vs. 15.2%) and less frequently had PVL of the prosthetic MV (16.7% vs. 25%) than patients without MV pannus (P>0.05). Prosthetic valve obstruction (PVO) due prosthetic MV pannus requiring redo-surgery was present in only five patients (11.9%). Cardiac CT detected MV pannus with sensitivity of 65.2% and specificity of 80.9% and showed better diagnostic performance than TEE (Ppannus can frequently be seen on cardiac CT. However, its clinical significance should be assessed with careful consideration, because PVO due to MV pannus is relatively uncommon, and pannus can be seen in patients without any clinical problems. Copyright © 2017 Elsevier B.V. All rights reserved.

BRCA1 and BRCA2 genetic testing—pitfalls and recommendations for managing variants of uncertain clinical significance

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Eccles, D. M.; Mitchell, G.; Monteiro, A. N. A.; Schmutzler, R.; Couch, F. J.; Spurdle, A. B.; Gómez-García, E. B.

2015-01-01

BackgroundIncreasing use of BRCA1/2 testing for tailoring cancer treatment and extension of testing to tumour tissue for somatic mutation is moving BRCA1/2 mutation screening from a primarily prevention arena delivered by specialist genetic services into mainstream oncology practice. A considerable number of gene tests will identify rare variants where clinical significance cannot be inferred from sequence information alone. The proportion of Variants of Uncertain clinical Significance (VUS) ...

Third Jesús Culebras Lecture: Molecular Biology and Clinical Nutrition; ¿where do we stand and where do we go?

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Gil, Ángel

2013-01-01

Nutrition plays a fundamental role in the maintenance of health and the treatment of disease, and serves as the crossroads for many disciplines. Biochemistry and Molecular Biology represents a key brand of science to ascertain the mechanism of action of nutrients and other food bioactive compounds in health and disease. The aim of the present Jesús M. Culebras lecture is to consider the future of the relationships between Molecular Biology and Clinical Nutrition and to discuss the use of mole...

Biological, medicinal and toxicological significance of Eucalyptus leaf essential oil: a review.

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Dhakad, Ashok K; Pandey, Vijay V; Beg, Sobia; Rawat, Janhvi M; Singh, Avtar

2018-02-01

The genus Eucalyptus L'Heritier comprises about 900 species, of which more than 300 species contain volatile essential oil in their leaves. About 20 species, within these, have a high content of 1,8-cineole (more than 70%), commercially used for the production of essential oils in the pharmaceutical and cosmetic industries. However, Eucalyptus is extensively planted for pulp, plywood and solid wood production, but its leaf aromatic oil has astounding widespread biological activities, including antimicrobial, antiseptic, antioxidant, chemotherapeutic, respiratory and gastrointestinal disorder treatment, wound healing, and insecticidal/insect repellent, herbicidal, acaricidal, nematicidal, and perfumes, soap making and grease remover. In the present review, we have made an attempt to congregate the biological ingredients of leaf essential oil, leaf oil as a natural medicine, and pharmacological and toxicological values of the leaf oil of different Eucalyptus species worldwide. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

A Personalized Approach to Biological Therapy Using Prediction of Clinical Response Based on MRP8/14 Serum Complex Levels in Rheumatoid Arthritis Patients.

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S C Nair

Full Text Available Measurement of MRP8/14 serum levels has shown potential in predicting clinical response to different biological agents in rheumatoid arthritis (RA. We aimed to develop a treatment algorithm based on a prediction score using MRP8/14 measurements and clinical parameters predictive for response to different biological agents.Baseline serum levels of MRP8/14 were measured in 170 patients starting treatment with infliximab, adalimumab or rituximab. We used logistic regression analysis to develop a predictive score for clinical response at 16 weeks. MRP8/14 levels along with clinical variables at baseline were investigated. We also investigated how the predictive effect of MRP8/14 was modified by drug type. A treatment algorithm was developed based on categorizing the expected response per drug type as high, intermediate or low for each patient and optimal treatment was defined. Finally, we present the utility of using this treatment algorithm in clinical practice.The probability of response increased with higher baseline MRP8/14 complex levels (OR = 1.39, differentially between the TNF-blockers and rituximab (OR of interaction term = 0.78, and also increased with higher DAS28 at baseline (OR = 1.28. Rheumatoid factor positivity, functional disability (a higher HAQ, and previous use of a TNF-inhibitor decreased the probability of response. Based on the treatment algorithm 80 patients would have been recommended for anti-TNF treatment, 8 for rituximab, 13 for another biological treatment (other than TNFi or rituximab and for 69 no recommendation was made. The predicted response rates matched the observed response in the cohort well. On group level the predicted response based on the algorithm resulted in a modest 10% higher response rate in our cohort with much higher differences in response probability in individual patients treated contrary to treatment recommendation.Prediction of response using MRP8/14 levels along with clinical predictors has

The clinical significance of lung hypoexpansion in acute childhood asthma

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Spottswood, Stephanie E.; Allison, Kelley Z.; Narla, Lakshmana D.; Lowry, Patricia A.; Lopatina, Olga A.; Sethi, Narinder N.; Nettleman, Mary D.

2004-01-01

Many children experiencing acute asthmatic episodes have chest radiographs, which may show lung hyperinflation, hypoinflation, or normal inflation. Lung hypoinflation may be a sign of respiratory fatigue and poor prognosis. To compare the clinical course in children with asthma according to the degree of lung inflation on chest radiographs. We conducted a retrospective study during a 24-month period (from July 1999 to July 2001) of children aged 0-17 years, who presented to a pediatric emergency department or outpatient clinic with an asthma exacerbation. Chest radiographs obtained at presentation were reviewed independently by three pediatric radiologists who were blinded to the admission status of the patient. The correlation between hypoinflation and hospital admission was assessed in three age groups: 0-2 years, 3-5 years, and 6-17 years. Hypoinflation on chest radiographs was significantly correlated with hospital admission for children aged 6-17 years (odds ratio 16.00, 95% confidence interval 1.89-135.43). The inter-reader agreement for interpretation of these radiographs was strong, with a kappa score of 0.76. Hypoinflation was not correlated with admission in younger children. Lung hypoinflation is associated with a greater likelihood of hospital admission in children aged 6 years or older. Therefore, hypoinflation was a poor prognostic sign and may warrant more aggressive therapy. (orig.)

The clinical significance of lung hypoexpansion in acute childhood asthma

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Spottswood, Stephanie E. [Department of Radiology, Medical College of Virginia, Virginia Commonwealth University Health System, Box 980615, 23298-0615, Richmond, VA (United States); Department of Radiology, The Children' s Hospital of the King' s Daughters, 601 Children' s Lane, Norfolk, VA 23507 (United States); Allison, Kelley Z.; Narla, Lakshmana D.; Lowry, Patricia A. [Department of Radiology, Medical College of Virginia, Virginia Commonwealth University Health System, Box 980615, 23298-0615, Richmond, VA (United States); Lopatina, Olga A.; Sethi, Narinder N. [School of Medicine, Medical College of Virginia, Virginia Commonwealth University Health System, Richmond, VA (United States); Nettleman, Mary D. [Department of Internal Medicine, B-427 Clinical Center, Michigan State University, East Lansing, MI 48824 (United States)

2004-04-01

Many children experiencing acute asthmatic episodes have chest radiographs, which may show lung hyperinflation, hypoinflation, or normal inflation. Lung hypoinflation may be a sign of respiratory fatigue and poor prognosis. To compare the clinical course in children with asthma according to the degree of lung inflation on chest radiographs. We conducted a retrospective study during a 24-month period (from July 1999 to July 2001) of children aged 0-17 years, who presented to a pediatric emergency department or outpatient clinic with an asthma exacerbation. Chest radiographs obtained at presentation were reviewed independently by three pediatric radiologists who were blinded to the admission status of the patient. The correlation between hypoinflation and hospital admission was assessed in three age groups: 0-2 years, 3-5 years, and 6-17 years. Hypoinflation on chest radiographs was significantly correlated with hospital admission for children aged 6-17 years (odds ratio 16.00, 95% confidence interval 1.89-135.43). The inter-reader agreement for interpretation of these radiographs was strong, with a kappa score of 0.76. Hypoinflation was not correlated with admission in younger children. Lung hypoinflation is associated with a greater likelihood of hospital admission in children aged 6 years or older. Therefore, hypoinflation was a poor prognostic sign and may warrant more aggressive therapy. (orig.)

Clinical significance of bone age estimation

International Nuclear Information System (INIS)

Heinrich, U.E.

1986-01-01

Skeletal development is an important maturity indicator during childhood. In clinical practice determination of skeletal age is helpful for the diagnosis of disorders of growth and development. Most hormones have specific effects on skeletal maturation. Thus, different disease states (growth disorders, disorders of pubertal development, chornic disorders of the bowels, kidneys, heart etc.) are characterized by retardation or acceleration of skeletal maturation. Therapeutic effects as well as side effects of hormones can be monitored by skeletal age determination. Typical disharmonic patterns in the appearance of bone centres of hand and wrist have been found in certain disorders of development. (orig.) [de

Clinical significance of lymph node metastasis in gastric cancer

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Deng, Jing-Yu; Liang, Han

2014-01-01

Gastric cancer, one of the most common malignancies in the world, frequently reveals lymph node, peritoneum, and liver metastases. Most of gastric cancer patients present with lymph node metastasis when they were initially diagnosed or underwent surgical resection, which results in poor prognosis. Both the depth of tumor invasion and lymph node involvement are considered as the most important prognostic predictors of gastric cancer. Although extended lymphadenectomy was not considered a survival benefit procedure and was reported to be associated with high mortality and morbidity in two randomized controlled European trials, it showed significant superiority in terms of lower locoregional recurrence and disease related deaths compared to limited lymphadenectomy in a 15-year follow-up study. Almost all clinical investigators have reached a consensus that the predictive efficiency of the number of metastatic lymph nodes is far better than the extent of lymph node metastasis for the prognosis of gastric cancer worldwide, but other nodal metastatic classifications of gastric cancer have been proposed as alternatives to the number of metastatic lymph nodes for improving the predictive efficiency for patient prognosis. It is still controversial over whether the ratio between metastatic and examined lymph nodes is superior to the number of metastatic lymph nodes in prognostic evaluation of gastric cancer. Besides, the negative lymph node count has been increasingly recognized to be an important factor significantly associated with prognosis of gastric cancer. PMID:24744586

Molecular Imaging in Synthetic Biology, and Synthetic Biology in Molecular Imaging.

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Gilad, Assaf A; Shapiro, Mikhail G

2017-06-01

Biomedical synthetic biology is an emerging field in which cells are engineered at the genetic level to carry out novel functions with relevance to biomedical and industrial applications. This approach promises new treatments, imaging tools, and diagnostics for diseases ranging from gastrointestinal inflammatory syndromes to cancer, diabetes, and neurodegeneration. As these cellular technologies undergo pre-clinical and clinical development, it is becoming essential to monitor their location and function in vivo, necessitating appropriate molecular imaging strategies, and therefore, we have created an interest group within the World Molecular Imaging Society focusing on synthetic biology and reporter gene technologies. Here, we highlight recent advances in biomedical synthetic biology, including bacterial therapy, immunotherapy, and regenerative medicine. We then discuss emerging molecular imaging approaches to facilitate in vivo applications, focusing on reporter genes for noninvasive modalities such as magnetic resonance, ultrasound, photoacoustic imaging, bioluminescence, and radionuclear imaging. Because reporter genes can be incorporated directly into engineered genetic circuits, they are particularly well suited to imaging synthetic biological constructs, and developing them provides opportunities for creative molecular and genetic engineering.

Linking MedDRA®-coded Clinical Phenotypes to Biological Mechanisms by The Ontology of Adverse Events: A pilot study on Tyrosine Kinase Inhibitors (TKIs)

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Sarntivijai, Sirarat; Zhang, Shelley; Jagannathan, Desikan G.; Zaman, Shadia; Burkhart, Keith K.; Omenn, Gilbert S.; He, Yongqun; Athey, Brian D.; Abernethy, Darrell R.

2016-01-01

Introduction A translational bioinformatics challenge lies in connecting population and individual’s clinical phenotypes in various formats to biological mechanisms. The Medical Dictionary for Regulatory Activities (MedDRA®) is the default dictionary for Adverse Event (AE) reporting in the FDA Adverse Event Reporting System (FAERS). The Ontology of Adverse Events (OAE) represents AEs as pathological processes occurring after drug exposures. Objectives The aim is to establish a semantic framework to link biological mechanisms to phenotypes of AEs by combining OAE with MedDRA® in FAERS data analysis. We investigated the AEs associated with Tyrosine Kinase Inhibitors (TKIs) and monoclonal antibodies (mAbs) targeting tyrosine kinases. The selected 5 TKIs/mAbs (i.e., dasatinib, imatinib, lapatinib, cetuximab, and trastuzumab) are known to induce impaired ventricular function (non-QT) cardiotoxicity. Results Statistical analysis of FAERS data identified 1,053 distinct MedDRA® terms significantly associated with TKIs/mAbs, where 884 did not have corresponding OAE terms. We manually annotated these terms, added them to OAE by the standard OAE development strategy, and mapped them to MedDRA®. The data integration to provide insights into molecular mechanisms for drug-associated AEs is performed by including linkages in OAE for all related AE terms to MedDRA® and existing ontologies including Human Phenotype Ontology (HP), Uber Anatomy Ontology (UBERON), and Gene Ontology (GO). Sixteen AEs are shared by all 5 TKIs/mAbs, and each of 17 cardiotoxicity AEs was associated with at least one TKI/mAb. As an example, we analyzed ‘cardiac failure’ using the relations established in OAE with other ontologies, and demonstrated that one of the biological processes associated with cardiac failure maps to the genes associated with heart contraction. Conclusion By expanding existing OAE ontological design, our TKI use case demonstrates that the combination of OAE and Med

Linking MedDRA(®)-Coded Clinical Phenotypes to Biological Mechanisms by the Ontology of Adverse Events: A Pilot Study on Tyrosine Kinase Inhibitors.

Science.gov (United States)

Sarntivijai, Sirarat; Zhang, Shelley; Jagannathan, Desikan G; Zaman, Shadia; Burkhart, Keith K; Omenn, Gilbert S; He, Yongqun; Athey, Brian D; Abernethy, Darrell R

2016-07-01

A translational bioinformatics challenge exists in connecting population and individual clinical phenotypes in various formats to biological mechanisms. The Medical Dictionary for Regulatory Activities (MedDRA(®)) is the default dictionary for adverse event (AE) reporting in the US Food and Drug Administration Adverse Event Reporting System (FAERS). The ontology of adverse events (OAE) represents AEs as pathological processes occurring after drug exposures. The aim of this work was to establish a semantic framework to link biological mechanisms to phenotypes of AEs by combining OAE with MedDRA(®) in FAERS data analysis. We investigated the AEs associated with tyrosine kinase inhibitors (TKIs) and monoclonal antibodies (mAbs) targeting tyrosine kinases. The five selected TKIs/mAbs (i.e., dasatinib, imatinib, lapatinib, cetuximab, and trastuzumab) are known to induce impaired ventricular function (non-QT) cardiotoxicity. Statistical analysis of FAERS data identified 1053 distinct MedDRA(®) terms significantly associated with TKIs/mAbs, where 884 did not have corresponding OAE terms. We manually annotated these terms, added them to OAE by the standard OAE development strategy, and mapped them to MedDRA(®). The data integration to provide insights into molecular mechanisms of drug-associated AEs was performed by including linkages in OAE for all related AE terms to MedDRA(®) and the existing ontologies, including the human phenotype ontology (HP), Uber anatomy ontology (UBERON), and gene ontology (GO). Sixteen AEs were shared by all five TKIs/mAbs, and each of 17 cardiotoxicity AEs was associated with at least one TKI/mAb. As an example, we analyzed "cardiac failure" using the relations established in OAE with other ontologies and demonstrated that one of the biological processes associated with cardiac failure maps to the genes associated with heart contraction. By expanding the existing OAE ontological design, our TKI use case demonstrated that the combination

Potentials of single-cell biology in identification and validation of disease biomarkers.

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Niu, Furong; Wang, Diane C; Lu, Jiapei; Wu, Wei; Wang, Xiangdong

2016-09-01

Single-cell biology is considered a new approach to identify and validate disease-specific biomarkers. However, the concern raised by clinicians is how to apply single-cell measurements for clinical practice, translate the message of single-cell systems biology into clinical phenotype or explain alterations of single-cell gene sequencing and function in patient response to therapies. This study is to address the importance and necessity of single-cell gene sequencing in the identification and development of disease-specific biomarkers, the definition and significance of single-cell biology and single-cell systems biology in the understanding of single-cell full picture, the development and establishment of whole-cell models in the validation of targeted biological function and the figure and meaning of single-molecule imaging in single cell to trace intra-single-cell molecule expression, signal, interaction and location. We headline the important role of single-cell biology in the discovery and development of disease-specific biomarkers with a special emphasis on understanding single-cell biological functions, e.g. mechanical phenotypes, single-cell biology, heterogeneity and organization of genome function. We have reason to believe that such multi-dimensional, multi-layer, multi-crossing and stereoscopic single-cell biology definitely benefits the discovery and development of disease-specific biomarkers. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Tumor significant dose

International Nuclear Information System (INIS)

Supe, S.J.; Nagalaxmi, K.V.; Meenakshi, L.

