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Sample records for age clinical stage

  1. Clinical stage of breast cancer by parity, age at birth, and time since birth: a progressive effect of pregnancy hormones?

    PubMed

    Albrektsen, Grethe; Heuch, Ivar; Thoresen, Steinar; Kvåle, Gunnar

    2006-01-01

    Breast cancer diagnosed during pregnancy or 1 to 2 years after birth often occurs at a late stage. Little is known about tumor characteristics in the high-risk period shortly after a childbirth. We here explore whether stage of disease differs according to timing of births. Results are based on 22,351 Norwegian breast cancer patients of parity 0 to 5, ages 20 to 74 years. The proportion of stage II to IV tumors was considerably higher among parous than nulliparous women at age <30 years (52.7% versus 36.8%, P=0.009), but similar or lower in other age groups (P(interaction)=0.029). In general, the largest proportion of stage II to IV tumors was found among women diagnosed during pregnancy or <2 years after birth. However, among women with late-age births (first or second birth >or=30 years, third birth >or=35 years), as well as women with an early second birth (<25 years), the proportion with advanced disease was rather similar or even higher among those diagnosed 2 to 6 years after birth (49.3-56.0%). The association between clinical stage and time since birth reached statistical significance among women with a late first or second birth and among all triparous women (P

  2. Clinical implications of aging.

    PubMed

    King, Mitch; Lipsky, Martin S

    2015-11-01

    Figure summarizes the major changes of aging and some key ways these changes affect pages. Though many changes occur with aging, under normal or resting conditions, there is usually very little functionally that is diminished solely on the basis of aging. The net effects are reductions in reserve capacity and placing geriatric patients at higher risk for adverse consequences related to medications and diseases. Interactions between lifestyle factors, such as exercise, diet, and environmental exposures, have a large impact on aging and lead to great individual variability. The interplay between these environmental factors, aging, and development of chronic diseases multiply the amount of variation seen as individual's age.

  3. Age and clinical dengue illness.

    PubMed

    Egger, Joseph R; Coleman, Paul G

    2007-06-01

    The relationship between age and risk for classic dengue fever has never been quantified. We use data from clinical patients to show that the relative risk of having classical disease after primary dengue virus infection increases with age. This relationship has implications for strategies aimed at controlling dengue fever.

  4. Ages & Stages Questionnaire–Brazil–2011

    PubMed Central

    Santana, Cristina M. T.; Filgueiras, Alberto; Landeira-Fernandez, J.

    2015-01-01

    Introduction. Professionals who assess early childhood development highly benefit from reliable development screening measures. The Ages & Stages Questionnaire was adapted Brazil in 2010 and named ASQ-BR. Modifications in some items were required to improve the instrument’s psychometric properties. The present study modified the ASQ-BR to verify if those changes increase its characteristics. Method. This study researched 67 522 children from 972 public day care centers and preschools. Changes in items were made considering Cronbach’s α and item-to-total correlations. Reliability, dimensionality, and item-to-total correlations were calculated. Results. Regarding dimensionality, 86.2% of the scales in ASQ-BR-2011 were unidimensional. Internal consistency showed improvement from 2010 to 2011: 53.8% of the scales increased the α statistics against 41.2% that decreased, and 5.0% remained the same. Finally, 65.2% of the modified items showed improvement. Conclusions. Overall, the instrument’s psychometrics improved from 2010 to 2011, especially in the personal/social domain. However, it still leaves room for improvement in future studies. PMID:27335984

  5. Biomarkers and clinical staging in psychiatry

    PubMed Central

    McGorry, Patrick; Keshavan, Matcheri; Goldstone, Sherilyn; Amminger, Paul; Allott, Kelly; Berk, Michael; Lavoie, Suzie; Pantelis, Christos; Yung, Alison; Wood, Stephen; Hickie, Ian

    2014-01-01

    Personalized medicine is rapidly becoming a reality in today's physical medicine. However, as yet this is largely an aspirational goal in psychiatry, despite significant advances in our understanding of the biochemical, genetic and neurobiological processes underlying major mental disorders. Preventive medicine relies on the availability of predictive tools; in psychiatry we still largely lack these. Furthermore, our current diagnostic systems, with their focus on well-established, largely chronic illness, do not support a pre-emptive, let alone a preventive, approach, since it is during the early stages of a disorder that interventions have the potential to offer the greatest benefit. Here, we present a clinical staging model for severe mental disorders and discuss examples of biological markers that have already undergone some systematic evaluation and that could be integrated into such a framework. The advantage of this model is that it explicitly considers the evolution of psychopathology during the development of a mental illness and emphasizes that progression of illness is by no means inevitable, but can be altered by providing appropriate interventions that target individual modifiable risk and protective factors. The specific goals of therapeutic intervention are therefore broadened to include the prevention of illness onset or progression, and to minimize the risk of harm associated with more complex treatment regimens. The staging model also facilitates the integration of new data on the biological, social and environmental factors that influence mental illness into our clinical and diagnostic infrastructure, which will provide a major step forward in the development of a truly pre-emptive psychiatry. PMID:25273285

  6. Clinical presentation and staging of Hodgkin lymphoma.

    PubMed

    Gallamini, Andrea; Hutchings, Martin; Ramadan, Safaa

    2016-07-01

    In the present chapter the authors present a brief overview of the diagnostic methods proposed over time for Hodgkin lymphoma (HL) spread detection, moving from surgical procedures, through standard radiological and functional imaging techniques to the present state of the art for HL staging. The main body of the review will be dedicated to the recently published guidelines for lymphoma staging (including HL) agreed by the experts during the 12th International Congress for Malignant Lymphoma in Lugano. The recommendations of the panel on how to integrate flurodeoxyglucose positron emission tomography (FDG-PET) scan in the armamentarium of staging procedures will be presented and commented, with a special emphasis on the utility of special procedures, such as bone marrow trephine biopsy, which is deemed no longer needed in the PET era. While the HL diagnosis is straightforward in most cases, sometimes HL is a subtle disease, difficult to diagnose for the paucity of symptoms, the absence of physical findings, or for concomitant immunologic disorders: a compete overview of the common and rare patterns of HL clinical presentation will be also offered. The future perspective of PET scan use will be based on a operator-independent, quantitative readings of the scan thanks to a plethora of sophisticated dedicated software, which are now available, able to quantify every voxel captured by the tumor to display the metabolically active tumor volume. Moreover, new tracers are now available able to track the new pathways of cellular metabolism beside glycolysis such as amino acids or purine-analogues or specific oncoproteins; the preliminary, promising results will be reported. Preliminary results from other imaging techniques, such as diffusion-weighted magnetic resonance (DW-MRI) will be also reported. PMID:27496305

  7. Development: Ages & Stages--Emerging Physical Skills

    ERIC Educational Resources Information Center

    Poole, Carla; Miller, Susan A.; Church, Ellen Booth

    2005-01-01

    In this article, the authors discuss how children develop their motor skills at different age levels. Newborn's movements are jerky and uncoordinated. Spending lots of floor time with a baby lying on her back or stomach helps her develop coordination, balance, and muscle strength during her earliest months. As locomotion enters a baby's life, she…

  8. Clinical pharmacology of old age syndromes

    PubMed Central

    Broadhurst, C; Wilson, K C M; Kinirons, M T; Wagg, A; Dhesi, J K

    2003-01-01

    Several syndromes occur in old age. They are often associated with increased mortality and in all there is a paucity of basic and clinical research. The recent developments in the clinical pharmacology of three common syndromes of old age (delirium, urinary incontinence, and falls) are discussed along with directions for future research. PMID:12919174

  9. Adaptive two-stage designs in phase II clinical trials.

    PubMed

    Banerjee, Anindita; Tsiatis, Anastasios A

    2006-10-15

    Two-stage designs have been widely used in phase II clinical trials. Such designs are desirable because they allow a decision to be made on whether a treatment is effective or not after the accumulation of the data at the end of each stage. Optimal fixed two-stage designs, where the sample size at each stage is fixed in advance, were proposed by Simon when the primary outcome is a binary response. This paper proposes an adaptive two-stage design which allows the sample size at the second stage to depend on the results at the first stage. Using a Bayesian decision-theoretic construct, we derive optimal adaptive two-stage designs; the optimality criterion being minimum expected sample size under the null hypothesis. Comparisons are made between Simon's two-stage fixed design and the new design with respect to this optimality criterion. PMID:16479547

  10. [Performing madness: the clinic as stage].

    PubMed

    Herrn, Rainer; Friedland, Alexander

    2014-12-01

    In the second half of the nine- teenth century, clinical demonstrations became the dominant teaching method in psychiatry, playing a key role in medical-professional disputes, as well. This paper traces this widely used though historiographically neglected practice of knowledge implementation and mediation, as demonstrated in the psychiatric clinic of the Berlin Charité (Psychiatrische und Nervenklinik der Berliner Charité) from 1881 to 1927. Documentation of this practice, found within individual medical records, forms the basis of this research. The concept of 'theatricality' assists in uncovering the dramatic quality of the clinical demonstration: Psychiatric knowledge was not simply disseminated through such a practice; rather, such knowledge was first performatively created through the very logic of its presentation of exemplary patient histories, as well as through the examination and diagnostic positioning of its patients. The 'success' of such presentations depended on many variables, related to staff, time, place, and other situational factors. These include the presence of appropriate lecture halls, the availability and calculated selection of patients, and the employment of specific performative techniques by doctors for the sake of producing desired results. As one effect, clinical demonstrations also encouraged patients to both learn and rehearse behavior considered relevant to the particular diagnosis that was to be demonstrated. PMID:25671967

  11. Age or stage structure? A comparison of dynamic outcomes from discrete age- and stage-structured population models.

    PubMed

    Wikan, Arild

    2012-06-01

    Discrete stage-structured density-dependent and discrete age-structured density-dependent population models are considered. Regarding the former, we prove that the model at hand is permanent (i.e., that the population will neither go extinct nor exhibit explosive oscillations) and given density dependent fecundity terms we also show that species with delayed semelparous life histories tend to be more stable than species which possess precocious semelparous life histories. Moreover, our findings together with results obtained from other stage-structured models seem to illustrate a fairly general ecological principle, namely that iteroparous species are more stable than semelparous species. Our analysis of various age-structured models does not necessarily support the conclusions above. In fact, species with precocious life histories now appear to possess better stability properties than species with delayed life histories, especially in the iteroparous case. We also show that there are dynamical outcomes from semelparous age-structured models which we are not able to capture in corresponding stage-structured cases. Finally, both age- and stage-structured population models may generate periodic dynamics of low period (either exact or approximate). The important prerequisite is to assume density-dependent survival probabilities. PMID:22297621

  12. Age and correlation of California Paleogene benthic foraminiferal stages

    USGS Publications Warehouse

    Poore, Richard Z.

    1980-01-01

    Comparisons of age determinations and correlations derived from calcareous plankton with those derived from benthic foraminifers in a number of sections in California show significant overlap in time of the Ynezian through the Ulatisian Stages. Thus interbasin time correlations deduced from these stage assignments must be treated with caution. Calcareous plankton occasionally associated with benthic foraminifers diagnostic of the Narizian through the Zemorrian Stages indicate that the Narizian-Refugian boundary is within the upper Eocene of international usage and that the Refugian is entirely upper Eocene. Overlap of the Narizian and the Refugian appears to be minimal. The Zemorrian correlates, mostly, with the Oligocene, although the upper limit of the Zemorrian might be in the lower Miocene.

  13. Automatic age-related macular degeneration detection and staging

    NASA Astrophysics Data System (ADS)

    van Grinsven, Mark J. J. P.; Lechanteur, Yara T. E.; van de Ven, Johannes P. H.; van Ginneken, Bram; Theelen, Thomas; Sánchez, Clara I.

    2013-03-01

    Age-related macular degeneration (AMD) is a degenerative disorder of the central part of the retina, which mainly affects older people and leads to permanent loss of vision in advanced stages of the disease. AMD grading of non-advanced AMD patients allows risk assessment for the development of advanced AMD and enables timely treatment of patients, to prevent vision loss. AMD grading is currently performed manually on color fundus images, which is time consuming and expensive. In this paper, we propose a supervised classification method to distinguish patients at high risk to develop advanced AMD from low risk patients and provide an exact AMD stage determination. The method is based on the analysis of the number and size of drusen on color fundus images, as drusen are the early characteristics of AMD. An automatic drusen detection algorithm is used to detect all drusen. A weighted histogram of the detected drusen is constructed to summarize the drusen extension and size and fed into a random forest classifier in order to separate low risk from high risk patients and to allow exact AMD stage determination. Experiments showed that the proposed method achieved similar performance as human observers in distinguishing low risk from high risk AMD patients, obtaining areas under the Receiver Operating Characteristic curve of 0.929 and 0.934. A weighted kappa agreement of 0.641 and 0.622 versus two observers were obtained for AMD stage evaluation. Our method allows for quick and reliable AMD staging at low costs.

  14. Advances take stage - Office of Cancer Clinical Proteomics Research

    Cancer.gov

    Regulatory advances in proteomics will be taking center stage at a Symposia scheduled to occur at the 2011 American Association for Clinical Chemistry (AACC) Annual Meeting. The symposium entitled "Enabling Translational Proteomics with NCI's Clinical Proteomic Technologies for Cancer" is scheduled for July 25, 2011 at AACC's annual Meeting.

  15. Magnetic Resonance Imaging of Adhesive Capsulitis: Correlation with Clinical Staging

    PubMed Central

    Ciavarra, Gina A.; Hannafin, Jo A.; Cordasco, Frank A.; Potter, Hollis G.

    2008-01-01

    The purpose of this study was to evaluate non-contrast magnetic resonance imaging (MRI) findings of adhesive capsulitis and correlate them with clinical stages of adhesive capsulitis. This will hopefully define a role for shoulder MR imaging in the diagnosis of adhesive capsulitis as well as in potentially directing appropriate treatment. Forty-seven consecutive non-contrast magnetic resonance imaging examinations of 46 patients with a clinical diagnosis of adhesive capsulitis were retrospectively reviewed and correlated with clinical staging. Specific MRI criteria correlated with the clinical stage of adhesive capsulitis, including the thickness and signal intensity of the joint capsule and synovium as well as the presence and severity of scarring in the rotator interval. Routine MRI of the shoulder without intraarticular administration of gadolinium can be used to diagnose all stages of adhesive capsulitis, including stage 1, where findings may be subtle on clinical examination. We believe that future studies assessing the role of MRI in guiding the initiation of appropriate treatment should be undertaken. PMID:18815860

  16. Eyelid aging: pathophysiology and clinical management.

    PubMed

    Damasceno, Renato Wendell; Avgitidou, Georgia; Belfort, Rubens; Dantas, Paulo Elias Correa; Holbach, Leonard M; Heindl, Ludwig M

    2015-01-01

    Life expectancy is increasing in most countries. With increasing age, many individuals may develop involutional ophthalmic diseases, such as eyelid aging. Dermatochalasis, ptosis, ectropion, and entropion are common disorders in middle-aged and older adults. This review outlines the pathophysiology and clinical management of these involutional eyelid disorders. Recently, a decrease in elastic fibers with ultrastructural abnormalities and an overexpression of elastin-degrading enzymes have been demonstrated in involutional ectropion and entropion. This may be the consequence of local ischemia, inflammation, and/or chronic mechanical stress. Eyelid aging with progressive loss of tone and laxity may affect the ocular surface and adnexal tissues, resulting in different clinical symptoms and signs. Surgical management depends on the appropriate correction of the underlying anatomical defect. PMID:26466237

  17. Clinical aspects of 2541 patients with second stage human African trypanosomiasis.

    PubMed

    Blum, Johannes; Schmid, Caecilia; Burri, Christian

    2006-01-01

    The clinical symptoms and signs of patients with second stage HAT are described for a large cohort of patients treated in a prospective multicentre, multinational study. Special emphasis is given to the influence of disease stage (duration, number of WBC in CSF) and patient age to the clinical picture. Even though the frequencies of symptoms and signs are highly variable between centres, the clinical picture of the disease is similar for all countries. Headache (78.7%), sleeping disorder (74.4%) and lymphadenopathy (56.1%) are the most frequent symptoms and signs and they are similar for all stages of the disease. Lymphadenopathy tends to be highest in the advanced second stage (59.0%). The neurological and psychiatric symptoms increase significantly with the number of WBC in the CSF indicating the stage of progression of the disease. Pruritus is observed in all stages and increases with the number of WBC in CSF from 30 to 55%. In children younger than 7 years, lymphadenopathy is less frequently reported (11.8-37.3%) than in older children or adults (56.4-61.2%). Fever is most frequently reported in children between 2 and 14 years of age (26.1-28.7%) and malnutrition is significantly more frequently observed in children of all ages (43-56%) than in adults (23.5%).

  18. Health utility decreases with increasing clinical stage in amyotrophic lateral sclerosis.

    PubMed

    Jones, Ashley R; Jivraj, Naheed; Balendra, Rubika; Murphy, Caroline; Kelly, Joanna; Thornhill, Marie; Young, Carolyn; Shaw, Pamela J; Leigh, P Nigel; Turner, Martin R; Steen, I Nick; McCrone, Paul; Al-Chalabi, Ammar

    2014-06-01

    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease typically causing death within three years. Understanding the impact of disease on patients using health utility at different stages of ALS would allow meaningful cost-benefit analysis of new potential therapies. A common health-related quality of life measurement, developed and validated for the UK, is the EQ-5D. Using clinical trial data from the LiCALS study, we calculated health utility using the EQ-5D for each King's ALS clinical stage from 214 patients. We analysed whether health utility, and other health-related measures, significantly changed between each of the clinical stages. Results showed that mean health utility decreased by 0.487 (the scale runs from 1 to - 0.594) between clinical stages 2A and 4. Emotional states, measured using the Hospital Anxiety and Depression Scale (HADS), showed worsening depression and anxiety scores as ALS progressed. Age of onset, disease onset, gender and treatment group were not predictors of EQ-5D, depression or anxiety. In conclusion, increasing severity of King's ALS Clinical Stage is associated with a progressive decrease in EQ-5D health utility. This is useful for cost-benefit analysis of new therapies and validates this ALS clinical staging system.

  19. Bone Mineral Density in Healthy Female Adolescents According to Age, Bone Age and Pubertal Breast Stage

    PubMed Central

    Moretto, M.R; Silva, C.C; Kurokawa, C.S; Fortes, C.M; Capela, R.C; Teixeira, A.S; Dalmas, J.C; Goldberg, T.B

    2011-01-01

    Objectives: This study was designed to evaluate bone mineral density (BMD) in healthy female Brazilian adolescents in five groups looking at chronological age, bone age, and pubertal breast stage, and determining BMD behavior for each classification. Methods: Seventy-two healthy female adolescents aged between 10 to 20 incomplete years were divided into five groups and evaluated for calcium intake, weight, height, body mass index (BMI), pubertal breast stage, bone age, and BMD. Bone mass was measured by bone densitometry (DXA) in lumbar spine and proximal femur regions, and the total body. BMI was estimated by Quetelet index. Breast development was assessed by Tanner’s criteria and skeletal maturity by bone age. BMD comparison according to chronologic and bone age, and breast development were analyzed by Anova, with Scheffe’s test used to find significant differences between groups at P≤0.05. Results: BMD (g·cm-2) increased in all studied regions as age advanced, indicating differences from the ages of 13 to 14 years. This group differed to the 10 and 11 to 12 years old groups for lumbar spine BMD (0.865±0.127 vs 0.672±0.082 and 0.689±0.083, respectively) and in girls at pubertal development stage B3, lumbar spine BMD differed from B5 (0.709±0.073 vs 0.936±0.130) and whole body BMD differed from B4 and B5 (0.867±0.056 vs 0.977±0.086 and 1.040±0.080, respectively). Conclusion: Bone mineralization increased in the B3 breast maturity group, and the critical years for bone mass acquisition were between 13 and 14 years of age for all sites evaluated by densitometry. PMID:21966336

  20. The relationship between cognitive reserve and the clinical stage of HIV infection.

    PubMed

    Alvarez-Tostado, Pablo; Inozemtseva, Olga; Aguiñiga, Miguel A; López, Enrique; Matute, Esmeralda

    2016-01-01

    The objective of this study was to determine whether the effect of cognitive reserve (CR) on neuropsychological functioning differs according to the clinical stage of HIV infection. A sample of 34 HIV-positive individuals aged 23-49, with a minimum of 9 years of formal education, was assessed. Participants were grouped according to the Centers for Disease Control and Prevention's (CDC) clinical stages (A = 10, B = 16, C = 8). CR was calculated for each clinical stage group in accordance with estimates of premorbid IQ, years of education, and occupational attainment. The sum of these three variables was then transformed into z-scores. Individuals above the median were classified as having "High" CR (HCR), those below the median were classified as "Low" CR (LCR). Participants completed an evaluation of cognitive and executive functions based on selected, modified tasks from the HIV University of Miami Annotated Neuropsychological test in Spanish (HUMANS). Assessment included the following domains: attention, memory (visual, verbal, and working memory), executive functions (cognitive flexibility, switching), language (naming), and visual constructive skills (block design). HCR outperformed LCR in all cognitive domains. Comparison of HCR and LCR in each clinical stage revealed that the effect of CR was stronger in stage B than in stages A and C, suggesting that this effect does indeed vary among stages.

  1. Clinical features of dysthymia and age: a clinical investigation.

    PubMed

    Bellino, S; Patria, L; Ziero, S; Rocca, G; Bogetto, F

    2001-09-20

    A few authors have described the clinical picture of dysthymia in groups of elderly patients and pointed out differences from literature reports of dysthymia in younger adults. The present study, an attempt to analyze age effects on clinical characteristics of dysthymia throughout a lifetime, was performed in a sample of 106 patients, all aged > or =18 years, who were diagnosed according to DSM-IV. The patients were evaluated using: (1) a semistructured interview to assess clinical features, family history and previous treatments; (2) the Hamilton Depression Rating Scale; (3) the Interview for Recent Life Events; and (4) the Structured Clinical Interview for DSM-IV Disorders. Statistical analysis with stepwise logistic regression revealed that age was positively related to concomitant medical illnesses and to the total score of recent life events, but negatively related to the presence of avoidant or dependent personality disorders. The data suggested different etiologic pathways in older and younger patients. Dysthymia appeared to be associated in younger adults with abnormalities of personality; in the elderly, with a history of health problems and life losses.

  2. Schizophrenia: analysis and psychological treatment according to the clinical staging.

    PubMed

    Ruiz-Iriondo, María; Salaberria, Karmele; Echeburúa, Enrique

    2013-01-01

    The present paper provides an overview of the recent contributions to the study of the course of schizophrenia. This is not a disorder as chronic and as acute at its start as traditionally thought. Beyond the positive and negative symptoms and different subtypes of illness, it is important to call attention to the development and course of schizophrenia. According to this approach, the aim of this paper is to review the most recent studies on schizophrenia according to clinical stages. With this aim, we review the research carried out by leading research teams and recently published clinical practice guidelines (Birmingham Group, Melbourne Group, GPCSNS, NICE) in relation to the course, the main features, and more adjusted treatment alternatives, aimed to improve the characteristic symptoms of each stage of the disease. Finally, we point out the necessity to integrate this approach with the proposed changes for the upcoming DSM-V. This review identifies effective treatment options for each of the phases of the disease defined by the clinical stage approach.

  3. The Edmonton Obesity Staging System for Pediatrics: A proposed clinical staging system for paediatric obesity

    PubMed Central

    Hadjiyannakis, Stasia; Buchholz, Annick; Chanoine, Jean-Pierre; Jetha, Mary M; Gaboury, Laurie; Hamilton, Jill; Birken, Catherine; Morrison, Katherine M; Legault, Laurent; Bridger, Tracey; Cook, Stephen R; Lyons, John; Sharma, Arya M; Ball, Geoff DC

    2016-01-01

    Traditionally, clinical recommendations for assessing and managing paediatric obesity have relied on anthropometric measures, such as body mass index (BMI), BMI percentile and/or BMI z-score, to monitor health risks and determine weight management success. However, anthropometric measures do not always accurately and reliably identify children and youth with obesity-related health risks or comorbidities. The authors propose a new clinical staging system (the Edmonton Obesity Staging System for Pediatrics, EOSS-P), adapted from the adult-oriented EOSS. The EOSS-P is used to stratify patients according to severity of obesity-related comorbidities and barriers to weight management into four graded categories (0 to 3) within four main health domains: metabolic, mechanical, mental health and social milieu (the 4Ms). The EOSS-P is based on common clinical assessments that are widely available and routinely completed by clinicians, and has the potential to provide clinical and prognostic information to help evaluate and inform the management of paediatric obesity. PMID:26941556

  4. The clinical profile of end-stage AIDS.

    PubMed

    Welch, K; Kissinger, P; Bessinger, R; Dascomb, K; Morse, A; Gleckler, E

    1998-02-01

    The purpose of this study was to describe the clinical profile of end-stage AIDS in patients 12 months before death. A cross-sectional examination of HIV-infected patients who attended a public HIV outpatient clinic between 1990 and 1996 and who died was conducted. The prevalence and first-time acquisition of AIDS-defining conditions 12 months before death were evaluated. The AIDS-defining conditions with the highest percentages of first-time acquisition in the last 12 months of life were progressive multifocal leukoencephalopathy (100%), lymphoma (96%), dementia (78.6%), Mycobacterium avium complex (MAC) infection (74.0%), toxoplasmosis (72.6%), and cytomegalovirus (CMV) infection (69.6%). Of the concomitant conditions studied, those with the highest percentages of first-time acquisition in the last 12 months of life were CMV with MAC (99%) and CMV with wasting (88%). Patients who acquire these AIDS-defining conditions may be eligible to receive information about end-stage options, such as hospice care. However, administration of aggressive antiretroviral treatments, such as the protease inhibitors, may affect this profile in the future, as the majority of the patients in this study were receiving the standard antiretroviral treatments of the time, primarily zidovudine.

  5. Atrophy patterns in early clinical stages across distinct phenotypes of Alzheimer's disease.

    PubMed

    Ossenkoppele, Rik; Cohn-Sheehy, Brendan I; La Joie, Renaud; Vogel, Jacob W; Möller, Christiane; Lehmann, Manja; van Berckel, Bart N M; Seeley, William W; Pijnenburg, Yolande A; Gorno-Tempini, Maria L; Kramer, Joel H; Barkhof, Frederik; Rosen, Howard J; van der Flier, Wiesje M; Jagust, William J; Miller, Bruce L; Scheltens, Philip; Rabinovici, Gil D

    2015-11-01

    Alzheimer's disease (AD) can present with distinct clinical variants. Identifying the earliest neurodegenerative changes associated with each variant has implications for early diagnosis, and for understanding the mechanisms that underlie regional vulnerability and disease progression in AD. We performed voxel-based morphometry to detect atrophy patterns in early clinical stages of four AD phenotypes: Posterior cortical atrophy (PCA, "visual variant," n=93), logopenic variant primary progressive aphasia (lvPPA, "language variant," n=74), and memory-predominant AD categorized as early age-of-onset (EOAD, <65 years, n=114) and late age-of-onset (LOAD, >65 years, n=114). Patients with each syndrome were stratified based on: (1) degree of functional impairment, as measured by the clinical dementia rating (CDR) scale, and (2) overall extent of brain atrophy, as measured by a neuroimaging approach that sums the number of brain voxels showing significantly lower gray matter volume than cognitively normal controls (n=80). Even at the earliest clinical stage (CDR=0.5 or bottom quartile of overall atrophy), patients with each syndrome showed both common and variant-specific atrophy. Common atrophy across variants was found in temporoparietal regions that comprise the posterior default mode network (DMN). Early syndrome-specific atrophy mirrored functional brain networks underlying functions that are uniquely affected in each variant: Language network in lvPPA, posterior cingulate cortex-hippocampal circuit in amnestic EOAD and LOAD, and visual networks in PCA. At more advanced stages, atrophy patterns largely converged across AD variants. These findings support a model in which neurodegeneration selectively targets both the DMN and syndrome-specific vulnerable networks at the earliest clinical stages of AD. PMID:26260856

  6. Decreased growth rate of P. falciparum blood stage parasitemia with age in a holoendemic population.

    PubMed

    Pinkevych, Mykola; Petravic, Janka; Chelimo, Kiprotich; Vulule, John; Kazura, James W; Moormann, Ann M; Davenport, Miles P

    2014-04-01

    In malaria holoendemic settings, decreased parasitemia and clinical disease is associated with age and cumulative exposure. The relative contribution of acquired immunity against various stages of the parasite life cycle is not well understood. In particular, it is not known whether changes in infection dynamics can be best explained by decreasing rates of infection, or by decreased growth rates of parasites in blood. Here, we analyze the dynamics of Plasmodium falciparum infection after treatment in a cohort of 197 healthy study participants of different ages. We use both polymerase chain reaction (PCR) and microscopy detection of parasitemia in order to understand parasite growth rates and infection rates over time. The more sensitive PCR assay detects parasites earlier than microscopy, and demonstrates a higher overall prevalence of infection than microscopy alone. The delay between PCR and microscopy detection is significantly longer in adults compared with children, consistent with slower parasite growth with age. We estimated the parasite multiplication rate from delay to PCR and microscopy detections of parasitemia. We find that both the delay between PCR and microscopy infection as well as the differing reinfection dynamics in different age groups are best explained by a slowing of parasite growth with age.