1983-01-01

In the practice of radiotherapy, various concepts like NSD, CRE, TDF, and BIR are being used to evaluate the biological effectiveness of the treatment schedules on the normal tissues. This has been accepted as the tolerance of the normal tissue is the limiting factor in the treatment of cancers. At present when various schedules are tried, attention is therefore paid to the biological damage of the normal tissues only and it is expected that the damage to the cancerous tissues would be extensive enough to control the cancer. Attempt is made in the present work to evaluate the concent of tumor significant dose (TSD) which will represent the damage to the cancerous tissue. Strandquist in the analysis of a large number of cases of squamous cell carcinoma found that for the 5 fraction/week treatment, the total dose required to bring about the same damage for the cancerous tissue is proportional to T/sup -0.22/, where T is the overall time over which the dose is delivered. Using this finding the TSD was defined as DxN/sup -p/xT/sup -q/, where D is the total dose, N the number of fractions, T the overall time p and q are the exponents to be suitably chosen. The values of p and q are adjusted such that p+q< or =0.24, and p varies from 0.0 to 0.24 and q varies from 0.0 to 0.22. Cases of cancer of cervix uteri treated between 1978 and 1980 in the V. N. Cancer Centre, Kuppuswamy Naidu Memorial Hospital, Coimbatore, India were analyzed on the basis of these formulations. These data, coupled with the clinical experience, were used for choice of a formula for the TSD. Further, the dose schedules used in the British Institute of Radiology fraction- ation studies were also used to propose that the tumor significant dose is represented by DxN/sup -0.18/xT/sup -0.06/

Clinical significance of atypical squamous cells of undetermined significance in detecting preinvasive cervical lesions in post- menopausal Turkish women.

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Tokmak, Aytekin; Guzel, Ali Irfan; Ozgu, Emre; Oz, Murat; Akbay, Serap; Erkaya, Salim; Gungor, Tayfun

2014-01-01

To evaluate the clinical significance of atypical squamous cells of undetermined significance (ASCUS) in PAP test in post-menopausal women and compare with reproductive age women. A total of 367 patients who referred to our gynecologic oncology clinic were included to the study between September 2012 and August 2013. Data for 164 post-menopausal (group 1) and 203 pre-menopausal (group 2) women with ASCUS cytology were evaluated retrospectively. Immediate colposcopy and endocervical curettage was performed for both groups and conization for all women with a result suggestive of CIN2-3. Histopathological results and demographic features of patients were compared between the two groups. Mean age of the patients was 54.6±6.5 years in group 1 and 38±6.6 years in group 2. Some 14 (8.5%) of post- menopausal women and 36 (17.7%) of pre-menopausal women were current smokers (p=011). Totals of 38 (23.2%) post-menopausal and 64 (31.5%) pre-menopausal women were assessed for HPV-DNA. High risk HPV was detected in 7 (4.3%) and 21 (10.3%), respectively (p=0.029). Final histopathological results recorded were normal cervix, low grade cervical intra-epithelial neoplasia (CIN 1), and high grade cervical intra-epithelial neoplasia (CIN2-3). In group 1 results were 84.8%, 12.2% and 1.8%, respectively, and in group 2 were 71.9%, 23.2% and 4.9%. There were no cases of micro invasive or invasive cervical carcinoma in either group. Two cases were detected as endometrial carcinoma in the menopausal group (1.2%). In current study we found that preinvasive lesions were statistically significantly higher in pre-menopausal women than post- menopausal women with ASCUS. Cervicitis was more common in menopausal women. Therefore, we think that in case of ASCUS in a post-menopausal woman there is no need for radical management.

Clinical significance of measurements of serum IL-6 levels in patients with cardiovascular and cerebrovascular diseases

International Nuclear Information System (INIS)

Wu Cuihua; Luo Nanping; Zhang Daojie; Wei Hong

2004-01-01

Objective: To explore the clinical significance of changes of serum IL-6 levels in patients with cardiovascular and cerebrovascular diseases. Methods: Serum IL-6 levels were determined with RIA in 35 patients with coronary heart disease, 20 patients with essential hypertension, 28 patients with cerebral infarction and 30 controls. Results: Serum IL-6 levels in patients with coronary heart disease and cerebral infarction were significantly higher than those in the controls (P 0.05). Conclusion: Serum IL-6 levels changes could reflect the severity of the inflammatory process and would be helpful in clinical assessment. (authors)

Clinical significance of determination of serum BGP levels in patients with Graves' disease

International Nuclear Information System (INIS)

Tu Liping; Zhang Chunyan; Wang Linglong; Yu Yuefang; Zhu Weijie; Cai Ao

2006-01-01

Objective: To study the clinical significance of changes of serum BGP levels in patients with Graves' disease. Methods: Serum BOP levels as well as T 3 , T 4 , FT 3 , FT 4 , TSH, TGA, TMA levels were determined with RIA in 158 patients with Graves' disease and 145 controls. Results: The serum BGP levels in patients with Graves' disease were significantly higher than those in controls (P 3 , T 4 , FT 3 , FT 4 levels, but not with TSH, TGA, TMA. Conclusion: Serum BGP levels is a useful marker for monitoring bone metabolism in patients with Graves' disease. (authors)

Molecular biology of breast cancer stem cells: potential clinical applications.

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Nguyen, Nam P; Almeida, Fabio S; Chi, Alex; Nguyen, Ly M; Cohen, Deirdre; Karlsson, Ulf; Vinh-Hung, Vincent

2010-10-01

Breast cancer stem cells (CSC) have been postulated recently as responsible for failure of breast cancer treatment. The purpose of this study is to review breast CSCs molecular biology with respect to their mechanism of resistance to conventional therapy, and to develop treatment strategies that may improve survival of breast cancer patients. A literature search has identified in vitro and in vivo studies of breast CSCs. Breast CSCs overexpress breast cancer resistance protein (BCRP) which allows cancer cells to transport actively chemotherapy agents out of the cells. Radioresistance is modulated through activation of Wnt signaling pathway and overexpression of genes coding for glutathione. Lapatinib can selectively target HER-2 positive breast CSCs and improves disease-free survival in these patients. Metformin may target basal type breast CSCs. Parthenolide and oncolytic viruses are promising targeting agents for breast CSCs. Future clinical trials for breast cancer should include anti-cancer stem cells targeting agents in addition to conventional chemotherapy. Hypofractionation radiotherapy may be indicated for residual disease post chemotherapy. 2010 Elsevier Ltd. All rights reserved.

Clinical significance of white matter hyperintensities in MRI in senile dementia of the Alzheimer type

International Nuclear Information System (INIS)

Takita, Masashi

1996-01-01

To elucidate clinical significance of white matter hyperintensities (WMH) in MRI, fifty patients with senile dementia of the Alzheimer type (SDAT) and twenty normal controls were studied. Twenty nine patients with SDAT (58.0%) had periventricular hyperintensities (PVH) and twenty three patients with SDAT (46.0%) had deep white matter hyperintensities (DWMH). Eight controls (40.0%) had PVH and ten controls (50.0%) had DWMH. There were no significant differences in frequency of WMH between patients with SDAT and normal controls. Past history of hypertension was more frequent in patients with PVH or DWMH than in patients without them. Serum cholesterol level was higher in patients with DWMH than in patients without them. However there were no significant differences in the other clinical features between patients with WMH and patients without them. The results of present study suggest that DWMH in patients with SDAT is associated with cerebrovascular risk factors such as hypertension and hyperlipidemia. (author)

Clinical significance of high-sensitivity C- reactive protein in systemic sclerosis

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T. A. Nevskaya

2007-01-01

Full Text Available Objective. To determine diagnostic and prognostic significance of high-sensitivity Creactive protein (hsCRP in systemic sclerosis (SS, to define relationship of this factor with activity of the disease and cardiovascular pathology, to assess role of pro-inflammatory cytokines in induction of acute phase proteins synthesis in SS.Material and methods. Serum levels of hsCRP, interleukin (IL 6, IL 1β, IL1ra, IL 10, sIL2r were evaluated by enzyme immunoassay (EIA in 40 pts with SS and 24 subjects of control group. Relationship with clinical features of the disease, endothelial dysfunction, capillaries structure changes, sub-clinical atherosclerosis, total coronary risk and some traditional cardiovascular risk factors was analyzed. Instrumental assessment included nailfold capillaroscopy, sonographic duplex examination of carotids , brachial arte ry sonographic examination. HsCRP prognostic significance was assessed in 51 pts with SS.Results. Elevated levels of hsCRP were found in 32% of SS pts and correlated with activity and severity of the disease, HAQ and SHAQ. Direct correlation of hsCRP with skin fibrosis distribution, interstitial lung disease, arthritis, laboratory indices of SS activity (ESR, sIL2r and Scl-70 was revealed. HsCRP concentration in SS did not depend on character and intensity of cardiovascular pathology, subclinical atherosclerosis, endothelial dysfunction and proinflammatory cytokines production.Conclusion. HsCRP in SS reflects intensity of immuno-inflammatory process, correlates with T-cell activation markers and can be used as index of the disease activity, severity of skin and lung fibrosis.

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

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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.

Levels and clinical significance of serum IGF-II in patients with five kinds of malignant tumors

International Nuclear Information System (INIS)

Qi Falian; Xu Jun; Du Xiumin; Ke Bingkun; Yang Daoli

2002-01-01

Objective: To study the levels and clinical significance of serum IGF-II in patients with malignant tumor. Methods: Levels of serum IGF-II were detected in patients with gastric cancer, lung cancer, liver cancer, ovarian carcinoma and endometrial carcinoma by radioimmunoassay, levels in patients with hepatic cirrhosis, uterine myoma and normal controls were also determined for comparison. Results: The levels of serum IGF-II in patients with gastric cancer, lung cancer and liver cancer were significantly higher than those in normal controls (p 0.05). Conclusion: The determination of serum IGF-II has no clinical significance in patients with endometrial carcinoma, ovarian carcinoma and uterine myoma but it could be useful to judge the severity and evaluate the prognosis in patients with gastric cancer, lung cancer, liver cancer and cirrhosis

CLINICAL AND FUNCTIONAL ASSESSMENT OF THE BIOLOGICAL PROSTHESIS “ASPIRE” FOR SURGICAL CORRECTION OF MITRAL VALVE DISEASE

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S. G. Esin

2015-01-01

Full Text Available Aim: To assess clinical and functional efficacy of implanted biological prosthesis “ASPIRE” (manufactured by Vascutek for correction of mitral valve disease.Materials and methods: From October 2008 to December 2013, biological prostheses “ASPIRE” (Vascutek were implanted to 34 patients with mitral valve disease (mean age 63.59 ± 4.96 years, 79.4% female. From these, 24 patients had mitral stenosis and 10 patients had mitral insufficiency. 73.5% of all patients had heart failure Strazhesko-Vasilenko IIA grade and 85.3% of patients had chronic heart failure NYHA III. Isolated mitral valve replacement was performed only in 8 (23.5% of patients. In 22 (64.7% of cases mitral valve replacement was combined with tricuspid valvuloplasty in various modifications. Duration of cardiopulmonary bypass and of aortic clamping was 88.09 ± 25.95 and 65.68 ± 25.51 minutes, respectively. Before and after surgery all patients underwent echocardiographic assessment and clinical assessment of their general status.Results: In-hospital mortality was 5.88% (n = 2 and was related to multiorgan failure in the early postoperative period. All 32 (94.12% surviving patients improved with decrease or complete disappearance of heart failure. Postoperative complications were typical for cardiac surgery. There were no episodes of embolism, structural dysfunction, thrombosis of the prosthesis and endocarditis of the prosthesis in the early postoperative period. Pressure gradients across prosthetic valves were not high and corresponded to good clinical and hemodynamic results in the early postoperative period.Conclusion: Taking into account good immediate results of mitral valve replacement, as well as no need in lifelong anticoagulation in patients with multiple concomitant disorders, implantation of the biological prosthesis “ASPIRE” (Vascutek could become a procedure of choice for correction of valve abnormalities in patients above 65 years. For more comprehensive

Study of the Clinical Proton Beam Relative Biological Effectiveness at the JINR Phasotron, Dubna

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Vitanova, A; Gaevskii, V N; Molokonov, A G; Spurny, F; Fadeeva, T A; Shmakova, N L

2002-01-01

Proton clinical beams contain particles with high linear energy transfer (LET). Secondary heavy charged particles produced from nuclear interactions and degraded protons at the Bragg peak region are particles with high LET. These particles could enhance the Relative Biological Effectiveness (RBE) of the proton beam. We have carried out two radiobiological experiments to investigate the RBE of 150 MeV clinical proton beam. The irradiation of the Chinese Hamster V79 cells were performed at two points of the depth-dose distribution - at the beam entrance and at the Bragg peak. The contribution of the high LET particles to dosimetric and microdosimetric characteristics in the various depth of proton beam was also experimentally studied using the CR-39 track etched detectors. The LET spectra between 10 and 700 keV/{\\mu}m were measured by means of track detectors and the automatic optical image analyzer LUCIA-II. The relative contribution of the high LET particles to ab! sorbed dose increases from several per cent ...

Is synthetic biology mechanical biology?

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Holm, Sune

2015-12-01

A widespread and influential characterization of synthetic biology emphasizes that synthetic biology is the application of engineering principles to living systems. Furthermore, there is a strong tendency to express the engineering approach to organisms in terms of what seems to be an ontological claim: organisms are machines. In the paper I investigate the ontological and heuristic significance of the machine analogy in synthetic biology. I argue that the use of the machine analogy and the aim of producing rationally designed organisms does not necessarily imply a commitment to mechanical biology. The ideal of applying engineering principles to biology is best understood as expressing recognition of the machine-unlikeness of natural organisms and the limits of human cognition. The paper suggests an interpretation of the identification of organisms with machines in synthetic biology according to which it expresses a strategy for representing, understanding, and constructing living systems that are more machine-like than natural organisms.

Childhood exposure to violence and lifelong health: Clinical intervention science and stress biology research join forces

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Moffitt, Terrie E.

2013-01-01

Many young people who are mistreated by an adult, victimized by bullies, criminally assaulted, or who witness domestic violence react to this violence exposure by developing behavioral, emotional, or learning problems. What is less well known is that adverse experiences like violence exposure can lead to hidden physical alterations inside a child’s body, alterations which may have adverse effects on life-long health. We discuss why this is important for the field of developmental psychopathology and for society, and we recommend that stress-biology research and intervention science join forces to tackle the problem. We examine the evidence base in relation to stress-sensitive measures for the body (inflammatory reactions, telomere erosion, epigenetic methylation, and gene expression) and brain (mental disorders, neuroimaging, and neuropsychological testing). We also review promising interventions for families, couples, and children that have been designed to reduce the effects of childhood violence exposure. We invite intervention scientists and stress-biology researchers to collaborate in adding stress-biology measures to randomized clinical trials of interventions intended to reduce effects of violence exposure and other traumas on young people. PMID:24342859

Uncovering biologically significant lipid isomers with liquid chromatography, ion mobility spectrometry and mass spectrometry

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Kyle, Jennifer E.; Zhang, Xing; Weitz, Karl K.; Monroe, Matthew E.; Ibrahim, Yehia M.; Moore, Ronald J.; Cha, Jeeyeon; Sun, Xiaofei; Lovelace, Erica S.; Wagoner, Jessica; Polyak, Steve; Metz, Thomas O.; Dey, Sudhansu K.; Smith, Richard D.; Burnum-Johnson, Kristin E.; Baker, Erin Shammel

2016-01-01

Understanding how biological molecules are generated, metabolized and eliminated in living systems is important for interpreting processes such as immune response and disease pathology. While genomic and proteomic studies have provided vast amounts of information over the last several decades, interest in lipidomics has also grown due to improved analytical technologies revealing altered lipid metabolism in type 2 diabetes, cancer, and lipid storage disease. Liquid chromatography and mass spectrometry (LC-MS) measurements are currently the dominant approach for characterizing the lipidome by providing detailed information on the spatial and temporal composition of lipids. However, interpreting lipids’ biological roles is challenging due to the existence of numerous structural and stereoisomers (i.e. distinct acyl chain and double-bond positions), which are unresolvable using present LC-MS approaches. Here we show that combining structurally-based ion mobility spectrometry (IMS) with LC-MS measurements distinguishes lipid isomers and allows insight into biological and disease processes.

Acrophialophora, a Poorly Known Fungus with Clinical Significance

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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

The expression of microRNA-324-3p as a tumor suppressor in nasopharyngeal carcinoma and its clinical significance

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Zhang H

2017-10-01

Full Text Available Han-qun Zhang,1,* Yi Sun,1,* Jian-quan Li,2,3,* Li-min Huang,1 Shi-sheng Tan,1 Fei-yue Yang,1 Hang Li1 1Department of Oncology, Guizhou Provincial People’s Hospital, Guizhou, People’s Republic of China; 2Institute for Cell and Molecular Biosciences, Newcastle University, Framlington Place, Newcastle upon Tyne, UK; 3Department of Intensive Care Unit, Guizhou Provincial People’s Hospital, Guizhou, People’s Republic of China *These authors contributed equally to this work Objective: This study aimed to determine the expression, clinical significance, and possible biologic function of microRNA-324-3p in nasopharyngeal carcinoma (NPC tissues.Methods: In total, 54 NPC and 35 control tissues were collected. The correlation between miR-324-3p expression and the clinicopathologic characteristics was analyzed. A dual-luciferase reporter gene assay was employed to examine the predicted target gene of miR-324-3p. The miR-324-3p expression level in 5–8F cells was determined with quantitative reverse transcription-polymerase chain reaction following the transfection of miR-324-3p mimics and inhibitors. Cell proliferation and the percentage of apoptosis were measured with MTT and flow cytometry. Cell invasion ability was assessed by Transwell invasion assay.Results: Our results showed that miR-324-3p was downregulated in the NPC tissues. The expression level of miR-324-3p in poorly differentiated NPC was significantly reduced in comparison with that in well/moderately differentiated NPC. The expression level in clinical stages III/IV was lower than that in clinical stages I/II. Moreover, the expression level of miR-324-3p was significantly lower in NPC patients with lymph node metastasis than that in NPC patients without lymph node metastasis. NPC patients with higher levels of miR-324-3p expression also demonstrated a longer survival time. Predictions from bioinformatics indicated the Hedgehog pathway transcription gene GLI3 as the target gene of

Childhood-compared to adolescent-onset bipolar disorder has more statistically significant clinical correlates.

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Holtzman, Jessica N; Miller, Shefali; Hooshmand, Farnaz; Wang, Po W; Chang, Kiki D; Hill, Shelley J; Rasgon, Natalie L; Ketter, Terence A

2015-07-01

The strengths and limitations of considering childhood-and adolescent-onset bipolar disorder (BD) separately versus together remain to be established. We assessed this issue. BD patients referred to the Stanford Bipolar Disorder Clinic during 2000-2011 were assessed with the Systematic Treatment Enhancement Program for BD Affective Disorders Evaluation. Patients with childhood- and adolescent-onset were compared to those with adult-onset for 7 unfavorable bipolar illness characteristics with replicated associations with early-onset patients. Among 502 BD outpatients, those with childhood- (adolescent- (13-18 years, N=218) onset had significantly higher rates for 4/7 unfavorable illness characteristics, including lifetime comorbid anxiety disorder, at least ten lifetime mood episodes, lifetime alcohol use disorder, and prior suicide attempt, than those with adult-onset (>18 years, N=174). Childhood- but not adolescent-onset BD patients also had significantly higher rates of first-degree relative with mood disorder, lifetime substance use disorder, and rapid cycling in the prior year. Patients with pooled childhood/adolescent - compared to adult-onset had significantly higher rates for 5/7 of these unfavorable illness characteristics, while patients with childhood- compared to adolescent-onset had significantly higher rates for 4/7 of these unfavorable illness characteristics. Caucasian, insured, suburban, low substance abuse, American specialty clinic-referred sample limits generalizability. Onset age is based on retrospective recall. Childhood- compared to adolescent-onset BD was more robustly related to unfavorable bipolar illness characteristics, so pooling these groups attenuated such relationships. Further study is warranted to determine the extent to which adolescent-onset BD represents an intermediate phenotype between childhood- and adult-onset BD. Copyright © 2015 Elsevier B.V. All rights reserved.

Expression of tumor necrosis factor receptor-associated protein 1 and its clinical significance in kidney cancer.

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Si, Tong; Yang, Guosheng; Qiu, Xiaofu; Luo, Youhua; Liu, Baichuan; Wang, Bingwei

2015-01-01

To investigate the expression and clinical significance of TRAP1 (tumor necrosis factor receptor-associated protein 1) in kidney cancer. TRAP1 expression was detected in kidney cancer and normal kidney tissues by qRT-PCR and immunohistochemistry (IHC), respectively. Then, the correlation of TRAP1 expression with clinicopathological characters and patients' prognosis was evaluated in kidney cancer. IHC results revealed that the high-expression rates of TRAP1 in kidney cancer tissues and normal kidney tissues were 51.3% (41/80), 23.3% (7/30), and the difference was statistically significant (P=0.01). Also, TRAP1 mRNA level in kidney cancer was found to be significantly greater compared with those in normal kidney by qRT-PCR. In addition, TRAP1 expression in kidney cancer significantly correlated with lymph node metastasis and clinical stage (Pkidney cancer and correlates with patients prognosis, which may be served as a potential marker for the diagnosis and treatment of kidney cancer.

Clinically significant fatigue: prevalence and associated factors in an international sample of adults with multiple sclerosis recruited via the internet.

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Tracey J Weiland

Full Text Available Fatigue contributes a significant burden of disease for people with multiple sclerosis (PwMS. Modifiable lifestyle factors have been recognized as having a role in a range of morbidity outcomes in PwMS. There is significant potential to prevent and treat fatigue in PwMS by addressing modifiable risk factors.To explore the associations between clinically significant fatigue and demographic factors, clinical factors (health-related quality of life, disability and relapse rate and modifiable lifestyle, disease-modifying drugs (DMD and supplement use in a large international sample of PwMS.PwMS were recruited to the study via Web 2.0 platforms and completed a comprehensive survey measuring demographic, lifestyle and clinical characteristics, including health-related quality of life, disability, and relapse rate.Of 2469 participants with confirmed MS, 2138 (86.6% completed a validated measure of clinically significant fatigue, the Fatigue Severity Scale. Participants were predominantly female from English speaking countries, with relatively high levels of education, and due to recruitment methods may have been highly pro-active about engaging in lifestyle management and self-help. Approximately two thirds of our sample (1402/2138; 65.6% (95% CI 63.7-67.7 screened positive for clinically significant fatigue. Bivariate associations were present between clinically significant fatigue and several demographic, clinical, lifestyle, and medication variables. After controlling for level of disability and a range of stable socio-demographic variables, we found increased odds of fatigue associated with obesity, DMD use, poor diet, and reduced odds of fatigue with exercise, fish consumption, moderate alcohol use, and supplementation with vitamin D and flaxseed oil.This study supports strong and significant associations between clinically significant fatigue and modifiable lifestyle factors. Longitudinal follow-up of this sample may help clarify the contribution

The Widespread Prevalence and Functional Significance of Silk-Like Structural Proteins in Metazoan Biological Materials.

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Carmel McDougall

Full Text Available In nature, numerous mechanisms have evolved by which organisms fabricate biological structures with an impressive array of physical characteristics. Some examples of metazoan biological materials include the highly elastic byssal threads by which bivalves attach themselves to rocks, biomineralized structures that form the skeletons of various animals, and spider silks that are renowned for their exceptional strength and elasticity. The remarkable properties of silks, which are perhaps the best studied biological materials, are the result of the highly repetitive, modular, and biased amino acid composition of the proteins that compose them. Interestingly, similar levels of modularity/repetitiveness and similar bias in amino acid compositions have been reported in proteins that are components of structural materials in other organisms, however the exact nature and extent of this similarity, and its functional and evolutionary relevance, is unknown. Here, we investigate this similarity and use sequence features common to silks and other known structural proteins to develop a bioinformatics-based method to identify similar proteins from large-scale transcriptome and whole-genome datasets. We show that a large number of proteins identified using this method have roles in biological material formation throughout the animal kingdom. Despite the similarity in sequence characteristics, most of the silk-like structural proteins (SLSPs identified in this study appear to have evolved independently and are restricted to a particular animal lineage. Although the exact function of many of these SLSPs is unknown, the apparent independent evolution of proteins with similar sequence characteristics in divergent lineages suggests that these features are important for the assembly of biological materials. The identification of these characteristics enable the generation of testable hypotheses regarding the mechanisms by which these proteins assemble and direct the

Sex as a Biological Variable: Who, What, When, Why, and How.

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Bale, Tracy L; Epperson, C Neill

2017-01-01

The inclusion of sex as a biological variable in research is absolutely essential for improving our understanding of disease mechanisms contributing to risk and resilience. Studies focusing on examining sex differences have demonstrated across many levels of analyses and stages of brain development and maturation that males and females can differ significantly. This review will discuss examples of animal models and clinical studies to provide guidance and reference for the inclusion of sex as an important biological variable relevant to a Neuropsychopharmacology audience.

Retention Esophagitis as a Significant Clinical Predictor of Progression to Esophageal Cancer in Achalasia

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Haewon Kim

2018-03-01

Full Text Available Background/Aims Chronic liquid and/or food stasis caused by retention esophagitis (RE in achalasia is a notable endoscopic finding because of the presence of a thickened or whitish esophageal mucosa and histologically altered squamous hyperplasia. We aimed to identify the clinical features of RE associated with achalasia and to clarify the clinical definition of RE in achalasia as a precancerous lesion identified by analyzing biomarker expressions. Methods From 2006 to 2015, we retrospectively reviewed 37 patients with achalasia without previous treatment. Among them, 21 patients had diagnostic findings of RE (RE+ and 16 patients had no diagnostic findings of RE (RE–. Immunohistochemical staining of p53, p16, and Ki-67 was performed on the endoscopic biopsy tissues from the patients with achalasia and 10 control patients with non-obstructive dysphagia. Results The symptom duration and transit delay were significantly longer in the RE+ group than in the RE– group. We found particularly high p53 positivity rates in the RE+ group (p<0.001. The rate of p16 expression was also significantly higher in the RE+ group than in the other two groups (p=0.003. Conclusions A high p53 expression rate was more frequently found in the RE+ group than in the other two groups. RE could be a meaningful clinical feature of achalasia for predicting esophageal carcinogenesis.

Clinical phenotypes and the biological parameters of Congolese patients suffering from sickle cell anemia: A first report from Central Africa.

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Mikobi, Tite M; Lukusa Tshilobo, Prosper; Aloni, Michel N; Akilimali, Pierre Z; Mvumbi-Lelo, Georges; Mbuyi-Muamba, Jean Marie

2017-11-01

The influence of phenotype on the clinical course and laboratory features of sickle cell anemia (SCA) is rarely described in sub-Saharan Africa. A cross-sectional study was conducted in Kinshasa. A clinical phenotype score was built up. The following definitions were applied: asymptomatic clinical phenotype (ACP; score≤5), moderate clinical phenotype (MCP; score between 6 and 15), and severe clinical phenotype (SCP; score≥16). ANOVA test were used to compare differences among categorical variables. We have studied 140 patients. The mean body mass index (BMI) value of three groups was lower (Sickle cell patients with ACP have a high mean steady-state hemoglobin concentration compared to those with MCP and SCP (Psickle cell anemia clinical and biological variability in our midst. © 2017 Wiley Periodicals, Inc.

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

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Koffi N. Maglo

2016-02-01

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

Theileriosis in six dogs in South Africa and its potential clinical significance

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Chantal T. Rosa

2014-08-01

Full Text Available Theileriosis is a tick-borne disease caused by a piroplasma of the genus Theileria that can causeanaemia and thrombocytopenia. Its clinical importance for dogs’ remains poorly understood,as only some develop clinical signs. In this study, physical and laboratory findings, treatment and outcomes of six client-owned diseased dogs presented at the Onderstepoort Veterinary Academic Hospital are described retrospectively. In the dogs, Theileria species (n = 4and Theileria equi (n = 2 were detected by a polymerase chain reaction (PCR-reverse blothybridisation assay in blood samples, whilst PCR for Babesia, Anaplasma and Ehrlichia were negative. The most common physical findings were pale mucous membranes (five out of six dogs, bleeding tendencies (five out of six dogs and lethargy (three out of six dogs. All dogs were thrombocytopenic [median 59.5 x 109/L (range 13–199] and five out of six dogs were anaemic [median haematocrit 18% (range 5–32]. Bone marrow core biopsies performed in two dogs showed myelofibrosis. Theileriosis was treated with imidocarb dipropionate and the suspected secondary immune-mediated haematological disorders with prednisolone and azathioprine. Five dogs achieved clinical cure and post-treatment PCR performed in three out of five dogs confirmed absence of circulating parasitaemia. An immune-mediated response to Theileria species is thought to result in anaemia and/or thrombocytopenia in diseased dogs with theileriosis. A bleeding tendency, most likely secondary to thrombocytopenia and/or thrombocytopathy, was the most significant clinical finding in these cases. The link between thrombocytopenia, anaemia and myelofibrosis in theileriosis requires further investigation and theileriosis should be considered a differential diagnosis for dogs presenting with anaemia and/or thrombocytopenia in endemic tick-borne disease areas.

A randomised comparative study of the short term clinical and biological effects of intravenous pulse methylprednisolone and infliximab in patients with active rheumatoid arthritis despite methotrexate treatment.

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Durez, P; Nzeusseu Toukap, A; Lauwerys, B R; Manicourt, D H; Verschueren, P; Westhovens, R; Devogelaer, J-P; Houssiau, F A

2004-09-01

To compare the short term clinical and biological effects of intravenous (i.v.) pulse methylprednisolone (MP) and infliximab (IFX) in patients with severe active rheumatoid arthritis (RA) despite methotrexate (MTX) treatment. Patients with active RA despite MTX treatment were randomly allocated to receive a single i.v. infusion of MP (1 g) or three i.v. infusions of IFX (3 mg/kg) on weeks 0, 2, and 6. Patients were "blindly" evaluated for disease activity measures. Quality of life (QoL) was evaluated through the SF-36 health survey. Serum matrix metalloproteinase-3 (MMP-3) titres were measured at baseline, weeks 2 and 6. Compared with baseline, significant improvement was noted in all activity measures, including serum C reactive protein (CRP) titres, in the IFX group only. At week 14, 6/9 (67%) and 4/9 (44%) IFX patients met the ACR20 and 50 response criteria, while this was the case in only 1/12 (8%) and 0/12 (0%) MP patients, respectively (ptreatment, whereas some did so in the IFX group. Serum MMP-3 titres significantly decreased (41% drop) at week 6 in the IFX group, while no changes were seen in patients given MP. This short term randomised comparative study demonstrates that TNF blockade is better than MP pulse therapy in a subset of patients with severe refractory RA, with improvement in not only clinical parameters of disease activity but also biological inflammatory indices, such as serum CRP and MMP-3 titres.

Clinical significance of C-reactive protein for assessment and outcomes of severe acute pancreatitis

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REN Linan

2015-05-01

Full Text Available ObjectiveTo study the change in serum CRP level in patients with severe acute pancreatitis (SAP, and to explore its clinical significance in predicting outcomes and assessing the severity of SAP. MethodsA retrospective analysis was performed on 52 SAP patients with complete case data and admitted to General Hospital of Shenyang Military Area Command from September 2013 to September 2014. Blood drawing was performed and serum CRP concentration was determined on admission and at 24, 48, 72, 96, 120, and 144 hours after admission. The pattern of its dynamic change was observed. ResultsSerum CRP level in SAP patients significantly increased, and had a positive correlation with clinical outcomes. Forty-two cases (80.77% gradually recovered with aggressive treatment and the serum CRP levels were also slowly reduced (P＜0.05. The serum CRP levels in four death cases (7.7% had no significant decrease and was maintained at a high level (P＜0.05. Six patients (11.53% had aggravated conditions and recovered after aggressive treatment; meanwhile, the serum CRP levels first increased and then decreased (P＜0.05. ConclusionFor SAP patients, serum CRP level fluctuates as their conditions change and can be considered as an important reference index for evaluating the severity and judging the outcomes of SAP.

Elements determination of clinical relevance in biological tissues Dmdmdx/J dystrophic mice strains investigated by NAA

International Nuclear Information System (INIS)

Metairon, Sabrina

2012-01-01

In this work the determination of chemistry elements in biological tissues (whole blood, bones and organs) of dystrophic mice, used as animal model of Duchenne Muscular Dystrophy (DMD), was performed using analytical nuclear technique. The aim of this work was to determine reference values of elements of clinical (Ca, Cl, K, Mg, Na) and nutritional (Br and S) relevance in whole blood, tibia, quadriceps and hearts from Dmdmdx/J (10 males and 10 females) dystrophic mice and C57BL/6J (10 males) control group mice, using Neutron Activation Analysis technique (NAA). To show in more details the alterations that this disease may cause in these biological tissues, correlations matrixes of the DMD mdx /J mouse strain were generated and compared with C57BL/6J control group. For this study 119 samples of biological tissue were irradiated in the IEA-R1 nuclear reactor at IPEN (Sao Paulo, Brazil). The concentrations of these elements in biological tissues of Dmd mdx /J and C57B/6J mice are the first indicative interval for reference values. Moreover, the alteration in some correlation coefficients data among the elements in the health status and in the diseased status indicates a connection between these elements in whole blood, tibia, quadriceps and heart. These results may help the researchers to evaluate the efficiency of new treatments and to compare the advantages of different treatment approaches before performing tests in patients with muscular dystrophy. (author)

Clinical application and evaluation of the diagnostic significance of NMR-tomography

International Nuclear Information System (INIS)

Bielke, G.; Higer, P.

1987-01-01

Aim of the project was the clinical application and evaluation of the diagnostic significance of NMR-tomography. About 3 000 patients have been examined especially with diseases of the brain. In 75% of all cases pathological findings could be detected. A subgroup of these patients was used for comprehensive studies with regard to tissue characterization based on the calculation of relaxation time parameters. With methods of image processing and classification techniques we tried to get a clear correlation between combined NMR-parameters and human tissue types. The results show that this procedure is able to improve the detectibility and the association to finding groups and tumorgradings in certain cases. (orig./ECB) With 134 refs., 17 tabs., 86 figs [de

[Nutritional risk screening and its clinical significance in 706 children hospitalized in the surgical department].

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Peng, Lu-Ting; Li, Rong; Zhao, Wei-Hua; Chen, Yin-Hua; Li, Xiao-Mei; Chen, Meng-Ying; Cao, Jia; Li, Xiao-Nan

2013-10-01

To investigate nutritional risk and its relationship with clinical outcome in children hospitalized in the surgical department, and to provide a scientific basis for clinical nutrition management. Nutritional risk screening was performed on 706 children hospitalized in the surgical department using the Screening Tool for Risk on Nutritional Status and Growth. The data on nutritional support during hospitalization, incidence of infectious complications, length of hospital stay, post operative length of hospital stay and total hospital expenses were recorded. Of the 706 cases, 11.5% had high nutritional risk, 46.0% had moderate nutritional risk, and 42.5% had low nutritional risk. Congenital hypertrophic pyloric stenosis, intestinal obstruction and congenital heart disease were the three most common types of high nutritional risk. The incidence of high nutritional risk was significantly higher in infants than in other age groups (Pnutritional risk received parenteral nutrition. Children with high nutritional risk were significantly more likely to have weight loss than children with low nutritional risk (Pnutritional risk had significantly increased incidence of infectious complications, length of hospital stay, post operative length of hospital stay and total hospital expenses compared with those with moderate or low nutritional risk (Pnutritional risk is seen in children hospitalized in the surgical department. Nutritional risk score is correlated with clinical outcome. Nutritional support for these children is not yet properly provided. Nutritional risk screening and standard nutritional support should be widely applied among hospitalized children.