  7. Early clinical characteristics according to developmental stage in children with definite moyamoya disease.

    PubMed

    Kim, Young Ok; Joo, Sung-Pil; Seo, Bo-Ra; Rho, Young Il; Yoon, Woong; Woo, Young Jong

    2013-06-01

    The objective is to clarify the early clinical characteristics in childhood moyamoya disease (MD). Epidemiologic characteristics, symptoms and diagnostic rates were assessed in 64 children (0-18 years) with definite MD according to developmental stage: infancy (5; 0-1 years); toddlerhood/preschool age (22; 2-5 years); school age (29; 6-10 years); and adolescence (8; 11-18 years). The median ages at onset was 6.25 years and the female to male ratio was 1.9 (~2.5 in toddlerhood/preschool age and in adolescence, P=0.71). Previous headache was observed in 23% (14/64): frequently in school age (38%, P=0.02) and within 6 months before main symptoms (6/11). As an initial symptom, weakness was observed in 78% (50/64) mainly as transient ischemic attack (TIA, 61%) in limbs (90%) and unilaterally (82%). TIA was less frequent in infancy (40%, P=0.04). Seizure was observed in 27% (17/64): frequently in infancy (100%, P<0.01), as the focal type (71%), and in the right extremity (3:1). Isolated seizures without other symptoms was frequent in children ~5 years (P<0.01). Severe headache associated with MD was observed in 14% (9/64). Provoking events were positive in 42% (27/64): in school age, frequently during eating (28%); and in toddlerhood/preschool age, during crying (27%). The diagnostic rates at 3 and 12 months from symptom-onset were 39% (80% during infancy vs. 28% in school age, P=0.14) and 67%, respectively. Symptomatic progression at diagnosis was observed in 38% (24/64). Initial clinical characteristics in childhood definite MD differed according to developmental stage and from at diagnosis.

  8. Mandibular third molar development staging to chronologic age and sex in north Indian children and young adults.

    PubMed

    Rai, B; Kaur, J; Anand, S C

    2009-12-01

    Age estimation is not only important for clinical but also for medico-legal purposes. The present study is an attempt to estimate the chronologic age based on the stages of third molar development following the eight stages (A-H) method of Demirjian et al8 and to compare third molar development by sex and age. We examined 250 orthopantomograms of young north Indian subjects of known chronologic age (range, 7-26 years). Statistical analysis was performed using the Mann-Whitney U-test and the Wilcoxon test between sex and age. Regression analysis was performed to obtain BR regression formulae for dental age calculation with the chronologic age. Statistically significant differences in mandibular third-molar development between males and females were revealed regarding the calcification stages D and G. The results further indicated that third-molar formation was attained earlier in females than in males. Statistical analysis showed a strong correlation between age and third-molar development for both the sexes.

  9. Dental age estimation from the developmental stage of the third molars in western Chinese population.

    PubMed

    Li, Guo; Ren, Jiayin; Zhao, Shuping; Liu, Yuanyuan; Li, Na; Wu, Wanhong; Yuan, Shanshan; Wang, Hu

    2012-06-10

    The purpose of this study is to provide reference data about estimating dental age from third molars of the western Chinese population for comparing with other populations and being applied to the age estimation of western Chinese juveniles and adolescents. A total of 2078 digital panoramic radiographs of 989 male and 1089 female Chinese subjects aged between 5 and 23 years were examined. The mineralization status of the third molars was assessed using the formation stages described by Demirjian et al. with two modifications. The results showed that the development of third molars in the western Chinese population was likely to begin at age 5 in both males and females. The third molars 28 and 48 showed significantly higher frequency in females than in males. The third molars 18 in the stage 1, 38 in the stages 1, A and G, and 48 in the stage H showed significantly older average age in females than in males. The Demirjian's stages C and D could be used as a reference stage to determine dichotomously whether a western Chinese is more likely to be under or above age 14 or 16, respectively. This study provided reference data for the age estimation of western Chinese juveniles and adolescents by the mineralization stages of the third molar. Apart from forensic age determination in living subjects, the presented reference data can also be used for age estimations of unidentified corpses and skeletons.

  10. Association of Insurance Status and Age With Cervical Cancer Stage at Diagnosis: National Cancer Database, 2000–2007

    PubMed Central

    Cokkinides, Vilma; Virgo, Katherine S.; Bandi, Priti; Saslow, Debbie; Ward, Elizabeth M.

    2012-01-01

    Objectives. We examined the relationship of age at diagnosis and insurance status with stage among cervical cancer patients aged 21 to 85 years. Methods. We selected data on women (n = 69 739) diagnosed with invasive cervical cancer between 2000 and 2007 from the National Cancer Database. We evaluated the association between late stage (stage III/IV) and both insurance and age, with adjustment for race/ethnicity and other sociodemographic and clinical factors. We used multivariable log binomial models to estimate risk ratios (RRs) and 95% confidence intervals (CIs). Results. The proportion of late-stage disease increased with age: from 16.53% (21–34 years) to 42.44% (≥ 70 years). The adjusted relative risk of advanced-stage disease among women aged 50 years and older was 2.2 to 2.5 times that of patients aged 21 to 34 years. Uninsured (RR = 1.44; 95% CI = 1.40, 1.49), Medicaid (RR = 1.37, 95% CI = 1.34, 1.41), younger Medicare (RR = 1.12, 95% CI = 1.06, 1.19), and older Medicare (RR = 1.20, 95% CI = 1.15, 1.26) patients had a higher risk of late-stage disease than did privately insured patients. Conclusions. Screening should be encouraged for women at high risk for advanced-stage disease. PMID:22742058

  11. Clinical therapeutic strategies for early stage of diabetic kidney disease

    PubMed Central

    Kitada, Munehiro; Kanasaki, Keizo; Koya, Daisuke

    2014-01-01

    Diabetic kidney disease (DKD) is the most common cause of chronic kidney disease, leading to end-stage renal disease and cardiovascular disease. The overall number of patients with DKD will continue to increase in parallel with the increasing global pandemic of type 2 diabetes. Based on landmark clinical trials, DKD has become preventable by controlling conventional factors, including hyperglycemia and hypertension, with multifactorial therapy; however, the remaining risk of DKD progression is still high. In this review, we show the importance of targeting remission/regression of microalbuminuria in type 2 diabetic patients, which may protect against the progression of DKD and cardiovascular events. To achieve remission/regression of microalbuminuria, several steps are important, including the early detection of microalbuminuria with continuous screening, targeting HbA1c < 7.0% for glucose control, the use of renin angiotensin system inhibitors to control blood pressure, the use of statins or fibrates to control dyslipidemia, and multifactorial treatment. Reducing microalbuminuria is therefore an important therapeutic goal, and the absence of microalbuminuria could be a pivotal biomarker of therapeutic success in diabetic patients. Other therapies, including vitamin D receptor activation, uric acid-lowering drugs, and incretin-related drugs, may also be promising for the prevention of DKD progression. PMID:24936255

  12. "Life Stage-Specific" Variations in Performance in Response to Age Stereotypes

    ERIC Educational Resources Information Center

    Hehman, Jessica A.; Bugental, Daphne Blunt

    2013-01-01

    In a test of life stage-specific responses to age-based stigma, older (n = 54, ages 62-92) and younger (n = 81, ages 17-22) adults were told that a task (Weschler Adult Intelligence Scale-III block design) required either (a) speed/contemporary knowledge (YA; "youth advantage") or (b) life experience/wisdom (OA; "age…

  13. Age and the Association of Kidney Measures with Mortality and End-Stage Renal Disease

    PubMed Central

    Hallan, Stein I.; Matsushita, Kunihiro; Sang, Yingying; Mahmoodi, Bakhtawar K.; Black, Corri; Ishani, Areef; Kleefstra, Nanne; Naimark, David; Roderick, Paul; Tonelli, Marcello; Wetzels, Jack F.M.; Astor, Brad C.; Gansevoort, Ron T.; Levin, Adeera; Wen, Chi-Pang; Coresh, Josef

    2014-01-01

    Context Chronic kidney disease (CKD) is prevalent in older individuals, but the risk implications of low estimated glomerular filtration rate (eGFR) and high albuminuria across the full age range are controversial. Objective To evaluate possible effect modification (interaction) of age on the association of estimated GFR and albuminuria with clinical risk examining both relative and absolute risk. Design, Setting, Participants We investigated 2,051,244 participants from 33 general population or high-risk (of vascular disease) cohorts and 13 CKD cohorts from Asia, Australesia, Europe, and North/South America conducted during 1972–2011 with mean follow-up time of 5.8 years (range 0–31 years). Main Outcome Measures Hazard ratios (HRs) of mortality and end-stage renal disease (ESRD) according to eGFR and albuminuria were meta-analyzed across age categories after adjusting for sex, race, cardiovascular disease, diabetes, systolic blood pressure, cholestserol, body mass index, and smoking. Absolute risks were estimated using HRs and average incidence rates. Results Mortality (112,325 deaths) and ESRD (8,411 events) risk were higher at lower eGFR and higher albuminuria in every age category. In general/high-risk cohorts, relative mortality risk for reduced eGFR decreased with increasing age: e.g., adjusted HRs (95% CI) at eGFR 45 vs. 80 ml/min/1.73m2 were 3.50 (2.55–4.81), 2.21 (2.02–2.41), 1.59 (1.42–1.77), and 1.35 (1.23–1.48) in age categories 18–54, 55–64, 65–74 and 75+ years, respectively (P-values for age interaction <0.05). Absolute risk differences for the same comparisons were higher at older age (9.0 [95% CI, 6.0–12.8], 12.2 [10.3–14.3], 13.3 [9.0–18.6], and 27.2 [13.5–45.5] excess deaths per 1,000 person-years, respectively). For increased albuminuria, reduction of relative risk with increasing age were less evident, while differences in absolute risk were higher in the older age categories (7.5 [95% CI, 4.3–11.9], 12.2 [7.9–17

  14. C5b-9 Staining Correlates With Clinical and Tumor Stage in Gastric Adenocarcinoma

    PubMed Central

    Chen, Jian; Yang, Wei-jun; Sun, Hai-jian; Wu, Yu-zhang

    2016-01-01

    The complement system is a critical part of the immune response, acting in defense against viral infections, clearance of immune complexes, and maintenance of tissue homeostasis. Upregulated expression of the terminal complement complex, C5b-9, has been observed on various tumor cells, such as stomach carcinoma cells, and on cells in the necrotic regions of these tumors as well; however, whether and how C5b-9 is related to gastric cancer progression and severity remains unknown. In this study, human gastric adenocarcinoma (HGAC) tissues (n=47 cases) and patient-matched adjacent nontumoral parenchyma (n=20 cases) were evaluated by tissue microarray and immunohistochemistry. The HGAC tissues showed upregulated C5b-9 expression. Multinomial logistic regression and likelihood ratio testing showed that overexpression of C5b-9 in HGAC tissue was significantly correlated with clinical stage (P=0.007) and tumor stage (P=0.005), but not with tumor distant organ metastasis, lymphoid nodal status, sex, or age. Patients with late-stage gastric adenocarcinoma had a higher amount of tumor cells showing positive staining for C5b-9 than patients with early-stage disease. These results may help in diagnosis and assessment of disease severity of human gastric carcinoma. PMID:26186252

  15. Median ages at stages of sexual maturity and excess weight in school children

    PubMed Central

    2013-01-01

    Background We aimed to estimate the median ages at specific stages of sexual maturity stratified by excess weight in boys and girls. Materials and method This was a cross-sectional study made in 2007 in Florianopolis, Brazil, with 2,339 schoolchildren between 8 to 14 years of age (1,107 boys) selected at random in two steps (by region and type of school). The schoolchildren were divided into: i) those with excess weight and ii) those without excess weight, according to the WHO 2007 cut-off points for gender and age. Sexual maturity was self-evaluated by the subjects according to the Tanner sexual development stages, and utilizing median ages for the genitalia, breasts, and pubic hair stages. Results In the boys with excess weight, precocity was observed in the stages 4 for genitals and pubic hair and 2 for pubic hair, with the values for excess and normal weight. The median ages at the beginning of puberty (stage 2–sexual development) for boys and girls in Florianopolis were 10.8 and 10.3 years, respectively. Conclusion Excess weight is associated with lower median ages in the sexual maturity stages in boys and girls and that it should be taken into account when evaluating sexual maturity in children and adolescents. PMID:24139334

  16. Treatment results in women with clinical stage I and pathologic stage II endometrial carcinoma.

    PubMed

    Jobsen, J J; Schutter, E M; Meerwaldt, J H; Van Der Palen, J; Van Der Sijde, R; Ten Cate, L N

    2001-01-01

    The aim of this study is to report survival and results of therapy and possible prognostic factors in women with pathologic stage II endometrial carcinoma. Forty-two patients with pathologic stage II endometrial carcinoma were treated at the department of Radiation Oncology of the Medisch Spectrum Twente between 1987 and 1998. All patients received external radiotherapy following standard surgical procedures and no adjuvant systemic therapy was given. From the 42 patients 21 had a pathologic stage IIA and 21 stage IIB. The median follow-up was 62 months. The overall recurrence rate was 21.5% (9/42). Seven patients had distant metastasis, of which three also had locoregional recurrence, vaginal vault and/or pelvic. The presence of myometrial invasion (> (1/2)) and/or lymph-angioinvasion showed a significant relation with distant metastasis (P = 0.017). Stage IIB showed more recurrences, 33% (7/21). There was a significant different 5-year disease specific survival for stage IIA and IIB, respectively, 95% and 74% (P = 0.0311). Patients with a differentiation grade 3 and stage IIB showed a significantly poorer (P = 0.003) 5-year survival of 48.6% (P = 0.003). Results obtained in the present series of patients are in accordance with the literature. The present treatment policy seems justified, except for patients with pathologic stage IIB and grade 3, in which a more aggressive treatment should be considered. PMID:11285033

  17. Treatment results in women with clinical stage I and pathologic stage II endometrial carcinoma.

    PubMed

    Jobsen, J J; Schutter, E M; Meerwaldt, J H; Van Der Palen, J; Van Der Sijde, R; Ten Cate, L N

    2001-01-01

    The aim of this study is to report survival and results of therapy and possible prognostic factors in women with pathologic stage II endometrial carcinoma. Forty-two patients with pathologic stage II endometrial carcinoma were treated at the department of Radiation Oncology of the Medisch Spectrum Twente between 1987 and 1998. All patients received external radiotherapy following standard surgical procedures and no adjuvant systemic therapy was given. From the 42 patients 21 had a pathologic stage IIA and 21 stage IIB. The median follow-up was 62 months. The overall recurrence rate was 21.5% (9/42). Seven patients had distant metastasis, of which three also had locoregional recurrence, vaginal vault and/or pelvic. The presence of myometrial invasion (> (1/2)) and/or lymph-angioinvasion showed a significant relation with distant metastasis (P = 0.017). Stage IIB showed more recurrences, 33% (7/21). There was a significant different 5-year disease specific survival for stage IIA and IIB, respectively, 95% and 74% (P = 0.0311). Patients with a differentiation grade 3 and stage IIB showed a significantly poorer (P = 0.003) 5-year survival of 48.6% (P = 0.003). Results obtained in the present series of patients are in accordance with the literature. The present treatment policy seems justified, except for patients with pathologic stage IIB and grade 3, in which a more aggressive treatment should be considered.

  18. Effect of age, sex and physiological stages on hematological indices of Banni buffalo (Bubalus bubalis)

    PubMed Central

    Patel, Mehul D.; Lateef, Abdul; Das, Hemen; Patel, Ajay S.; Patel, Ajay G.; Joshi, Axay B.

    2016-01-01

    Aim: To determine the physiological baseline values for hematological indices of Banni buffalo (Bubalus bubalis) as well as to assess their alteration due to age, sex and physiological stages. Materials and Methods: A total of 42 clinically healthy Banni buffaloes were categorized into seven groups (n=6): Group I (male calves ≤1 year), Group II (bulls >1 year), Group III (female calves ≤1 year), Group IV (pregnant lactating buffaloes), Group V (non-pregnant lactating buffaloes), Group VI (pregnant dry buffaloes), and Group VII (non-pregnant dry buffaloes). Blood samples collected aseptically from all the experimental groups were analyzed employing automated hematology analyzer. The data obtained were statistically analyzed; the mean and standard deviations were calculated and set as the reference values. Results: The erythrocytic indices viz. total erythrocytes count (TEC), hemoglobin, and packed cell volume (PCV) were significantly higher in bulls as compared to that of male calves unlike mean corpuscular volume, mean corpuscular hemoglobin (MCH), and MCH concentration. The female calves had higher TEC and PCV than the adult buffaloes irrespective of sex. The total leukocyte count (TLC) and neutrophil counts in male calves were significantly lower than the bulls unlike the eosinophil, while monocyte and basophil remained unchanged with age. The TLC, differential leukocyte count and platelet count varied non-significantly among the adult female groups at different physiological stages. However, neutrophils were found to be apparently higher in lactating buffaloes. Conclusion: The present study would be helpful for physiological characterization of this unique buffalo breed of Gujarat. Further, data generated may be a tool for monitoring the health and prognosis as well as diagnosis of diseases. PMID:27051182

  19. Clinical Applications of Dexamethasone for Aged Eyes.

    PubMed

    Abadia, Beatriz; Calvo, Pilar; Ferreras, Antonio; Bartol, Fran; Verdes, Guayente; Pablo, Luis

    2016-09-01

    The risk of severe eye problems has been found to increase significantly with age, particularly between the fifth and sixth decades of life. Cataracts, dry eye, neovascular age-related macular degeneration, diabetic retinopathy and retinal vein occlusion (RVO) are very common and very different age-related ocular diseases that reduce the patient's quality of life. The rationale for using corticosteroids to treat anterior and posterior ocular segment diseases is driven by inflammation. Dexamethasone, one of the most powerful corticosteroids available, is widely used for topical or intravitreal administration. Topical dexamethasone has proven efficacy for the management of postoperative inflammation in the anterior segment after cataract surgery and symptom relief in dry-eye disease. A new sustained-release 700 µg dexamethasone intravitreal implant (DEX) was recently approved for the treatment of macular edema following RVO, diabetic macular edema, or non-infectious uveitis, and its use is increasing, especially when other therapeutic agents have failed. The most common side effects are increased intraocular pressure and cataract formation. The potency of DEX, alone or in combination with other agents, makes DEX a promising option for treating several retinal diseases. PMID:27566619

  20. Wound staging: can nurses apply classroom education to the clinical setting?

    PubMed

    Arnold, N; Watterworth, B

    1995-06-01

    Traditionally, education on wound staging has been conducted in the classroom using drawings, photographs or slides to illustrate examples of wound stages. These methods portray wounds two-dimensionally, but clinically, wounds are three-dimensional. Seven home care nurses in central Florida were given a pre-test and post-test of 16 slides, four of each stage. Field visits with three of these nurses were then conducted by an ET nurse to evaluate the application of this education into clinical practice in the home setting. The questions studied were: Do nurses learn to accurately assess stages of wounds from classroom education? Does classroom ability to stage wounds equate to ability to stage correctly in the clinical setting? Test results showed Stage II and Stage III wounds to be most problematic in the classroom. The most improvement was seen in the staging of Stage II and Stage IV wounds two-dimensionally. In the field, one nurse consistently staged wounds correctly while two had problems with correct staging. Additional investigation is required to determine if these results can be generalized to other home health nurses and if changes in clinical ability will occur over time. PMID:7612139

  1. How Applicable Are "Ages and Stages Questionnaires" for Use with Turkish Children?

    ERIC Educational Resources Information Center

    Kapci, Emine Gul; Kucuker, Sevgi; Uslu, Runa I.

    2010-01-01

    The majority of eligible children cannot access early intervention services in Turkey, often because they are not assessed. The authors adapted the "Ages and Stages Questionnaires" (ASQ) for Turkish children ages 3 to 72 months. Study participants consisted of 375 children who were classified as at risk for developmental delays, 564 children…

  2. [Clinical aspect of new international gastric cancer staging system].

    PubMed

    Liang, Han

    2013-02-01

    The 7th UICC/AJCC Gastric Cancer TNM Staging System includes major revisions of pT and pN classification. The Japanese Classification and UICC/AJCC TNM System have reached consistency in staging of gastric cancer. There are some new topics of lymphadenectomy in the new guidelines. The new TNM system accepts the database from Japan and Korea and it will be more accurate to predict the prognosis of gastric cancer patients. The rationality of splenectomy, total bursectomy, dissection of No.13 and No.14 lymph nodes is still not very clear and needs more evidences. D2 lymphadenectomy is the recommended surgical approach both in Eastern and Western countries. The benefit of paraaortic lymphadenectmoy for selected patients needs further evidences as well. The international gastric cancer staging project will collect the data from 23 countries and the new staging system will be applicable worldwide. PMID:23446465

  3. Dementia in Ageing Mental Defectives: A Clinical and Neuropathological Study.

    ERIC Educational Resources Information Center

    Reid, A. H.; And Others

    1978-01-01

    The study was aimed at establishing the prevalence and clinical features of the psychoses of senescence (senile, presenile, and cerebral arteriosclerotic dementias) in 155 mentally retarded patients over the age of 45. (SBH)

  4. RACIAL DISPARITIES IN BREAST CANCER SURVIVAL: AN ANALYSIS BY AGE AND STAGE

    PubMed Central

    Deshpande, Anjali D.; Jeffe, Donna B.; Gnerlich, Jennifer; Iqbal, Ayesha Z.; Thummalakunta, Abhishek; Margenthaler, Julie A.

    2011-01-01

    Background Black women often present with advanced-stage breast cancer compared with White women, which may result in the observed higher mortality among Black women. Age-related factors (e.g., comorbidity) also affect mortality. Whether racial disparities in mortality are evident within age and/or stage groups has not been reported, and risk factors for greater mortality among Black women are not well defined. Methods Using the 1988–2003 Surveillance, Epidemiology, and End Results (SEER) Program data, we conducted a retrospective, population-based cohort study to compare overall and stage-specific breast-cancer mortality between Black and White women within each age (<40, 40–49, 50–64, and 65+) and stage (stage 0–IV and unstaged) group at diagnosis. Cox regression models calculated unadjusted and adjusted hazard ratios (HR) and 95% confidence intervals (CI), the latter controlling for potential confounders of the relationship between race and survival. Results In the 1988–2003 SEER data, 20,424 Black and 204,506 White women were diagnosed with first primary breast cancer. In unadjusted models, Black women were more likely than White women to die from breast cancer (HR: 1.90, 95% CI: 1.83–1.96) and from all causes (HR: 1.52, 95% CI: 1.48–1.55) during follow-up. In models stratified by age and stage, Black women were at increased risk of breast-cancer-specific mortality within each stage group among women <65 years. Conclusion Racial disparities in breast-cancer-specific mortality were predominantly observed within each stage at diagnosis among women <65 years old. This greater mortality risk for Black women was largely not observed among women ≥65 years of age. PMID:19084242

  5. Reassessing the NTCTCS Staging Systems for Differentiated Thyroid Cancer, Including Age at Diagnosis

    PubMed Central

    McLeod, Donald S.A.; Jonklaas, Jacqueline; Brierley, James D.; Ain, Kenneth B.; Cooper, David S.; Fein, Henry G.; Haugen, Bryan R.; Ladenson, Paul W.; Magner, James; Ross, Douglas S.; Skarulis, Monica C.; Steward, David L.; Xing, Mingzhao; Litofsky, Danielle R.; Maxon, Harry R.

    2015-01-01

    Background: Thyroid cancer is unique for having age as a staging variable. Recently, the commonly used age cut-point of 45 years has been questioned. Objective: This study assessed alternate staging systems on the outcome of overall survival, and compared these with current National Thyroid Cancer Treatment Cooperative Study (NTCTCS) staging systems for papillary and follicular thyroid cancer. Methods: A total of 4721 patients with differentiated thyroid cancer were assessed. Five potential alternate staging systems were generated at age cut-points in five-year increments from 35 to 70 years, and tested for model discrimination (Harrell's C-statistic) and calibration (R2). The best five models for papillary and follicular cancer were further tested with bootstrap resampling and significance testing for discrimination. Results: The best five alternate papillary cancer systems had age cut-points of 45–50 years, with the highest scoring model using 50 years. No significant difference in C-statistic was found between the best alternate and current NTCTCS systems (p = 0.200). The best five alternate follicular cancer systems had age cut-points of 50–55 years, with the highest scoring model using 50 years. All five best alternate staging systems performed better compared with the current system (p = 0.003–0.035). There was no significant difference in discrimination between the best alternate system (cut-point age 50 years) and the best system of cut-point age 45 years (p = 0.197). Conclusions: No alternate papillary cancer systems assessed were significantly better than the current system. New alternate staging systems for follicular cancer appear to be better than the current NTCTCS system, although they require external validation. PMID:26203804

  6. SEOM clinical guidelines in early-stage breast cancer 2015.

    PubMed

    Garcia-Saenz, J A; Bermejo, B; Estevez, L G; Palomo, A G; Gonzalez-Farre, X; Margeli, M; Pernas, S; Servitja, S; Rodriguez, C A; Ciruelos, E

    2015-12-01

    Breast cancer is a major public health problem. Despite remarkable advances in early diagnosis and treatment, one in three women may have metastases since diagnosis. Better understanding of prognostic and predictive factors allows us to select the most appropriate adjuvant therapy in each patient. In these guidelines, we summarize current evidence for the medical management of early-stage breast cancer.

  7. Strategies and Challenges in Clinical Trials Targeting Human Aging

    PubMed Central

    Newman, John C.; Milman, Sofiya; Hashmi, Shahrukh K.; Austad, Steve N.; Kirkland, James L.; Halter, Jeffrey B.

    2016-01-01

    Interventions that target fundamental aging processes have the potential to transform human health and health care. A variety of candidate drugs have emerged from basic and translational research that may target aging processes. Some of these drugs are already in clinical use for other purposes, such as metformin and rapamycin. However, designing clinical trials to test interventions that target the aging process poses a unique set of challenges. This paper summarizes the outcomes of an international meeting co-ordinated by the NIH-funded Geroscience Network to further the goal of developing a translational pipeline to move candidate compounds through clinical trials and ultimately into use. We review the evidence that some drugs already in clinical use may target fundamental aging processes. We discuss the design principles of clinical trials to test such interventions in humans, including study populations, interventions, and outcomes. As examples, we offer several scenarios for potential clinical trials centered on the concepts of health span (delayed multimorbidity and functional decline) and resilience (response to or recovery from an acute health stress). Finally, we describe how this discussion helped inform the design of the proposed Targeting Aging with Metformin study. PMID:27535968

  8. Recent decline in prostate cancer incidence in the United States, by age, stage, and Gleason score.

    PubMed

    Herget, Kimberly A; Patel, Darshan P; Hanson, Heidi A; Sweeney, Carol; Lowrance, William T

    2016-01-01

    Prostate cancer incidence is sensitive to screening practices, however the impact of recent screening recommendations from the United States Preventative Services Task Force on prostate cancer incidence by age, stage, race, and Gleason score is unknown. This study described the timing and magnitude of changes in prostate cancer incidence trends in the United States by month of diagnosis, and evaluated trends by age, Gleason score, and stage at diagnosis. We analyzed prostate cancer incidence trends using Surveillance, Epidemiology, and End Results (SEER) program data for men diagnosed with invasive prostate cancer from 2007 through 2012. JoinPoint analysis was used to detect changes in the rate of annual percent change (APC) in prostate cancer incidence for all diagnoses and by age, Gleason score, race, and stage. Prostate cancer incidence declined at an estimated -19.6% APC beginning May 2011. This decline was observed in all age groups. Low-grade tumors (Gleason score ≤6) showed a steeper decline (-29.1% APC) than high-grade tumors (Gleason score 8-10: -10.8% APC). Only stage I/II and stage III tumors saw declines (-24.2% and -16.7% APC, respectively). A sharp decline in prostate cancer incidence began before release of the United States Preventative Services Task Force October 2011 draft and May 2012 final screening recommendation. The greatest change occurred with incidence of low-grade tumors, although there is concern that some high-grade tumors may now go undetected.