Clinical significance of hypoalbuminemia in outcome of patients with scrub typhus

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Kwon Keun-Sang

2010-07-01

Full Text Available Abstract Background This study was designed to investigate the clinical significance of hypoalbuminemia as a marker of severity and mortality in patients with Scrub typhus. Methods The patients with scrub typhus were divided into two groups based on the serum albumin levels; Group I (serum albumin Results Of the total 246 patients who underwent the study, 84 patients (34.1% were categorized as Group I and 162 patients were (65.9% as Group II. Group I showed significantly higher incidence of confusion (24.6% vs. 5.3%, p p = 0.002, pleural effusion (22.8% vs. 11.1%, p = 0.03, arrhythmia (12.3% vs. 2.6%, p = 0.008 and non-oliguric acute renal failure (40.4% vs. 11.1%, p p p = 0.012, and higher hospital cost compared to Group II. Conclusions This study showed hypoalbuminemia in scrub typhus was closely related to the frequency of various complication, longer hospital stay, consequently the higher medical cost, necessitating more efficient management of patients, including medical resources.

Anatomic and functional leg-length inequality: A review and recommendation for clinical decision-making. Part I, anatomic leg-length inequality: prevalence, magnitude, effects and clinical significance

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Knutson Gary A

2005-07-01

Full Text Available Abstract Background Leg-length inequality is most often divided into two groups: anatomic and functional. Part I of this review analyses data collected on anatomic leg-length inequality relative to prevalence, magnitude, effects and clinical significance. Part II examines the functional "short leg" including anatomic-functional relationships, and provides an outline for clinical decision-making. Methods Online database – Medline, CINAHL and MANTIS – and library searches for the time frame of 1970–2005 were done using the term "leg-length inequality". Results and Discussion Using data on leg-length inequality obtained by accurate and reliable x-ray methods, the prevalence of anatomic inequality was found to be 90%, the mean magnitude of anatomic inequality was 5.2 mm (SD 4.1. The evidence suggests that, for most people, anatomic leg-length inequality does not appear to be clinically significant until the magnitude reaches ~ 20 mm (~3/4". Conclusion Anatomic leg-length inequality is near universal, but the average magnitude is small and not likely to be clinically significant.

Measurement and Clinical Significance of Biomarkers of Oxidative Stress in Humans

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Ilaria Marrocco

2017-01-01

Full Text Available Oxidative stress is the result of the imbalance between reactive oxygen species (ROS formation and enzymatic and nonenzymatic antioxidants. Biomarkers of oxidative stress are relevant in the evaluation of the disease status and of the health-enhancing effects of antioxidants. We aim to discuss the major methodological bias of methods used for the evaluation of oxidative stress in humans. There is a lack of consensus concerning the validation, standardization, and reproducibility of methods for the measurement of the following: (1 ROS in leukocytes and platelets by flow cytometry, (2 markers based on ROS-induced modifications of lipids, DNA, and proteins, (3 enzymatic players of redox status, and (4 total antioxidant capacity of human body fluids. It has been suggested that the bias of each method could be overcome by using indexes of oxidative stress that include more than one marker. However, the choice of the markers considered in the global index should be dictated by the aim of the study and its design, as well as by the clinical relevance in the selected subjects. In conclusion, the clinical significance of biomarkers of oxidative stress in humans must come from a critical analysis of the markers that should give an overall index of redox status in particular conditions.

Deciphering cancer heterogeneity: the biological space

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Stephanie eRoessler

2014-04-01

Full Text Available Most lethal solid tumors including hepatocellular carcinoma (HCC are considered incurable due to extensive heterogeneity in clinical presentation and tumor biology. Tumor heterogeneity may result from different cells of origin, patient ethnicity, etiology, underlying disease and diversity of genomic and epigenomic changes which drive tumor development. Cancer genomic heterogeneity thereby impedes treatment options and poses a significant challenge to cancer management. Studies of the HCC genome have revealed that although various genomic signatures identified in different HCC subgroups share a common prognosis, each carries unique molecular changes which are linked to different sets of cancer hallmarks whose misregulation has been proposed by Hanahan and Weinberg to be essential for tumorigenesis. We hypothesize that these specific sets of cancer hallmarks collectively occupy different tumor biological space representing the misregulation of different biological processes. In principle, a combination of different cancer hallmarks can result in new convergent molecular networks that are unique to each tumor subgroup and represent ideal druggable targets. Due to the ability of the tumor to adapt to external factors such as treatment or changes in the tumor microenvironment, the tumor biological space is elastic. Our ability to identify distinct groups of cancer patients with similar tumor biology who are most likely to respond to a specific therapy would have a significant impact on improving patient outcome. It is currently a challenge to identify a particular hallmark or a newly emerged convergent molecular network for a particular tumor. Thus, it is anticipated that the integration of multiple levels of data such as genomic mutations, somatic copy number aberration, gene expression, proteomics, and metabolomics, may help us grasp the tumor biological space occupied by each individual, leading to improved therapeutic intervention and outcome.

BRCA1 and BRCA2 genetic testing—pitfalls and recommendations for managing variants of uncertain clinical significance

Science.gov (United States)

Eccles, D. M.; Mitchell, G.; Monteiro, A. N. A.; Schmutzler, R.; Couch, F. J.; Spurdle, A. B.; Gómez-García, E. B.

2015-01-01

Background Increasing use of BRCA1/2 testing for tailoring cancer treatment and extension of testing to tumour tissue for somatic mutation is moving BRCA1/2 mutation screening from a primarily prevention arena delivered by specialist genetic services into mainstream oncology practice. A considerable number of gene tests will identify rare variants where clinical significance cannot be inferred from sequence information alone. The proportion of variants of uncertain clinical significance (VUS) is likely to grow with lower thresholds for testing and laboratory providers with less experience of BRCA. Most VUS will not be associated with a high risk of cancer but a misinterpreted VUS has the potential to lead to mismanagement of both the patient and their relatives. Design Members of the Clinical Working Group of ENIGMA (Evidence-based Network for the Interpretation of Germline Mutant Alleles) global consortium (www.enigmaconsortium.org) observed wide variation in practices in reporting, disclosure and clinical management of patients with a VUS. Examples from current clinical practice are presented and discussed to illustrate potential pitfalls, explore factors contributing to misinterpretation, and propose approaches to improving clarity. Results and conclusion Clinicians, patients and their relatives would all benefit from an improved level of genetic literacy. Genetic laboratories working with clinical geneticists need to agree on a clinically clear and uniform format for reporting BRCA test results to non-geneticists. An international consortium of experts, collecting and integrating all available lines of evidence and classifying variants according to an internationally recognized system, will facilitate reclassification of variants for clinical use. PMID:26153499

Space radiation-induced bystander effect: kinetics of biologic responses, mechanisms, and significance of secondary radiations

International Nuclear Information System (INIS)

Gonon, Geraldine

2011-01-01

Widespread evidence indicates that exposure of cell cultures to a particles results in significant biological changes in both the irradiated and non-irradiated bystander cells in the population. The induction of non-targeted biological responses in cell cultures exposed to low fluences of high charge (Z) and high energy (E) particles is relevant to estimates of the health risks of space radiation and to radiotherapy. Here, we investigated the mechanisms underlying the induction of stressful effects in confluent normal human fibroblast cultures exposed to low fluences of 1000 MeV/u iron ions (linear energy transfer (LET) 151 keV/μm), 600 MeV/u silicon ions (LET 50 keV/μm) or 290 MeV/u carbon ions (LET 13 keV/μm). We compared the results with those obtained in cell cultures exposed, in parallel, to low fluences of 0.92 MeV/u a particles (LET 109 keV/μm). Induction of DNA damage, changes in gene expression, protein carbonylation and lipid peroxidation during 24 h after exposure of confluent cultures to mean doses as low as 0.2 cGy of iron or silicon ions strongly supported the propagation of stressful effects from irradiated to bystander cells. At a mean dose of 0.2 cGy, only 1 and 3 % of the cells would be targeted through the nucleus by an iron or silicon ion, respectively. Within 24 h post-irradiation, immunoblot analyses revealed significant increases in the levels of phospho-TP53 (serine 15), p21Waf1 (also known as CDKN1A), HDM2, phospho-ERK1/2, protein carbonylation and lipid peroxidation. The magnitude of the responses suggested participation of non-targeted cells in the response. Furthermore, when the irradiated cell populations were subcultured in fresh medium shortly after irradiation, greater than expected increases in the levels of these markers were also observed during 24 h. Together, the results imply a rapidly propagated and persistent bystander effect. In situ analyses in confluent cultures showed 53BP1 foci formation, a marker of DNA damage, in

Biological and Clinical Aspects of an Olive Oil-Based Lipid Emulsion—A Review

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Wei Cai

2018-06-01

Full Text Available Intravenous lipid emulsions (ILEs have been an integral component of parenteral nutrition for more than 50 years. Numerous formulations are available and are based on vegetable (soybean, olive, coconut and animal (fish oils. Therefore, each of these formulations has a unique fatty acid composition that offers both benefits and limitations. As clinical experience and our understanding of the effects of fatty acids on various physiological processes has grown, there is evidence to suggest that some ILEs may have benefits compared with others. Current evidence suggests that olive oil-based ILE may preserve immune, hepatobiliary, and endothelial cell function, and may reduce lipid peroxidation and plasma lipid levels. There is good evidence from a large randomized controlled study to support a benefit of olive oil-based ILE over soybean oil-based ILE on reducing infections in critically ill patients. At present there is limited evidence to demonstrate a benefit of olive oil-based ILE over other ILEs on glucose metabolism, and few data exist to demonstrate a benefit on clinical outcomes such as hospital or intensive care unit stay, duration of mechanical ventilation, or mortality. We review the current research and clinical evidence supporting the potential positive biological and clinical aspects of olive oil-based ILE and conclude that olive oil-based ILE is well tolerated and provides effective nutritional support to various PN-requiring patient populations. Olive oil-based ILE appears to support the innate immune system, is associated with fewer infections, induces less lipid peroxidation, and is not associated with increased hepatobiliary or lipid disturbances. These data would suggest that olive oil-based ILE is a valuable option in various PN-requiring patient populations.

Thresholds for statistical and clinical significance in systematic reviews with meta-analytic methods

DEFF Research Database (Denmark)

Jakobsen, Janus Christian; Wetterslev, Jorn; Winkel, Per

2014-01-01

BACKGROUND: Thresholds for statistical significance when assessing meta-analysis results are being insufficiently demonstrated by traditional 95% confidence intervals and P-values. Assessment of intervention effects in systematic reviews with meta-analysis deserves greater rigour. METHODS......: Methodologies for assessing statistical and clinical significance of intervention effects in systematic reviews were considered. Balancing simplicity and comprehensiveness, an operational procedure was developed, based mainly on The Cochrane Collaboration methodology and the Grading of Recommendations...... Assessment, Development, and Evaluation (GRADE) guidelines. RESULTS: We propose an eight-step procedure for better validation of meta-analytic results in systematic reviews (1) Obtain the 95% confidence intervals and the P-values from both fixed-effect and random-effects meta-analyses and report the most...

Molecular biology - Part II: Beneficial liaisons: Radiobiology meets cellular and molecular biology

International Nuclear Information System (INIS)

Stevenson, Mary Ann; Coleman, C. Norman

1997-01-01

Purpose: The purpose of this course is to familiarize radiation oncologists with the concepts and terminology of molecular and cellular biology that are especially relevant to radiation oncology. The ability of radiation oncologists to remain current with the new discoveries of modern biology is essential to the development of improved therapeutic strategies and, importantly, to the proper balance between investment in technology and biology. Objective: This year, this Refresher Course is part of a three-part ''series'' including Drs. McKenna and Dritschilo. The objective is to provide continuing education for the academic and practicing radiation oncologist, physicist and biologist in the modern biologic concepts of cancer and its treatment. An effort will be made to relate these general concepts to the clinic by providing a broad view as to potential new biological treatments which might enhance the efficacy of radiation therapy. The specific focus of this Course will vary from year to year. Some of the classic radiation biology models which form the basis of clinical practice and laboratory research will be examined and 'newer' models will be presented which take into account the emerging knowledge of cellular and molecular biology. A few techniques in molecular and cellular biology will be described to the extent necessary to understand their basic concepts and their applicability. Aspects of radiation biology which will be covered include cell cycle, radiation-induced changes in the cellular phenotype, and considerations of the effect of the tumor microenvironment. It is not the expectation that the attendees will become experts in the particular subjects presented. Rather, it is the intent to increase their curiosity as to the new knowledge that is emerging and to demonstrate that these seemingly complicated areas can be understood and appreciated with a modicum of the effort

Molecular biology - Part II: Beneficial liaisons: Radiobiology meets cellular and molecular biology

International Nuclear Information System (INIS)

Stevenson, Mary Ann; Coleman, C. Norman

1996-01-01

Purpose: The purpose of this course is to familiarize radiation oncologists with the concepts and terminology of molecular and cellular biology that are especially relevant to radiation oncology. The ability of radiation oncologists to remain current with the new discoveries of modern biology is essential to the development of improved therapeutic strategies and, importantly, to the proper balance between investment in technology and biology. Objective: This year, this Refresher Course is part of a three-part 'series' including Drs. Martin Brown and Amato Giaccia. The objective is to provide continuing education for the academic and practicing radiation oncologist, physicist and biologist in the modern biologic concepts of cancer and its treatment. An effort will be made to relate these general concepts to the clinic by providing a broad view as to potential new biological treatments which might enhance the efficacy of radiation therapy. The specific focus of this Course will vary from year to year. Some of the classic radiation biology models which form the basis of clinical practice and laboratory research will be examined and 'newer' models will be presented which take into account the emerging knowledge of cellular and molecular biology. A few techniques in molecular and cellular biology will be described to the extent necessary to understand their basic concepts and their applicability. Aspects of radiation biology which will be covered include cell cycle, radiation-induced changes in the cellular phenotype, and considerations of the effect of the tumor microenvironment. It is not the expectation that the attendees will become experts in the particular subjects presented. Rather, it is the intent to increase their curiosity as to the new knowledge that is emerging and to demonstrate that these seemingly complicated areas can be understood and appreciated with a modicum of the effort

Evaluating the informatics for integrating biology and the bedside system for clinical research

Directory of Open Access Journals (Sweden)

Meystre Stéphane M

2009-10-01

Full Text Available Abstract Background Selecting patient cohorts is a critical, iterative, and often time-consuming aspect of studies involving human subjects; informatics tools for helping streamline the process have been identified as important infrastructure components for enabling clinical and translational research. We describe the evaluation of a free and open source cohort selection tool from the Informatics for Integrating Biology and the Bedside (i2b2 group: the i2b2 hive. Methods Our evaluation included the usability and functionality of the i2b2 hive using several real world examples of research data requests received electronically at the University of Utah Health Sciences Center between 2006 - 2008. The hive server component and the visual query tool application were evaluated for their suitability as a cohort selection tool on the basis of the types of data elements requested, as well as the effort required to fulfill each research data request using the i2b2 hive alone. Results We found the i2b2 hive to be suitable for obtaining estimates of cohort sizes and generating research cohorts based on simple inclusion/exclusion criteria, which consisted of about 44% of the clinical research data requests sampled at our institution. Data requests that relied on post-coordinated clinical concepts, aggregate values of clinical findings, or temporal conditions in their inclusion/exclusion criteria could not be fulfilled using the i2b2 hive alone, and required one or more intermediate data steps in the form of pre- or post-processing, modifications to the hive metadata, etc. Conclusion The i2b2 hive was found to be a useful cohort-selection tool for fulfilling common types of requests for research data, and especially in the estimation of initial cohort sizes. For another institution that might want to use the i2b2 hive for clinical research, we recommend that the institution would need to have structured, coded clinical data and metadata available that can be

Practical considerations in clinical strategy to support the development of injectable drug-device combination products for biologics.

Science.gov (United States)

Li, Zhaoyang; Easton, Rachael

2018-01-01

The development of an injectable drug-device combination (DDC) product for biologics is an intricate and evolving process that requires substantial investments of time and money. Consequently, the commercial dosage form(s) or presentation(s) are often not ready when pivotal trials commence, and it is common to have drug product changes (manufacturing process or presentation) during clinical development. A scientifically sound and robust bridging strategy is required in order to introduce these changes into the clinic safely. There is currently no single developmental paradigm, but a risk-based hierarchical approach has been well accepted. The rigor required of a bridging package depends on the level of risk associated with the changes. Clinical pharmacokinetic/pharmacodynamic comparability or outcome studies are only required when important changes occur at a late stage. Moreover, an injectable DDC needs to be user-centric, and usability assessment in real-world clinical settings may be required to support the approval of a DDC. In this review, we discuss the common issues during the manufacturing process and presentation development of an injectable DDC and practical considerations in establishing a clinical strategy to address these issues, including key elements of clinical studies. We also analyze the current practice in the industry and review relevant and status of regulatory guidance in the DDC field.

Radiation biology: a century of hopes and disappointments

International Nuclear Information System (INIS)

Singh, B.B.

1998-01-01

In the history of science, radiation biology will rank perhaps as the most popular subject to have attracted researchers from many disciplines of basic as well as applied sciences. Apart from the excitement arising in clinics relating to radiation treatment of cancers the tragedies in Hiroshima and Nagasaki brought numerous scientists together to investigate the harmful biological effects of ionizing radiation. It is then radiation biology picked up a great momentum. It started developing in two different directions what may be called basic radiation biology and radiation biology applied to radiotherapy of cancer. While great strides were being made in basic radiation biology trying to understand the biological effects of radiation and mechanisms thereof, clinical aspect remained confined mainly to the medical fraternity where empiricalism became the rule

Biological augmentation and tissue engineering approaches in meniscus surgery.