  9. Estimation of legal age using calcification stages of third molars in living individuals.

    PubMed

    Streckbein, Philipp; Reichert, Isabelle; Verhoff, Marcel A; Bödeker, Rolf-Hasso; Kähling, Christopher; Wilbrand, Jan-Falco; Schaaf, Heidrun; Howaldt, Hans-Peter; May, Andreas

    2014-12-01

    The increased number of adolescents and young adults with unknown or inaccurately given date of birth is a current issue in justice and legal medicine. The objective of this study was to determine the extent to which third molar calcification stages assessed on panoramic X-rays could be useful as additional criteria for forensic age estimation in living individuals, focusing on the legally important ages 17 and 18. In a retrospective multi-center study, the developmental stage of each individual's third molar was analyzed using Demirjian's scale in 2360 cases. Additionally, sex, age and ancestry were assessed. Individuals with the lowest calcification stage of all present molars in stage H were ≥18 years with a likelihood of ≥99.05% in the female (n=388), and ≥99.24% in the male (n=482) population. The lowest calcification stage of all present third molars proved to be useful as an additional reliable criterion for the determination of an age ≥18 years.

  10. KRAS Mutation in Stage III Colon Cancer and Clinical Outcome Following Intergroup Trial CALGB 89803

    PubMed Central

    Ogino, Shuji; Meyerhardt, Jeffrey A.; Irahara, Natsumi; Niedzwiecki, Donna; Hollis, Donna; Saltz, Leonard B.; Mayer, Robert J.; Schaefer, Paul; Whittom, Renaud; Hantel, Alexander; Benson, Al B.; Goldberg, Richard M.; Bertagnolli, Monica M.; Fuchs, Charles S.

    2009-01-01

    Purpose Alterations in the RAS and RAF pathway relate to epigenetic and epigenomic aberrations, and are important in colorectal carcinogenesis. KRAS mutation in metastatic colorectal cancer predicts resistance to anti-EGFR targeted therapy (cetuximab or panitumumab). However, it remains uncertain whether KRAS mutation predicts prognosis or clinical outcome of colon cancer patients independent of anti-EGFR therapy. Methods We conducted a study of 508 cases identified among 1264 patients with stage III colon cancer who enrolled in a randomized adjuvant chemotherapy trial (5-fluorouracil, leucovorin with or without irinotecan) in 1999–2001 (CALGB 89803). KRAS mutations were detected in 178 tumors (35%) by Pyrosequencing. Kaplan-Meier and Cox proportional hazard models assessed the prognostic significance of KRAS mutation and adjusted for potential confounders including age, sex, tumor location, tumor/node stage, performance status, adjuvant chemotherapy arm and microsatellite instability (MSI) status. Results Compared to patients with KRAS-wild-type tumors, patients with KRAS-mutated tumors did not experience any difference in disease-free (DFS), recurrence-free (RFS), or overall survival (OS). Five-year DFS, RFS and OS (KRAS-mutated vs. KRAS-wild-type patients) were: 62% vs. 63% (log-rank p=0.89); 64% vs. 66% (p=0.84); and 75% vs. 73% (p=0.56), respectively. The effect of KRAS mutation on patient survival did not significantly differ according to clinical features, chemotherapy arm or MSI status, and the effect of adjuvant chemotherapy assignment on outcome did not differ according to KRAS status. Conclusions In this large trial of chemotherapy in stage III colon cancer patients, KRAS mutational status was not associated with any significant influence on disease-free or overall survival. PMID:19934290

  11. Different clinical characteristics in sporadic young-age onset colorectal cancer.

    PubMed

    Lee, Jieun; Kim, In-Ho; Kim, Jin Su; Kim, Sang Woo; Kim, Jun Gi; Oh, Seung Tack; Kang, Won Kyung; Lee, Myung Ah

    2016-09-01

    The incidence of colorectal cancer (CRC) is increasing in young-age patients, but the clinical history is not established. Authors analyzed the clinical characteristics of young-age onset CRC to support basic information for setting treatment policies.Between January 2006 to January 2014, 100 CRC patients diagnosed at the age of 10 to 39 were analyzed. The clinicopathologic characteristics were reviewed based on medical records. Survival outcomes including overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS) were analyzed. This study was conducted as a retrospective, observation study.Among 100 patients, 86 patients were diagnosed as CRC at their thirties. Seventy-nine patients had no familial history of cancer. At initial diagnosis, 59 patients showed the normal CEA level (≤3 ng/mL), and 61 patients were diagnosed as advanced CRC (40% stage III, 21% stage IV). Sixty-four patients had lower location-sigmoid colon, rectosigmoid junction, or rectum. Recurrence rate was 7.9% in stage I to III CRC. Although median OS was not reached, patients with normal CEA level showed better survival outcome (P = 0.013) and patients with perineural invasion showed poorer survival (P = 0.011). The 5-year survival rate of total patient population was estimated as 75%. However, median OS of stage IV patients were 19 months (range 7.9-60.63 months), shorter than historical data of >24 months.Young-age CRC was most commonly diagnosed at their thirties, with no familial history, normal range of CEA and located below sigmoid colon. In young-age onset stage IV CRC, patients showed inferior OS compared to historical data. Based on our data, different surveillance program other than serum CEA level (e.g., sigmoidoscopy) is needed in young-age patient population. PMID:27631240

  12. Implants for the aged patient: biological, clinical and sociological considerations.

    PubMed

    Bartold, P Mark; Ivanovski, Saso; Darby, Ivan

    2016-10-01

    Until recently, age, particularly old age, was considered a contraindication to the placement of dental implants. However, this was based largely on anecdotal dogma rather than on empirical information. This review considers the biological, clinical and socio-economic implications of implants placed in the aged population. Aging has been shown to have an influence on the biological aspects of soft- and hard-tissue wound healing and tissue remodeling, which may influence the establishment and maintenance of implant integration. However, information to date indicates that age should not be an a priori contraindication for implant placement and there is good evidence to indicate that dental implants can be placed successfully in the elderly with good clinical and socio-economic outcomes. PMID:27501495

  13. Clinical ramifications of "genomic staging" of low-grade gliomas.

    PubMed

    Verma, Vivek; Mehta, Minesh P

    2016-09-01

    "Low-grade gliomas" (LGGs), classification of which is derived from histopathological observations, exhibit significant heterogeneity in clinical behavior. Recently, increasing attention has been paid to genomic analyses of these tumors, to aid in treatment and prognostic decision-making. We discuss herein the recent genomic analysis of gliomas from two major recent publications, and also the results of seminal LGG trials in the context of molecular and genomic stratification, with respect to both prognosis and response to therapy. We also analyze implications of these "molecular classifications". We propose separating out the worst prognostic subsets, whose outcomes resemble those of glioblastoma patients. Lastly, a brief discussion is provided regarding translating this collective knowledge into the clinic and in treatment decisions; also addressed are some of the many questions that still need to be examined in light of these strong and emerging data. PMID:27401152

  14. A modified varying-stage adaptive phase II/III clinical trial design.

    PubMed

    Dong, Gaohong; Vandemeulebroecke, Marc

    2016-07-01

    Conventionally, adaptive phase II/III clinical trials are carried out with a strict two-stage design. Recently, a varying-stage adaptive phase II/III clinical trial design has been developed. In this design, following the first stage, an intermediate stage can be adaptively added to obtain more data, so that a more informative decision can be made. Therefore, the number of further investigational stages is determined based upon data accumulated to the interim analysis. This design considers two plausible study endpoints, with one of them initially designated as the primary endpoint. Based on interim results, another endpoint can be switched as the primary endpoint. However, in many therapeutic areas, the primary study endpoint is well established. Therefore, we modify this design to consider one study endpoint only so that it may be more readily applicable in real clinical trial designs. Our simulations show that, the same as the original design, this modified design controls the Type I error rate, and the design parameters such as the threshold probability for the two-stage setting and the alpha allocation ratio in the two-stage setting versus the three-stage setting have a great impact on the design characteristics. However, this modified design requires a larger sample size for the initial stage, and the probability of futility becomes much higher when the threshold probability for the two-stage setting gets smaller. Copyright © 2016 John Wiley & Sons, Ltd.

  15. The Relationship among Pubertal Stage, Age, and Drinking in Adolescent Boys and Girls

    ERIC Educational Resources Information Center

    Faden, Vivian B.; Ruffin, Beverly; Newes-Adeyi, Gabriella; Chen, Chiung

    2010-01-01

    This study used data from the Third National Household and Nutrition Examination Survey (NHANES) to examine the association between pubertal status (Tanner staging for boys and girls and menarche for girls) and alcohol use in a nationally representative sample of youths ages 12 to 17. Logistic regression was used to model the relationship. In…

  16. Middle-Aged More Often Diagnosed with Late-Stage Lung Cancer

    MedlinePlus

    ... Middle-Aged More Often Diagnosed With Late-Stage Lung Cancer British study highlights the need for better early detection, researchers say To use the sharing features on this page, please enable JavaScript. (*this news item will not ...

  17. Developmental Screening Using the Ages and Stages Questionnaire: Standardized versus Real-World Conditions

    ERIC Educational Resources Information Center

    San Antonio, Marianne C.; Fenick, Ada M.; Shabanova, Veronika; Leventhal, John M.; Weitzman, Carol C.

    2014-01-01

    Developmental screens are often used in nonstandardized conditions, such as pediatric waiting rooms, despite validation under standardized conditions. We examined the reproducibility of the Ages and Stages Questionnaire (ASQ), a developmental screening instrument commonly used in pediatric practices, under standardized versus nonstandardized…

  18. [Diagnostics and therapy of dysphonia suitable for the ages and developmental stages of children and adolescents (part 2)].

    PubMed

    Fuchs, M

    2008-02-01

    The incidence of dysphonia among children and adolescents is evaluated internationally at 6 % to 25 %. Nonetheless, hoarseness as a leading symptom among children is often insufficiently recognized by their parents/attachment figures, by the young patients themselves, and even by physicians. In an overview, the hereditary and acquired organic and functional causes - including secondary organic lesions of the vocal folds - their pathomechanisms and the symptoms typical for this age group are presented. For diagnostics suitable for these age groups and developmental stages, modern methods of laryngoscopy (including stoboscopy and real-time laryngoscopy), of functional diagnostics of vocal capacity and quality as well as anamnestic and psychometric procedures for the investigation of possible psychosomatic genesis are available. Frequent therapeutic measures are vocal hygienic counseling and psycho- and family dynamic therapies. Vocal exercise treatments are particularly employed for the consequences of laryngeal surgery and with voice techniques unfavorable as a precondition for increased vocal activity. Operative measures in the sound-producing areas of the vocal apparatus and in the framework of plastic reconstruction concentrate on the optimizing of vocal capacity and quality. In clinical routine, symptoms of dysphonia in children and adolescents should be consciously registered, and any long-term hoarseness, in this age group as well, should be examined by specialized physicians using the methods suitable to the age group and the developmental stage. When the appropriate indications are present, all of the therapeutic options currently available should be discussed.

  19. From stage to age in variable environments: life expectancy and survivorship.

    PubMed

    Tuljapurkar, Shripad; Horvitz, Carol C

    2006-06-01

    Stage-based demographic data are now available on many species of plants and some animals, and they often display temporal and spatial variability. We provide exact formulas to compute age-specific life expectancy and survivorship from stage-based data for three models of temporal variability: cycles, serially independent random variation, and a Markov chain. These models provide a comprehensive description of patterns of temporal variation. Our formulas describe the effects of cohort (birth) environmental condition on mortality at all ages, and of the effects on survivorship of environmental variability experienced over the course of life. This paper complements existing methods for time-invariant stage-based data, and adds to the information on population growth and dynamics available from stochastic demography. PMID:16869426

  20. From stage to age in variable environments: life expectancy and survivorship.

    PubMed

    Tuljapurkar, Shripad; Horvitz, Carol C

    2006-06-01

    Stage-based demographic data are now available on many species of plants and some animals, and they often display temporal and spatial variability. We provide exact formulas to compute age-specific life expectancy and survivorship from stage-based data for three models of temporal variability: cycles, serially independent random variation, and a Markov chain. These models provide a comprehensive description of patterns of temporal variation. Our formulas describe the effects of cohort (birth) environmental condition on mortality at all ages, and of the effects on survivorship of environmental variability experienced over the course of life. This paper complements existing methods for time-invariant stage-based data, and adds to the information on population growth and dynamics available from stochastic demography.

  1. [Efficacy of neoadjuvant chemoradiation therapy for clinical Stage II cholangiocarcinoma as a preoperative diagnosis].

    PubMed

    Nakagawa, Kei; Katayose, Yu; Unno, Michiaki

    2012-11-01

    We performed a clinical trial of neoadjuvant chemoradiation therapy for cholangiocarcinoma with a preoperative diagnoses of clinical Stage III and IV. We examined the effect of preoperative chemoradiation for cStage II bile duct cancer. From 2008 until 2011, 75 cases were compared in terms of the preoperative diagnosis and pathological diagnosis of cholangiocarcinoma in our department. Additionally, 19 cases had been diagnosed as cStage II. However, 12 cases were higher than pStage III in their pathological diagnosis. We did not obtain pCur A in only 12 cases(63%). On the other hand, we obtained HM0, DM0, EM0, and pCur A in 5 patients with cStage II cholangiocarcinoma who underwent preoperative chemoradiation therapy. The neoadjuvant chemoradiation therapy for cholangiocarcinoma may control local cancer progression, thereby improving the surgical results of cStage II cholangiocarcinoma in this study. PMID:23267938

  2. Dating age and stage as correlates of adolescent sexual attitudes and behavior.

    PubMed

    Miller, B C; Mccoy, J K; Olson, T D

    1986-01-01

    Dating experiences, especially the type or stage of dating, have consistently been found to be related to premarital sexual behavior. Findings regarding the age at 1st date and sexual behavior have been less consistent. This paper examined the age at which dating began and the type of dating relationship as correlates of premarital sexual attitudes and behavior among mid-teen adolescents. The analyses were based on a sample of high school students (n=836), most of whom were between the ages of 15 and 18 when the surveys were conducted. Early dating, especially early steady dating, was related to permissive attitudes and to premarital sexual experience among both males and females. The relationship between early dating and intercourse experience was particulary strong among Mormons, a religious group which has institutionalized age 16 as the legitimate age to begin dating. PMID:12341601

  3. Revisiting the Biomedicalization of Aging: Clinical Trends and Ethical Challenges

    ERIC Educational Resources Information Center

    Kaufman, Sharon R.; Shim, Janet K.; Russ, Ann J.

    2004-01-01

    Developments in the realms of medical innovation and geriatric clinical intervention impact our understanding of the nature of late life, the possibilities for health in advanced age, medical decision making, and family responsibility in ways that could not have been predicted 15 years ago. This essay begins to map new forms of biomedicalization…

  4. Transitions in Physiologic Coupling: Sleep Stage and Age Dependence of Cardio-respiratory Phase Synchronization

    NASA Astrophysics Data System (ADS)

    Bartsch, Ronny P.; Ivanov, Plamen Ch.

    2012-02-01

    Recent studies have focused on various features of cardiac and respiratory dynamics with the aim to better understand key aspects of the underlying neural control of these systems. We investigate how sleep influences cardio-respiratory coupling, and how the degree of this coupling changes with transitions across sleep stages in healthy young and elderly subjects. We analyze full night polysomnographic recordings of 189 healthy subjects (age range: 20 to 90 years). To probe cardio-respiratory coupling, we apply a novel phase synchronization analysis method to quantify the adjustment of rhythms between heartbeat and breathing signals. We investigate how cardio-respiratory synchronization changes with sleep-stage transitions and under healthy aging. We find a statistically significant difference in the degree of cardio-respiratory synchronization during different sleep stages for both young and elderly subjects and a significant decline of synchronization with age. This is a first evidence of how sleep regulation and aging influence a key nonlinear mechanism of physiologic coupling as quantified by the degree of phase synchronization between the cardiac and respiratory systems, which is of importance to develop adequate modeling approaches.

  5. Influence of age, breed, and stage of pregnancy on hepatic ultrasonographic findings in cows.

    PubMed

    Braun, U; Gerber, D

    1994-09-01

    Influence of age, breed, and stage of pregnancy on hepatic ultrasonographic findings of cows was determined. In addition, the relation between body weight, height at the withers, milk production, and the measurements determined via ultrasonography was investigated. The liver of 186 cows was examined ultrasonographically. The cows comprised Swiss Braunvieh, Simmental, and Holstein breeds, and age ranged from 2.5 to 11.5 years. The ultrasonographic findings of the liver, gallbladder, caudal vena cava, and portal vein were described, and the position, size, thickness, and distal angle of the liver were determined. In addition, the position and diameter of the caudal vena cava and portal vein were determined. There was no significant difference between any of the variables determined and breed or age. Therefore, measurements for the 3 breeds and for the various ages were summarized into 1 group. There were significant correlations between body weight, milk production, and size and thickness of the liver. In 3 pregnant cows, the liver was examined ultrasonographically 8 times during the course of pregnancy. Positive correlation was detected between stage of pregnancy and diameter of the caudal vena cava. There was a negative correlation between stage of pregnancy and diameter of the portal vein. In 23 cows, the ultrasonographically determined measurements of the liver were compared with those determined at slaughter. Weight of the liver correlated well to thickness of the liver determined via ultrasonography.

  6. Correlation between histologic staging, hepatitis C virus genotypes and clinical features in HCV chronic hepatitis: evidence of a new pattern.

    PubMed

    Di Tommaso, L; Macchia, S; Morandi, L; Leoncini, S; Pession, A; Dal Monte, P R; Foschini, M P

    2003-07-01

    Genome heterogeneity may be related to the wide variability of clinical and pathological features in hepatitis C virus (HCV)-related chronic liver disease. This paper addresses the possible association between HCV subtypes and clinical and histological features of chronically infected patients. Sixty-eight consecutive liver biopsies of chronic hepatitis constituted the basis of the study. HCV genotyping was performed on frozen tissue. Grading of necroinflammatory activity and staging of fibrosis were histologically assessed. Serologic HCV-RNA and liver function were assessed at the same time. All information was compared with clinical data including age, sex, HCV serology, and probable data and route of infection. Two cases were excluded as inadequate tissue was available. Five cases were negative to HCV-RNA in both serum and tissue. In 61 cases HCV RNA was present at the same time in serum and liver tissue. Forty-four patients were men (72%) and 17 (28%) were women. Two peaks of age were observed: 1 in the 4th decade of life, the 2nd in the 7th. The 2 groups had different HCV genotypes. Patients with genotypes 1b (mean age 50.7 years), 2c (mean age 61.3 years), and a subgroup of coinfections (mean age 60 years) were older than patients with genotypes 1a (mean age 35.5 years), 3 (mean age 36 years), and a subgroup of coinfections (mean age 33 years). Patients with genotypes 1b, 2, or 2c and a subgroup of coinfections more frequently had a history of blood transfusion and or surgical intervention dating up to 49 years previously. Patients with HCV 1a, 3, and a subgroup of coinfections frequently admitted a period of intravenous drug abuse. Patients with advanced liver disease, i.e., severe fibrosis and cirrhosis, showed the same 2 peaks of incidence: in the 4th and 7th decades of life, the first group mainly comprising patients with HCV types 1a and 3, the second, patients with HCV types 1b and 2c. Both these groups shared a clinical history of a long

  7. [Clinical efficacy of octreotide acetate in cancer patients with malignant bowel symptoms depend on terminal stage].

    PubMed

    Uchino, Ryojin; Kusano, Shuichi; Hanada, Norihisa; Ohara, Chitoshi; Okino, Tetsuya; Yamaguchi, Kenji

    2011-02-01

    There are many reports that octreotide acetate(SMS)is effective for terminally ill cancer patients with malignant bowel obstructions such as nausea, vomiting and abdominal distension. We retrospectively found that the clinical efficacy of SMS in 23 patients with these symptoms depended on the early terminal stage(about six months until death)or middle terminal stage(within one month until death). SMS was more effective to relieve abdominal distension(p=0. 01)and these bowel symptoms occurred among cancer patients in the early terminal stage rather than in the middle terminal stage(p<0. 001).

  8. Oophorectomy, menopause, estrogen treatment, and cognitive aging: clinical evidence for a window of opportunity.

    PubMed

    Rocca, Walter A; Grossardt, Brandon R; Shuster, Lynne T

    2011-03-16

    The neuroprotective effects of estrogen have been demonstrated consistently in cellular and animal studies but the evidence in women remains conflicted. We explored the window of opportunity hypothesis in relation to cognitive aging and dementia. In particular, we reviewed existing literature, reanalyzed some of our data, and combined results graphically. Current evidence suggests that estrogen may have beneficial, neutral, or detrimental effects on the brain depending on age at the time of treatment, type of menopause (natural versus medically or surgically induced), or stage of menopause. The comparison of women who underwent bilateral oophorectomy with referent women provided evidence for a sizeable neuroprotective effect of estrogen before age 50 years. Several case-control studies and cohort studies also showed neuroprotective effects in women who received estrogen treatment (ET) in the early postmenopausal stage (most commonly at ages 50-60 years). The majority of women in those observational studies had undergone natural menopause and were treated for the relief of menopausal symptoms. However, recent clinical trials by the Women's Health Initiative showed that women who initiated ET alone or in combination with a progestin in the late postmenopausal stage (ages 65-79 years) experienced an increased risk of dementia and cognitive decline regardless of the type of menopause. The current conflicting data can be explained by the window of opportunity hypothesis suggesting that the neuroprotective effects of estrogen depend on age at the time of administration, type of menopause, and stage of menopause. Therefore, women who underwent bilateral oophorectomy before the onset of menopause or women who experienced premature or early natural menopause should be considered for hormonal treatment until approximately age 51 years.

  9. Identification of morphological markers of sarcopenia at early stage of aging in skeletal muscle of mice.

    PubMed

    Sayed, Ramy K A; de Leonardis, Erika Chacin; Guerrero-Martínez, José A; Rahim, Ibtissem; Mokhtar, Doaa M; Saleh, Abdelmohaimen M; Abdalla, Kamal E H; Pozo, María J; Escames, Germaine; López, Luis C; Acuña-Castroviejo, Darío

    2016-10-01

    The gastrocnemius muscle (GM) of young (3months) and aged (12months) female wild-type C57/BL6 mice was examined by light and electron microscopy, looking for the presence of structural changes at early stage of the aging process. Morphometrical parameters including body and gastrocnemius weights, number and type of muscle fibers, cross section area (CSA), perimeter, and Feret's diameter of single muscle fiber, were measured. Moreover, lengths of the sarcomere, A-band, I-band, H-zone, and number and CSA of intermyofibrillar mitochondria (IFM), were also determined. The results provide evidence that 12month-old mice had significant changes on skeletal muscle structure, beginning with the reduction of gastrocnemius weight to body weight ratio, compatible with an early loss of skeletal muscle function and strength. Moreover, light microscopy revealed increased muscle fibers size, with a significant increase on their CSA, perimeter, and diameter of both type I and type II muscle fibers, and a reduction in the percentage of muscle area occupied by type II fibers. Enhanced connective tissue infiltrations, and the presence of centrally nucleated muscle fibers, were also found in aged mice. These changes may underlie an attempt to compensate the loss of muscle mass and muscle fibers number. Furthermore, electron microscopy discovered a significant age-dependent increase in the length of sarcomeres, I and H bands, and reduction on the overlapped actin/myosin length, supporting contractile force loss with age. Electron microscopy also showed an increased number and CSA of IFM with age, which may reveal more endurance at 12months of age. Together, mice at early stage of aging already show significant changes in gastrocnemius muscle morphology and ultrastructure that are suggestive of the onset of sarcopenia.

  10. Aging Effects on Cardiac and Respiratory Dynamics in Healthy Subjects across Sleep Stages

    PubMed Central

    Schumann, Aicko Y.; Bartsch, Ronny P.; Penzel, Thomas; Ivanov, Plamen Ch.; Kantelhardt, Jan W.

    2010-01-01

    Study Objectives: Respiratory and heart rate variability exhibit fractal scaling behavior on certain time scales. We studied the short-term and long-term correlation properties of heartbeat and breathing-interval data from disease-free subjects focusing on the age-dependent fractal organization. We also studied differences across sleep stages and night-time wake and investigated quasi-periodic variations associated with cardiac risk. Design: Full-night polysomnograms were recorded during 2 nights, including electrocardiogram and oronasal airflow. Setting: Data were collected in 7 laboratories in 5 European countries. Participants: 180 subjects without health complaints (85 males, 95 females) aged from 20 to 89 years. Interventions: None. Measurements and Results: Short-term correlations in heartbeat intervals measured by the detrended fluctuation analysis (DFA) exponent α1 show characteristic age dependence with a maximum around 50–60 years disregarding the dependence on sleep and wake states. Long-term correlations measured by α2 differ in NREM sleep when compared with REM sleep and wake, besides weak age dependence. Results for respiratory intervals are similar to those for α2 of heartbeat intervals. Deceleration capacity (DC) decreases with age; it is lower during REM and deep sleep (compared with light sleep and wake). Conclusion: The age dependence of α1 should be considered when using this value for diagnostic purposes in post-infarction patients. Pronounced long-term correlations (larger α2) for heartbeat and respiration during REM sleep and wake indicate an enhanced control of higher brain regions, which is absent during NREM sleep. Reduced DC possibly indicates an increased cardiovascular risk with aging and during REM and deep sleep. Citation: Schumann AY; Bartsch RP; Penzel T; Ivanov PC; Kantelhardt JW. Aging effects on cardiac and respiratory dynamics in healthy subjects across sleep stages. SLEEP 2010;33(7):943-955. PMID:20614854

  11. Identification of morphological markers of sarcopenia at early stage of aging in skeletal muscle of mice.

    PubMed

    Sayed, Ramy K A; de Leonardis, Erika Chacin; Guerrero-Martínez, José A; Rahim, Ibtissem; Mokhtar, Doaa M; Saleh, Abdelmohaimen M; Abdalla, Kamal E H; Pozo, María J; Escames, Germaine; López, Luis C; Acuña-Castroviejo, Darío

    2016-10-01

    The gastrocnemius muscle (GM) of young (3months) and aged (12months) female wild-type C57/BL6 mice was examined by light and electron microscopy, looking for the presence of structural changes at early stage of the aging process. Morphometrical parameters including body and gastrocnemius weights, number and type of muscle fibers, cross section area (CSA), perimeter, and Feret's diameter of single muscle fiber, were measured. Moreover, lengths of the sarcomere, A-band, I-band, H-zone, and number and CSA of intermyofibrillar mitochondria (IFM), were also determined. The results provide evidence that 12month-old mice had significant changes on skeletal muscle structure, beginning with the reduction of gastrocnemius weight to body weight ratio, compatible with an early loss of skeletal muscle function and strength. Moreover, light microscopy revealed increased muscle fibers size, with a significant increase on their CSA, perimeter, and diameter of both type I and type II muscle fibers, and a reduction in the percentage of muscle area occupied by type II fibers. Enhanced connective tissue infiltrations, and the presence of centrally nucleated muscle fibers, were also found in aged mice. These changes may underlie an attempt to compensate the loss of muscle mass and muscle fibers number. Furthermore, electron microscopy discovered a significant age-dependent increase in the length of sarcomeres, I and H bands, and reduction on the overlapped actin/myosin length, supporting contractile force loss with age. Electron microscopy also showed an increased number and CSA of IFM with age, which may reveal more endurance at 12months of age. Together, mice at early stage of aging already show significant changes in gastrocnemius muscle morphology and ultrastructure that are suggestive of the onset of sarcopenia. PMID:27435496

  12. The Benefit of Adjuvant Chemotherapy in Elderly Patients with Stage III Colorectal Cancer is Independent of Age and Comorbidity

    PubMed Central

    Wildes, Tanya M.; Kallogjeri, Dorina; Powers, Brian; Vlahiotis, Anna; Mutch, Matthew; Spitznagel, Edward L.; Tan, Benjamin; Piccirillo, Jay F.

    2010-01-01

    Objectives To determine the combined effect of age and comorbidity on receipt of chemotherapy and its impact on survival in elderly patients with stage III colorectal cancer (CRC). Materials and methods All patients over age 65 with Stage III CRC diagnosed 1996–2006 were identified from the Barnes-Jewish Hospital Oncology Data Services registry. An age/comorbidity staging system was created using the ACE-27 comorbidity index and data from both Stage II and III CRC. The staging system was then applied to patients with Stage III CRC. Odds of receiving chemotherapy were calculated, and survival analyses determined the impact of chemotherapy on overall survival in each age/comorbidity stage. Results 435 patients with Stage III CRC were evaluated [median age 75 years (range 65–99)]. Advancing age/comorbidity stage (Alpha, Beta, Gamma) was associated with decreasing odds of receiving chemotherapy for Stage III CRC [Odds Ratio 0.83 (95% CI, 0.51–1.35) for Beta and 0.14 (95% CI, 0.08–0.24) for Gamma, compared to Alpha]. Chemotherapy was associated with lower risk of death in each of the age/comorbidity stages, compared to those who underwent surgery only. The hazard ratio for death in patients who did not receive chemotherapy, relative to those who did, within each age/comorbidity stage was 1.8 [95%CI 1.06–3.06] for Alpha, 2.24 [95%CI 1.38–3.63] for Beta and 2.10 [95% CI 1.23–3.57] for Gamma. Conclusion While stage III CRC patients with increasing age and comorbidity are less likely to receive chemotherapy, receipt of chemotherapy is associated with a lower risk of death. PMID:21113435

  13. Microstructural evolution of 7012 alloy during the early stages of artificial ageing

    SciTech Connect

    Ferragut, R.; Somoza, A.; Tolley, A.

    1999-11-26

    A study of the microstructural evolution of a commercial 7012 (Al-Zn-Mg-Cu) age-hardenable alloy following artificial ageing by high resolution and conventional transmission electron microscopy and positron annihilation lifetime spectroscopy is presented. At the early stages of decomposition, the microstructure included precipitation of either pre-precipitate solute clusters or Guinier-Preston zones and semi-coherent {eta}{prime} precipitates, with typical sizes between 1 and 10 nm. Quantitative information on the size, number density and morphology of the particles present in the microstructure was obtained. The results were correlated with those obtained using positron annihilation lifetime spectroscopy.

  14. Virtual anthropology: useful radiological tools for age assessment in clinical forensic medicine and thanatology.

    PubMed

    Dedouit, Fabrice; Saint-Martin, Pauline; Mokrane, Fatima-Zohra; Savall, Frédéric; Rousseau, Hervé; Crubézy, Eric; Rougé, Daniel; Telmon, Norbert

    2015-09-01

    Virtual anthropology consists of the introduction of modern slice imaging to biological and forensic anthropology. Thanks to this non-invasive scientific revolution, some classifications and staging systems, first based on dry bone analysis, can be applied to cadavers with no need for specific preparation, as well as to living persons. Estimation of bone and dental age is one of the possibilities offered by radiology. Biological age can be estimated in clinical forensic medicine as well as in living persons. Virtual anthropology may also help the forensic pathologist to estimate a deceased person's age at death, which together with sex, geographical origin and stature, is one of the important features determining a biological profile used in reconstructive identification. For this forensic purpose, the radiological tools used are multislice computed tomography and, more recently, X-ray free imaging techniques such as magnetic resonance imaging and ultrasound investigations. We present and discuss the value of these investigations for age estimation in anthropology.

  15. Virtual anthropology: useful radiological tools for age assessment in clinical forensic medicine and thanatology.

    PubMed

    Dedouit, Fabrice; Saint-Martin, Pauline; Mokrane, Fatima-Zohra; Savall, Frédéric; Rousseau, Hervé; Crubézy, Eric; Rougé, Daniel; Telmon, Norbert

    2015-09-01

    Virtual anthropology consists of the introduction of modern slice imaging to biological and forensic anthropology. Thanks to this non-invasive scientific revolution, some classifications and staging systems, first based on dry bone analysis, can be applied to cadavers with no need for specific preparation, as well as to living persons. Estimation of bone and dental age is one of the possibilities offered by radiology. Biological age can be estimated in clinical forensic medicine as well as in living persons. Virtual anthropology may also help the forensic pathologist to estimate a deceased person's age at death, which together with sex, geographical origin and stature, is one of the important features determining a biological profile used in reconstructive identification. For this forensic purpose, the radiological tools used are multislice computed tomography and, more recently, X-ray free imaging techniques such as magnetic resonance imaging and ultrasound investigations. We present and discuss the value of these investigations for age estimation in anthropology. PMID:25735613

  16. Aging assessment and license renewals: Plant life management for the first stage boiling water reactor

    SciTech Connect

    Tezuka, Kenichi; Kawamura, Shinichi; Aoki, Masataka; Mori, Tsuguo

    1996-09-01

    The first stage Boiling Water Reactors (BWRs) have been operating more than 25 years. Some components have potential of failure by aging. So, evaluations have been done for the main components such as Reactor Pressure Vessel (RPV), Reactor Internals, Primary Coolant Piping, Reactor Recirculation Pump, Cable (Inside PCV), Primary Containment Vessel (PCV) and Concrete Structure. This evaluation has been done by joint study between electric utilities and manufacturers to confirm integrity and identify necessary development.

  17. Optimal and minimax three-stage designs for phase II oncology clinical trials.

    PubMed

    Chen, Kun; Shan, Michael

    2008-01-01

    The common objective of oncology phase II trials is to evaluate the anti-tumor activity of a new agent and to determine whether the new drug warrants further investigation. For cancer drugs that significantly shrink tumors, response (CR and PR) rate is usually the primary endpoint in cancer phase II trials for testing H(0): Por=P(1), where P(0) and P(1) are response rates which does not or does warrant further investigation given the rate of false positive (alpha) and false negative (beta). Multiple-stage designs including two-stage and three-stage have been developed by several authors. For example, Simon's optimal two-stage design [Simon R. Optimal two-stage designs for phase II clinical trials. Control Clin Trials 1989;10:1-10], Ensign et al. optimal three-stage design with restriction at the first stage [Ensign LG, Gehan EA, Kamen DS, Thall PF. An optimal three-stage design for phase II clinical trials. Stat Med 1994;13:1727-1736], Chen's optimal three-stage design without any restriction [Chen TT. Optimal three-stage designs for phase II clinical trials. Stat Med 1997;16:2701-2711], etc. However, all the above designs only early terminate a trial due to lack of activity of the study drug. Fleming's multiple-stage design [Fleming TR. One-sample multiple testing procedure for phase II clinical trials. Biometrics 1982;38:143-151] allows early stopping for either sufficient activity or lack of activity. But his design does not attempt to optimize its efficiency. We extend Chen's [Chen TT. Optimal three-stage designs for phase II clinical trials Stat Med 1997;16:2701-2711] design and propose an optimal and a minimax design for three-stage cancer phase II trials which allows early stopping under both hypotheses. The design is optimal in the sense that the average sample number (ASN) is minimized under P=P(0). The minimax design minimizes the maximal sample size (N) and then given this value of N minimizes the average sample number under P=P(0

  18. Systemic Therapy for Stage IV Non–Small-Cell Lung Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update

    PubMed Central

    Masters, Gregory A.; Temin, Sarah; Azzoli, Christopher G.; Giaccone, Giuseppe; Baker, Sherman; Brahmer, Julie R.; Ellis, Peter M.; Gajra, Ajeet; Rackear, Nancy; Schiller, Joan H.; Smith, Thomas J.; Strawn, John R.; Trent, David; Johnson, David H.

    2015-01-01

    Purpose To provide evidence-based recommendations to update the American Society of Clinical Oncology guideline on systemic therapy for stage IV non–small-cell lung cancer (NSCLC). Methods An Update Committee of the American Society of Clinical Oncology NSCLC Expert Panel based recommendations on a systematic review of randomized controlled trials from January 2007 to February 2014. Results This guideline update reflects changes in evidence since the previous guideline. Recommendations There is no cure for patients with stage IV NSCLC. For patients with performance status (PS) 0 to 1 (and appropriate patient cases with PS 2) and without an EGFR-sensitizing mutation or ALK gene rearrangement, combination cytotoxic chemotherapy is recommended, guided by histology, with early concurrent palliative care. Recommendations for patients in the first-line setting include platinum-doublet therapy for those with PS 0 to 1 (bevacizumab may be added to carboplatin plus paclitaxel if no contraindications); combination or single-agent chemotherapy or palliative care alone for those with PS 2; afatinib, erlotinib, or gefitinib for those with sensitizing EGFR mutations; crizotinib for those with ALK or ROS1 gene rearrangement; and following first-line recommendations or using platinum plus etoposide for those with large-cell neuroendocrine carcinoma. Maintenance therapy includes pemetrexed continuation for patients with stable disease or response to first-line pemetrexed-containing regimens, alternative chemotherapy, or a chemotherapy break. In the second-line setting, recommendations include docetaxel, erlotinib, gefitinib, or pemetrexed for patients with nonsquamous cell carcinoma; docetaxel, erlotinib, or gefitinib for those with squamous cell carcinoma; and chemotherapy or ceritinib for those with ALK rearrangement who experience progression after crizotinib. In the third-line setting, for patients who have not received erlotinib or gefitinib, treatment with erlotinib is

  19. Human dental age estimation using third molar developmental stages: Accuracy of age predictions not using country specific information.

    PubMed

    Thevissen, P W; Alqerban, A; Asaumi, J; Kahveci, F; Kaur, J; Kim, Y K; Pittayapat, P; Van Vlierberghe, M; Zhang, Y; Fieuws, S; Willems, G

    2010-09-10

    Unquestionable forensic age investigations are based on statistical models constructed on a sample containing subjects of identical origin as the examined individual. In cases where corresponding models are unavailable, the established report has to describe the possible effects of this unrelated information on the predicted age outcome. The aim of this study is to collect country specific databases of third molar development and to verify how the related dental age estimations are influenced if we were to use dental developmental information only from Belgium or from all collected countries together. Data containing third molar developmental stages scored following Gleiser and Hunt (modified by Köhler) were collected from 9 country specific populations (Belgium, China, Japan, Korea, Poland, Thailand, Turkey, Saudi-Arabia and South-India). Age predictions were obtained from a training dataset and validated on a test dataset. Bayes rule using the repeated third molar scores is applied to get age predictions and prediction intervals. Three age predictions were compared for males and females separately. For the first prediction, the training dataset contains only Belgian subjects. For the second prediction, the training dataset for each country consists only of subjects of the country itself. For the final prediction, subjects from all countries are pooled into one common training dataset. Besides the (absolute) difference between the chronological age and the predicted age, specific interest lies in the juvenile-adult distinction. In the age range from 16 to 22 years 6982 subjects (3189 male and 3793 female) were analyzed. Using information on third molar development from Belgium compared to information from the country specific databases hardly increased the mean absolute differences (MAD) and mean squared errors (MSE): the MAD and MSE increased on average with 0.5 and 2.5 months with maximal increases of, respectively 1.6 and 7.3 months. Using information from all

  20. Human dental age estimation using third molar developmental stages: Accuracy of age predictions not using country specific information.

    PubMed

    Thevissen, P W; Alqerban, A; Asaumi, J; Kahveci, F; Kaur, J; Kim, Y K; Pittayapat, P; Van Vlierberghe, M; Zhang, Y; Fieuws, S; Willems, G

    2010-09-10

    Unquestionable forensic age investigations are based on statistical models constructed on a sample containing subjects of identical origin as the examined individual. In cases where corresponding models are unavailable, the established report has to describe the possible effects of this unrelated information on the predicted age outcome. The aim of this study is to collect country specific databases of third molar development and to verify how the related dental age estimations are influenced if we were to use dental developmental information only from Belgium or from all collected countries together. Data containing third molar developmental stages scored following Gleiser and Hunt (modified by Köhler) were collected from 9 country specific populations (Belgium, China, Japan, Korea, Poland, Thailand, Turkey, Saudi-Arabia and South-India). Age predictions were obtained from a training dataset and validated on a test dataset. Bayes rule using the repeated third molar scores is applied to get age predictions and prediction intervals. Three age predictions were compared for males and females separately. For the first prediction, the training dataset contains only Belgian subjects. For the second prediction, the training dataset for each country consists only of subjects of the country itself. For the final prediction, subjects from all countries are pooled into one common training dataset. Besides the (absolute) difference between the chronological age and the predicted age, specific interest lies in the juvenile-adult distinction. In the age range from 16 to 22 years 6982 subjects (3189 male and 3793 female) were analyzed. Using information on third molar development from Belgium compared to information from the country specific databases hardly increased the mean absolute differences (MAD) and mean squared errors (MSE): the MAD and MSE increased on average with 0.5 and 2.5 months with maximal increases of, respectively 1.6 and 7.3 months. Using information from all

  1. Systematic genomic identification of colorectal cancer genes delineating advanced from early clinical stage and metastasis

    PubMed Central

    2013-01-01

    Background Colorectal cancer is the third leading cause of cancer deaths in the United States. The initial assessment of colorectal cancer involves clinical staging that takes into account the extent of primary tumor invasion, determining the number of lymph nodes with metastatic cancer and the identification of metastatic sites in other organs. Advanced clinical stage indicates metastatic cancer, either in regional lymph nodes or in distant organs. While the genomic and genetic basis of colorectal cancer has been elucidated to some degree, less is known about the identity of specific cancer genes that are associated with advanced clinical stage and metastasis. Methods We compiled multiple genomic data types (mutations, copy number alterations, gene expression and methylation status) as well as clinical meta-data from The Cancer Genome Atlas (TCGA). We used an elastic-net regularized regression method on the combined genomic data to identify genetic aberrations and their associated cancer genes that are indicators of clinical stage. We ranked candidate genes by their regression coefficient and level of support from multiple assay modalities. Results A fit of the elastic-net regularized regression to 197 samples and integrated analysis of four genomic platforms identified the set of top gene predictors of advanced clinical stage, including: WRN, SYK, DDX5 and ADRA2C. These genetic features were identified robustly in bootstrap resampling analysis. Conclusions We conducted an analysis integrating multiple genomic features including mutations, copy number alterations, gene expression and methylation. This integrated approach in which one considers all of these genomic features performs better than any individual genomic assay. We identified multiple genes that robustly delineate advanced clinical stage, suggesting their possible role in colorectal cancer metastatic progression. PMID:24308539

  2. Age estimation by dental developmental stages in children and adolescents in Iceland.

    PubMed

    Vidisdottir, Sigridur Rosa; Richter, Svend

    2015-12-01

    Studies have shown that it is necessary to create a database for dental maturity for every population and compare it to others. The present study is the first one for dental development in the Icelandic population the age range being 4-24 years. It will help in forensic dental age estimation and will also help dentists, physicians, anthropologists, archaeologists and other professionals who rely on developmental age assessment in children and adolescents. In this present retrospective cross-sectional study, dental maturity was determined in 1100 Icelandic children and adolescents from orthopantomograms (OPGs). The first 100 were used for a pilot study and the remaining 1000 for the main study. A total of 23 subjects were excluded. The sample consisted of 508 girls and 469 boys from the age of 4-24 years and a dental developmental scoring system was used as a standard for determination of dental maturity stages. A total of 200 OPGs were studied both on the left and right side and the remaining on the right side. Dental maturity was established for all teeth and both genders, when the sample permitted, from the beginning of crown formation to the root apex closure. The Cronbach's Alpha reliability test showed high reliability, R=0.982. Girls in Iceland reach dental maturity root completed (stage 10, Rc) at 17.81 years of age for the maxillary and at 18.47 years for the mandibular teeth. Boys reach dental maturity root completed (stage 10, Rc) at 18.00 years of age in the maxilla and 17.63 in the mandible. There was no significant difference between left and right side (r=0.95-1.00) and there was no gender difference, except in root formation in maxillary and mandibular canines where girls reached root completed earlier than boys. A reliable database has been established in Iceland for tooth development in the age range of 4-24 years, which is compatible with international studies. These results will help forensic odontologists and other professionals to estimate with

  3. Understanding age-related reductions in visual working memory capacity: Examining the stages of change detection

    PubMed Central

    Duda, Bryant; Hussey, Erin; Mason, Emily; Molitor, Robert J.; Woodman, Geoffrey F.; Ally, Brandon A.

    2014-01-01

    Visual working memory (VWM) capacity is reduced in older adults. Research has shown age-related impairments to VWM encoding, but aging is likely to affect multiple stages of VWM. In the present study, we recorded the event-related potentials (ERPs) of younger and older adults during VWM maintenance and retrieval. We measured encoding-stage processing with the P1 component, maintenance-stage processing with the contralateral delay activity (CDA), and retrieval-stage processing by comparing the activity for old and new items (old–new effect). Older adults showed lower behavioral capacity estimates (K) than did younger adults, but surprisingly, their P1 components and CDAs were comparable to those of younger adults. This remarkable dissociation between neural activity and behavior in the older adults indicated that the P1 and CDA did not accurately assess their VWM capacity. However, the neural activity evoked during VWM retrieval yielded results that helped clarify the age-related differences. During retrieval, younger adults showed early old–new effects in frontal and occipital areas and a late central–parietal old–new effect, whereas older adults showed a late right-lateralized parietal old–new effect. The younger adults’ early old–new effects strongly resembled an index of perceptual fluency, suggesting that perceptual implicit memory was activated. The activation of implicit memory could have facilitated the younger adults’ behavior, and the lack of these early effects in older adults may suggest that they have much lower-resolution memory than do younger adults. From these data, we speculated that younger and older adults store the same number of items in VWM, but that younger adults store a higher-resolution representation than do older adults. PMID:24420648

  4. A behavioral stages model of classical (Pavlovian) conditioning: application to cognitive aging.

    PubMed

    Powell, D A

    1999-01-01

    In the present article, it is argued that a five-stage sequential model of the behavioral and neurophysiological events that occur when organisms are exposed to signals predicting significant events suggests that classical conditioning produces multiple memory traces involving both excitatory and inhibitory processes. Further, these multiple brain structures and associated neurophysiological mechanisms are beginning to be understood; thus, using Pavlovian conditioning techniques to study aging and cognitive functions may provide insights into which brain structures or mechanisms are responsible for more general age-related declines in associative learning and memory. The evidence for this model is briefly reviewed and studies suggesting age-related effects on classical conditioning of various response systems are described within the context of the brain structures implicated by the model.

  5. [Research of Embryonic Mortality Stages of Drosophila melanogaster Depending on Age and Starvation of an Imago].

    PubMed

    Kostenko, V V; Kolot, N V; Vorobyova, L I

    2015-01-01

    Influence of age of parents and duration of starvation on egg production and demonstration of embryonic mortality at different stages of egg development has been studied. It is shown that, with increasing age of organisms, the overall egg production reduces and the percentage of embryonic mortality increases at 0-5.5 and 5.5-17 h of development. An increase in the duration of starvation also promotes a reduction in egg production in 3- and 10-day-old adult D. melanogaster compared with short-term starvation. A statistically significant effect of factors, such as the allelic state of the white locus, the genetic background, the age of the parents, and the duration of starvation, on all studied parameters was established.

  6. Complications of radical hysterectomy: clinical experience of 115 early stage cervical cancers.

    PubMed

    Zorlu, C G; Aydoğlu, T; Ergün, Y; Kuşçu, E; Cobanoğlu, O; Koçak, S

    1998-01-01

    We evaluated the clinical experience of 115 women with early stage cervical cancer who had been operated in our Gynecologic Oncology Clinic. Of these, 85 were in stage I, and 30 in stage II. Intraoperative complications occurred in 16 patients including 3 cases concerning bladder, 1 ureter, 1 aorta, 5 v.cava inferior, 1 internal iliac a., 3 internal iliac v., 1 obturator nerve and 1 rectovaginal septum hematoma formation. Postoperative complications were observed in 38 patients. These were 14 bladder dysfunctions, 10 lymphocyst formations, 6 urinary infections, 12 wound infections, 3 pelvic infections, 2 eviscerations and 1 incisional hernia. However, no death occurred due to intraoperative or postoperative complications. Pelvic lymph node metastases were observed in 32 patients of whom 17 had only unilateral involvement, most often in the obturator region. Para-aortic lymph node metastases were diagnosed in 4 patients, all of whom were in stage II.

  7. Inherited leukoencephalopathies with clinical onset in middle and old age.

    PubMed

    Nannucci, Serena; Donnini, Ida; Pantoni, Leonardo

    2014-12-15

    The currently widespread use of neuroimaging has led neurologists to often face the problem of the differential diagnosis of white matter diseases. There are various forms of leukoencephalopathies (vascular, inflammatory and immunomediated, infectious, metabolic, neoplastic) and sometimes white matter lesions are expression of a genetic disease. While many inherited leukoencephalopathies fall in the child neurologist's interest, others may have a delayed or even a typical onset in the middle or old age. This field is rapidly growing and, in the last few years, many new inherited white matter diseases have been described and genetically defined. A non-delayed recognition of middle and old age inherited leukoencephalopathies appears important to avoid unnecessary tests and therapies in the patient and to possibly anticipate the diagnosis in relatives. The aim of this review is to provide a guide to direct the diagnostic process when facing a patient with a suspicion of an inherited form of leukoencephalopathy and with clinical onset in middle or old age. Based on a MEDLINE search from 1990 to 2013, we identified 24 middle and old age onset inherited leukoencephalopathies and reviewed in this relation the most recent findings focusing on their differential diagnosis. We provide summary tables to use as a check list of clinical and neuroimaging findings that are most commonly associated with these forms of leukoencephalopathies. When present, we reported specific characteristics of single diseases. Several genetic diseases may be suspected in patients with middle or old age and white matter abnormalities. In only few instances, pathognomonic clinical or associated neuroimaging features help identifying a specific disease. Therefore, a comprehensive knowledge of the characteristics of these inherited white matter diseases appears important to improve the diagnostic work-up, optimize the choice of genetic tests, increase the number of diagnosed patients, and stimulate

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

    PubMed Central

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

    2016-01-01

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

  9. Age and petrology of alkalic postshield and rejuvenated-stage lava from Kauai, Hawaii

    USGS Publications Warehouse

    Clague, D.A.; Dalrymple, G.B.

    1988-01-01

    At the top of the Waimea Canyon Basalt on the island of Kauai, rare flows of alkalic postshield-stage hawaiite and mugearite overlie tholeiitic flows of the shield stage. These postshield-stage flows are 3.92 Ma and provide a younger limit for the age of the tholeiitic shield stage. The younger Koloa Volcanics consist of widespread alkalic rejuvenated-stage flows and vents of alkalic basalt, basanite, nephelinite, and nepheline melilitite that erupted between 3.65 and 0.52 Ma. All the flows older than 1.7 Ma occur in the west-northwestern half of the island and all the flows younger than 1.5 Ma occur in the east-southeastern half. The lithologies have no spatial or chronological pattern. The flows of the Koloa Volcanics are near-primary magmas generated by variable small degrees of partial melting of a compositionally heterogeneous garnet-bearing source that has about two-thirds the concentration of P2O5, rare-earth elements, and Sr of the source of the Honolulu Volcanics on the island of Oahu. The same lithology in the Koloa and Honolulu Volcanics is generated by similar degrees of partial melting of distinct source compositions. The lavas of the Koloa Volcanics can be generated by as little as 3 percent to as much as 17 percent partial melting for nepheline melilitite through alkalic basalt, respectively. Phases that remain in the residue of the Honolulu Volcanics, such as rutile and phlogopite, are exhausted during formation of the Koloa Volcanics at all but the smallest degrees of partial melting. The mantle source for Kauai lava becomes systematically more depleted in 87Sr/86Sr as the volcano evolves from the tholeiitic shield stage to the alkalic postshield stage to the alkalic rejuvenated stage: at the same time, the lavas become systematically more enriched in incompatible trace elements. On a shorter timescale, the lavas of the Koloa Volcanics display the same compositional trends, but at a lower rate of change. The source characteristics of the Koloa

  10. Dental age estimation from the developmental stage of the third molars in Iranian population.

    PubMed

    Rai, Balwant; Kaur, Jasdeep; Jafarzadeh, Hamid

    2010-08-01

    A sharp increase in forensic age estimation of living persons has been observed in recent years. However, ethnic populations residing in different countries have been insufficiently analyzed. The aim of this study was to achieve a referral database and regression equations for dental age estimation of unaccompanied minors of Iran nationality. A total of 1200 orthopantomograms were collected from original Iran and equally divided in age categories between 10 and 27 years. On the radiographs, the developmental stage of the third molars was scored applying a Demirjian et al. scoring technique. Inter- and intra-observer reliabilities were tested using kappa statistics. Correlation between the scores of all four wisdom maxillary and mandibular third molars teeth and left/right symmetry were evaluated with spearman correlation coefficient. Student's t-test on asymmetry was performed and regression formulas were calculated. The present database was the first to assemble third molar developmental scores on radiographs of Iran individuals and provided more appropriate dental age estimation of unaccompanied Iran minors. To enhance the accuracy of forensic age estimates based on third molars mineralization, the use of population-specific standards is recommended.