Science.gov (United States)

Moran, Cathal J; Busilacchi, Alberto; Lee, Cassandra A; Athanasiou, Kyriacos A; Verdonk, Peter C

2015-05-01

biochemical cues in this process, however, and it is hoped that this may lead to improvements in this strategy. There appears to be significant potential for biological augmentation and tissue engineering strategies in meniscus surgery to enhance options for repair and replacement. However, there are still relatively few clinical studies being reported in this regard. There is a strong need for improved translational activities and infrastructure to link the large amounts of in vitro and preclinical biological and tissue engineering data to clinical application. Level IV, systematic review of Level I-IV studies. Copyright © 2015 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Clinical significance of FLG gene mutations in children with atopic dermatitis

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E. E. Varlamov

2015-01-01

Full Text Available Skin barrier dysfunction due to deficiency of the skin protein filaggrin is one of the factors involved in the pathogenesis of atopic dermatitis. Objective: to determine the clinical significance of 2282 del CAGT, R501X, R2447X, and S3247X mutations in the FLG gene in children with atopic dermatitis. The investigation included 58 children with atopic dermatitis. A molecular genetic analysis of the four mutations in the FLG gene was done in all the children. In the patients with FLG gene mutations, there was a tendency towards a higher frequency of sensitization to house dust allergens, significantly more often sensitization to cat epidermal allergen, and significantly higher levels of specific IgE to the cat epidermis. Conclusion. Mutations in the FLG gene encoding the protein filaggrin raise the risk for sensitization to domestic and epidermal allergens and, in case of already existing sensitization to the cat epidermis, the patients are found with a high degree of probability to have the high concentration of specific IgE to this allergen. The above fact justifies the need to place special emphasis on measures to eliminate house dust allergens, and cat epidermis allergen in particular, and to personalize approaches to therapy and prevention of atopic dermatitis in children. 

Chemical and Biological Significance of Oenothein B and Related Ellagitannin Oligomers with Macrocyclic Structure

Directory of Open Access Journals (Sweden)

Takashi Yoshida

2018-03-01

Full Text Available In 1990, Okuda et al. reported the first isolation and characterization of oenothein B, a unique ellagitannin dimer with a macrocyclic structure, from the Oenothera erythrosepala leaves. Since then, a variety of macrocyclic analogs, including trimeric–heptameric oligomers have been isolated from various medicinal plants belonging to Onagraceae, Lythraceae, and Myrtaceae. Among notable in vitro and in vivo biological activities reported for oenothein B are antioxidant, anti-inflammatory, enzyme inhibitory, antitumor, antimicrobial, and immunomodulatory activities. Oenothein B and related oligomers, and/or plant extracts containing them have thus attracted increasing interest as promising targets for the development of chemopreventive agents of life-related diseases associated with oxygen stress in human health. In order to better understand the significance of this type of ellagitannin in medicinal plants, this review summarizes (1 the structural characteristics of oenothein B and related dimers; (2 the oxidative metabolites of oenothein B up to heptameric oligomers; (3 the distribution of oenotheins and other macrocyclic analogs in the plant kingdom; and (4 the pharmacological activities hitherto documented for oenothein B, including those recently found by our laboratory.

Differential expression patterns and clinical significance of estrogen receptor-α and β in papillary thyroid carcinoma

International Nuclear Information System (INIS)

Huang, Yanhong; Dong, Wenwu; Li, Jing; Zhang, Hao; Shan, Zhongyan; Teng, Weiping

2014-01-01

The incidence of papillary thyroid cancer (PTC) is markedly higher in women than men during the reproductive years. In vitro studies have suggested that estrogen may play an important role in the development and progression of PTC through estrogen receptors (ERs). This study aimed to investigate the expression patterns of the two main ER subtypes, α and β1 (wild-type ERβ), in PTC tissue and their clinical significance. Immunohistochemical staining of thyroid tissue sections was performed to detect ER expression in female patients with PTC (n = 89) and nodular thyroid goiter (NTG; n = 30) using the Elivision™ plus two-step system. The relationships between ER subtype expression and clinicopathological/biological factors were further analyzed. The positive percentage and expression levels of ERα were significantly higher in female PTC patients of reproductive age (18–45 years old; n = 50) than age-matched female NTG patients (n = 30), while ERβ1 exhibited the opposite pattern. There was no difference in ERα or ERβ1 expression between female PTC patients of reproductive age and those of advanced reproductive age (>45 years old; n = 39). In the female PTC patients of reproductive age, ERα expression level was positively correlated with that of Ki-67, while ERβ1 was negatively correlated with mutant P53. Furthermore, more patients with exclusively nuclear ERα expression had extrathyroidal extension (ETE) as compared with those with extranuclear ERα localization. VEGF expression was significantly decreased in female PTC patients of reproductive age with only nuclear ERβ1 expression when compared with those with extranuclear ERβ1 localization. In PTC patients of advanced reproductive age, neither ERα nor ERβ1 expression showed any correlation with that of Ki-67, mutant P53, VEGF, tumor size, TNM stage, ETE, or lymph node metastases. The differential expression patterns of the two ER subtypes between PTC and NTG indicate that ERα may be a useful

Clinical response to anti-TNFα therapy in patients with rheumatoid arthritis faulted or intolerance in non-biological DMARD in the Hospital San Juan de Dios in the period January 2006 to December 2011

International Nuclear Information System (INIS)

Salas Mena, Claudio

2014-01-01

Various clinical studies are performed globally using anti-TNFα therapy and has proven its clinical effectiveness in the management of rheumatoid arthritis patients, that have failed or have presented intolerance to the use of non-biological DMARDs. The clinical response to treatment of anti-TNFα was determined in patients with rheumatoid arthritis who have presented without respond, have showed intolerance or secondary effects to DMARDs no biological, in the Servicio de Reumatologia del Hospital San Juan de Dios, in the period January 2006 to December 2011. Study has been descriptive, retrospective, observational, by reviewing dossiers of patients with rheumatoid arthritis to initiate anti-TNFα therapy where has valued the DAS28 and initial VES, then at 6 months and 12 months after starting treatment. In the period analyzed, 47 patients evaluated with traditional DMARD failure who have received anti-TNFα therapy, according to DAS28, 32 patients were cataloged as severe activity and 15 of them with moderate activity. A total of 41 patients have used etanercept, with adalimumab 6 patients. The DAS28 initial average was 5,63 in all patients, 6,16 in the subgroup of patients with severe activity, and 4,49 in the subgroup of moderate activity. After 6 months of treatment, the DAS28 has descended to 3,25 in all patients, with 3,67 in the subgroup of severe clinical activity, and 2,35 in the subgroup of moderate clinical activity. One year after treatment values DAS28 have been 3,13 for all patients, 3,53 in severe activity and 2,28 in the subgroup of activity clinical moderate. In all groups and subgroups of patients, difference was demonstrated statistically significant at p less than 0,05. Between the subgroups of patients according to clinical activity is keeped without significant difference, or the type of anti-TNFα therapy employed. The anti-TNFα therapy has proven to be effective for improvement of clinical activity of rheumatoid arthritis, regardless of

About the significance of biological factors affecting pregnancy a married couple

Directory of Open Access Journals (Sweden)

V. V. Yarman

2013-01-01

Full Text Available A brief review of the literature analysis of the importance and interdependence of the main factors influencing the occurrence of pregnancy as a pair in the treatment of infertility, such as the woman's age, ovarian reserve, the semen of a man and the duration of infertility. The review also presents the data concerning the practical implications of sexual constitution and sexual maturation in men and women in the pubertal period. When evaluating male fertility invariably significant factor in the prediction of pregnancy are, impregnating ability to ejaculate. Infertility is more common in males with delayed development in the pubertal period with a weak type of sexual constitution. Results of treatment of male infertility, the dynamics of the semen and pregnancy of the couple on the background of pathogenetic therapy correlates with the type of sexual constitution. Widely deployed discussion about the existence of the male equivalent of female menopause mainly concerns the problems of men's sexual health. Of exceptional importance for the prediction of treatment of infertility has ovarian reserve, which is closely associated with age women. Formation of menstrual function occurs in the pubertal period of sexual development, in this age of menarche is the leading symptom of type of sexual constitution of women that do not change throughout the life hereafter. The presence of menstrual function and even ovulation does not reflect the reproductive capacity of women. Insufficient information content of the chronological age of a woman, as an indicator of the reproductive capacity of ovarian dictates the necessity of the development of tests that determine individual biological age of a woman, perhaps connected with the type of sexual constitution. In this regard, the study of sexual constitution partners is of great scientific and practical interest.

About the significance of biological factors affecting pregnancy a married couple

Directory of Open Access Journals (Sweden)

V. V. Yarman

2014-11-01

Full Text Available A brief review of the literature analysis of the importance and interdependence of the main factors influencing the occurrence of pregnancy as a pair in the treatment of infertility, such as the woman's age, ovarian reserve, the semen of a man and the duration of infertility. The review also presents the data concerning the practical implications of sexual constitution and sexual maturation in men and women in the pubertal period. When evaluating male fertility invariably significant factor in the prediction of pregnancy are, impregnating ability to ejaculate. Infertility is more common in males with delayed development in the pubertal period with a weak type of sexual constitution. Results of treatment of male infertility, the dynamics of the semen and pregnancy of the couple on the background of pathogenetic therapy correlates with the type of sexual constitution. Widely deployed discussion about the existence of the male equivalent of female menopause mainly concerns the problems of men's sexual health. Of exceptional importance for the prediction of treatment of infertility has ovarian reserve, which is closely associated with age women. Formation of menstrual function occurs in the pubertal period of sexual development, in this age of menarche is the leading symptom of type of sexual constitution of women that do not change throughout the life hereafter. The presence of menstrual function and even ovulation does not reflect the reproductive capacity of women. Insufficient information content of the chronological age of a woman, as an indicator of the reproductive capacity of ovarian dictates the necessity of the development of tests that determine individual biological age of a woman, perhaps connected with the type of sexual constitution. In this regard, the study of sexual constitution partners is of great scientific and practical interest.

BRCA1 and BRCA2 genetic testing-pitfalls and recommendations for managing variants of uncertain clinical significance.

Science.gov (United States)

Eccles, D M; Mitchell, G; Monteiro, A N A; Schmutzler, R; Couch, F J; Spurdle, A B; Gómez-García, E B

2015-10-01

Increasing use of BRCA1/2 testing for tailoring cancer treatment and extension of testing to tumour tissue for somatic mutation is moving BRCA1/2 mutation screening from a primarily prevention arena delivered by specialist genetic services into mainstream oncology practice. A considerable number of gene tests will identify rare variants where clinical significance cannot be inferred from sequence information alone. The proportion of variants of uncertain clinical significance (VUS) is likely to grow with lower thresholds for testing and laboratory providers with less experience of BRCA. Most VUS will not be associated with a high risk of cancer but a misinterpreted VUS has the potential to lead to mismanagement of both the patient and their relatives. Members of the Clinical Working Group of ENIGMA (Evidence-based Network for the Interpretation of Germline Mutant Alleles) global consortium (www.enigmaconsortium.org) observed wide variation in practices in reporting, disclosure and clinical management of patients with a VUS. Examples from current clinical practice are presented and discussed to illustrate potential pitfalls, explore factors contributing to misinterpretation, and propose approaches to improving clarity. Clinicians, patients and their relatives would all benefit from an improved level of genetic literacy. Genetic laboratories working with clinical geneticists need to agree on a clinically clear and uniform format for reporting BRCA test results to non-geneticists. An international consortium of experts, collecting and integrating all available lines of evidence and classifying variants according to an internationally recognized system, will facilitate reclassification of variants for clinical use. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Vesicular monoamine transporter protein expression correlates with clinical features, tumor biology, and MIBG avidity in neuroblastoma: a report from the Children's Oncology Group

International Nuclear Information System (INIS)

Temple, William; Mendelsohn, Lori; Nekritz, Erin; Gustafson, W.C.; Matthay, Katherine K.; Kim, Grace E.; Lin, Lawrence; Giacomini, Kathy; Naranjo, Arlene; Van Ryn, Collin; Yanik, Gregory A.; Kreissman, Susan G.; Hogarty, Michael; DuBois, Steven G.

2016-01-01

Vesicular monoamine transporters 1 and 2 (VMAT1 and VMAT2) are thought to mediate MIBG uptake in adult neuroendocrine tumors. In neuroblastoma, the norepinephrine transporter (NET) has been investigated as the principal MIBG uptake protein, though some tumors without NET expression concentrate MIBG. We investigated VMAT expression in neuroblastoma and correlated expression with MIBG uptake and clinical features. We evaluated VMAT1 and VMAT2 expression by immunohistochemistry (IHC) in neuroblastoma tumors from 76 patients with high-risk metastatic disease treated in a uniform cooperative group trial (COG A3973). All patients had baseline MIBG diagnostic scans centrally reviewed. IHC results were scored as the product of intensity grading (0 - 3+) and percent of tumor cells expressing the protein of interest. The association between VMAT1 and VMAT2 scores and clinical and biological features was tested using Wilcoxon rank-sum tests. Patient characteristics were typical of high-risk neuroblastoma, though the cohort was intentionally enriched in patients with MIBG-nonavid tumors (n = 20). VMAT1 and VMAT2 were expressed in 62 % and 75 % of neuroblastoma tumors, respectively. VMAT1 and VMAT2 scores were both significantly lower in MYCN amplified tumors and in tumors with high mitotic karyorrhectic index. MIBG-avid tumors had significantly higher VMAT2 scores than MIBG-nonavid tumors (median 216 vs. 45; p = 0.04). VMAT1 expression did not correlate with MIBG avidity. VMAT1 and VMAT2 are expressed in the majority of neuroblastomas. Expression correlates with other biological features. The expression level of VMAT2 but not that of VMAT1 correlates with avidity for MIBG. (orig.)

Vesicular monoamine transporter protein expression correlates with clinical features, tumor biology, and MIBG avidity in neuroblastoma: a report from the Children's Oncology Group

Energy Technology Data Exchange (ETDEWEB)

Temple, William; Mendelsohn, Lori; Nekritz, Erin; Gustafson, W.C.; Matthay, Katherine K. [UCSF School of Medicine, Department of Pediatrics, San Francisco, CA (United States); UCSF Benioff Children' s Hospital, San Francisco, CA (United States); Kim, Grace E. [UCSF School of Medicine, Department of Pathology, San Francisco, CA (United States); Lin, Lawrence; Giacomini, Kathy [UCSF School of Pharmacy, Department of Bioengineering and Therapeutic Sciences, San Francisco, CA (United States); Naranjo, Arlene; Van Ryn, Collin [University of Florida, Children' s Oncology Group Statistics and Data Center, Gainesville, FL (United States); Yanik, Gregory A. [University of Michigan, CS Mott Children' s Hospital, Ann Arbor, MI (United States); Kreissman, Susan G. [Duke University Medical Center, Durham, NC (United States); Hogarty, Michael [University of Pennsylvania, Children' s Hospital of Philadelphia and Perelman School of Medicine, Philadelphia, PA (United States); DuBois, Steven G. [UCSF School of Medicine, Department of Pediatrics, San Francisco, CA (United States); UCSF Benioff Children' s Hospital, San Francisco, CA (United States); UCSF School of Medicine, San Francisco, CA (United States)

2016-03-15

Vesicular monoamine transporters 1 and 2 (VMAT1 and VMAT2) are thought to mediate MIBG uptake in adult neuroendocrine tumors. In neuroblastoma, the norepinephrine transporter (NET) has been investigated as the principal MIBG uptake protein, though some tumors without NET expression concentrate MIBG. We investigated VMAT expression in neuroblastoma and correlated expression with MIBG uptake and clinical features. We evaluated VMAT1 and VMAT2 expression by immunohistochemistry (IHC) in neuroblastoma tumors from 76 patients with high-risk metastatic disease treated in a uniform cooperative group trial (COG A3973). All patients had baseline MIBG diagnostic scans centrally reviewed. IHC results were scored as the product of intensity grading (0 - 3+) and percent of tumor cells expressing the protein of interest. The association between VMAT1 and VMAT2 scores and clinical and biological features was tested using Wilcoxon rank-sum tests. Patient characteristics were typical of high-risk neuroblastoma, though the cohort was intentionally enriched in patients with MIBG-nonavid tumors (n = 20). VMAT1 and VMAT2 were expressed in 62 % and 75 % of neuroblastoma tumors, respectively. VMAT1 and VMAT2 scores were both significantly lower in MYCN amplified tumors and in tumors with high mitotic karyorrhectic index. MIBG-avid tumors had significantly higher VMAT2 scores than MIBG-nonavid tumors (median 216 vs. 45; p = 0.04). VMAT1 expression did not correlate with MIBG avidity. VMAT1 and VMAT2 are expressed in the majority of neuroblastomas. Expression correlates with other biological features. The expression level of VMAT2 but not that of VMAT1 correlates with avidity for MIBG. (orig.)

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

Science.gov (United States)

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

1997-01-01

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

CLASSIFICATION OF TEMPOROMANDIBULAR-JOINT OSTEOARTHROSIS AND INTERNAL DERANGEMENT .1. DIAGNOSTIC-SIGNIFICANCE OF CLINICAL AND RADIOGRAPHIC SYMPTOMS AND SIGNS

NARCIS (Netherlands)

STEGENGA, B; DEBONT, LGM; VANDERKUIJL, B; BOERING, G

In the clinical setting, diagnosis primarily depends on the history and present status of the patient, and on the examiner's expertise in physical examination and interpretation of conventional radiographs. In order to evaluate the diagnostic significance of clinical and radiographic variables, the

Clinical and radiographic outcomes of meniscus surgery and future targets for biologic intervention: A review of data from the MOON Group.

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Westermann, Robert W; Jones, Morgan; Wasserstein, David; Spindler, Kurt P

Meniscus injury and treatment occurred with the majority of anterior cruciate ligament reconstructions (ACLR) in the multicenter orthopedic outcomes (MOON) cohort. We describe the patient-reported outcomes, radiographic outcomes, and predictors of pain from meniscus injuries and treatment in the setting of ACLR. Patient-reported outcomes improve significantly following meniscus repair with ACLR, but differences exist based on the meniscus injury laterally (medial or lateral). Patients undergoing medial meniscus repair have worse patient-reported outcomes and more pain compared to those with uninjured menisci. However, lateral meniscal tears can be repaired with similar outcomes as uninjured menisci. Medial meniscal treatment (meniscectomy or repair) results in a significant loss of joint space at 2 years compared to uninjured menisci. Menisci treated with excision had a greater degree of joint space loss compared to those treated with repair. Clinically significant knee pain is more common following injuries to the medial meniscus and increased in patients who undergo early re-operation after initial ACLR. Future research efforts aimed at improving outcomes after combined ACLR and meniscus treatment should focus on optimizing biologic and mechanical environments that promote healing of medial meniscal tears sustained during ACL injury.

Dioxin exposure of human CD34+ hemopoietic cells induces gene expression modulation that recapitulates its in vivo clinical and biological effects

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Fracchiolla, Nicola Stefano; Todoerti, Katia; Bertazzi, Pier Alberto; Servida, Federica; Corradini, Paolo; Carniti, Cristiana; Colombi, Antonio; Cecilia Pesatori, Angela; Neri, Antonino; Deliliers, Giorgio Lambertenghi

2011-01-01

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) has a large number of biological effects, including skin, cardiovascular, neurologic diseases, diabetes, infertility, cancers and immunotoxicity. We analysed the in vitro TCDD effects on human CD34 + cells and tested the gene expression modulation by means of microarray analyses before and after TCDD exposure. We identified 257 differentially modulated probe sets, identifying 221 well characterized genes. A large part of these resulted associated to cell adhesion and/or angiogenesis and to transcription regulation. Synaptic transmission and visual perception functions, with the particular involvement of the GABAergic pathway were also significantly modulated. Numerous transcripts involved in cell cycle or cell proliferation, immune response, signal transduction, ion channel activity or calcium ion binding, tissue development and differentiation, female or male fertility or in several metabolic pathways were also affected after dioxin exposure. The transcriptional profile induced by TCDD treatment on human CD34 + cells strikingly reproduces the clinical and biological effects observed in individuals exposed to dioxin and in biological experimental systems. Our data support a role of dioxin in the neoplastic transformation of hemopoietic stem cells and in immune modulation processes after in vivo exposure, as indicated by the epidemiologic data in dioxin accidentally exposed populations, providing a molecular basis for it. In addition, TCDD alters genes associated to glucidic and lipidic metabolisms, to GABAergic transmission or involved in male and female fertility, thus providing a possible explanation of the diabetogenic, dyslipidemic, neurologic and fertility effects induced by TCDD in vivo exposure.

Dental anxiety: a comparison of students of dentistry, biology, and psychology

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Storjord HP

2014-09-01

Full Text Available Helene Persen Storjord,1 Mari Mjønes Teodorsen,1 Jan Bergdahl,1 Rolf Wynn,2,3 Jan-Are Kolset Johnsen1 1Department of Clinical Dentistry, 2Department of Clinical Medicine, UiT - The Arctic University of Norway, 3Division of Addictions and Specialized Psychiatric Services, University Hospital of North Norway, Tromsø, Norway Introduction: Dental anxiety is an important challenge for many patients and clinicians. It is thus of importance to know more about dental students' own experiences with dental anxiety and their understanding of dental anxiety. The aim was to investigate differences in dental anxiety levels between dental students, psychology students, and biology students at a Norwegian university. Materials and methods: A total of 510 students of dentistry, psychology, and biology at the University of Tromsø received a questionnaire consisting of the Modified Dental Anxiety Scale, demographic questions, and questions relating to their last visit to the dentist/dental hygienist; 169 students gave complete responses. Nonparametric tests were used to investigate differences between the student groups. Results: The respondents were 78% female and 22% male; their mean age was 24 years. The dental students showed a significantly lower degree of dental anxiety than the psychology (P<0.001 and biology students (P<0.001. A significant decrease in dental anxiety levels was found between novice and experienced dentistry students (P<0.001. Discussion: The dental students had less dental anxiety compared to psychology students and biology students. Experienced dental students also had less dental anxiety than novice dental students. This could indicate that the dentistry program structure at the university may influence dental anxiety levels. Conclusion: Dental anxiety seemed to be less frequent in dentistry students compared to students of biology or clinical psychology. The practice-oriented dentistry education at the university might contribute to

Treatment with biologic agents improves the prognosis of patients with rheumatoid arthritis and amyloidosis.

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Kuroda, Takeshi; Tanabe, Naohito; Kobayashi, Daisuke; Sato, Hiroe; Wada, Yoko; Murakami, Shuichi; Saeki, Takako; Nakano, Masaaki; Narita, Ichiei

2012-07-01

Reactive amyloid A (AA) amyloidosis is a serious and life-threatening systemic complication of rheumatoid arthritis (RA). We evaluated the safety of therapy with anti-tumor necrosis factor and anti-interleukin 6 biologic agents in RA patients with reactive AA amyloidosis, together with prognosis and hemodialysis (HD)-free survival, in comparison with patients with AA amyloidosis without such therapy. One hundred thirty-three patients with an established diagnosis of reactive AA amyloidosis participated in the study. Clinical data were assessed from patient records at the time of amyloid detection and administration of biologics. Survival was calculated from the date when amyloid was first demonstrated histologically or the date when biologic therapy was started until the time of death or to the end of 2010 for surviving patients. Patients who had started HD were selected for inclusion only after the presence of amyloid was demonstrated. Fifty-three patients were treated with biologic agents (biologic group) and 80 were not (nonbiologic group). Survival rate was significantly higher in the biologic group than in the nonbiologic group. Nine patients in the biologics group and 33 in the nonbiologic group started HD. Biologic therapy had a tendency for reduced risk of initiation of HD without any statistical significance. Patients with amyloidosis have a higher mortality rate, but the use of biologic agents can reduce risk of death. The use of biologics may not significantly influence the HD-free survival rate.

Pancreatic cancer stromal biology and therapy

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Xie, Dacheng; Xie, Keping

2015-01-01

Pancreatic cancer is one of the most lethal malignancies. Significant progresses have been made in understanding of pancreatic cancer pathogenesis, including appreciation of precursor lesions or premalignant pancreatic intraepithelial neoplasia (PanINs), description of sequential transformation from normal pancreatic tissue to invasive pancreatic cancer and identification of major genetic and epigenetic events and the biological impact of those events on malignant behavior. However, the currently used therapeutic strategies targeting tumor epithelial cells, which are potent in cell culture and animal models, have not been successful in the clinic. Presumably, therapeutic resistance of pancreatic cancer is at least in part due to its drastic desmoplasis, which is a defining hallmark for and circumstantially contributes to pancreatic cancer development and progression. Improved understanding of the dynamic interaction between cancer cells and the stroma is important to better understanding pancreatic cancer biology and to designing effective intervention strategies. This review focuses on the origination, evolution and disruption of stromal molecular and cellular components in pancreatic cancer, and their biological effects on pancreatic cancer pathogenesis. PMID:26114155

Gastric tumours in hereditary cancer syndromes: clinical features, molecular biology and strategies for prevention.

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Sereno, María; Aguayo, Cristina; Guillén Ponce, Carmen; Gómez-Raposo, César; Zambrana, Francisco; Gómez-López, Miriam; Casado, Enrique

2011-09-01

Gastric cancer is the major cause of cancer-related deaths worldwide. The majority of them are classified as sporadic, whereas the remaining 10% exhibit familial clustering. Hereditary diffuse gastric cancer (HDGC) syndrome is the most important condition that leads to hereditary gastric cancer. However, other hereditary cancer syndromes, such as hereditary non-polyposis colorectal cancer, familial adenomatous polyposis, Peutz-Jeghers syndrome, Li-Fraumeni syndrome and hereditary breast and ovarian cancer, entail a higher risk compared to the general population for developing this kind of neoplasia. In this review, we describe briefly the most important aspects related to clinical features, molecular biology and strategies for prevention in hereditary gastric associated to different cancer syndromes.

Biological significance of facilitated diffusion in protein-DNA interactions. Applications to T4 endonuclease V-initiated DNA repair

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Dowd, D.R.; Lloyd, R.S.

1990-01-01

Facilitated diffusion along nontarget DNA is employed by numerous DNA-interactive proteins to locate specific targets. Until now, the biological significance of DNA scanning has remained elusive. T4 endonuclease V is a DNA repair enzyme which scans nontarget DNA and processively incises DNA at the site of pyrimidine dimers which are produced by exposure to ultraviolet (UV) light. In this study we tested the hypothesis that there exists a direct correlation between the degree of processivity of wild type and mutant endonuclease V molecules and the degree of enhanced UV resistance which is conferred to repair-deficient Eshcerichia coli. This was accomplished by first creating a series of endonuclease V mutants whose in vitro catalytic activities were shown to be very similar to that of the wild type enzyme. However, when the mechanisms by which these enzymes search nontarget DNA for its substrate were analyzed in vitro and in vivo, the mutants displayed varying degrees of nontarget DNA scanning ranging from being nearly as processive as wild type to randomly incising dimers within the DNA population. The ability of these altered endonuclease V molecules to enhance UV survival in DNA repair-deficient E. coli then was assessed. The degree of enhanced UV survival was directly correlated with the level of facilitated diffusion. This is the first conclusive evidence directly relating a reduction of in vivo facilitated diffusion with a change in an observed phenotype. These results support the assertion that the mechanisms which DNA-interactive proteins employ in locating their target sites are of biological significance

Changes in biological markers, particularly hormone receptors, due to pre-operative chemotherapy (epirubicin/docetaxel in operable breast cancer

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Rumiko Tashima

2011-12-01

Full Text Available We investigated the correlation between biological markers prior to pre-operative chemotherapy with epirubicin and docetaxel (ET therapy and the effect of treatment as well as the clinically significant changes in biological markers before and after chemotherapy. Since April 2002, 52 patients with tumors ≥3 cm in diameter or lymph node metastases have received pre-operative ET chemotherapy. The items investigated were ER/PgR, proliferative activity (MIB-1, etc. The correlation of changes in these factors between pre- and post-treatment status and the clinical and pathological responses was investigated. Clinical response was 82%, BCS rate was 67%. Pathological response was 31.4%. The ER/PgR positive cell rate significantly decreased from 48%/32% to 37%/14%. The MIB-1 decreased from 48% to 27%. The pathological response was significantly high in patients with low ER/PgR-positive rates and those with high MIB-1 values.

Expression and clinical significance of ATM and PUMA gene in patients with colorectal cancer.

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Xiong, Hui; Zhang, Jiangnan

2017-12-01

The expression of ataxia-telangiectasia mutated (ATM) and p53 upregulated modulator of apoptosis (PUMA) genes in patients with colorectal cancer were investigated, to explore the correlation between the expression of ATM and PUMA and tumor development, to evaluate the clinical significance of ATM and PUMA in the treatment of colorectal cancer. Quantitative real-time PCR was used to detect the expression of ATM and PUMA in tumor tissue and adjacent healthy tissue of 67 patients with colorectal cancer and in normal colorectal tissue of 33 patients with colorectal polyps at mRNA level. The expression level of ATM mRNA in colorectal cancer tissues was significantly higher than that in normal mucosa tissues and adjacent non-cancerous tissue (P≤0.05), while no significant differences in expression level of ATM mRNA were found between normal mucosa tissues and adjacent noncancerous tissue (P=0.07). There was a negative correlation between the expression of ATM mRNA and the degree of differentiation of colorectal cancer (r= -0.312, P=0.013), while expression level of ATM mRNA was not significantly correlated with the age, sex, tumor invasion, lymph node metastasis or clinical stage (P>0.05). Expression levels of PUMA mRNA in colorectal cancer tissues, adjacent noncancerous tissue and normal tissues were 0.68±0.07, 0.88±0.04 and 1.76±0.06, respectively. Expression level of PUMA mRNA in colorectal cancer tissues and adjacent noncancerous tissue was significantly lower than that in normal colorectal tissues (PATM mRNA is expressed abnormally in colorectal cancer tissues. Expression of PUMA gene in colorectal carcinoma is downregulated, and is negatively correlated with the occurrence of cancer.

An initiative to improve the management of clinically significant test results in a large health care network.

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Roy, Christopher L; Rothschild, Jeffrey M; Dighe, Anand S; Schiff, Gordon D; Graydon-Baker, Erin; Lenoci-Edwards, Jennifer; Dwyer, Cheryl; Khorasani, Ramin; Gandhi, Tejal K

2013-11-01

The failure of providers to communicate and follow up clinically significant test results (CSTR) is an important threat to patient safety. The Massachusetts Coalition for the Prevention of Medical Errors has endorsed the creation of systems to ensure that results can be received and acknowledged. In 2008 a task force was convened that represented clinicians, laboratories, radiology, patient safety, risk management, and information systems in a large health care network with the goals of providing recommendations and a road map for improvement in the management of CSTR and of implementing this improvement plan during the sub-force sequent five years. In drafting its charter, the task broadened the scope from "critical" results to "clinically significant" ones; clinically significant was defined as any result that requires further clinical action to avoid morbidity or mortality, regardless of the urgency of that action. The task force recommended four key areas for improvement--(1) standardization of policies and definitions, (2) robust identification of the patient's care team, (3) enhanced results management/tracking systems, and (4) centralized quality reporting and metrics. The task force faced many challenges in implementing these recommendations, including disagreements on definitions of CSTR and on who should have responsibility for CSTR, changes to established work flows, limitations of resources and of existing information systems, and definition of metrics. This large-scale effort to improve the communication and follow-up of CSTR in a health care network continues with ongoing work to address implementation challenges, refine policies, prepare for a new clinical information system platform, and identify new ways to measure the extent of this important safety problem.

Role of MLH1 methylation in esophageal cancer carcinogenesis and its clinical significance.

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Li, Jinyun; Ye, Dong; Wang, Lei; Peng, Yingying; Li, Qun; Deng, Hongxia; Zhou, Chongchang

2018-01-01

The mutL homolog-1 ( MLH1 ) is a DNA mismatch repair gene and has been reported to be frequently methylated in numerous cancers. However, the association between MLH1 methylation and esophageal cancer (EC), as well as its clinical significance, remains unclear. Hence, we conducted a systematic meta-analysis based on 19 articles (including 1384 ECs, 345 premalignant lesions, and 1244 healthy controls). Our analysis revealed that the frequency of MLH1 methylation was significantly elevated during EC carcinogenesis. In addition, we observed that MLH1 promoter methylation was associated with age (odds ratio [OR]=1.79; 95% CI =1.20-2.66), advanced tumor grade (OR=3.7; 95% CI =2.37-5.77), lymph node metastasis (OR=2.65; 95% CI =1.81-3.88), distant metastasis (OR=7.60; 95% CI =1.23-47.19), advanced clinical stage (OR=4.46; 95% CI =2.88-6.91), and poor prognosis in EC patients (hazard ratio =1.64, 95% CI =1.00-2.69). The pooled sensitivity, specificity, and area under the curve of MLH1 methylation in EC patients versus healthy individuals were 0.15, 0.99, and 0.77, respectively. Our findings indicate that MLH1 methylation is involved in the carcinogenesis, progression, and metastasis of EC. Moreover, methylated MLH1 could be a potential diagnostic and prognostic biomarker for EC.

Necrotizing pneumonia: CT findings and its clinical significance

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Park, Hong Suk; Im, Jung Gi; Ryoo, Jae Wook; Yeon, Kyung Mo; Han, Man Chung

1995-01-01

To analyze CT and follow-up chest radiographic findings in patients with necrotizing pneumonia and to evaluate clinical significance of the extent of necrosis. We reviewed medical records and retrospectively analysed CT scans and follow-up chest radiographs of 22 patients with necrotizing pneumonia, confirmed by biopsy (n = 7) and culture (n = 15). Inclusion criteria for necrotizing pneumonia was necrotic low attenuation, with or without cavitation on postcontrast enhanced CT scan. The study group included 15 men and seven women, aged 11-66 years (average: 47 years). The pathogens of necrotizing pneumonia were Klebsiella spp (n = 7), Enterobacter spp (n = 5), Actinomyces spp (n = 4), Pseudomonas spp (n = 4), Nocardia spp (n = 4), and others (n = 5). Average duration of pneumonia was 4.1 months. On CT scan, pneumonic consolidations were well-marginated in 14 patients and there were cavities on initial CT scan in 16 cases. Margins of the necrotic portion on CT scan were well-demarcated in majority of the patients (16/22). Low attenuation areas on initial CT scan resulted in cavitation, fibrosis and volume loss as shown on follow-up chest radiographs. The larger the necrotic areas on CT, the more the volume loss was. CT findings of necrotizing pneumonia were well-marginated air-space consolidation with low attenuation area, with or without cavity. The extent of necrotic area was closely related with the degree of fibrotic change later on. CT is important tool for diagnosis and prediction of parenchymal damage in necrotizing pneumonia

The clinical significance of fatty acid binding proteins

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Barbara Choromańska

2011-11-01

Full Text Available Excessive levels of free fatty acids are toxic to cells. The human body has evolved a defense mechanism in the form of small cytoplasmic proteins called fatty acid binding proteins (FABPs that bind long-chain fatty acids (LCFA, and then refer them to appropriate intracellular disposal sites (oxidation in mitochondria and peroxisomes or storage in the endoplasmic reticulum. So far, nine types of these proteins have been described, and their name refers to the place in which they were first identified or where they can be found in the greatest concentration. The most important FABPs were isolated from the liver (L-FABP, heart (H-FABP, intestine (I-FABP, brain (B-FABP, epidermis (E-FABP and adipocytes (A-FABP. Determination of H-FABP is used in the diagnosis of myocardial infarction, and L-FABP in kidney lesions of different etiologies. It is postulated that FABPs play an important role in the pathogenesis of metabolic diseases. Elevated levels of A-FABP have been found in the pericardial fat tissue and were associated with cardiac dysfunction in obese people. A rise in A-FABP has been observed in patients with type II diabetes. I-FABP is known as a marker of cell damage in the small intestine. Increased concentration of B-FABP has been associated with human brain tumors such as glioblastoma and astrocytoma, as well as with neurodegenerative diseases (Alzheimer’s, Parkinson’s and other disorders of cognitive function. The aim of this work was to present current data on the clinical significance of fatty acid binding proteins.