  11. Variation in honey bee gut microbial diversity affected by ontogenetic stage, age and geographic location.

    PubMed

    Hroncova, Zuzana; Havlik, Jaroslav; Killer, Jiri; Doskocil, Ivo; Tyl, Jan; Kamler, Martin; Titera, Dalibor; Hakl, Josef; Mrazek, Jakub; Bunesova, Vera; Rada, Vojtech

    2015-01-01

    Social honey bees, Apis mellifera, host a set of distinct microbiota, which is similar across the continents and various honey bee species. Some of these bacteria, such as lactobacilli, have been linked to immunity and defence against pathogens. Pathogen defence is crucial, particularly in larval stages, as many pathogens affect the brood. However, information on larval microbiota is conflicting. Seven developmental stages and drones were sampled from 3 colonies at each of the 4 geographic locations of A. mellifera carnica, and the samples were maintained separately for analysis. We analysed the variation and abundance of important bacterial groups and taxa in the collected bees. Major bacterial groups were evaluated over the entire life of honey bee individuals, where digestive tracts of same aged bees were sampled in the course of time. The results showed that the microbial tract of 6-day-old 5th instar larvae were nearly equally rich in total microbial counts per total digestive tract weight as foraging bees, showing a high percentage of various lactobacilli (Firmicutes) and Gilliamella apicola (Gammaproteobacteria 1). However, during pupation, microbial counts were significantly reduced but recovered quickly by 6 days post-emergence. Between emergence and day 6, imago reached the highest counts of Firmicutes and Gammaproteobacteria, which then gradually declined with bee age. Redundancy analysis conducted using denaturing gradient gel electrophoresis identified bacterial species that were characteristic of each developmental stage. The results suggest that 3-day 4th instar larvae contain low microbial counts that increase 2-fold by day 6 and then decrease during pupation. Microbial succession of the imago begins soon after emergence. We found that bacterial counts do not show only yearly cycles within a colony, but vary on the individual level. Sampling and pooling adult bees or 6th day larvae may lead to high errors and variability, as both of these stages may

  12. Variation in Honey Bee Gut Microbial Diversity Affected by Ontogenetic Stage, Age and Geographic Location

    PubMed Central

    Hroncova, Zuzana; Havlik, Jaroslav; Killer, Jiri; Doskocil, Ivo; Tyl, Jan; Kamler, Martin; Titera, Dalibor; Hakl, Josef; Mrazek, Jakub; Bunesova, Vera; Rada, Vojtech

    2015-01-01

    Social honey bees, Apis mellifera, host a set of distinct microbiota, which is similar across the continents and various honey bee species. Some of these bacteria, such as lactobacilli, have been linked to immunity and defence against pathogens. Pathogen defence is crucial, particularly in larval stages, as many pathogens affect the brood. However, information on larval microbiota is conflicting. Seven developmental stages and drones were sampled from 3 colonies at each of the 4 geographic locations of A. mellifera carnica, and the samples were maintained separately for analysis. We analysed the variation and abundance of important bacterial groups and taxa in the collected bees. Major bacterial groups were evaluated over the entire life of honey bee individuals, where digestive tracts of same aged bees were sampled in the course of time. The results showed that the microbial tract of 6-day-old 5th instar larvae were nearly equally rich in total microbial counts per total digestive tract weight as foraging bees, showing a high percentage of various lactobacilli (Firmicutes) and Gilliamella apicola (Gammaproteobacteria 1). However, during pupation, microbial counts were significantly reduced but recovered quickly by 6 days post-emergence. Between emergence and day 6, imago reached the highest counts of Firmicutes and Gammaproteobacteria, which then gradually declined with bee age. Redundancy analysis conducted using denaturing gradient gel electrophoresis identified bacterial species that were characteristic of each developmental stage. The results suggest that 3-day 4th instar larvae contain low microbial counts that increase 2-fold by day 6 and then decrease during pupation. Microbial succession of the imago begins soon after emergence. We found that bacterial counts do not show only yearly cycles within a colony, but vary on the individual level. Sampling and pooling adult bees or 6th day larvae may lead to high errors and variability, as both of these stages may

  13. Variation in honey bee gut microbial diversity affected by ontogenetic stage, age and geographic location.

    PubMed

    Hroncova, Zuzana; Havlik, Jaroslav; Killer, Jiri; Doskocil, Ivo; Tyl, Jan; Kamler, Martin; Titera, Dalibor; Hakl, Josef; Mrazek, Jakub; Bunesova, Vera; Rada, Vojtech

    2015-01-01

    Social honey bees, Apis mellifera, host a set of distinct microbiota, which is similar across the continents and various honey bee species. Some of these bacteria, such as lactobacilli, have been linked to immunity and defence against pathogens. Pathogen defence is crucial, particularly in larval stages, as many pathogens affect the brood. However, information on larval microbiota is conflicting. Seven developmental stages and drones were sampled from 3 colonies at each of the 4 geographic locations of A. mellifera carnica, and the samples were maintained separately for analysis. We analysed the variation and abundance of important bacterial groups and taxa in the collected bees. Major bacterial groups were evaluated over the entire life of honey bee individuals, where digestive tracts of same aged bees were sampled in the course of time. The results showed that the microbial tract of 6-day-old 5th instar larvae were nearly equally rich in total microbial counts per total digestive tract weight as foraging bees, showing a high percentage of various lactobacilli (Firmicutes) and Gilliamella apicola (Gammaproteobacteria 1). However, during pupation, microbial counts were significantly reduced but recovered quickly by 6 days post-emergence. Between emergence and day 6, imago reached the highest counts of Firmicutes and Gammaproteobacteria, which then gradually declined with bee age. Redundancy analysis conducted using denaturing gradient gel electrophoresis identified bacterial species that were characteristic of each developmental stage. The results suggest that 3-day 4th instar larvae contain low microbial counts that increase 2-fold by day 6 and then decrease during pupation. Microbial succession of the imago begins soon after emergence. We found that bacterial counts do not show only yearly cycles within a colony, but vary on the individual level. Sampling and pooling adult bees or 6th day larvae may lead to high errors and variability, as both of these stages may

  14. Optimal adaptive two-stage designs for early phase II clinical trials.

    PubMed

    Shan, Guogen; Wilding, Gregory E; Hutson, Alan D; Gerstenberger, Shawn

    2016-04-15

    Simon's optimal two-stage design has been widely used in early phase clinical trials for Oncology and AIDS studies with binary endpoints. With this approach, the second-stage sample size is fixed when the trial passes the first stage with sufficient activity. Adaptive designs, such as those due to Banerjee and Tsiatis (2006) and Englert and Kieser (2013), are flexible in the sense that the second-stage sample size depends on the response from the first stage, and these designs are often seen to reduce the expected sample size under the null hypothesis as compared with Simon's approach. An unappealing trait of the existing designs is that they are not associated with a second-stage sample size, which is a non-increasing function of the first-stage response rate. In this paper, an efficient intelligent process, the branch-and-bound algorithm, is used in extensively searching for the optimal adaptive design with the smallest expected sample size under the null, while the type I and II error rates are maintained and the aforementioned monotonicity characteristic is respected. The proposed optimal design is observed to have smaller expected sample sizes compared to Simon's optimal design, and the maximum total sample size of the proposed adaptive design is very close to that from Simon's method. The proposed optimal adaptive two-stage design is recommended for use in practice to improve the flexibility and efficiency of early phase therapeutic development. PMID:26526165

  15. A clinical staging system and treatment guidelines for maxillary osteoradionecrosis in irradiated nasopharyngeal carcinoma patients

    SciTech Connect

    Cheng, S.-J.; Lee, J.-J.; Ting, L.-L.; Tseng, I.-Y.; Chang, H.-H.; Chen, H.-M.; Kuo, Y.-S.; Hahn, L.-J.; Kok, S.-H. . E-mail: kok@ha.mc.ntu.edu.tw

    2006-01-01

    Purpose: To develop a clinical staging system for maxillary osteoradionecrosis (ORN) in irradiated nasopharyngeal carcinoma (NPC) patients. Methods and Materials: The data of maxillary ORN cases among 1,758 irradiated NPC patients were analyzed. A staging system based on the degrees of bone exposure (E), infection (I), and bleeding (B) was developed. Correlations between various clinical parameters and stages of maxillary ORN and relationships between treatment modalities and outcomes at each stage were evaluated. Cumulative success of treatment and risk factors that affect treatment outcomes were analyzed. Results: The incidence of maxillary ORN was 2.7% (48/1,758). TNM stage of NPC (p < 0.001), radiation dose (p = 0.029), and tooth extraction (p < 0.001) appeared to have significant influences on disease severity. Success rates between conservative therapy and surgical treatment were not significantly different for Stage I ORN but differed significantly for Stage II (p = 0.013) and Stage III (p = 0.008) lesions. Grade 3 infection and bleeding significantly jeopardized treatment success (p = 0.043 and 0.015, respectively). The risk ratios of treatment failure for Grade 3 infection and bleeding were 2.523 (p = 0.034) and 3.141 (p = 0.027), respectively. Conclusions: More serious maxillary ORN tended to occur in cases with more advanced NPC, higher radiation dose, and history of tooth extraction. Surgical treatment was usually required in Stage II and III ORN. The grades of infection and bleeding are important factors in guidance of treatment and prediction of outcomes.

  16. Photoacoustic intra-operative nodal staging using clinically approved superparamagnetic iron oxide nanoparticles

    NASA Astrophysics Data System (ADS)

    Grootendorst, Diederik J.; Fratila, Raluca M.; Visscher, Martijn; Ten Haken, Bennie; van Wezel, Richard; Steenbergen, Wiendelt; Manohar, Srirang; Ruers, Theo J. M.

    2013-02-01

    Detection of tumor metastases in the lymphatic system is essential for accurate staging of various malignancies, however fast, accurate and cost-effective intra-operative evaluation of the nodal status remains difficult to perform with common available medical imaging techniques. In recent years, numerous studies have confirmed the additional value of superparamagnetic iron oxide dispersions (SPIOs) for nodal staging purposes, prompting the clearance of different SPIO dispersions for clinical practice. We evaluate whether a combination of photoacoustic (PA) imaging and a clinically approved SPIO dispersion, could be applied for intra-operative nodal staging. Metastatic adenocarcinoma was inoculated in Copenhagen rats for 5 or 8 days. After SPIO injection, the lymph nodes were photoacoustically imaged both in vivo and ex vivo whereafter imaging results were correlated with MR and histology. Results were compared to a control group without tumor inoculation. In the tumor groups clear irregularities, as small as 1 mm, were observed in the PA contrast pattern of the nodes together with an decrease of PA response. These irregularities could be correlated to the absence of contrast in the MR images and could be linked to metastatic deposits seen in the histological slides. The PA and MR images of the control animals did not show these features. We conclude that the combination of photoacoustic imaging with a clinically approved iron oxide nanoparticle dispersion is able to detect lymph node metastases in an animal model. This approach opens up new possibilities for fast intra-operative nodal staging in a clinical setting.

  17. Robot-assisted laparoscopic retroperitoneal lymph node dissection in clinical stage II testicular cancer.

    PubMed

    Annerstedt, Magnus; Gudjonsson, Sigurdur; Wullt, Björn; Uvelius, Bengt

    2008-09-01

    Robot-assisted retroperitoneal lymph node dissections were performed in three patients after chemotherapy for clinical stage II testicular cancer. Although our experience is still limited, we think that the outcomes of the cases suggest a role for robot-assisted surgery in selected cases undergoing post-chemotherapy retroperitoneal lymph node dissection. PMID:27628259

  18. Influences of competition level, gender, player nationality, career stage and playing position on relative age effects.

    PubMed

    Schorer, J; Cobley, S; Büsch, D; Bräutigam, H; Baker, J

    2009-10-01

    Relative age, referring to the chronological age differences between individuals within annually age-grouped cohorts, is regarded as influential to an athlete's development, constraining athletic skill acquisition. While many studies have suggested different mechanisms for this effect, they have typically examined varying sports, precluding an examination of the possible inter-play between factors. Our three studies try to bridge this gap by investigating several moderators for relative age effects (RAEs) in one sport. Handball is a sport with position-specific demands, high cultural relevance and a performance context with established developmental structures and levels of representation for males and females. In Study 1, we investigated the influence of competition level and gender on RAEs before adulthood. In Study 2, elite participation, player nationality and stage of career are considered during adulthood. In Study 3, playing position and laterality (i.e., right vs left handedness) are investigated as moderators. Collectively, the results emphasize the complex inter-play of direct and indirect influences on RAEs in sports, providing evidence toward explaining how RAEs influence the development and maintenance of expertise.

  19. The clinical implications of HIV infection and aging.

    PubMed

    John, M

    2016-04-01

    The objectives of this study, presented as part of a plenary session at WW7 in Hyderabad, India were to review (i) the epidemiology and current clinical issues of HIV infection with regard to HIV and older populations and (ii) models for increased morbidity and mortality in older HIV-positive individuals with implications for clinical care. HIV infection for those in treatment has become a complex chronic disease in which end-organ injury and resulting morbidity, functional decline, and mortality do not have a single etiology but reflect cumulative loss of organ system reserve from multiple interacting sources leading to functional decline, organ system failure, and death. Emerging guidelines and recommendations suggest a need for increased awareness and treatment of the multifaceted needs of the aging HIV-infected patient. PMID:27109276

  20. Clinical correlates of age of onset in psychotic depression.

    PubMed

    Gournellis, Rossetos; Oulis, Panagiotis; Rizos, Emmanuel; Chourdaki, Evgenia; Gouzaris, Agis; Lykouras, Lefteris

    2011-01-01

    The issue whether the clinical characteristics of unipolar psychotic major depression (PMD) vary according to the age of onset remains still unclear. Thus, the aim of this study was to assess comparatively a broad set of clinical characteristics of three groups of PMD patients, namely young early-onset (n=30), elderly early-onset (n=34) and elderly late-onset (n=35). Ninety-nine inpatients suffering from DSM-IV unipolar PMD were assessed on the basis of Structured Clinical Interview for DSM-IV (SCID-IV), Hamilton Rating Scale for Depression (HRSD) and a physical impairment rating scale. The elderly late-onset patients suffered from overall more severe depression compared to both early-onset ones, more psychic anxiety compared to elderly early-onset patients and more gastrointestinal symptoms compared to young early-onset patients. Additionally, they expressed significantly more frequently delusions of somatic content and higher scores on the HRSD item of hypochondriasis than their young early-onset counterparts. The group of elderly early-onset PMD patients was found to hold an intermediate position between the young early-onset and elderly late-onset PMD patients with regard to hypochondriacal ideation, gastrointestinal symptoms and delusions of somatic, guilt, and paranoid content. Their stability of delusional content across successive episodes was found to extend into old age. Nevertheless, they expressed additional somatic delusions. Overall, the findings of the present study suggest considerable differences between young early-onset, elderly early-onset and elderly late-onset PMD patients with respect to their clinical features.

  1. Blood-Borne Activity-Dependent Neuroprotective Protein (ADNP) is Correlated with Premorbid Intelligence, Clinical Stage, and Alzheimer's Disease Biomarkers.

    PubMed

    Malishkevich, Anna; Marshall, Gad A; Schultz, Aaron P; Sperling, Reisa A; Aharon-Peretz, Judith; Gozes, Illana

    2015-01-01

    Biomarkers for Alzheimer's disease (AD) are vital for disease detection in the clinical setting. Discovered in our laboratory, activity-dependent neuroprotective protein (ADNP) is essential for brain formation and linked to cognitive functions. Here, we revealed that blood borne expression of ADNP and its paralog ADNP2 is correlated with premorbid intelligence, AD pathology, and clinical stage. Age adjustment showed significant associations between: 1) higher premorbid intelligence and greater serum ADNP, and 2) greater cortical amyloid and lower ADNP and ADNP2 mRNAs. Significant increases in ADNP mRNA levels were observed in patients ranging from mild cognitive impairment (MCI) to AD dementia. ADNP2 transcripts showed high correlation with ADNP transcripts, especially in AD dementia lymphocytes. ADNP plasma/serum and lymphocyte mRNA levels discriminated well between cognitively normal elderly, MCI, and AD dementia participants. Measuring ADNP blood-borne levels could bring us a step closer to effectively screening and tracking AD.

  2. Genetics of Unilateral and Bilateral Age-Related Macular Degeneration Severity Stages

    PubMed Central

    Schick, Tina; Altay, Lebriz; Viehweger, Eva; Hoyng, Carel B.; den Hollander, Anneke I.; Felsch, Moritz; Fauser, Sascha

    2016-01-01

    Background Age-related macular degeneration (AMD) is a common disease causing visual impairment and blindness. Various gene variants are strongly associated with late stage AMD, but little is known about the genetics of early forms of the disease. This study evaluated associations of genetic factors and different AMD stages depending on unilateral and bilateral disease severity. Methods In this case-control study, participants were assigned to nine AMD severity stages based on the characteristics of each eye. 18 single nucleotide polymorphisms (SNPs) were genotyped and attempted to correlate with AMD severity stages by uni- and multivariate logistic regression analyses and trend analyses. Area under the receiver operating characteristic curves (AUC) were calculated. Results Of 3444 individuals 1673 were controls, 379 had early AMD, 333 had intermediate AMD and 989 showed late AMD stages. With increasing severity of disease and bilateralism more SNPs with significant associations were found. Odds ratios, especially for the main risk polymorphisms in ARMS2 (rs10490924) and CFH (rs1061170), gained with increasing disease severity and bilateralism (exemplarily: rs1061170: unilateral early AMD: OR = 1.18; bilateral early AMD: OR = 1.20; unilateral intermediate AMD: OR = 1.28; bilateral intermediate AMD: OR = 1.39, unilateral geographic atrophy (GA): OR = 1.50; bilateral GA: OR = 1.71). Trend analyses showed p<0.0001 for ARMS2 (rs10490924) and for CFH (rs1061170), respectively. AUC of risk models for various AMD severity stages was lowest for unilateral early AMD (AUC = 0.629) and showed higher values in more severely and bilaterally affected individuals being highest for late AMD with GA in one eye and neovascular AMD in the other eye (AUC = 0.957). Conclusion The association of known genetic risk factors with AMD became stronger with increasing disease severity, which also led to an increasing discriminative ability of AMD cases and controls. Genetic predisposition was

  3. Low Level of Microsatellite Instability Correlates with Poor Clinical Prognosis in Stage II Colorectal Cancer Patients

    PubMed Central

    Mojarad, Ehsan Nazemalhosseini; Kashfi, Seyed Mohammad Hossein; Mirtalebi, Hanieh; Taleghani, Mohammad Yaghoob; Azimzadeh, Pedram; Savabkar, Sanaz; Pourhoseingholi, Mohammad Amin; Jalaeikhoo, Hasan; Asadzadeh Aghdaei, Hamid; Kuppen, Peter J. K.; Zali, Mohammad Reza

    2016-01-01

    The influence of microsatellite instability (MSI) on the prognosis of colorectal cancer (CRC) requires more investigation. We assessed the role of MSI status in survival of individuals diagnosed with primary colorectal cancer. In this retrospective cross-sectional study the MSI status was determined in 158 formalin-fixed paraffin-embedded tumors and their matched normal tissues from patients who underwent curative surgery. Cox proportional hazard modeling was performed to assess the clinical prognostic significance. In this study we found that MSI-H tumors were predominantly located in the colon versus rectum (p = 0.03), associated with poorer differentiation (p = 0.003) and TNM stage II/III of tumors (p = 0.02). In CRC patients with stage II, MSI-L cases showed significantly poorer survival compared with patients who had MSI-H or MSS tumors (p = 0.04). This study indicates that MSI-L tumors correlate with poorer clinical outcome in patients with stage II tumors (p = 0.04) or in tumors located in the colon (p = 0.02). MSI-L characterizes a distinct subgroup of CRC patients who have a poorer outcome. This study suggests that MSI status in CRC, as a clinical prognostic marker, is dependent on other factors, such as tumor stage and location. PMID:27429617

  4. Atomic structure of Cu-10. 9 at % Be alloys in the early stages of aging

    SciTech Connect

    Koo, Y.M.

    1987-01-01

    Diffuse x-ray scattering was employed to investigate the local atomic structure and static strains in a single crystal of a Cu-10.9 at. % Be alloy in the early stages of aging. In addition to these experiments, neutron elastic and inelastic scattering were obtained to investigate the phonon properties in the as-quenched state of this alloy. In the as-quenched state, there is a nearly regular array of small ellipsoidal Be clusters aligned along <100> directions (This produces the tweed contrast seen in TEM). The density of these clusters is 7.5 x 10/sup 26//m/sup 3/. The diffuse streaks seen in electron diffraction patterns are due largely to thermal diffuse scattering. Phonon-dispersion curves show no large differences from those of pure copper, except at (xi xi xi)/sub T/ zone boundary, where there is softening. This difference may be due to a Kohn anomaly. The elastic anisotropy of this alloy increases considerably with alloying, which probably leads to the plate-like GP zone morphology in subsequent aging treatments. The structure of the GP zones is a mixture of Be-rich single- and multi-layered zones. As aging proceeds, the zones grow in thickness.

  5. Clinical experience in staging of lung cancer at Martin-Luther University Halle-Wittenberg.

    PubMed

    Neef, H

    1999-01-01

    Staging of lung cancer needs an accurate diagnostic programme resulting in therapeutic and prognostic consequences. A modern, articulate flow-chart is presented and discussed. As a result, the rate of exploratory thoracotomy was reduced from 15.1% in 1988 to 2.1% in 1997 and the rate of resectability raised up to 30%. Preoperative over-staging was found in about 25% and the same value for understaging. Looking to the N-values, there was concordance of clinical and postoperative data in 61.9% of cases.

  6. The Living Stage Improvisational Theatre Demonstration Project for Orthopedically Handicapped Children, Ages 4-8. Overview, 1978-1981.

    ERIC Educational Resources Information Center

    Alexander, Robert; Haynes, Wendy

    The Living Stage Improvisational Theatre Demonstration Project (Washington, D.C.) conducts weekly workshops to enhance the creative expression and self esteem of orthopedically handicapped children, aged 4 to 8 years. The Living Stage program is designed to demonstrate that methods of improvisational theatre can have a positive impact on parental…

  7. Late-stage clinical development in lower urogenital targets: sexual dysfunction

    PubMed Central

    Azam, Usman

    2006-01-01

    In recent years, late-stage clinical drug development that primarily focuses on urogenital targets has centered around four areas of medical need (both unmet need and aiming to improve on existing therapies). These include male sexual dysfunction (MSD), female sexual dysfunction (FSD), prostatic pathology (neoplastic, pre-neoplasitic, and non-neoplastic), and improvement in lower urinary tract symptoms. Despite the regulatory approval of compounds to treat erectile dysfunction (ED), benign prostatic hyperplasia, a number of treatments for overactive bladder, and stress urinary incontinence, there remains a deficiency in addressing a number of conditions that arise out of pathophysiological dysfunction resulting in lower urogenital tract sexual conditions. In terms of late-stage clinical development, significant progress has most recently been made in MSD development, especially in understanding further a common and complex sexual dysfunction – that of premature ejaculation. The search also continues for compounds that improve ED in terms of better efficacy and superior safety profile compared to the currently marketed phosphodiesterase-5-inhibitors. Whilst there are no approved medications to treat the subtypes of FSD, there has been significant progress in attempting to better understand how to appropriately assess treatment benefit in clinical trial settings for this difficult to diagnose and treat condition. This review will focus on late-stage human clinical development pertaining to MSD and FSD. PMID:16465180

  8. Does Islamic spiritual program lead to successful aging? A randomized clinical trial

    PubMed Central

    Moeini, Mahin; Sharifi, Somaye; Zandiyeh, Zahra

    2016-01-01

    Context: Successful aging is a pattern of aging that has gained much attention during recent years. One factor that has a negative impact on successful aging variables is hypertension. The phenomenon of aging when accompanied with hypertension promotes spiritual needs. The aim of this study was to examine the effect of the Islamic spiritual program on successful aging in elderly patients with hypertension who were referred to health centers of Isfahan, Iran, in 2014. Settings and Design: This study was a randomized clinical trial. Materials and Methods: The participants (52 elderly patients with hypertension) were randomly divided into experimental and control groups. While the control group received training related to health promotion, the Islamic spiritual program was implemented in the experimental group for eight sessions in two health centers of Isfahan. The data collection tools consisted of the 12-item General Health Questionnaire developed by Goldberg and the satisfaction with life scale developed by Diener. The questionnaires were completed in three steps; pretest, posttest, and follow-up (1-month). Statistical Analysis Used: Data were analyzed using SPSS statistical software version 20 and Chi-square, independent t-test, and repeated measures ANOVA. Results: Statistical tests showed that the mean score of general health and life satisfaction of the experiment group had a meaningful difference from that of the control group in the posttest stage (P < 0.001). This difference was also meaningful in the follow-up stage (P < 0.001). Conclusion: The results of the study indicated the effectiveness of an Islamic spiritual program on successful aging variables. PMID:27512694

  9. General guidance on exploratory and confirmatory subgroup analysis in late-stage clinical trials.

    PubMed

    Dmitrienko, Alex; Muysers, Christoph; Fritsch, Arno; Lipkovich, Ilya

    2016-01-01

    This article focuses on a broad class of statistical and clinical considerations related to the assessment of treatment effects across patient subgroups in late-stage clinical trials. This article begins with a comprehensive review of clinical trial literature and regulatory guidelines to help define scientifically sound approaches to evaluating subgroup effects in clinical trials. All commonly used types of subgroup analysis are considered in the article, including different variations of prospectively defined and post-hoc subgroup investigations. In the context of confirmatory subgroup analysis, key design and analysis options are presented, which includes conventional and innovative trial designs that support multi-population tailoring approaches. A detailed summary of exploratory subgroup analysis (with the purpose of either consistency assessment or subgroup identification) is also provided. The article promotes a more disciplined approach to post-hoc subgroup identification and formulates key principles that support reliable evaluation of subgroup effects in this setting.

  10. Age and stage dependency of estrogen receptor expression by lymphocyte precursors

    PubMed Central

    Igarashi, Hideya; Kouro, Taku; Yokota, Takafumi; Comp, Phillip C.; Kincade, Paul W.

    2001-01-01

    Sex steroids negatively regulate B lymphopoiesis in adult mice. Paradoxically, lymphocytes arise during fetal life, when estrogen levels are high and maternal lymphopoiesis is suppressed. Here we demonstrate that embryonic B lymphopoiesis was unaffected by estrogen, but sensitive to glucocorticoids. Both fetal and adult precursors contained glucocorticoid receptor transcripts, but only adult precursors expressed estrogen receptor α and β together with the androgen receptor. Fetal hematopoietic cells did not efficiently acquire functional estrogen receptors after transplantation to irradiated adult mice. Sex steroid receptors were also expressed in a stage- and developmental age-dependent fashion in human precursors. A developmental switch in responsiveness of hematopoietic cells to sex steroids may be essential for formation of the immune system. PMID:11752459

  11. Clinical outcome of fiducial-less CyberKnife radiosurgery for stage I non-small cell lung cancer

    PubMed Central

    Jung, In-Hye; Jung, Jinhong; Cho, Byungchul; Kwak, Jungwon; Je, Hyoung Uk; Choi, Wonsik; Jung, Nuri Hyun; Kim, Su Ssan; Choi, Eun Kyung

    2015-01-01

    Purpose To evaluate the treatment results in early stage non-small cell lung cancer patients who have undergone fiducial-less CyberKnife radiosurgery (CKRS). Materials and Methods From June 2011 to November 2013, 58 patients underwent CKRS at Asan Medical Center for stage I lung cancer. After excluding 14 patients, we retrospectively reviewed the records of the remaining 44 patients. All analyses were performed using SPSS ver. 21. Results The median age at diagnosis was 75 years. Most patients had inoperable primary lung cancer with a poor pulmonary function test with comorbidity or old age. The clinical stage was IA in 30 patients (68.2%), IB in 14 (31.8%). The mean tumor size was 2.6 cm (range, 1.2 to 4.8 cm), and the tumor was smaller than 2 cm in 12 patients (27.3%). The radiation dose given was 48-60 Gy in 3-4 fractions. In a median follow-up of 23.1 months, local recurrence occurred in three patients (2-year local recurrence-free survival rate, 90.4%) and distant metastasis occurred in 13 patients. All patients tolerated the radiosurgery well, only two patients developing grade 3 dyspnea. The most common complications were radiation-induced fibrosis and pneumonitis. Eight patients died due to cancer progression. Conclusion The results showed that fiducial-less CKRS shows comparable local tumor control and survival rates to those of LINAC-based SABR or CKRS with a fiducial marker. Thus, fiducial-less CKRS using Xsight lung tracking system can be effectively and safely performed for patients with medically inoperable stage I non-small cell lung cancer without any risk of procedure-related complication. PMID:26157678

  12. A comparative study between cleavage stage embryo transfer at day 3 and blastocyst stage transfer at day 5 in in-vitro fertilization/intra-cytoplasmic sperm injection on clinical pregnancy rates

    PubMed Central

    Kaur, Prabhleen; Swarankar, M. L.; Maheshwari, Manju; Acharya, Veena

    2014-01-01

    OBJECTIVE: To evaluate the efficacy of blastocyst transfer in comparison with cleavage stage transfer. STUDY DESIGN: A randomized, prospective study was conducted in Infertility clinic, Department of Obstetrics and Gynecology, Mahatma Gandhi Hospital, Jaipur on 300 patients aged 25-40 years undergoing in-vitro fertilization (IVF)/intra-cytoplasmic sperm injection (ICSI) cycle from May 2010-April 2011. When three or more Grade-I embryos were observed on day 2 of culture, patients were divided randomly into two study groups, cleavage stage transfer and blastocyst transfer group having 150 patients each. Primary outcomes evaluated were, Clinical pregnancy rate and Implantation rate. The results were analyzed using proportions, standard deviation and Chi-square test. RESULTS: Both the groups were similar for age, indication and number of embryos transferred. Clinical pregnancies after blastocyst transfer were significantly higher 66 (44.0%) compared to cleavage stage embryo transfer 44 (29.33%) (P < 0.01). Implantation rate for blastocyst transfer group was also significantly higher (P < 0.001). CONCLUSION: Blastocyst transfer having higher implantation rate and clinical pregnancy rate lead to reduction in multiple pregnancies. PMID:25395745

  13. A review of ageing and an examination of clinical methods in the assessment of ageing skin. Part 2: Clinical perspectives and clinical methods in the evaluation of ageing skin.

    PubMed

    Callaghan, T M; Wilhelm, K-P

    2008-10-01

    With the advancement of skin research, today's consumer has increased access to technological information about ageing skin and hair care products. As a result, there is a rapidly increasing demand for proof of efficacy of these products. Recognizing these demands has led to the development and validation of many clinical methods to measure and quantify ageing skin and the effects of anti-ageing treatments. Many of the current testing methods used to research and evaluate anti-ageing product claim to employ sophisticated instruments alongside more traditional clinical methods. Intelligent use of combined clinical methods has enabled the development of technologically advanced consumer products providing enhanced efficacy and performance. Of non-invasive methods for the assessment and quantification of ageing skin, there is a plethora of tools available to the clinical researcher as defined by key clinically observed ageing parameters: skin roughness and surface texture; fine lines and wrinkles; skin pigmentation; skin colour; firmness and elasticity; hair loss; and proliferative lesions. Furthermore, many clinical procedures for the evaluation of ageing skin treatments are combined with invasive procedures, which enable added-value to claims (such as identification and alteration of biochemical markers), particularly in those cases where perception of product effect needs additional support. As discussed herein, clinical methods used in the assessment of skin ageing are many and require a disciplined approach to their use in such investigations.

  14. Energy expenditure and substrate oxidation in patients with cirrhosis: the impact of cause, clinical staging and nutritional state.

    PubMed

    Müller, M J; Lautz, H U; Plogmann, B; Bürger, M; Körber, J; Schmidt, F W

    1992-05-01

    Many clinicians subjectively feel that cirrhotic patients frequently have clinical signs of hypermetabolism. However, it is unknown whether hypermetabolism is a constant feature of chronic liver disease, corresponds to liver destruction and repair or is of prognostic value. This article is about resting energy expenditure and substrate oxidation rates in 123 patients with biopsy-proven cirrhosis differing with respect to cause, duration of the disease, biochemical parameters of parenchymal cell damage, cholestasis, liver function, number of complications, clinical staging and nutritional state. Resting energy expenditure varied between 1,090 and 2,300 kcal/day and differed from the predicted values in 70% of the patients. Resting energy expenditure was closely related to fat-free mass, and 52% of the variability could be explained by fat-free mass, age and sex. Of all the patients, 18% were hypermetabolic and 31% were hypometabolic. Hypermetabolism showed no strict association with the cause of cirrhosis, the duration of the disease, liver function, cholestasis, cell damage, clinical staging, blood hemoglobin, plasma thyroid hormone levels or human leukocyte antigens. An increased resting energy expenditure was associated with significant losses of muscle, body cell mass and extracellular mass at unchanged body fat, whereas fat and fat-free mass were increased in hypometabolic patients when compared with normometabolic patients. Lipid oxidation was increased, but glucose oxidation was reduced in nearly all patients with cirrhosis. This was most pronounced at advanced stages of liver disease. Although similar with respect to liver function and clinical staging, 76.2% of hypermetabolic patients had transplants within the observation period, compared with only 16.7% and 8.1% in the normometabolic group and hypometabolic group, respectively. Posttransplantation mortality was independent of pretransplantation resting energy expenditure, but it increased significantly in

  15. Early-Stage Breast Cancer in the Octogenarian: Tumor Characteristics, Treatment Choices, and Clinical Outcomes

    PubMed Central

    Mamtani, Anita; Gonzalez, Julie J.; Neo, Dayna; Slanetz, Priscilla J.; Houlihan, Mary Jane; Herold, Christina I.; Recht, Abram; Hacker, Michele R.; Sharma, Ranjna

    2016-01-01

    Background Nodal staging with sentinel node biopsy (SLNB), post-lumpectomy radiotherapy (RT), and endocrine therapy (ET) for estrogen receptor-positive (ER+) tumors is valuable in the treatment of early-stage (stages 1 or 2) breast cancer but used less often for elderly women. Methods This retrospective study investigated women referred for surgical evaluation of biopsy-proven primary early-stage invasive breast cancer from January 2001 to December 2010. Clinicopathologic features, treatment course, and outcomes for women ages 80–89 years and 50–59 years were compared. Results The study identified 178 eligible women ages 80–89 years and 169 women ages 50–59 years. The elderly women more often had grade 1 or 2 disease (p = 0.003) and ER+ tumors (p = 0.007) and less frequently had undergone adjuvant therapies (all p ≤ 0.001). Lumpectomy was performed more commonly for the elderly (92 vs. 83 %, p = 0.02), and axillary surgery was less commonly performed (46 vs. 96 %; p < 0.001). Fewer elderly women had undergone post-lumpectomy RT (42 vs. 89 %; p < 0.001) and ET for ER+ tumors (72 vs. 95 %; p < 0.001). During the median follow-up period of 56 months for the 80- to 89-year old group and 98 months for the 50- to 59-year-old group, death from breast cancer was similar (4 vs. 5 %; p = 0.5). The two groups respectively experienced 7 versus 6 locoregional recurrences and 11 versus 13 distant recurrences. Conclusions The octogenarians had disease survivorship similar to that of the younger women despite less frequent use of adjuvant therapies, likely reflecting lower-risk disease features. Whether increased use of axillary surgery, post-lumpectomy RT, and/or ET for ER+ tumors would further improve outcomes is an important area for further study, but treatment should not be deferred solely on the basis of age. PMID:27364507

  16. Correlation analysis of urine metabolites and clinical staging in patients with ovarian cancer.

    PubMed

    Jiang, Ting; Lin, Yunliang; Yin, Haiqin; Wang, Shanshan; Sun, Qinglei; Zhang, Peihai; Bi, Wenxiang

    2015-01-01

    This study is to investigate the correlation between urine metabolites and clinical staging in patients with ovarian cancer. The urina sanguinis from 56 cases of primary epithelial ovarian cancer patients and 15 healthy volunteers was collected and the urine metabolites were extracted. Ultra high performance liquid chromatography/time-of-flight mass spectrometry (UPLC-Q-TOF-MS) analysis was performed. Principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were used to analyze the mass spectrometry data. Database retrieval and comparison of the screened metabolites were performed and one-way ANOVA and least significant difference (LSD) t test were carried out. PCA analysis of UPLC-Q-TOF-MS results showed that the score plots of samples from healthy people and patients with ovarian cancer at different clinical stages were separated. Further PLS-DA analysis significantly improved the classification results. The R(2)X was 0.757, the R(2)Y was 0.977 and the Q(2)Y was 0.87, indicating that the model stability and predictability were good. Eight metabolites, including N-acetylneuraminic acid-9-phosphate, 5'-methioadenosine, uric acid-3-nucleoside, pseudouridine, L-valine, succinic acid, L-proline and β-nicotinamide mononucleotide were identified. The contents of these metabolites increased with the development of the disease. There was correlation between urine metabolites and clinical staging in patients with ovarian cancer. PMID:26770415

  17. Clinical Presentation of Klinefelter's Syndrome: Differences According to Age.

    PubMed

    Pacenza, Néstor; Pasqualini, Titania; Gottlieb, Silvia; Knoblovits, Pablo; Costanzo, Pablo R; Stewart Usher, Jorge; Rey, Rodolfo A; Martínez, María P; Aszpis, Sergio

    2012-01-01

    The aim of the study was to establish the characteristics of presentation of 94 patients with Kinelfelter's syndrome (KS) referred to the endocrinologist at different ages. The diagnosis of KS was more frequent in the age group between 11 and 20 years (46.8%). Most of the patients (83.7%) showed the classic 47,XXY karyotype and 7.1% showed a 47,XXY/46,XY mosaicism. Half of the patients younger than 18 years presented mild neurodevelopmental disorders. The most frequent clinical findings were cryptorchidism in prepubertal patients, and small testes, cryptorchidism, and gynecomastia in pubertal patients. FSH, LH, AMH, and inhibin B levels were normal in prepubertal patients and became abnormal from midpuberty. Most adults were referred for small testes, infertility, and gynecomastia; 43.6% had sexual dysfunction. Testosterone levels were low in 45%. Mean stature was above the 50th percentile, and 62.5% had BMI ≥25.0 kg/m(2). In conclusion, the diagnosis of Klinefelter syndrome seems to be made earlier nowadays probably because pediatricians are more aware that boys and adolescents with neuro-developmental disorders and cryptorchidism are at increased risk. The increasing use of prenatal diagnosis has also decreased the mean age at diagnosis and allowed to get insight into the evolution of previously undiagnosed cases, which probably represent the mildest forms. In adults average height and weight are slightly higher than those in the normal population. Bone mineral density is mildly affected, more at the spine than at the femoral neck level, in less than half of cases. PMID:22291701

  18. Clinical Presentation of Klinefelter's Syndrome: Differences According to Age.

    PubMed

    Pacenza, Néstor; Pasqualini, Titania; Gottlieb, Silvia; Knoblovits, Pablo; Costanzo, Pablo R; Stewart Usher, Jorge; Rey, Rodolfo A; Martínez, María P; Aszpis, Sergio

    2012-01-01

    The aim of the study was to establish the characteristics of presentation of 94 patients with Kinelfelter's syndrome (KS) referred to the endocrinologist at different ages. The diagnosis of KS was more frequent in the age group between 11 and 20 years (46.8%). Most of the patients (83.7%) showed the classic 47,XXY karyotype and 7.1% showed a 47,XXY/46,XY mosaicism. Half of the patients younger than 18 years presented mild neurodevelopmental disorders. The most frequent clinical findings were cryptorchidism in prepubertal patients, and small testes, cryptorchidism, and gynecomastia in pubertal patients. FSH, LH, AMH, and inhibin B levels were normal in prepubertal patients and became abnormal from midpuberty. Most adults were referred for small testes, infertility, and gynecomastia; 43.6% had sexual dysfunction. Testosterone levels were low in 45%. Mean stature was above the 50th percentile, and 62.5% had BMI ≥25.0 kg/m(2). In conclusion, the diagnosis of Klinefelter syndrome seems to be made earlier nowadays probably because pediatricians are more aware that boys and adolescents with neuro-developmental disorders and cryptorchidism are at increased risk. The increasing use of prenatal diagnosis has also decreased the mean age at diagnosis and allowed to get insight into the evolution of previously undiagnosed cases, which probably represent the mildest forms. In adults average height and weight are slightly higher than those in the normal population. Bone mineral density is mildly affected, more at the spine than at the femoral neck level, in less than half of cases.

  19. Clinical Presentation of Klinefelter's Syndrome: Differences According to Age

    PubMed Central

    Pacenza, Néstor; Pasqualini, Titania; Gottlieb, Silvia; Knoblovits, Pablo; Costanzo, Pablo R.; Stewart Usher, Jorge; Rey, Rodolfo A.; Martínez, María P.; Aszpis, Sergio

    2012-01-01

    The aim of the study was to establish the characteristics of presentation of 94 patients with Kinelfelter's syndrome (KS) referred to the endocrinologist at different ages. The diagnosis of KS was more frequent in the age group between 11 and 20 years (46.8%). Most of the patients (83.7%) showed the classic 47,XXY karyotype and 7.1% showed a 47,XXY/46,XY mosaicism. Half of the patients younger than 18 years presented mild neurodevelopmental disorders. The most frequent clinical findings were cryptorchidism in prepubertal patients, and small testes, cryptorchidism, and gynecomastia in pubertal patients. FSH, LH, AMH, and inhibin B levels were normal in prepubertal patients and became abnormal from midpuberty. Most adults were referred for small testes, infertility, and gynecomastia; 43.6% had sexual dysfunction. Testosterone levels were low in 45%. Mean stature was above the 50th percentile, and 62.5% had BMI ≥25.0 kg/m2. In conclusion, the diagnosis of Klinefelter syndrome seems to be made earlier nowadays probably because pediatricians are more aware that boys and adolescents with neuro-developmental disorders and cryptorchidism are at increased risk. The increasing use of prenatal diagnosis has also decreased the mean age at diagnosis and allowed to get insight into the evolution of previously undiagnosed cases, which probably represent the mildest forms. In adults average height and weight are slightly higher than those in the normal population. Bone mineral density is mildly affected, more at the spine than at the femoral neck level, in less than half of cases. PMID:22291701

  20. Pattern of humoral immune response to Plasmodium falciparum blood stages in individuals presenting different clinical expressions of malaria

    PubMed Central

    Leoratti, Fabiana MS; Durlacher, Rui R; Lacerda, Marcus VG; Alecrim, Maria G; Ferreira, Antonio W; Sanchez, Maria CA; Moraes, Sandra L

    2008-01-01

    Background The development of protective immunity against malaria is slow and to be maintained, it requires exposure to multiple antigenic variants of malaria parasites and age-associated maturation of the immune system. Evidence that the protective immunity is associated with different classes and subclasses of antibodies reveals the importance of considering the quality of the response. In this study, we have evaluated the humoral immune response against Plasmodium falciparum blood stages of individuals naturally exposed to malaria who live in endemic areas of Brazil in order to assess the prevalence of different specific isotypes and their association with different malaria clinical expressions. Methods Different isotypes against P. falciparum blood stages, IgG, IgG1, IgG2, IgG3, IgG4, IgM, IgE and IgA, were determined by ELISA. The results were based on the analysis of different clinical expressions of malaria (complicated, uncomplicated and asymptomatic) and factors related to prior malaria exposure such as age and the number of previous clinical malaria attacks. The occurrence of the H131 polymorphism of the FcγIIA receptor was also investigated in part of the studied population. Results The highest levels of IgG, IgG1, IgG2 and IgG3 antibodies were observed in individuals with asymptomatic and uncomplicated malaria, while highest levels of IgG4, IgE and IgM antibodies were predominant among individuals with complicated malaria. Individuals reporting more than five previous clinical malaria attacks presented a predominance of IgG1, IgG2 and IgG3 antibodies, while IgM, IgA and IgE antibodies predominated among individuals reporting five or less previous clinical malaria attacks. Among individuals with uncomplicated and asymptomatic malaria, there was a predominance of high-avidity IgG, IgG1, IgG2 antibodies and low-avidity IgG3 antibodies. The H131 polymorphism was found in 44.4% of the individuals, and the highest IgG2 levels were observed among asymptomatic

  1. Clinical Phenotype Predicts Early Staged Bilateral Deep Brain Stimulation in Parkinson’s Disease

    PubMed Central

    Sung, Victor W.; Watts, Ray L.; Schrandt, Christian J.; Guthrie, Stephanie; Wang, Deli; Amara, Amy W.; Guthrie, Barton L.; Walker, Harrison C.

    2014-01-01

    Object While many centers place bilateral DBS systems simultaneously, unilateral STN DBS followed by a staged contralateral procedure has emerged as a treatment option for many patients. However little is known about whether the preoperative phenotype predicts when staged placement of a DBS electrode in the opposite subthalamic nucleus will be required. We aimed to determine whether preoperative clinical phenotype predicts early staged placement of a second subthalamic deep brain stimulation (DBS) electrode in patients who undergo unilateral subthalamic DBS for Parkinson's disease (PD). Methods Eighty-two consecutive patients with advanced PD underwent unilateral subthalamic DBS contralateral to the most affected hemibody and had at least 2 years of follow-up. Multivariate logistic regression determined preoperative characteristics that predicted staged placement of a second electrode in the opposite subthalamic nucleus. Preoperative measurements included aspects of the Unified Parkinson Disease Rating Scale (UPDRS), motor asymmetry index, and body weight. Results At 2 years follow-up, 28 of the 82 patients (34%) had undergone staged placement of a contralateral electrode while the remainder chose to continue with unilateral stimulation. Statistically significant improvements in UPDRS total and part 3 scores were retained at the end of the 2 year follow-up period in both subsets of patients. Multivariate logistic regression showed that the most important predictors for early staged placement of a second subthalamic stimulator were low asymmetry index (odds ratio 13.4; 95% confidence interval 2.8, 64.9), high tremor subscore (OR 7.2; CI 1.5, 35.0), and low body weight (OR 5.5; CI 1.4, 22.3). Conclusions This single center study provides evidence that elements of the preoperative PD phenotype predict whether patients will require early staged bilateral subthalamic DBS. These data may aid in the management of patients with advanced PD who undergo subthalamic DBS. PMID

  2. Age matters: Developmental stage of Danio rerio larvae influences photomotor response thresholds to diazinion or diphenhydramine

    PubMed Central

    Kristofco, Lauren A.; Cruz, Luis Colon; Haddad, Samuel P.; Behra, Martine L; Chambliss, C. Kevin; Brooks, Bryan W.

    2016-01-01

    Because basic toxicological data is unavailable for the majority of industrial compounds, High Throughput Screening (HTS) assays using the embryonic and larval zebrafish provide promising approaches to define bioactivity profiles and identify potential adverse outcome pathways for previously understudied chemicals. Unfortunately, standardized approaches, including HTS experimental designs, for examining fish behavioral responses to contaminants are rarely available. In the present study, we examined movement behavior of larval zebrafish over 7 days (4–10 days post fertilization or dpf) during typical daylight workday hours to determine whether intrinsic activity differed with age and time of day. We then employed an early life stage approach using the Fish Embryo Test (FET) at multiple developmental ages to evaluate whether photomotor response (PMR) behavior differed with zebrafish age following exposure to diazinon (DZN), a well-studied orthophosphate insecticide, and diphenhydramine (DPH), an antihistamine that also targets serotonin reuptake transporters and the acetylcholine receptor. 72 h studies were conducted at 1–4, 4–7 and 7–10 dpf, followed by behavioral observations using a ViewPoint system at 4, 7 and 10 dpf. Distance traveled and swimming speeds were quantified; nominal treatment levels were analytically verified by isotope-dilution LC-MSMS. Larval zebrafish locomotion displayed significantly different (p < 0.05) activity profiles over the course of typical daylight and workday hours, and these time of day PMR activity profiles were similar across ages examined (4–10 dpf). 10 dpf zebrafish larvae were consistently more sensitive to DPH than either the 4 or 7 dpf larvae with an environmentally realistic lowest observed effect concentration of 200 ng/L. Though ELS and FET studies with zebrafish typically focus on mortality or teratogenicity in 0–4 dpf organisms, behavioral responses of slightly older fish were several orders of magnitude more

  3. Clinical implications of aging skin: cutaneous disorders in the elderly.

    PubMed

    Farage, Miranda A; Miller, Kenneth W; Berardesca, Enzo; Maibach, Howard I

    2009-01-01

    Aging skin undergoes progressive degenerative change. Structural and physiologic changes that occur as a natural consequence of intrinsic aging combined with the effects of a lifetime of ongoing cumulative extrinsic damage and environment insult (e.g. overexposure to solar radiation) can produce a marked susceptibility to dermatologic disorders in the elderly. As skin ages, the vasculature progressively atrophies. The supporting dermis also deteriorates, with collagen and elastin fibers becoming sparse and increasingly disordered. These changes leave the elderly increasingly susceptible to both vascular disorders such as stasis dermatitis and skin injuries such as pressure ulcers and skin tears, with a steadily decreasing ability to effect skin repair. A parallel erosion of normal immune function produces higher levels of autoimmune skin disorders such as bullous pemphigoid, benign mucous membrane pemphigoid, paraneoplastic pemphigoid, and pemphigus vulgaris. Lichen sclerosus, an autoimmune disorder often occurring in the genital area in older women, is not common but is an important development because of the potential for substantial discomfort as well as serious complications. The prevalence of polypharmacy in this population increases the risk for autoimmune drug reactions, and diagnosis should be undertaken with an awareness that polypharmacy in this population creates a greatly increased susceptibility to drug eruptions that can mimic other cutaneous disorders. Immunologic senescence in the elderly also sets the stage for potential reactivation of the Varicella zoster virus, in which initial dermatologic involvement expands into the major sensory ganglia. Known as shingles, this disorder can be excruciatingly painful with the potential to cause blindness if the optic nerve becomes involved. Dermatoses such as xerosis, pruritus, and eczema are also widespread in the elderly, create substantial suffering in those afflicted, and often prove recalcitrant to

  4. The assessment of developmental status using the Ages and Stages questionnaire-3 in nutritional research in north Indian young children

    PubMed Central

    2013-01-01

    Objective and background For large epidemiological studies in low and middle-income countries, inexpensive and easily administered developmental assessment tools are called for. This report evaluates the feasibility of the assessment tool Ages and Stages Questionnaire 3.edition (ASQ-3) “home procedure” in a field trial in 422 North Indian young children. Methods ASQ-3 was translated and adjusted for a North Indian Hindi setting. Three examiners were trained by a clinical psychologist to perform the assessments. During the main study, ten % of the assessments were done by two examiners to estimate inter-observer agreement. During all sessions, the examiners recorded whether the scoring was based on observation of the skill during the session, or on caregiver’s report of the child’s skill. Intra class correlation coefficient was calculated to estimate the agreement between the raters and between the raters and a gold standard. Pearson product moment correlation coefficient and standardized alphas were calculated to measure internal consistency. Principal findings Inter-observer agreement was strong both during training exercises and during the main study. In the Motor subscales and the Problem Solving subscale most items could be observed during the session. The standardized alphas for the total ASQ-3 scale across all ages were strong, while the alpha values for the different subscales and age levels varied. The correlations between the total score and the subscale scores were consistently strong, while the correlations between subscale scores were moderate. Conclusions/significance We found that the translated and adjusted ASQ-3 “home procedure” was a feasible procedure for the collection of reliable data on the developmental status in infants and young children. Examiners were effectively trained over a short period of time, and the total ASQ scores showed adequate variability. However, further adjustments are needed to obtain satisfying alpha values in

  5. Novel modulators of senescence, aging, and longevity: Small non-coding RNAs enter the stage.

    PubMed

    Grillari, Johannes; Grillari-Voglauer, Regina

    2010-04-01

    RNA world into the field of biogerontology certainly holds additional surprises and promises. Even more so, as miRNAs are implicated in many age-associated pathologies, and as RNAi and miRNA based therapeutics are on their way to clinics.

  6. Interobserver consistency of digital rectal examination in clinical staging of localized prostatic carcinoma.

    PubMed

    Angulo, J C; Montie, J E; Bukowsky, T; Chakrabarty, A; Grignon, D J; Sakr, W; Shamsa, F H; Edson Pontes, J

    1995-01-01

    A prospective study was undertaken to determine the reproducibility of clinical staging based on digital rectal examination (DRE) in prostate carcinoma. We evaluated 48 consecutive patients diagnosed with localized prostatic cancer. Four urologists performed DRE and sorted the patients according to the 1992 American Joint Committee on Cancer Classification for prostate cancer. Both the percentage observed total agreement among each couple of two different observers and the interobserver variability (Kappa index) were analyzed. The percentage observed total agreement among observers in distinguishing five clinical subcategories (T1c, T2a, T2b, T2c, and T3a) ranged between 38-60% (mean 49%) and the Kappa index showed interobserver agreement was poor (overall Kappa = 0.3 1). All four examiners agreed in assigning the same subcategory in only 21 % of cases, and 90% of them were T I. If only categories are distinguished (T I, T2, or T3), the percentage observed total agreement rises to 60-71% (mean 66%) and the interexaminer agreement improves to good (overall Kappa = 0.4 1). Accurate pathologic staging was obtained in every patient and the percentage observed agreement between every examiner and the pathologist was calculated, excluding cases interpreted as T I c. Regarding subcategories, clinicopathologic agreement ranges between 17-46%. If only categories T2 and9T3 are distinguished, agreement rises to 57-69%. In summary, the ability to reproduce clinical staging based on DRE among multiple examiners is disappointingly low and understandably correlates poorly with pathologic stage.

  7. Clinical nodal staging scores for prostate cancer: a proposal for preoperative risk assessment

    PubMed Central

    Kluth, L A; Abdollah, F; Xylinas, E; Rieken, M; Fajkovic, H; Seitz, C; Sun, M; Karakiewicz, P I; Schramek, P; Herman, M P; Becker, A; Hansen, J; Ehdaie, B; Loidl, W; Pummer, K; Lee, R K; Lotan, Y; Scherr, D S; Seiler, D; Ahyai, S A; Chun, F K-H; Graefen, M; Tewari, A; Nonis, A; Bachmann, A; Montorsi, F; Gönen, M; Briganti, A; Shariat, S F

    2014-01-01

    Background: Pelvic lymph node dissection in patients undergoing radical prostatectomy for clinically localised prostate cancer is not without morbidity and its therapeutical benefit is still a matter of debate. The objective of this study was to develop a model that allows preoperative determination of the minimum number of lymph nodes needed to be removed at radical prostatectomy to ensure true nodal status. Methods: We analysed data from 4770 patients treated with radical prostatectomy and pelvic lymph node dissection between 2000 and 2011 from eight academic centres. For external validation of our model, we used data from a cohort of 3595 patients who underwent an anatomically defined extended pelvic lymph node dissection. We estimated the sensitivity of pathological nodal staging using a beta-binomial model and developed a novel clinical (preoperative) nodal staging score (cNSS), which represents the probability that a patient has lymph node metastasis as a function of the number of examined nodes. Results: In the development and validation cohorts, the probability of missing a positive lymph node decreases with increase in the number of nodes examined. A 90% cNSS can be achieved in the development and validation cohorts by examining 1–6 nodes in cT1 and 6–8 nodes in cT2 tumours. With 11 nodes examined, patients in the development and validation cohorts achieved a cNSS of 90% and 80% with cT3 tumours, respectively. Conclusions: Pelvic lymph node dissection is the only reliable technique to ensure accurate nodal staging in patients treated with radical prostatectomy for clinically localised prostate cancer. The minimum number of examined lymph nodes needed for accurate nodal staging may be predictable, being strongly dependent on prostate cancer characteristics at diagnosis. PMID:25003663

  8. [The age of formation of Czech clinical medicine].

    PubMed

    Sváb, J

    2002-11-22

    Era of Emperor Francis Joseph I is said to be a golden age for the Czech nation. It can be found in numerous panegyric articles to any jubilee of the emperor's rule. What was formally dictated by respect brought by education and by the system of the Greek and Roman tradition adopted in Austria in Middle Ages, seams to be valid today as most of the contemporary technical and economical progress roots within those days. The Czech cultures namely music and art reached international acknowledgement. Though with difficulties, Czech achieved in education and in science as a full-fledged language. After the year 1848 an average citizen was entitled to such freedom as never before. Technical, economical and cultural progress enabled real ascent of the Czech society and its social differentiation. In sixties, after the Austria-Hungary Alignment, Hapsburg government undertook no serious restrains. Such development was nothing unusual. Similar one underwent after the period of storms all European societies from south to north and form west to east. They brought ideas of the French revolution and years 1848/1849 are therefore called "the spring of European nations". In all countries where revolutionary ideas were represented and various countermeasures were accepted, governments were forced to accept temporary arrangements (in Austrian monarchy it was the promise of constitution, language compromise etc.). Nevertheless, in the second half of the 19th century the most important condition for further revival was the long period of peace and stability of international relations. The internal stability of the Austrian monarchy was achieved for long time by the Austria-Hungary Alignment in 1867. After the lost battle at Hradec Kralove in summer 1866 it became clear that contemporary centralistic organization of the state, balancing between absolutism and constitutionalism is not further tenable. Years long pressure of patriotic forces in the parliament brought about division of the

  9. [The age of formation of Czech clinical medicine].