Targeted Nanoparticles for Image-guided Treatment of Triple Negative Breast Cancer: Clinical Significance and Technological Advances

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Miller-Kleinhenz, Jasmine M.; Bozeman, Erica N.

2015-01-01

Effective treatment of triple negative breast cancer (TNBC) with its aggressive tumor biology, highly heterogeneous tumor cells, and poor prognosis requires an integrated therapeutic approach that addresses critical issues in cancer therapy. Multifunctional nanoparticles with the abilities of targeted drug delivery and non-invasive imaging for monitoring drug delivery and responses to therapy, such as theranostic nanoparticles, hold great promise towards the development of novel therapeutic approaches for the treatment of TNBC using a single therapeutic platform. The biological and pathological characteristics of TNBC provide insight into several potential molecular targets for current and future nanoparticle based therapeutics. Extensive tumor stroma, highly proliferative cells, and a high rate of drug-resistance are all barriers that must be appropriately addressed in order for these nanotherapeutic platforms to be effective. Utilization of the enhanced permeability and retention (EPR) effect coupled with active targeting of cell surface receptors expressed by TNBC cells, and tumor associated endothelial cells, stromal fibroblasts and macrophages is likely to overcome such barriers to facilitate more effective drug delivery. An in depth summary of current studies investigating targeted nanoparticles in preclinical TNBC mouse and human xenograft models is presented. This review aims to outline the current status of nanotherapeutic options for TNBC patients, identification of promising molecular targets, challenges associated with the development of targeted nanotherapeutics, the research done by our group as well as others and future perspectives on the nanomedicine field and ways to translate current preclinical studies into the clinic. PMID:25966677

Clinical significance of DVM and its prevalence in pre-gestational diabetes cases versus normal pregnancies

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Farideh Akhlaghi

2015-06-01

Full Text Available Pre-gestational diabetes mellitus affects less than 1% of all pregnancies and is a significant cause of fetal morbidity and mortality. It is hypothesized that impaired placental function, in the form of abnormal placental weight and/or abnormal placental histology, may be responsible for this event in such pregnancies. Delayed villous maturation of placental villi, which is one of the findings associated with pre-gestational diabetes increases the rate of perinatal mortality. There is limited literature regarding the delayed maturation of placental villous. This review included trials (randomized and non-randomized, cohort and case-control studies registered in Medline/PubMed database, from January 2001 to September 2012 that evaluated the clinical significance of delayed villous maturation and its prevalence in pre-gestational diabetic cases compared to normal pregnancies.It emphasizes that further studies with focus on possible clinical or ultrasound markers of placental delayed villous maturation, especially in a high risk-group such as women with pre-gestational diabetes mellitus are highly recommended.

Hyperthermia: from the clinic to the laboratory and back again

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Maher, E.J.

1989-01-01

Murine tumours have been used extensively to investigate the effects of heat and radiation, but there are significant differences between controlled laboratory studies and relatively uncontrolled clinical experience. From 1983 to 1986 a simple clinical system was developed in order to investigate biological questions in the clinic. This involved identifying a suitable patient population, reliable heating and thermometry, and methods of evaluating response of human tumours and their vasculature. (author)

Clinical Significance of Reticulocyte Hemoglobin Content in the Diagnosis of Iron Deficiency Anemia

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Mustafa Karagülle

2013-06-01

Full Text Available OBJECTIVE: The aim of this study was to evaluate the clinical significance of reticulocyte hemoglobin content (CHr in the diagnosis of iron deficiency anemia (IDA and to compare it with other conventional iron parameters. METHODS: A total of 32 female patients with IDA (serum hemoglobin 120 g/L and serum ferritin <20 ng/mL were enrolled. RESULTS: CHr was 24.95±3.92 pg in female patients with IDA and 29.93±2.96 pg in female patients with iron deficiency. CHr showed a significant positive correlation with hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, serum iron, and transferrin saturation and a significant negative correlation with transferrin and total iron-binding capacity. The cut-off value of CHr for detecting IDA was 29 pg. CONCLUSION: Our data demonstrate that CHr is a useful parameter that can be confidently used in the diagnosis of IDA, and a CHr cut-off value of 29 pg predicts IDA.

The molecular biology of WHO grade I astrocytomas.

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Marko, Nicholas F; Weil, Robert J

2012-12-01

World Health Organization (WHO) grade I astrocytomas include pilocytic astrocytoma (PA) and subependymal giant cell astrocytoma (SEGA). As technologies in pharmacologic neo-adjuvant therapy continue to progress and as molecular characteristics are progressively recognized as potential markers of both clinically significant tumor subtypes and response to therapy, interest in the biology of these tumors has surged. An updated review of the current knowledge of the molecular biology of these tumors is needed. We conducted a Medline search to identify published literature discussing the molecular biology of grade I astrocytomas. We then summarized this literature and discuss it in a logical framework through which the complex biology of these tumors can be clearly understood. A comprehensive review of the molecular biology of WHO grade I astrocytomas is presented. The past several years have seen rapid progress in the level of understanding of PA in particular, but the molecular literature regarding both PA and SEGA remains nebulous, ambiguous, and occasionally contradictory. In this review we provide a comprehensive discussion of the current understanding of the chromosomal, genomic, and epigenomic features of both PA and SEGA and provide a logical framework in which these data can be more readily understood.

Clinical significance of the radioimmunological determination of C-peptide

International Nuclear Information System (INIS)

Dudczak, R.; Waldhaeusl, W.

1979-01-01

The aim of this study was to investigate the relationship of metabolic control to insulinogenic reserve in insulin-dependent diabetics. Thus, the secretory reserve of the pancreatic beta cell was estimated in insulin-dependent diabetics by measuring changes in peripheral serum immunoreactive C-peptide (IRCP) concentrations in response to intravenous arginine (n = 19; 0.5 g/kg,t = 30 min) or glibenclamide-glucose (n = 6; 2 mg HB 419 - 0.33 g/kg intravenously). In the majority of ''stable'' diabetics a small secretory reserve of the beta cell was demonstrated, but both the absolute and relative increase in IRCP was reduced after intravenous arginine or glibenclamide-glucose in comparison with normal controls. In ''unstable'' diabetics a decreased basal concentration of IRCP, significantly smaller than that seen in ''stable'' diabetics (p < 0.01), was accompanied by a complete lack of IRCP release on intravenous arginine administration. Thus, we conclude that the radioimmunological determination of IRCP is of clinical interest in assessing the residual secretory capacity of the beta cell in insulin-dependent diabetics. In revealing a lack of insulin this diagnostic tool seems to detect a group of potentially ''unstable'' diabetics in need of strict observation, which would minimize the risks of bad metabolic control. (author)

Clinical significance of the radioimmunological determination of C-peptide

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Dudczak, R; Waldhaeusl, W [Vienna Univ. (Austria). 1. Medizinische Klinik

1979-10-12

The aim of this study was to investigate the relationship of metabolic control to insulinogenic reserve in insulin-dependent diabetics. Thus, the secretory reserve of the pancreatic beta cell was estimated in insulin-dependent diabetics by measuring changes in peripheral serum immunoreactive C-peptide (IRCP) concentrations in response to intravenous arginine (n = 19; 0.5 g/kg,t = 30 min) or glibenclamide-glucose (n = 6; 2 mg HB 419 - 0.33 g/kg intravenously). In the majority of stable diabetics a small secretory reserve of the beta cell was demonstrated, but both the absolute and relative increase in IRCP was reduced after intravenous arginine or glibenclamide-glucose in comparison with normal controls. In unstable diabetics a decreased basal concentration of IRCP, significantly smaller than that seen in stable diabetics (p < 0.01), was accompanied by a complete lack of IRCP release on intravenous arginine administration. Thus, we conclude that the radioimmunological determination of IRCP is of clinical interest in assessing the residual secretory capacity of the beta cell in insulin-dependent diabetics. In revealing a lack of insulin this diagnostic tool seems to detect a group of potentially unstable diabetics in need of strict observation, which would minimize the risks of bad metabolic control.

Clinical, pathologic, and biologic features associated with BRAF mutations in non-small cell lung cancer.

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Cardarella, Stephanie; Ogino, Atsuko; Nishino, Mizuki; Butaney, Mohit; Shen, Jeanne; Lydon, Christine; Yeap, Beow Y; Sholl, Lynette M; Johnson, Bruce E; Jänne, Pasi A

2013-08-15

BRAF mutations are found in a subset of non-small cell lung cancers (NSCLC). We examined the clinical characteristics and treatment outcomes of patients with NSCLC harboring BRAF mutations. Using DNA sequencing, we successfully screened 883 patients with NSCLC for BRAF mutations between July 1, 2009 and July 16, 2012. Baseline characteristics and treatment outcomes were compared between patients with and without BRAF mutations. Wild-type controls consisted of patients with NSCLC without a somatic alteration in BRAF, KRAS, EGFR, and ALK. In vitro studies assessed the biologic properties of selected non-V600E BRAF mutations identified from patients with NSCLC. Of 883 tumors screened, 36 (4%) harbored BRAF mutations (V600E, 18; non-V600E, 18) and 257 were wild-type for BRAF, EGFR, KRAS, and ALK negative. Twenty-nine of 36 patients with BRAF mutations were smokers. There were no distinguishing clinical features between BRAF-mutant and wild-type patients. Patients with advanced NSCLC with BRAF mutations and wild-type tumors showed similar response rates and progression-free survival (PFS) to platinum-based combination chemotherapy and no difference in overall survival. Within the BRAF cohort, patients with V600E-mutated tumors had a shorter PFS to platinum-based chemotherapy compared with those with non-V600E mutations, although this did not reach statistical significance (4.1 vs. 8.9 months; P = 0.297). We identified five BRAF mutations not previously reported in NSCLC; two of five were associated with increased BRAF kinase activity. BRAF mutations occur in 4% of NSCLCs and half are non-V600E. Prospective trials are ongoing to validate BRAF as a therapeutic target in NSCLC. ©2013 AACR.

A contribution to the study of the biological dosimetry in clinical radiopathology

International Nuclear Information System (INIS)

Eston, T.E. de.

1983-01-01

The effects of total body irradiation with different radiation doses from a 4MeV linear accelerator on organs and tissues of adult male rabbits were studied. Doses of 0.50, 2.00, 6.00 and 8.00 Gy were applied. Different organic parameters were evaluated before and after various periods of the post-irradiation time. Mortality did not occured for 0.50 or 2.00 Gy, but morbility was greater in comparison with the control; sexual potency was maintained. 'Impotentia colundi' occured with 6 Gy. A small loss of weight occured with 2.00 Gy and a higher loss for 6.00 Gy, with later recovery. Blood parameters varied even for lowest dose. Alterations were evident in the bone marrow activity for 2.00 and 6.00 Gy. Spermatides, spermatocytes and mature spermatozoids were affect even by low doses, the laters loosing motility. Significant difference was observed in the relation DNA/RNA for irradiated-and control animals. The results showed that T3 asssay could serve as 'biological indicator' of irradiation in a period of at least 7 hours and for doses of 4Gy or more. Using the kinetic method, an increase of glutamic oxalacetic transaminase (GOT) seric levels was observed for 6.00 Gy after 7 hours and a decrease for the glutamic pyruvic transaminase (GPT). Fasting glycemy and catecolamines urinary extraction were not statiscally significants. The study of chromosomal aberrations that occur in lymphocytes after 'in vitro' irradiation showed that this is at the present moment the most efficient method for biological dosimetry. (M.A.) [pt

Clinical significance of determination of serum cortisol and insulin levels in neonates with asphyxia

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Yao Yingfei; Chen Linxing; Chen Sihong; Zhang Jinchi; Huang Hua

2004-01-01

Objective: To investigate the clinical significance of the changes of serum cortisol and insulin levels in neonates with asphyxia. Methods: Serum cortisol levels were determined with CLIA and serum insulin levels with RIA in 38 neonates with asphyxia (mild degree 20, advanced 18) and 30 controls. Results: 1) In mild cases, serum insulin levels were significantly higher than those in controls (p<0.01) and serum cortisol levels were very significantly higher (p<0.001). 2) In advanced cases, both serum insulin and cortisol levels were very significantly higher than those in the controls (p<0.001). Conclusion: Hypoxia in the neonates with asphyxia is a very severe stress and will induce hypersecretion of cortisol and hyperglycemia which is detrimental to the patients. However hypersecretion of insulin will result in hypoglycemia, which is also very damaging. Physicians in charge should be aware of these possibilities and deal with them appropriately

Clinical Significance of Contralateral Reactive Lesion in Vocal Fold Polyp and Cyst.

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Cho, Jung-Hae; Choi, Yong-Sug; Joo, Young-Hoon; Park, Young-Hak; Sun, Dong-Il

2018-01-01

We investigated the clinical significance of contralateral reactive lesions in patients undergoing laryngeal microsurgery for benign vocal fold lesions such as vocal polyps and cysts. This was a retrospective, single institution cohort study. Patient medical records were reviewed for demographic characteristics; acoustic, aerodynamic, and perceptual analyses; and Voice Handicap Index score before and after laryngeal microsurgery. Definitive diagnoses were made via intraoperative microlaryngoscopic evaluations. Clinical parameters were assessed to identify risk factors for contralateral reactive lesions. We evaluated surgical outcome using voice analysis. We enrolled 268 patients (109 men and 159 women) with benign vocal fold lesions. A total of 195 (72.8%) had a contralateral reactive vocal fold lesion. A multivariable analysis revealed that being a never smoker and having a hoarseness duration ≥6 months, vocal polyps, and small primary lesions were independent risk factors for contralateral reactive lesions (P vocal fold lesions are frequently detected in patients with vocal polyp and cyst. The reactive lesions had an adverse effect on voice quality. Simultaneous excision of primary and contralateral reactive lesions may be an alternative treatment for better voice outcome. Copyright © 2018 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Practical considerations in clinical strategy to support the development of injectable drug-device combination products for biologics

Science.gov (United States)

Easton, Rachael

2018-01-01

ABSTRACT The development of an injectable drug-device combination (DDC) product for biologics is an intricate and evolving process that requires substantial investments of time and money. Consequently, the commercial dosage form(s) or presentation(s) are often not ready when pivotal trials commence, and it is common to have drug product changes (manufacturing process or presentation) during clinical development. A scientifically sound and robust bridging strategy is required in order to introduce these changes into the clinic safely. There is currently no single developmental paradigm, but a risk-based hierarchical approach has been well accepted. The rigor required of a bridging package depends on the level of risk associated with the changes. Clinical pharmacokinetic/pharmacodynamic comparability or outcome studies are only required when important changes occur at a late stage. Moreover, an injectable DDC needs to be user-centric, and usability assessment in real-world clinical settings may be required to support the approval of a DDC. In this review, we discuss the common issues during the manufacturing process and presentation development of an injectable DDC and practical considerations in establishing a clinical strategy to address these issues, including key elements of clinical studies. We also analyze the current practice in the industry and review relevant and status of regulatory guidance in the DDC field. PMID:29035675

Clinical significance of determination of serum TRAb levels in patients with thyroid diseases

International Nuclear Information System (INIS)

Wu Lijian; Tang Bing; Yang Chunying; Lin Jun

2005-01-01

Objective: To investigate the clinical Significance of determination of serum thyroid stimulating hormone receptor antibody (TRAb) levels in patients with thyroid diseases, especially in patients with Graves' disease. Methods: Serum TRAb levels were determined with radio-receptor assay (RRA) in 302 patients with various thyroid diseases and 52 controls. Results: In patients with Graves' disease before treatment (n=62) the positive rate of TRAb was 86.3%. In patients with Graves' diseases improved after treatment (n=60), the positive rate was 74.5%; in those clinically cured (n=68) the positive rate was 32.1%. In 58 patients with Graves' disease who relapsed after apparently cure, the positive rate of TRAb rose to 90.3 %. However, there were no positive TRAb cases in 23 patients with simple goiter and 31 patients with benign thyroid adenomas. Also, there were no positive TRAb cases in the controls. Conclusion: TRAb levels correspond well with the severity of Graves' disease. (authors)

[Study on computed tomography features of nasal septum cellule and its clinical significance].

Science.gov (United States)

Huang, Dingqiang; Li, Wanrong; Gao, Liming; Xu, Guanqiang; Ou, Xiaoyi; Tang, Guangcai

2008-03-01

To investigate the features of nasal septum cellule in computed tomographic (CT) images and its clinical significance. CT scans data of nasal septum in 173 patients were randomly obtained from January 2001 to June 2005. Prevalence and clinical features were summarized in the data of 19 patients with nasal septum cellule retrospectively. (1) Nineteen cases with nasal septum cellule were found in 173 patients. (2) All nasal septum cellule of 19 cases located in perpendicular plate of the ethmoid bone, in which 8 cases located in upper part of nasal septum and 11 located in middle. (3) There were totally seven patients with nasal diseases related to nasal septum cellule, in which 3 cases with inflammation, 2 cases with bone fracture, 1 case with cholesterol granuloma, 1 case with mucocele. Nasal septum cellule is an anatomic variation of nasal septum bone, and its features can provide further understanding of some diseases related to nasal septum cellule.

Use of Digital Rectal Examination as an Adjunct to Prostate Specific Antigen in the Detection of Clinically Significant Prostate Cancer.

Science.gov (United States)

Halpern, Joshua A; Oromendia, Clara; Shoag, Jonathan E; Mittal, Sameer; Cosiano, Michael F; Ballman, Karla V; Vickers, Andrew J; Hu, Jim C

2018-04-01

Guidelines from the NCCN ® (National Comprehensive Cancer Network®) advocate digital rectal examination screening only in men with elevated prostate specific antigen. We investigated the effect of prostate specific antigen on the association of digital rectal examination and clinically significant prostate cancer in a large American cohort. We evaluated the records of the 35,350 men who underwent digital rectal examination in the screening arm of the Prostate, Lung, Colorectal and Ovarian Cancer Screening trial for the development of clinically significant prostate cancer (Gleason 7 or greater). Followup was 343,273 person-years. The primary outcome was the rate of clinically significant prostate cancer among men with vs without suspicious digital rectal examination. We performed competing risks regression to evaluate the interaction between time varying suspicious digital rectal examination and prostate specific antigen. A total of 1,713 clinically significant prostate cancers were detected with a 10-year cumulative incidence of 5.9% (95% CI 5.6-6.2). Higher risk was seen for suspicious vs nonsuspicious digital rectal examination. Increases in absolute risk were small and clinically irrelevant for normal (less than 2 ng/ml) prostate specific antigen (1.5% vs 0.7% risk of clinically significant prostate cancer at 10 years), clinically relevant for elevated (3 ng/ml or greater) prostate specific antigen (23.0% vs 13.7%) and modestly clinically relevant for equivocal (2 to 3 ng/ml) prostate specific antigen (6.5% vs 3.5%). Digital rectal examination demonstrated prognostic usefulness when prostate specific antigen was greater than 3 ng/ml, limited usefulness for less than 2 ng/ml and marginal usefulness for 2 to 3 ng/ml. These findings support the restriction of digital rectal examination to men with higher prostate specific antigen as a reflex test to improve specificity. It should not be used as a primary screening modality to improve sensitivity. Copyright �

Chapter 24: the coming of molecular biology and its impact on clinical neurology.

Science.gov (United States)

Smith, Christopher U M

2010-01-01

Although the chemical study of the nervous system dates back well into the 19th century, molecular biology and especially molecular neurobiology only began to be established in the second half of the 20th century. This chapter reviews their impact on clinical neuroscience during the 50 years since Watson and Crick published their seminal paper. After a short review of the part played by F.O. Schmitt in establishing molecular neuroscience the chapter outlines work that led to a detailed understanding of the biochemical structure and function of nerve cell membranes and their embedded channel proteins, receptors, and other molecules. The chapter then turns to the numerous pathologies that result from disorders of these elements: the various channel and gap-junction pathologies. The chapter continues with a discussion of some of the diseases caused by defective DNA, especially the trinucleotide repeat expansion diseases (TREDs) and ends with a short account of the development of molecular approaches to prion diseases, myasthenia gravis, and the neurodegenerative diseases of old age. Francis Bacon said long ago that "knowledge is power." The hope is that increasing molecular knowledge will help cure some of the human suffering seen in the neurological ward and clinic.

Using redescription mining to relate clinical and biological characteristics of cognitively impaired and Alzheimer's disease patients.

Science.gov (United States)

Mihelčić, Matej; Šimić, Goran; Babić Leko, Mirjana; Lavrač, Nada; Džeroski, Sašo; Šmuc, Tomislav

2017-01-01

Based on a set of subjects and a collection of attributes obtained from the Alzheimer's Disease Neuroimaging Initiative database, we used redescription mining to find interpretable rules revealing associations between those determinants that provide insights about the Alzheimer's disease (AD). We extended the CLUS-RM redescription mining algorithm to a constraint-based redescription mining (CBRM) setting, which enables several modes of targeted exploration of specific, user-constrained associations. Redescription mining enabled finding specific constructs of clinical and biological attributes that describe many groups of subjects of different size, homogeneity and levels of cognitive impairment. We confirmed some previously known findings. However, in some instances, as with the attributes: testosterone, ciliary neurotrophic factor, brain natriuretic peptide, Fas ligand, the imaging attribute Spatial Pattern of Abnormalities for Recognition of Early AD, as well as the levels of leptin and angiopoietin-2 in plasma, we corroborated previously debatable findings or provided additional information about these variables and their association with AD pathogenesis. Moreover, applying redescription mining on ADNI data resulted with the discovery of one largely unknown attribute: the Pregnancy-Associated Protein-A (PAPP-A), which we found highly associated with cognitive impairment in AD. Statistically significant correlations (p ≤ 0.01) were found between PAPP-A and clinical tests: Alzheimer's Disease Assessment Scale, Clinical Dementia Rating Sum of Boxes, Mini Mental State Examination, etc. The high importance of this finding lies in the fact that PAPP-A is a metalloproteinase, known to cleave insulin-like growth factor binding proteins. Since it also shares similar substrates with A Disintegrin and the Metalloproteinase family of enzymes that act as α-secretase to physiologically cleave amyloid precursor protein (APP) in the non-amyloidogenic pathway, it could be

Using redescription mining to relate clinical and biological characteristics of cognitively impaired and Alzheimer's disease patients.

Directory of Open Access Journals (Sweden)

Matej Mihelčić

Full Text Available Based on a set of subjects and a collection of attributes obtained from the Alzheimer's Disease Neuroimaging Initiative database, we used redescription mining to find interpretable rules revealing associations between those determinants that provide insights about the Alzheimer's disease (AD. We extended the CLUS-RM redescription mining algorithm to a constraint-based redescription mining (CBRM setting, which enables several modes of targeted exploration of specific, user-constrained associations. Redescription mining enabled finding specific constructs of clinical and biological attributes that describe many groups of subjects of different size, homogeneity and levels of cognitive impairment. We confirmed some previously known findings. However, in some instances, as with the attributes: testosterone, ciliary neurotrophic factor, brain natriuretic peptide, Fas ligand, the imaging attribute Spatial Pattern of Abnormalities for Recognition of Early AD, as well as the levels of leptin and angiopoietin-2 in plasma, we corroborated previously debatable findings or provided additional information about these variables and their association with AD pathogenesis. Moreover, applying redescription mining on ADNI data resulted with the discovery of one largely unknown attribute: the Pregnancy-Associated Protein-A (PAPP-A, which we found highly associated with cognitive impairment in AD. Statistically significant correlations (p ≤ 0.01 were found between PAPP-A and clinical tests: Alzheimer's Disease Assessment Scale, Clinical Dementia Rating Sum of Boxes, Mini Mental State Examination, etc. The high importance of this finding lies in the fact that PAPP-A is a metalloproteinase, known to cleave insulin-like growth factor binding proteins. Since it also shares similar substrates with A Disintegrin and the Metalloproteinase family of enzymes that act as α-secretase to physiologically cleave amyloid precursor protein (APP in the non-amyloidogenic pathway

Statistical significance versus clinical relevance.

Science.gov (United States)

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

2017-04-01

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

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

DEFF Research Database (Denmark)

Nielsen, Mette J; Kazankov, Konstantin; Leeming, Diana J

2015-01-01

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... the markers C3M, C4M, C6M and P4NP7S were significantly elevated in patients with advanced fibrosis (≥F3) compared to F0-F2 (pC1M 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...

Clinical significance of changes of plasma TNF-α and CRP levels in patients with acute cerebral infarction

International Nuclear Information System (INIS)

Liu Xiaoyang; Xiao Changqing; He Yunnan

2006-01-01

Objective: To investigate the clinical significance of the changes of serum TNF-α and CRP levels in patients with acute cerebral infarction. Methods: Serum TNF-α (with RIA) and CRP (with scatter velocity turbidimetry) levels were determined in 50 patients with acute cerebral infarction and 62 controls. Results: The serum levels of TNF-α and CRP in patients with acute cerebral infarction were significantly higher than those in controls (P <0.01). Moreover, the levels were positively correlated with the size of the infarction (P<0.05). Conclusion: Changes of serum TNF-α and CRP levels during acute stage of cerebral infarction were closely related the clinical progression of the disease process. (authors)

Assessment of Sexual Desire for Clinical Trials of Women With Hypoactive Sexual Desire Disorder: Measures, Desire-Related Behavior, and Assessment of Clinical Significance.

Science.gov (United States)

Pyke, Robert E; Clayton, Anita H

2018-01-19

The Female Sexual Function Index-desire subscale is the standard measure for clinical trials of hypoactive sexual desire disorder (HSDD), but lacks items assessing sexually related behaviors and attitudes toward partner. Counting satisfying sexual events is criticized, but sexual behavior remains important. Mean treatment differences cannot define clinical significance; responder and remitter analyses help. We reviewed measures on sexual desire and sexual behavior relevant to HSDD, and how to assess clinical significance. We conducted a literature review of measures of sexual desire comparing expert-proposed criteria for dysfunctional desire, expert-developed scales, and scales from patient input. Commonly recognized symptoms of HSDD were identified. Results of HSDD trials and scale validation studies were evaluated to extract responder and remitter values. The utility of distribution-based measures of responders and remitters was assessed. Symptom relevance was evaluated as the proportion of symptom sets that included the item; responder and remitter cut points were determined by distribution-based methods. 12 Validated rating scales, 5 scales primarily derived from expert recommendations and 7 scales initially from patient input, and 5 sets of diagnostic criteria for conditions like HSDD were compared. Content varied highly between scales despite compliance with U.S. Food and Drug Administration recommendations for patient-reported outcomes. This disunity favors an expert-recommended scale such as the Elements of Desire Questionnaire with each of the common items, plus a measure of frequency of sexual activity, eg, item in the Patient Reported Outcomes Measurement Information System. Registrational drug trials, but not psychological treatment trials, usually give responder/remitter analyses, using dichotomized global impressions or anchor-based definitions. Distribution-based methods are more uniformly applicable to define responder and remitter status. The

The clinical significance of determining the plasma superoxide dismutase and neuropeptide Y in newborn hypoxic-ischemic encephalopathy

International Nuclear Information System (INIS)

Xu Xuezhong; Cui Zhenxing

2002-01-01

Objective: To investigate the contents of plasma superoxide dismutase (SOD) and neuropeptide Y (NPY) in newborn hypoxic-ischemic encephalopathy (HIE) babies in various clinic stages and their clinical significance. Methods: The plasma levels of SOD and NPY of 63 HIE babies and controls were determined by radioimmunoassay (RIA) and the values were studied for different clinical stages (severe 22, moderate 7 and mild 24). Results: The contents of plasma SOD and NPY of HIE babies of various stages were different and there existed remarkable contrast between those in patients and controls (p<0.05 or p<0.01). Conclusion: The contents of plasma SOD and NPY in HIE neonates were correlated to the clinic stage and severeness of the disease process

Changes and clinical significance of liver function and myocardial zymogram in children with rotavirus enteritis

Directory of Open Access Journals (Sweden)

Lan-Ping Yang

2016-12-01

Full Text Available Objective: To explore the changes and clinical significance of liver function and myocardial zymogram in children with rotavirus (RV enteritis. Methods: A total of 70 children with RV enteritis who were admitted in our hospital were included in the study and served as the observation group. The liver function and myocardial zymogram before and after treatment were detected. The proportion of RV enteritis children with liver and myocardial damage was calculated. The effect of dehydration on the liver function and myocardial zymogram in children with RV enteritis was analyzed. A total of 65 children with non-RV enteritis who were admitted in our hospital at the same stage were served as the control group. Results: The serum ALT, AST, CK, CK-MB, LDH, and α-HBDH levels, and liver myocardial damage children proportion in the observation group were significantly higher than those in the control group (P<0.05. The serum ALT, AST, CK, CK-MB, LDH, and α-HBDH levels in the observation group were significantly elevated with the acceleration of dehydration degree (P<0.05. In the observation group, 45 children had liver and myocardial damage, whose ALT, AST, CK, CKMB, LDH, and α-HBDH levels after treatment were significantly reduced when compared with before treatment (P<0.05. Conclusions: Early detection of liver function and myocardial zymogram can accurately reflect the condition in children with RV enteritis, which can provide an evidence for the formulation of clinical treatment protocol.

Intraocular pressure asymmetry is not a clinically-significant feature when using the PULSAIR non-contact tonometer.

Science.gov (United States)

Pointer, J S

1997-11-01

This report describes the results of a retrospective analysis of intraocular pressure (i.o.p.) values recorded from the right (R) and left (L) eyes of middle-aged and elderly at-risk but assumed non-glaucomatous subjects. The tensions had been measured using the Keeler PULSAIR non-contact tonometer (NCT) in the course of routine optometric practice when individuals attended for a sight test. These bilateral IOP data were collated on the basis of each subject's gender, (male/female), age (40-59 years/60+ years) and the time of the tonometry assessment (a.m./p.m.). Wherever possible material was equi-partitioned across these three bipartite variables producing balanced data groupings. Pair-wise testing of R versus L absolute values of pneumo-applanation pressures across any of the balanced data groupings failed to reveal a statistically-significant difference between the paired IOP distributions. There was a consistent but small relative IOP asymmetry (L > R) in these data. Further analysis indicated that this asymmetry only attained borderline statistical significance with respect to subject's age: neither gender nor the time of assessment were statistically significant features, and there were no statistically-significant interactions between any of the three variables. In conclusion, provided that the manufacturer's operating instructions are adhered to, IOP asymmetry is not a clinically-significant feature when using the PULSAIR NCT on a clinical population at risk of developing glaucoma.

Clinical significance of changes of plasma CGRP and VIP levels in infants with bronchiolitis

International Nuclear Information System (INIS)

Yang Chun; Gu Ling; Zhang Yanjun; Xin Haiyan

2005-01-01

Objective: To explore the clinical significance of changes of calcitonin gene-related peptide (CGRP) and vasoactive intestinal peptide (VIP) levels in infants (2-24months) with bronchiolitis. Methods: Plasma levels of CGRP and VIP were determined with RIA in 31 infants with bronchiolitis both during acute infection and convalescence as well as in 35 controls. Results: Plasma CGRP levels in patients during acute infection were significantly higher than those in patients during convalescence and in controls (P<0.05). Levels of CGRP dropped during convalescence, but still remained significantly higher than those in controls (P<0.05). The reverse was true for the plasma VIP levels. The plasma VIP levels in patients during acute infection were significantly lower than those in patients during convalescence and in controls (P<0.05). During convalescence, the plasma VIP levels rose but remained significantly lower than those in controls (P<0.05). Conclusion: There were dynamic changes of plasma CGRP and VIP levels in the course of infant bronchiolitis and the two peptides played opposite roles. (authors)

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

International Nuclear Information System (INIS)

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

2014-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2014-03-15

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

Neurosurgery clinical registry data collection utilizing Informatics for Integrating Biology and the Bedside and electronic health records at the University of Rochester.

Science.gov (United States)

Pittman, Christine A; Miranpuri, Amrendra S

2015-12-01

In a population health-driven health care system, data collection through the use of clinical registries is becoming imperative to continue to drive effective and efficient patient care. Clinical registries rely on a department's ability to collect high-quality and accurate data. Currently, however, data are collected manually with a high risk for error. The University of Rochester's Department of Neurosurgery in conjunction with the university's Clinical and Translational Science Institute has implemented the integrated use of the Informatics for Integrating Biology and the Bedside (i2b2) informatics framework with the Research Electronic Data Capture (REDCap) databases.

Dispersed repetitive sequences in eukaryotic genomes and their possible biological significance

International Nuclear Information System (INIS)

Georgiev, G.P.; Kramerov, D.A.; Ryskov, A.P.; Skryabin, K.G.; Lukanidin, E.M.

1983-01-01

In this paper is described the properties of a novel mouse mdg-like element, the A2 sequence, which is the most abundant repetitive sequence. We also characterized an ubiquitous B2 sequence that represents, after B1, the dominant family among the short interspersed repeats of the mouse genome. The existence of some putative transposition intermediates was shown for repeats of both A and B types of the mouse genome. These are closed circular DNA of the A type and small polyadenylated B + RNAs. The fundamental question that arises is whether these sequences are simply selfish DNA capable of transpositions or do they fulfill some useful biological functions within the genome. 66 references, 11 figures, 1 table

Clinical Significance of 18F-FDG-PET in Invasive Lobular Carcinoma.

Science.gov (United States)

Fujii, Takaaki; Yajima, Reina; Kurozumi, Sasagu; Higuchi, Toru; Obayashi, Sayaka; Tokiniwa, Hideaki; Nagaoka, Rin; Takata, Daisuke; Horiguchi, Jun; Kuwano, Hiroyuki

2016-10-01

The diagnostic utility of 18 F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) for breast cancer is controversial. The histological type or tumor size of breast cancer has been reported to be associated with a greater likelihood of positive FDG uptake. Compared to invasive ductal carcinomas (IDCs), invasive lobular carcinomas (ILCs) have a lower level of FDG uptake and are detected at a significantly lower sensitivity. The role of preoperative FDG-PET for ILCs may, thus, be limited. Few data evaluating the significance of FDG-PET in ILCs are available. Here, we evaluated the clinical significance of FDG-PET for ILC patients. We retrospectively investigated the cases of 196 consecutive patients with primary breast cancer who were diagnosed as having ILC (n=15) or IDC (n=181) and underwent FDG-PET preoperatively. Fifteen (7.7%) of patients were histopathologically diagnosed as ILC. A univariate analysis revealed that tumor size, extent of tumor, estrogen receptor (ER) expression and progesterone receptor (PgR) expression were significantly different between the ILC and IDC groups. The maximum standardized uptake value (SUV max ) values of the primary tumors were not significantly different between the two groups but, regardless of the larger size of tumor or ductal spread, the SUV max was relatively lower in the ILC group compared to the IDC group. The tumors in two ILC cases showed no FDG uptake. Among the ILC cases, there were linear associations between SUV max and tumor size and between SUV max and the nuclear grade by Pearson correlation (r=0.447, p=0.048 and r=0.519, p=0.024, respectively). Our findings imply that the preoperative FDG uptake in ILC may be reflective of the tumor size and the nuclear grade of the tumor. FDG uptake may be useful and predictive of aggressive features or prognosis in ILC patients. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Current dichotomy between traditional molecular biological and omic research in cancer biology and pharmacology.

Science.gov (United States)

Reinhold, William C