    PubMed

    Sváb, J

    2002-11-22

    Era of Emperor Francis Joseph I is said to be a golden age for the Czech nation. It can be found in numerous panegyric articles to any jubilee of the emperor's rule. What was formally dictated by respect brought by education and by the system of the Greek and Roman tradition adopted in Austria in Middle Ages, seams to be valid today as most of the contemporary technical and economical progress roots within those days. The Czech cultures namely music and art reached international acknowledgement. Though with difficulties, Czech achieved in education and in science as a full-fledged language. After the year 1848 an average citizen was entitled to such freedom as never before. Technical, economical and cultural progress enabled real ascent of the Czech society and its social differentiation. In sixties, after the Austria-Hungary Alignment, Hapsburg government undertook no serious restrains. Such development was nothing unusual. Similar one underwent after the period of storms all European societies from south to north and form west to east. They brought ideas of the French revolution and years 1848/1849 are therefore called "the spring of European nations". In all countries where revolutionary ideas were represented and various countermeasures were accepted, governments were forced to accept temporary arrangements (in Austrian monarchy it was the promise of constitution, language compromise etc.). Nevertheless, in the second half of the 19th century the most important condition for further revival was the long period of peace and stability of international relations. The internal stability of the Austrian monarchy was achieved for long time by the Austria-Hungary Alignment in 1867. After the lost battle at Hradec Kralove in summer 1866 it became clear that contemporary centralistic organization of the state, balancing between absolutism and constitutionalism is not further tenable. Years long pressure of patriotic forces in the parliament brought about division of the

  10. Developing criteria for evaluation of geroprotectors as a key stage toward translation to the clinic.

    PubMed

    Moskalev, Alexey; Chernyagina, Elizaveta; Tsvetkov, Vasily; Fedintsev, Alexander; Shaposhnikov, Mikhail; Krut'ko, Vyacheslav; Zhavoronkov, Alex; Kennedy, Brian K

    2016-06-01

    In the coming decades, a massive shift in the aging segment of the population will have major social and economic consequences around the world. One way to offset this increase is to expedite the development of geroprotectors, substances that slow aging, repair age-associated damage and extend healthy lifespan, or healthspan. While over 200 geroprotectors are now reported in model organisms and some are in human use for specific disease indications, the path toward determining whether they affect aging in humans remains obscure. Translation to the clinic is hampered by multiple issues including absence of a common set of criteria to define, select, and classify these substances, given the complexity of the aging process and their enormous diversity in mechanism of action. Translational research efforts would benefit from the formation of a scientific consensus on the following: the definition of 'geroprotector', the selection criteria for geroprotectors, a comprehensive classification system, and an analytical model. Here, we review current approaches to selection and put forth our own suggested selection criteria. Standardizing selection of geroprotectors will streamline discovery and analysis of new candidates, saving time and cost involved in translation to clinic. PMID:26970234

  11. Developing criteria for evaluation of geroprotectors as a key stage toward translation to the clinic.

    PubMed

    Moskalev, Alexey; Chernyagina, Elizaveta; Tsvetkov, Vasily; Fedintsev, Alexander; Shaposhnikov, Mikhail; Krut'ko, Vyacheslav; Zhavoronkov, Alex; Kennedy, Brian K

    2016-06-01

    In the coming decades, a massive shift in the aging segment of the population will have major social and economic consequences around the world. One way to offset this increase is to expedite the development of geroprotectors, substances that slow aging, repair age-associated damage and extend healthy lifespan, or healthspan. While over 200 geroprotectors are now reported in model organisms and some are in human use for specific disease indications, the path toward determining whether they affect aging in humans remains obscure. Translation to the clinic is hampered by multiple issues including absence of a common set of criteria to define, select, and classify these substances, given the complexity of the aging process and their enormous diversity in mechanism of action. Translational research efforts would benefit from the formation of a scientific consensus on the following: the definition of 'geroprotector', the selection criteria for geroprotectors, a comprehensive classification system, and an analytical model. Here, we review current approaches to selection and put forth our own suggested selection criteria. Standardizing selection of geroprotectors will streamline discovery and analysis of new candidates, saving time and cost involved in translation to clinic.

  12. Distribution of Resistant Esophageal Adenocarcinoma in the Resected Specimens of Clinical Stage III Patients After Chemoradiation: Its Clinical Implications

    PubMed Central

    Neishaboori, Nastaran; Wadhwa, Roopma; Nogueras-González, Graciela M.; Elimova, Elena; Shiozaki, Hironori; Sudo, Kazuki; Charalampakis, Nikolaos; Hiremath, Adarsh; Lee, Jeffrey H.; Bhutani, Manoop S.; Weston, Brian; Blum, Mariela A.; Rogers, Jane E.; Garris, Jeana L.; Rice, David C.; Komaki, Ritsuko; Swisher, Stephen G.; Skinner, Heath D.; Hofstetter, Wayne L.; Ajani, Jaffer A.

    2015-01-01

    Background We have limited knowledge of the geographic distribution of resistant EAC in the resected specimen and its clinical importance can be enormous. Method We selected patients with baseline stage III EAC who had chemoradiation followed by surgery, and had residual EAC (resistant cases only). Outcomes were correlated with various endpoints (% of resistant EAC, anatomic distribution). Results 100 clinical stage III patients were studied. 90% had an R0 resection. 99% had either moderate or poorly differentiated EAC. 12% had >50% residual cancer, 31% had 11–50% residual cancer, 53% had 1–10% residual cancer, and 3% had positive nodes only. Each compartment was frequently involved: mucosa/submucosa=66%, muscularis propria=76%, serosa=62%, and all=35%. Lack of EAC (meaning response) was observed in mucosa/submucosa (34%), muscularis propria (24%), serosa (38%), and nodes (42%). Although the endoscopic biopsies prior to surgery had no EAC in 79% of patients, in the surgical specimen, however, resistant EAC was frequent (66%) in mucosa/submucosa. Conclusion Contrary to our belief that resistant EAC would be frequent in the nodes, our data show that its distribution is heterogeneous and unpredictable. Most importantly, the post-chemoradiation biopsies are misleading and a decision to delay/avoid surgery based on negative biopsies can be detrimental for the patients. PMID:25765719

  13. Statistics and outlook of primary hepatic angiosarcoma based on clinical stage

    PubMed Central

    HUANG, I-HSUAN; WU, YI-YING; HUANG, TZU-CHUAN; CHANG, WEI-KUO; CHEN, JIA-HONG

    2016-01-01

    Hepatic angiosarcoma is a rare condition that has been associated with exposure to colloidal solutions of thorium dioxide, vinyl chloride, arsenic and radiation. Therapeutic guidelines have not been definitively established due to the small number of cases of this disease. The present study reviewed 28 cases of hepatic angiosarcoma from studies that had been published between January 2000 and December 2012, in addition to 6 cases diagnosed at Tri-Service General Hospital (Taipei, Taiwan). Clinical staging was based on American Joint Committee on Cancer staging system for soft tissue sarcoma (2014). With a mean follow-up of 27.5 months (range, 0.27–102 months), 18% (6/34) of the patients survived. The 1-, 3- and 5-year survival rates were 68.0±9.3, 42.1±10.2 and 32.7±9.8% for patients with stage I disease (mean follow-up, 32.7 months), whilst the 1- and 3-year survival rates were 33.3±15.7 and 22.2±13.9% for patients with stage IV disease (mean follow-up, 13.0 months). Determining an appropriate therapeutic strategy for this patient group is necessary. New studies encompassing larger patient populations are required in order to analyze and define standard prognostic parameters and to standardize a treatment approach for this extremely rare neoplasm. PMID:27123094

  14. Flexible design of two-stage adaptive procedures for phase III clinical trials.

    PubMed

    Koyama, Tatsuki

    2007-07-01

    The recent popularity of two-stage adaptive designs has fueled a number of proposals for their use in phase III clinical trials. Many of these designs assign certain restrictive functional forms to the design elements of stage 2, such as sample size, critical value and conditional power functions. We propose a more flexible method of design without imposing any particular functional forms on these design elements. Our methodology permits specification of a design based on either conditional or unconditional characteristics, and allows accommodation of sample size limit. Furthermore, we show how to compute the P value, confidence interval and a reasonable point estimate for any design that can be placed under the proposed framework. PMID:17307399

  15. Age-dependent postdiapause development in the gypsy moth (Lepidoptera: Lymantriidae) life stage model.

    PubMed

    Gray, David R

    2009-02-01

    For the last approximately 10 yr, the Gypsy Moth Life Stage (GLS) model has been used by pest managers to predict when important events in the gypsy moth, Lymantria dispar L., life cycle will occur (e.g., peak second larval instar population and male moth flight). Although the GLS model has been shown to outperform other gypsy moth phenology models, its predictions have not always been as accurate as desired. Differences between predicted and observed egg hatch phenology prompted a re-examination of the original experimental data that were used in the construction of the egg hatch submodels of the original GLS model, and a data processing error was discovered to have truncated the postdiapause experimental data. Analysis of the complete data set confirmed that developmental rates in the postdiapause phase were age and temperature dependent but that the developmental response to temperature is distinctly nonlinear at postdiapause initiation, in contrast to the indeterminate response previously reported. By incorporating the new estimates of developmental rate patterns and parameters into the GLS model, errors in the GLS-simulated egg hatch period were reduced by 33-71% and error in date of 50% cumulative egg hatch by 25-100%.

  16. Phosphate Binders and Clinical Outcomes in Patients with Stage 5D Chronic Kidney Disease.

    PubMed

    Zoccali, Carmine; Mallamaci, Francesca; Cannata-Andía, Jorge

    2015-01-01

    Knowledge informing the prescription and the choice of phosphate binders in end stage kidney disease (ESKD) patients has a weak evidentiary base. To date, no placebo-controlled trial based on meaningful clinical endpoints (death, cardiovascular events, bone fractures) has been performed to test the efficacy of these drugs. By the same token, we still lack solid proof that noncalcium binders afford better clinical outcomes as compared with calcium-based binders. Without proper trials, clinical decisions about the treatment of hyperphosphatemia rest on experience and contingent clinical judgment. The use of huge doses of calcium-based binders typically prescribed in the nineties now appears unwarranted. The relationship between phosphate and the risk of death is U shaped and moderate hyperphosphatemia carries just a mild-to-moderate risk excess and may not be seen as a compelling indication for the prescription of phosphate binders. Placebo-controlled randomized clinical trials assessing whether non-calcium and calcium-based binders reduce the risk of death and cardiovascular disease events in ESKD patients remain a public health priority. PMID:26278591

  17. Prognostic indicators of laparotomy findings in clinical stage I-II supradiaphragmatic Hodgkin's disease.

    PubMed

    Leibenhaut, M H; Hoppe, R T; Efron, B; Halpern, J; Nelsen, T; Rosenberg, S A

    1989-01-01

    Between July 1968 and July 1986, 915 patients with clinical stage (CS) I and II Hodgkin's disease limited to sites above the diaphragm underwent laparotomy and splenectomy at Stanford University. Fifteen percent were CS I, of whom 76% had cervical/supraclavicular disease, 13% axillary disease, and 9% mediastinal presentations. CS I patients were more likely to be male, were significantly older, and were significantly less likely to have nodular sclerosis (NS) histology than CS II patients. Twenty percent of CS I patients and 30% of CS II patients were pathologically upstaged. No CS I patients were upstaged to pathological stage (PS) IV. Univariate and multivariate analyses of presenting clinical characteristics were performed to predict staging laparotomy findings. CS I women, CS I patients with mediastinal-only disease, and CS I men with either lymphocyte predominance or interfollicular histologies were at low risk for having disease below the diaphragm (5%) or requiring chemotherapy (0%). CS II women who were less than 27 years old and had only two or three sites of disease were also at low risk for upstaging (9%) or requiring chemotherapy (2%). Mixed cellularity histology and male gender were associated with increased risk for subdiaphragmatic disease and require laparotomy; the presence of systemic symptoms was not correlated with laparotomy findings. These results confirm the importance of performing staging laparotomy for the majority of patients who present with supradiaphragmatic Hodgkin's disease if treatment programs are based on the presence and extent of subdiaphragmatic disease. Selected subgroups are at low risk for subdiaphragmatic disease and might be spared laparotomy if they are treated with mantle, paraaortic, and splenic irradiation.

  18. Relationship between Age and pre-End Stage Renal Disease Care in Elderly Patients Treated With Hemodialysis

    PubMed Central

    Harford, Rubette; Clark, Mary Jo; Norris, Keith C.; Yan, Guofen

    2016-01-01

    Receipt of pre-end-stage renal disease (ESRD) clinical care can improve outcomes for patients treated with maintenance hemodialysis (MHD). The study addressed age-related variations in receipt of a composite of recommended care to include nephrologist and dietician care and use of arterio-venous fistula at first outpatient MHD. Less than 2% of patients treated with MHD received all three forms of pre-ESRD care, and 63.3% received none of the three elements of care. The mean number of pre-ESRD care elements received by the oldest group (≥80 years) did not differ from the youngest group (<55 years), but was less than the 55-66 and 67-79 years groups; adjusted ratios of 0.93 (0.92-0.94; p<0.001) and 0.94 (0.92-0.95; p<0.001), respectively. A major effort is needed to ensure comprehensive pre-ESRD care for all patients with advanced CKD, especially for the youngest and oldest patient groups, who were less likely to receive recommended pre-ESRD care. PMID:27254965

  19. Relationship Between Age and Pre-End Stage Renal Disease Care in Elderly Patients Treated with Maintenance Hemodialysis.

    PubMed

    Harford, Rubette; Clark, Mary Jo; Norris, Keith C; Yan, Guofen

    2016-01-01

    Receipt of pre-end stage renal disease (ESRD) clinical care can improve outcomes for patients treated with maintenance hemodialysis (HD). This study addressed age-related variations in receipt of a composite of recommended care to include nephrologist and dietician care, and use of an arteriovenous fistula at first outpatient maintenance HD. Less than 2% of patients treated with maintenance HD received all three forms of pre-ESRD care, and 63.3% received none of the three elements of care. The mean number of pre-ESRD care elements received by the oldest group (80 years and older) did not differ from the youngest group (less than 55 years), but was less than the 55 to 66 and 67 to 79 years groups; adjusted ratios of 0.93 (0.92 to 0.94; p < 0.001) and 0.94 (0.92 to 0.95; p < 0.001), respectively. A major effort is needed to ensure comprehensive pre-ESRD care for all patients with advanced chronic kidney disease (CKD), especially for the youngest and oldest patient groups, who were less likely to receive recommended pre-ESRD care.

  20. Relationship Between Age and Pre-End Stage Renal Disease Care in Elderly Patients Treated with Maintenance Hemodialysis.

    PubMed

    Harford, Rubette; Clark, Mary Jo; Norris, Keith C; Yan, Guofen

    2016-01-01

    Receipt of pre-end stage renal disease (ESRD) clinical care can improve outcomes for patients treated with maintenance hemodialysis (HD). This study addressed age-related variations in receipt of a composite of recommended care to include nephrologist and dietician care, and use of an arteriovenous fistula at first outpatient maintenance HD. Less than 2% of patients treated with maintenance HD received all three forms of pre-ESRD care, and 63.3% received none of the three elements of care. The mean number of pre-ESRD care elements received by the oldest group (80 years and older) did not differ from the youngest group (less than 55 years), but was less than the 55 to 66 and 67 to 79 years groups; adjusted ratios of 0.93 (0.92 to 0.94; p < 0.001) and 0.94 (0.92 to 0.95; p < 0.001), respectively. A major effort is needed to ensure comprehensive pre-ESRD care for all patients with advanced chronic kidney disease (CKD), especially for the youngest and oldest patient groups, who were less likely to receive recommended pre-ESRD care. PMID:27254965

  1. [Stages in the establishment and the developmental outlook of clinical ultrasonic diagnosis].

    PubMed

    Bakharev, A M; Moshkovskiĭ, G Iu; Terzova, T B; Shcherbina, S I

    1997-01-01

    The ultrasonic semiotics of different diseases of hepar, pancreas, gallbladder, colon, postoperative complications was elaborated and complicated. New and complicated technological procedures for the complex ultrasonic investigation in before, intra- and postoperative periods were proposed. Minor traumatic transcutaneous intervention procedures under the ultrasonic control for the abdominal cavity and retroperitoneal space abscess, cysts of various localization were used for the first time in domestic practice. The treatment procedures applied ranged from puncture with subtle aspirating needle to one- or two-staged drainage performance. Clinical effectiveness constituted 85.2%.

  2. Clinical outcomes of stage I endometrial carcinoma patients treated with surgery alone: Siriraj Hospital experiences

    PubMed Central

    2016-01-01

    Objective To evaluate the recurrence rates and patterns of failure in patients with stage I endometrial carcinoma after surgical staging without adjuvant therapy. Methods Medical records of 229 patients with stage I endometrial carcinoma, treated with surgery alone between 2002 and 2010 at Siriraj Hospital were retrospectively reviewed. The primary objective of this study was recurrence rates. The secondary objectives were patterns of failure, disease-free survival, overall survival, and prognostic factors related to outcomes. Results During median follow-up time of 53.3 months, 11 recurrences (4.8%) occurred with a median time to recurrence of 21.2 months (range, 7.7 to 77.8 months). Vaginal recurrence was the most common pattern of failure (8/11 patients, 72.7%). Other recurrences were pelvic, abdominal and multiple metastases. Factors that appeared to be prognostic factors on univariate analyses were age and having high intermediate risk (HIR) (Gynecologic Oncology Group [GOG] 99 criteria), none of which showed significance in multivariate analysis. The recurrence rates were higher in the patients with HIR criteria (22.2% vs. 4.1%, p=0.013) or patients with stage IB, grade 2 endometrioid carcinoma (9.4% vs. 4.3%, p=0.199). Five-year disease-free survival and 5-year overall survival were 93.9% (95% CI, 89.9 to 5.86) and 99.5% (95% CI, 97.0 to 99.9), respectively. Conclusion The patients with low risk stage I endometrial carcinoma had excellent outcomes with surgery alone. Our study showed that no single factor was demonstrated to be an independent predictor for recurrence. PMID:27329196

  3. Osteonecrosis of Femoral Head Treated with Extracorporeal Shock Wave Therapy: Analysis of Short-term Clinical Outcomes of Treatment with Radiologic Staging

    PubMed Central

    Lee, Jin-Young; Kwon, Jae-Woo; Park, Jung-Seob; Han, Kyeol; Shin, Woo-jin; Lee, Jeong-Gil

    2015-01-01

    Purpose To evaluate clinical results of extracorporeal shock wave therapy (ESWT) with radiographic staging on patients with avascular necrosis of femoral head (AVNFH). Materials and Methods We evaluated 24 patients diagnosed with AVNFH (32 hip joints) who were treated with ESWT from 1993 to 2012. Average follow-up period was 27 months, and the average age of patients was 47.8 years. The Association Research Circulation Osseous (ARCO) system was used to grade radiographic stage prior to treatment. For this study patients were divided into two groups based on their ARCO stage, group 1 (ARCO stages I and II) and group 2 (ARCO stage III). Comparative analyses were done between the two groups using the visual analogue scale (VAS) score and the Harris hip score (HHS) at pre-treatment and 3, 6, 12, and 24 months after treatment. Failure was defined when radiographic stage progressed or arthroplasty surgery was needed due to clinical exacerbation. Results Both groups showed clinical improvements with VAS scoring at final follow-up (group 1: median 7 to 1.5, P<0.001; group 2: mean 7 to 4, P=0.056). Using HHS, group 1 showed a significant improvement (from 65.5 to 95 [P<0.001]), while no significance was observed for group 2 (P=0.280). At final follow-up, 3 hips from group 1 and one hip from group 2 showed radiographic improvement; however, two patients underwent total hip arthroplasty due to persistent pain and dysfunction. Conclusion ESWT can be considered as an interventional option before surgical treatment in patients with not only early stage AVNFH but also with mid stage. PMID:27536633

  4. Public funding of clinical-stage antibiotic development in the United States and European Union.

    PubMed

    Eichberg, Michael J

    2015-01-01

    The health and national security challenge of antibiotic resistance has led governments to adopt policies to stimulate new antibiotic R&D. Government programs that directly fund late-stage clinical development of antibiotics have emerged, including the Broad Spectrum Antimicrobial Program of the Biomedical Advanced Research and Development Authority in the United States, and the New Drugs for Bad Bugs program of the Innovative Medicines Initiative in the European Union. These efforts are collectively investing nearly $1 billion and are supporting nearly 20% of the global antibiotic pipeline. This article describes these programs, including the antibiotics and their targeted pathogens and clinical indications, as well as program mechanisms for project eligibility, selection, governance, funding, and IP management. Preliminary assessment of the impact of these mechanisms on the success of the programs is provided. PMID:26042859

  5. Public funding of clinical-stage antibiotic development in the United States and European Union.

    PubMed

    Eichberg, Michael J

    2015-01-01

    The health and national security challenge of antibiotic resistance has led governments to adopt policies to stimulate new antibiotic R&D. Government programs that directly fund late-stage clinical development of antibiotics have emerged, including the Broad Spectrum Antimicrobial Program of the Biomedical Advanced Research and Development Authority in the United States, and the New Drugs for Bad Bugs program of the Innovative Medicines Initiative in the European Union. These efforts are collectively investing nearly $1 billion and are supporting nearly 20% of the global antibiotic pipeline. This article describes these programs, including the antibiotics and their targeted pathogens and clinical indications, as well as program mechanisms for project eligibility, selection, governance, funding, and IP management. Preliminary assessment of the impact of these mechanisms on the success of the programs is provided.

  6. Public Funding of Clinical-Stage Antibiotic Development in the United States and European Union

    PubMed Central

    2015-01-01

    The health and national security challenge of antibiotic resistance has led governments to adopt policies to stimulate new antibiotic R&D. Government programs that directly fund late-stage clinical development of antibiotics have emerged, including the Broad Spectrum Antimicrobial Program of the Biomedical Advanced Research and Development Authority in the United States, and the New Drugs for Bad Bugs program of the Innovative Medicines Initiative in the European Union. These efforts are collectively investing nearly $1 billion and are supporting nearly 20% of the global antibiotic pipeline. This article describes these programs, including the antibiotics and their targeted pathogens and clinical indications, as well as program mechanisms for project eligibility, selection, governance, funding, and IP management. Preliminary assessment of the impact of these mechanisms on the success of the programs is provided. PMID:26042859

  7. A genomic and clinical prognostic index for hepatitis C-related early-stage cirrhosis that predicts clinical deterioration

    PubMed Central

    King, Lindsay Y.; Canasto-Chibuque, Claudia; Johnson, Kara B.; Yip, Shun; Chen, Xintong; Kojima, Kensuke; Deshmukh, Manjeet; Venkatesh, Anu; Tan, Poh Seng; Sun, Xiaochen; Villanueva, Augusto; Sangiovanni, Angelo; Nair, Venugopalan; Mahajan, Milind; Kobayashi, Masahiro; Kumada, Hiromitsu; Iavarone, Massimo; Colombo, Massimo; Fiel, Maria Isabel; Friedman, Scott L.; Llovet, Josep M.; Chung, Raymond T.; Hoshida, Yujin

    2014-01-01

    Objective The number of patients with hepatitis C virus (HCV)-related cirrhosis is increasing, leading to a rising risk of complications and death. Prognostic stratification in patients with early-stage cirrhosis is still challenging. We aimed to develop and validate a clinically useful prognostic index based on genomic and clinical variables to identify patients at high risk of disease progression. Design We developed a prognostic index, comprised of a 186-gene signature validated in our previous genome-wide profiling study, bilirubin (>1mg/dL), and platelet count (<100,000/mm3), in an Italian HCV cirrhosis cohort (training cohort, n=216, median follow-up 10 years). The gene signature test was implemented utilizing a digital transcript counting (nCounter) assay specifically developed for clinical use, and the prognostic index was evaluated using archived specimens from an independent cohort of HCV-related cirrhosis in the U.S. (validation cohort, n=145, median follow-up 8 years). Results In the training cohort, the prognostic index was associated with hepatic decompensation (HR=2.71, p=0.003), overall death (HR=6.00, p<0.001), hepatocellular carcinoma (HR=3.31, p=0.001), and progression of Child-Turcotte-Pugh class (HR=6.70, p<0.001). The patients in the validation cohort were stratified into high (16%), intermediate (42%), or low (42%) risk group by the prognostic index. The high-risk group had a significantly increased risk of hepatic decompensation (HR=7.36, p<0.001), overall death (HR=3.57, p=0.002), liver-related death (HR=6.49, p<0.001), and all liver-related adverse events (HR=4.98, p<0.001). Conclusion A genomic and clinical prognostic index readily available for clinical use was successfully validated, warranting further clinical evaluation for prognostic prediction, and clinical trial stratification and enrichment for preventive interventions. PMID:25143343

  8. Static Strain Aging Behavior of a Manganese-Silicon Steel After Single and Multi-stage Straining

    NASA Astrophysics Data System (ADS)

    Seraj, P.; Serajzadeh, S.

    2016-03-01

    In this work, static strain aging behavior of an alloy steel containing high amounts of silicon and manganese was examined while the influences of initial microstructure and pre-strain on the aging kinetics were evaluated as well. The rate of strain aging in a low carbon steel was also determined and compared with that occurred in the alloy steel. The rates of static strain aging in the steels were defined at room temperature and at 95 °C by means of double-hit tensile testing and hardness measurements. In addition, three-stage aging experiments at 80 °C were carried out to estimate aging behavior under multi-pass deformation processing. The results showed that in-solution manganese and silicon atoms could significantly affect the aging behavior of the steel and reduce the kinetics of static strain aging as compared to the low carbon steel. The initial microstructure also played an important role on the aging behavior. The rapidly cooled steel having mean ferrite grain size of 9.7 μm showed the least aging susceptibility index during the aging experiments. Accordingly, the activation energies for static strain aging were calculated as 93.2 and 85.7 kJ/mole for the alloy steel having fine and coarse ferrite-pearlite structures, respectively while it was computed as 79.1 kJ/mole for the low carbon steel with ferrite mean grain size of about 16.2 μm.

  9. Clinical Scenarios in Chronic Kidney Disease: Kidneys' Structural Changes in End-Stage Renal Disease.

    PubMed

    Meola, Mario; Samoni, Sara; Petrucci, Ilaria

    2016-01-01

    Acquired cystic kidney disease (ACKD) and renal cell carcinoma (RCC) are the most important manifestations of end-stage kidneys' structural changes. ACKD is caused by kidney damage or scarring and it is characterized by the presence of small, multiple cortical and medullary cysts filled with a fluid similar to preurine. ACKD prevalence varies according to predialysis and dialysis age and its pathogenesis is unknown, although it is stated that progressive destruction of renal tissue induces hypertrophy/compensatory hyperplasia of residual nephrons and may trigger the degenerative process. ACKD is almost asymptomatic, but it can lead to several complications (bleeding, rupture, infections, RCC). Ultrasound (US) is the first level imaging technique in ACKD, because of its sensitivity and reliability. The most serious complication of ACKD is RCC, which is stimulated by the same growth factors and proto-oncogenes that lead to the genesis of cysts. Two different histological types of RCC have been identified: (1) RCC associated with ACKD and (2) papillary renal clear cell carcinoma. Tumors in end-stage kidneys are mainly small, multifocal and bilateral, with a papillary structure and a low degree of malignancy. At US, RCC appears as a small inhomogeneous nodule (<3 cm), clearly outlined from the renal profile and hypoechoic if compared with sclerotic parenchyma. In some cases, tumor appears as a homogeneous and hyperechoic multifocal mass. The most specific US sign of a small tumor in end-stage kidney is the important arterial vascularization, in contrast with renal parenchymal vascular sclerosis. PMID:27169876

  10. Clinical Scenarios in Chronic Kidney Disease: Kidneys' Structural Changes in End-Stage Renal Disease.

    PubMed

    Meola, Mario; Samoni, Sara; Petrucci, Ilaria

    2016-01-01

    Acquired cystic kidney disease (ACKD) and renal cell carcinoma (RCC) are the most important manifestations of end-stage kidneys' structural changes. ACKD is caused by kidney damage or scarring and it is characterized by the presence of small, multiple cortical and medullary cysts filled with a fluid similar to preurine. ACKD prevalence varies according to predialysis and dialysis age and its pathogenesis is unknown, although it is stated that progressive destruction of renal tissue induces hypertrophy/compensatory hyperplasia of residual nephrons and may trigger the degenerative process. ACKD is almost asymptomatic, but it can lead to several complications (bleeding, rupture, infections, RCC). Ultrasound (US) is the first level imaging technique in ACKD, because of its sensitivity and reliability. The most serious complication of ACKD is RCC, which is stimulated by the same growth factors and proto-oncogenes that lead to the genesis of cysts. Two different histological types of RCC have been identified: (1) RCC associated with ACKD and (2) papillary renal clear cell carcinoma. Tumors in end-stage kidneys are mainly small, multifocal and bilateral, with a papillary structure and a low degree of malignancy. At US, RCC appears as a small inhomogeneous nodule (<3 cm), clearly outlined from the renal profile and hypoechoic if compared with sclerotic parenchyma. In some cases, tumor appears as a homogeneous and hyperechoic multifocal mass. The most specific US sign of a small tumor in end-stage kidney is the important arterial vascularization, in contrast with renal parenchymal vascular sclerosis.

  11. On efficient two-stage adaptive designs for clinical trials with sample size adjustment.

    PubMed

    Liu, Qing; Li, Gang; Anderson, Keaven M; Lim, Pilar

    2012-01-01

    Group sequential designs are rarely used for clinical trials with substantial over running due to fast enrollment or long duration of treatment and follow-up. Traditionally, such trials rely on fixed sample size designs. Recently, various two-stage adaptive designs have been introduced to allow sample size adjustment to increase statistical power or avoid unnecessarily large trials. However, these adaptive designs can be seriously inefficient. To address this infamous problem, we propose a likelihood-based two-stage adaptive design where sample size adjustment is derived from a pseudo group sequential design using cumulative conditional power. We show through numerical examples that this design cannot be improved by group sequential designs. In addition, the approach may uniformly improve any existing two-stage adaptive designs with sample size adjustment. For statistical inference, we provide methods for sequential p-values and confidence intervals, as well as median unbiased and minimum variance unbiased estimates. We show that the claim of inefficiency of adaptive designs by Tsiatis and Mehta ( 2003 ) is logically flawed, and thereby provide a strong defense of Cui et al. ( 1999 ). PMID:22651105

  12. Testosterone related to age and life-history stages in male baboons and geladas

    PubMed Central

    Beehner, Jacinta C.; Gesquiere, Laurence; Seyfarth, Robert M.; Cheney, Dorothy L.; Alberts, Susan C.; Altmann, Jeanne

    2013-01-01

    Despite significant advances in our knowledge of how testosterone mediates life-history trade-offs, this research has primarily focused on seasonal species. We know comparatively little about the relationship between testosterone and life-history stages for non-seasonally breeding species. Here we examine testosterone profiles across the lifespan of males from three non-seasonally breeding primates: yellow baboons (Papio cynocephalus or P. hamadryas cynocephalus), chacma baboons (Papio ursinus or P. h. ursinus), and geladas (Theropithecus gelada). First, we predict that testosterone profiles will track the reproductive profiles of each taxon across their respective breeding years. Second, we evaluate age-related changes in testosterone to determine whether several life-history transitions are associated with these changes. Subjects include males (>2.5 years) from wild populations of each taxon from whom we had fecal samples for hormone determination. Although testosterone profiles across species were broadly similar, considerable variability was found in the timing of two major changes: (1) the attainment of adult levels of testosterone, and (2) the decline in testosterone after the period of maximum production. Attainment of adult testosterone levels was delayed by one year in chacmas compared with yellows and geladas. With respect to the decline in testosterone, geladas and chacmas exhibited a significant drop after three years of maximum production, while yellows declined so gradually that no significant annual drop was ever detected. For both yellows and chacmas, increases in testosterone production preceded elevations in social dominance rank. We discuss these differences in the context of ecological and behavioral differences exhibited by these taxa. PMID:19712676

  13. Neuroimaging and treatment evidence for clinical staging in psychotic disorders: from the at-risk mental state to chronic schizophrenia.

    PubMed

    Wood, Stephen J; Yung, Alison R; McGorry, Patrick D; Pantelis, Christos

    2011-10-01

    A new approach to understanding severe mental disorders such as schizophrenia is to adopt a clinical staging model. Such a model defines the extent of the illness such that earlier and milder phenomena are distinguished from later, more impairing features. Specifically, a clinical staging model makes three key predictions. First, pathologic measures should be more abnormal in more severe stages. Second, patients who progress between the stages should show change in these same pathologic measures. Finally, treatment should be more effective in the earlier stages, as well as more benign. In this article, we review the evidence for these three predictions from studies of psychotic disorders, with a focus on neuroimaging data. For all three, the balance of evidence supports the predictions of the staging model. However, there are a number of alternative explanations for these findings, including the effects of medication and symptom heterogeneity. PMID:21762875

  14. Validity of the Fine Motor Area of the 12-Month Ages and Stages Questionnaire in Infants Following Major Surgery

    ERIC Educational Resources Information Center

    Smith, Cally; Wallen, Margaret; Walker, Karen; Bundy, Anita; Rolinson, Rachel; Badawi, Nadia

    2012-01-01

    The Ages and Stages Questionnaires (ASQ) are parent-report screening tools to identify infants at risk of developmental difficulties. The purpose of this study was to examine validity and internal reliability of the fine motor developmental area of the ASQ, 2nd edition (ASQ2-FM) for screening 12-month-old infants following major surgery. The…

  15. Clinical Outcome and Prognostic Factors of Intensity-Modulated Radiotherapy for T4 Stage Nasopharyngeal Carcinoma

    PubMed Central

    Luo, Yangkun; Gao, Yang; Yang, Guangquan; Lang, Jinyi

    2016-01-01

    Objective. To analyze the clinical outcomes and prognostic factors of intensity-modulated radiotherapy (IMRT) for T4 stage nasopharyngeal carcinoma (NPC). Methods. Between March 2005 and March 2010, 110 patients with T4 stage NPC without distant metastases were treated. All patients received IMRT. Induction and/or concurrent chemotherapy were given. 47 (42.7%) patients received IMRT replanning. Results. The 5-year local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) rates were 90.1%, 97.0%, 67.5%, 63.9%, and 64.5%, respectively. Eleven patients experienced local-regional failure and total distant metastasis occurred in 34 patients. 45 patients died and 26 patients died of distant metastasis alone. The 5-year LRFS rates were 97.7% and 83.8% for the patients that received and did not receive IMRT replanning, respectively (P = 0.023). Metastasis to the retropharyngeal lymph nodes (RLN) was associated with inferior 5-year OS rate (61.0% versus 91.7%, P = 0.034). The gross tumor volume of the right/left lymph nodes (GTVln) was an independent prognostic factor for DMFS (P = 0.006) and PFS (P = 0.018). GTVln was with marginal significance as the prognostic factor for OS (P = 0.050). Conclusion. IMRT provides excellent local-regional control for T4 stage NPC. Benefit of IMRT replanning may be associated with improvement in local control. Incorporating GTVln into the N staging system may provide better prognostic information. PMID:27195286

  16. Toward comprehensive management tailored to prognostic factors of patients with clinical stages I and II in Hodgkin's disease. The EORTC Lymphoma Group controlled clinical trials: 1964-1987.

    PubMed

    Tubiana, M; Henry-Amar, M; Carde, P; Burgers, J M; Hayat, M; Van der Schueren, E; Noordijk, E M; Tanguy, A; Meerwaldt, J H; Thomas, J

    1989-01-01

    From 1964 to 1987, the EORTC Lymphoma Group conducted four consecutive controlled clinical trials on clinical stages I and II Hodgkin's disease in which 1,579 patients were entered. From the onset the main aim of these trials was to identify the subsets of patients who could be treated safely by regional radiotherapy (RT). Therefore, several prognostic indicators were prospectively registered and progressively used in the trial protocols for the delineation of the favorable and unfavorable subgroups as soon as they were recognized of high predictive value. In the H2 trial (1972 to 1976), the histologic subtype was the only variable taken into account for the therapeutic strategy and the staging laparotomy findings were found to be of prognostic value only in patients with favorable prognostic indicators. In the H5 trial (1977 to 1982), patients were subdivided into two subgroups according to six prognostic indicators. Patients with favorable features were submitted to a staging laparotomy (lap); lap negative patients were randomized between mantle field RT and mantle field plus paraaortic RT. Disease free survival (DFS) and total survival (S) were similar in the two arms. Among patients with unfavorable features, DFS and S were significantly higher in the arm treated by combination of mechlorethamine, vincristine, procarbazine, prednisone (MOPP) chemotherapy (CT) and RT than in the arm treated by total nodal irradiation. Nevertheless, in patients below the age of 40, the overall survival rates were equivalent in the two arms. In the H6 trial, the delineation of the favorable subgroup was based on (a) absence of systemic symptoms and elevated ESR, (b) no more than one or two lymph node areas involved. The aim of the study was to assess the impact on survival of a therapeutic strategy including staging laparotomy. At a 4-year follow-up, no difference in survival was evidenced. In patients with unfavorable prognostic indicators, 3 MOPP-RT-3 MOPP were compared with 3

  17. Effect of Maternal Age on the Ratio of Cleavage and Mitochondrial DNA Copy Number in Early Developmental Stage Bovine Embryos

    PubMed Central

    TAKEO, Shun; GOTO, Hiroya; KUWAYAMA, Takehito; MONJI, Yasunori; IWATA, Hisataka

    2012-01-01

    Abstract Age-associated deterioration in both the quality and quantity of mitochondria occurs in older women. The main aim of this study was to examine the effect of age on mitochondrial DNA copy number (mtDNA number) in early developmental stage bovine embryos as well as the dynamics of mtDNA number during early embryo development. Real-time PCR was used to determine mtDNA number. In vitro-produced embryos 48 h after insemination derived from Japanese black cows, ranging in age from 25 to 209 months were categorized based on their cleavage status. There was an overall negative relationship between the age of the cow and cleavage status, to the extent that the ratio of embryos cleaved over the 4-cell stage was greater in younger cows. The mtDNA number did not differ among the cleaved status of embryos. In the next experiment, oocytes collected from each donor cow were divided into 2 groups containing 10 oocytes each, in order to compare the mtDNA number of mature oocytes and early developmental stage embryos within individuals. Upon comparing the mtDNA number between oocytes at the M2 stage and early developmental stage 48 h post insemination, mtDNA number was found to decrease in most cows, but was found to increase in some cows. In conclusion, age affects the cleaving ability of oocytes, and very old cows (> 180 months) tend to have lower mtDNA numbers in their oocytes. The change in mtDNA number during early development varied among individual cows, although overall, it showed a tendency to decrease. PMID:23269452

  18. Learning Multiple Band-Pass Filters for Sleep Stage Estimation: Towards Care Support for Aged Persons

    NASA Astrophysics Data System (ADS)

    Takadama, Keiki; Hirose, Kazuyuki; Matsushima, Hiroyasu; Hattori, Kiyohiko; Nakajima, Nobuo

    This paper proposes the sleep stage estimation method that can provide an accurate estimation for each person without connecting any devices to human's body. In particular, our method learns the appropriate multiple band-pass filters to extract the specific wave pattern of heartbeat, which is required to estimate the sleep stage. For an accurate estimation, this paper employs Learning Classifier System (LCS) as the data-mining techniques and extends it to estimate the sleep stage. Extensive experiments on five subjects in mixed health confirm the following implications: (1) the proposed method can provide more accurate sleep stage estimation than the conventional method, and (2) the sleep stage estimation calculated by the proposed method is robust regardless of the physical condition of the subject.

  19. Multifocal FIGO Stage IA1 Squamous Carcinoma of the Cervix: Criteria for Identification, Staging, and its Good Clinical Outcome.

    PubMed

    Day, Elizabeth; Duffy, Siobhan; Bryson, Gareth; Syed, Sheeba; Shanbhag, Smruta; Burton, Kevin; Lindsay, Rhona; Siddiqui, Nadeem; Millan, David

    2016-09-01

    Multifocal squamous cervical carcinomas account for up to 25% of IA1 tumors identified on excisional biopsy, yet there are no uniformly accepted histopathologic criteria for defining and staging these lesions. Here, we use a strict case definition and meticulous specimen processing from colposcopist to pathologist to identify and follow-up 25 cases of multifocal IA1 cervical squamous carcinomas identified in excisional biopsies. We stage these tumors using the dimensions of the largest focus and a minimum of 2 mm between each foci to define multifocality. The cases are followed up for a median of 7 yr with no episodes of tumor recurrence or metastasis. We also show that the prevalence of residual preinvasive (20%) and invasive disease (5%) on repeat excision/surgery are comparable to data available for unifocal IA1 cases. Our study supports the hypothesis that multifocal lesions should be staged according to largest individual focus of invasion and we emphasize the importance of meticulous specimen handling to appropriately identify multifocal tumors. In addition, our analysis suggests that outcomes are comparable to unifocal lesions and supports the hypothesis that they may be managed in a similar manner. PMID:26863478

  20. The clinical consequences of an ageing world and preventive strategies

    PubMed Central

    Lunenfeld, Bruno; Stratton, Pamela

    2013-01-01

    Over the past century, the world has seen unprecedented declines in mortality rates, leading to an accelerated increase in the world population. This century will realise falling fertility rates alongside ageing populations. The 20th century was the century of population growth; the 21st century will be remembered as the century of ageing. Increase in life expectancy is one of the highest achievements of humankind; however, ageing and age-related disease is a mounting challenge for individuals, families, and for social, economic, and healthcare systems. Since healthy life expectancy has lagged behind the increase in life expectancy, the rise in morbidity will increase the burden on healthcare systems. Implementation of preventive health strategies to decrease, delay or prevent frailty, lung, breast and colon cancer, cardiovascular disease, metabolic syndrome, osteoporosis and osteopaenia, may increase health expectancy, and permit women to age gracefully and maintain independent living, without disability, for as long as possible. PMID:23541823

  1. Chronic kidney disease: a clinical model of premature aging.

    PubMed

    Stenvinkel, Peter; Larsson, Tobias E

    2013-08-01

    Premature aging is a process associated with a progressive accumulation of deleterious changes over time, an impairment of physiologic functions, and an increase in the risk of disease and death. Regardless of genetic background, aging can be accelerated by the lifestyle choices and environmental conditions to which our genes are exposed. Chronic kidney disease is a common condition that promotes cellular senescence and premature aging through toxic alterations in the internal milieu. This occurs through several mechanisms, including DNA and mitochondria damage, increased reactive oxygen species generation, persistent inflammation, stem cell exhaustion, phosphate toxicity, decreased klotho expression, and telomere attrition. Because recent evidence suggests that both increased local signaling of growth factors (through the nutrient-sensing mammalian target of rapamycin) and decreased klotho expression are important modulators of aging, interventions that target these should be tested in this prematurely aged population.

  2. Human African trypanosomiasis in Angola: clinical observations, treatment, and use of PCR for stage determination of early stage of the disease.

    PubMed

    Truc, P; Lando, A; Penchenier, L; Vatunga, G; Josenando, T

    2012-01-01

    Biological and clinical observations are described for 224 patients infected by human African trypanosomiasis (HAT) in Angola in 2007 and 2008. Seven patients were initially classified in stage 1 (S1), 17 intermediate stage (IS) (WBC <20 lymphocytes/μl with absence of trypanosomes in cerebrospinal fluid (CSF) and no neurological signs), and 200 in stage 2 (S2). Out of 224 patients, 165 (73.6%) presented one or more neurological signs. During treatment with eflornithine, six deaths of S2 patients occurred, five of which were because of an encephalopathy syndrome. Nine patients were diagnosed with a relapse or suspected treatment failure during the follow-up: eight patients after treatment with eflornithine (relapse rate 4.1%) and one patient after pentamidine (6.6%). The contribution of PCR for stage determination evaluated for S1 and IS confirms the difficulty of stage determination, as one S1 patient and two IS patients were carriers of trypanosomes detected a posteriori by PCR in CSF but were treated with pentamidine while follow-up did not confirm treatment efficacy. Since 2001 in Angola, either by passive or active mode detection, approximately 80% of the new cases every year were in S2, whereas the annual number of cases has regressed, probably because the transmission of HAT is decreasing. However, stage determination and treatment remain two major issues for the chronic form of sleeping sickness.

  3. [Age associated clinical features of odontogenic maxillary sinusitis].

    PubMed

    Iordanishvili, A K; Nikitenko, V V; Balin, D V

    2013-01-01

    Detailed analysis of odontogenic maxillary sinusitis clinical course allowed identifying clinical features of the disease specific for elderly and senile patients. The paper describes the peculiarities of odontogenic maxillary sinusitis in elderly and senile patients including those having oroantral sinus tract.

  4. Comparative Study of Clinical Staging of Oral Submucous Fibrosis with Qualitative Analysis of Collagen Fibers Under Polarized Microscopy

    PubMed Central

    Modak, Neha; Tamgadge, Sandhya; Tamgadge, Avinash; Bhalerao, Sudhir

    2015-01-01

    Background & Objectives: Oral submucous fibrosis (OSMF) is a condition where excessive deposition of dense collagen fibers occurred in the connective tissue of oral mucosa. An alteration of collagen necessitates an in depth understanding of collagen in oral tissues as no breakthrough studies have been reported. T herefore the aim was to correlate the clinical, functional and histopathological staging and to analyze the polarization colors and thickness of the collagen fibers in different stages of OSMF using picrosirius red stain under polarizing microscopy so as to assess the severity of disease. Methods: The study was conducted in the department of Oral Pathology and Microbiology at Padm. Dr. D. Y Patil Dental and Hospital, Navi Mumbai, India (2012-13). A sample size was of a total 40 subjects, of which 30 patients had OSMF, and 10 were in control group. Clinical, functional and histopathological staging were done depending upon definite criteria. Collagen fibers were analyzed for polarizing colors and thickness. Further clinical, functional and histopathological stages as well as qualitative parameters of collagen fibers were compared. Results: The correlation between clinical and functional staging was not significant ( P >0.05) whereas the comparison of the functional staging with histopathological staging was more reliable (P <0.01) as an indication to the severity of the disease rather than clinical staging. One-way ANOVA analysis showed highly significant correlation between functional staging and polarization colors and thickness of collagen fibers (P <0.001). Conclusion: The qualitative change in the collagen fibers of OSMF patients using polarized microscopy would help to assess its role in diagnostic evaluation, to determine the prognosis of the disease as well as to provide useful predictive treatment modalities to them. PMID:26351471

  5. Adjuvant sorafenib after heptectomy for Barcelona Clinic Liver Cancer-stage C hepatocellular carcinoma patients

    PubMed Central

    Xia, Feng; Wu, Li-Li; Lau, Wan-Yee; Huan, Hong-Bo; Wen, Xu-Dong; Ma, Kuan-Sheng; Li, Xiao-Wu; Bie, Ping

    2016-01-01

    AIM: To investigate the efficacy and safety of adjuvant sorafenib after curative resection for patients with Barcelona Clinic Liver Cancer (BCLC)-stage C hepatocellular carcinoma (HCC). METHODS: Thirty-four HCC patients, classified as BCLC-stage C, received adjuvant sorafenib for high-risk of tumor recurrence after curative hepatectomy at a tertiary care university hospital. The study group was compared with a case-matched control group of 68 patients who received curative hepatectomy for HCC during the study period in a 1:2 ratio. RESULTS: The tumor recurrence rate was markedly lower in the sorafenib group (15/34, 44.1%) than in the control group (51/68, 75%, P = 0.002). The median disease-free survival was 12 mo in the study group and 10 mo in the control group. Tumor number more than 3, macrovascular invasion, hilar lymph nodes metastasis, and treatment with sorafenib were significant factors of disease-free survival by univariate analysis. Tumor number more than 3 and treatment with sorafenib were significant risk factors of disease-free survival by multivariate analysis in the Cox proportional hazards model. The disease-free survival and cumulative overall survival in the study group were significantly better than in the control group (P = 0.034 and 0.016, respectively). CONCLUSION: Our study verifies the potential benefit and safety of adjuvant sorafenib for both decreasing HCC recurrence and extending disease-free and overall survival rates for patients with BCLC-stage C HCC after curative resection. PMID:27340354

  6. Clinical significance of aberrant mammalian target of rapamycin expression in stage IIIB colon cancer

    PubMed Central

    WEN, MEILING; LI, BAOXIU; CAO, XIAOFEI; WENG, CHENGYIN; WU, YONG; FANG, XISHENG; ZHANG, XIAOSHI; LIU, GUOLONG

    2014-01-01

    The aim of the present study was to investigate the significance of aberrant expression of mammalian target of rapamycin (mTOR) and the activated form of mTOR kinase, phosphorylated mTOR (pmTOR), in human stage IIIB colon cancer. The expression of mTOR and pmTOR was detected by immunohistochemistry in the tumor tissue of stage IIIB colon cancer patients. The association between the expression of mTOR, pmTOR and clinicopathological parameters of patients was analyzed. The positive expression of mTOR and pmTOR was observed to be higher in 75.5% (80/106) and 76.4% (81/106) of the 106 colon cancer specimens, compared with the adjacent normal tissues. The high level of pmTOR expression was found to be significantly higher in the invasive tumor front cells and resulted in a higher risk of mortality. The results suggested that mTOR and pmTOR may be promising clinical markers and present novel molecular targets for designing novel therapeutic strategies to treat this malignancy. PMID:25120661

  7. Clinical operations generation next… The age of technology and outsourcing.

    PubMed

    Temkar, Priya

    2015-01-01

    Huge cost pressures and the need to drive faster approvals has driven a technology transformation in the clinical trial (CT) industry. The CT industry is thus leveraging mobile data, cloud computing, social media, robotic automation, and electronic source to drive efficiencies in a big way. Outsourcing of clinical operations support services to technology companies with a clinical edge is gaining tremendous importance. This paper provides an overview of current technology trends, applicable Food and Drug Administration (FDA) guidelines, basic challenges that the pharma industry is facing in trying to implement such changes and its shift towards outsourcing these services to enable it to focus on site operations. PMID:26623386

  8. Clinical operations generation next… The age of technology and outsourcing

    PubMed Central

    Temkar, Priya

    2015-01-01

    Huge cost pressures and the need to drive faster approvals has driven a technology transformation in the clinical trial (CT) industry. The CT industry is thus leveraging mobile data, cloud computing, social media, robotic automation, and electronic source to drive efficiencies in a big way. Outsourcing of clinical operations support services to technology companies with a clinical edge is gaining tremendous importance. This paper provides an overview of current technology trends, applicable Food and Drug Administration (FDA) guidelines, basic challenges that the pharma industry is facing in trying to implement such changes and its shift towards outsourcing these services to enable it to focus on site operations. PMID:26623386

  9. Clinical operations generation next… The age of technology and outsourcing.

    PubMed

    Temkar, Priya

    2015-01-01

    Huge cost pressures and the need to drive faster approvals has driven a technology transformation in the clinical trial (CT) industry. The CT industry is thus leveraging mobile data, cloud computing, social media, robotic automation, and electronic source to drive efficiencies in a big way. Outsourcing of clinical operations support services to technology companies with a clinical edge is gaining tremendous importance. This paper provides an overview of current technology trends, applicable Food and Drug Administration (FDA) guidelines, basic challenges that the pharma industry is facing in trying to implement such changes and its shift towards outsourcing these services to enable it to focus on site operations.

  10. Management of cervical cancer and surgical-pathological staging (SPS). Report of our clinical case series.

    PubMed

    Onnis, A; Marchetti, M; Maggino, T; Cascio, A; Cerri, G; Dipasquale, C; Meneghello, E; Romagnolo, C; Rozzo, M L

    1988-01-01

    FIGO staging is imprecise in a relevant number of cases of cervical cancer, especially in advanced stages, when the prognosis and the choice of the therapy are most delicate. The Authors examine their case series about the index of correction of FIGO staging after Surgical Pathological Staging (SPS). Surgical Pathological Staging was applied systematically in 788 cases and revealed errors in FIGO staging in 16% of cases at stage I; 77% at stage II; and 96% at stage III. SPS allows a more precise knowledge of neoplastic diffusion and consequently to the elimination of many false advanced stages and to adequate the treatment. Furthermore 5 year survival rate confirms the role of SPS and Surgical therapy alone or combined with Radiotherapy and Chemotherapy in every stages of diffusion of cervical cancer. PMID:3383889

  11. Neoadjuvant therapy for early-stage breast cancer: the clinical utility of pertuzumab.

    PubMed

    Gollamudi, Jahnavi; Parvani, Jenny G; Schiemann, William P; Vinayak, Shaveta

    2016-01-01

    Approximately 20% of breast cancer patients harbor tumors that overexpress human epidermal growth factor receptor 2 (HER2; also known as ErbB2), a receptor tyrosine kinase that belongs to the epidermal growth factor receptor family of receptor tyrosine kinases. HER2 amplification and hyperactivation drive the growth and survival of breast cancers through the aberrant activation of proto-oncogenic signaling systems, particularly the Ras/MAP kinase and PI3K/AKT pathways. Although HER2-positive (HER2(+)) breast cancer was originally considered to be a highly aggressive form of the disease, the clinical landscape of HER2(+) breast cancers has literally been transformed by the approval of anti-HER2 agents for adjuvant and neoadjuvant settings. Indeed, pertuzumab is a novel monoclonal antibody that functions as an anti-HER2 agent by targeting the extracellular dimerization domain of the HER2 receptor; it is also the first drug to receive an accelerated approval by the US Food and Drug Administration for use in neoadjuvant settings in early-stage HER2(+) breast cancer. Here, we review the molecular and cellular factors that contribute to the pathophysiology of HER2 in breast cancer, as well as summarize the landmark preclinical and clinical findings underlying the approval and use of pertuzumab in the neoadjuvant setting. Finally, the molecular mechanisms operant in mediating resistance to anti-HER2 agents, and perhaps to pertuzumab as well, will be discussed, as will the anticipated clinical impact and future directions of pertuzumab in breast cancer patients. PMID:26937204

  12. Neoadjuvant therapy for early-stage breast cancer: the clinical utility of pertuzumab

    PubMed Central

    Gollamudi, Jahnavi; Parvani, Jenny G; Schiemann, William P; Vinayak, Shaveta

    2016-01-01

    Approximately 20% of breast cancer patients harbor tumors that overexpress human epidermal growth factor receptor 2 (HER2; also known as ErbB2), a receptor tyrosine kinase that belongs to the epidermal growth factor receptor family of receptor tyrosine kinases. HER2 amplification and hyperactivation drive the growth and survival of breast cancers through the aberrant activation of proto-oncogenic signaling systems, particularly the Ras/MAP kinase and PI3K/AKT pathways. Although HER2-positive (HER2+) breast cancer was originally considered to be a highly aggressive form of the disease, the clinical landscape of HER2+ breast cancers has literally been transformed by the approval of anti-HER2 agents for adjuvant and neoadjuvant settings. Indeed, pertuzumab is a novel monoclonal antibody that functions as an anti-HER2 agent by targeting the extracellular dimerization domain of the HER2 receptor; it is also the first drug to receive an accelerated approval by the US Food and Drug Administration for use in neoadjuvant settings in early-stage HER2+ breast cancer. Here, we review the molecular and cellular factors that contribute to the pathophysiology of HER2 in breast cancer, as well as summarize the landmark preclinical and clinical findings underlying the approval and use of pertuzumab in the neoadjuvant setting. Finally, the molecular mechanisms operant in mediating resistance to anti-HER2 agents, and perhaps to pertuzumab as well, will be discussed, as will the anticipated clinical impact and future directions of pertuzumab in breast cancer patients. PMID:26937204

  13. The new life stage of emerging adulthood at ages 18-29 years: implications for mental health.

    PubMed

    Arnett, Jeffrey J; Žukauskienė, Rita; Sugimura, Kazumi

    2014-12-01

    Since 1960 demographic trends towards longer time in education and late age to enter into marriage and of parenthood have led to the rise of a new life stage at ages 18-29 years, now widely known as emerging adulthood in developmental psychology. In this review we present some of the demographics of emerging adulthood in high-income countries with respect to the prevalence of tertiary education and the timing of parenthood. We examine the characteristics of emerging adulthood in several regions (with a focus on mental health implications) including distinctive features of emerging adulthood in the USA, unemployment in Europe, and a shift towards greater individualism in Japan. PMID:26361316

  14. Variation in body condition indices of crimson finches by sex, breeding stage, age, time of day, and year

    PubMed Central

    Milenkaya, Olga; Weinstein, Nicole; Legge, Sarah; Walters, Jeffrey R.

    2013-01-01

    Body condition indices are increasingly applied in conservation to assess habitat quality, identify stressed populations before they decline, determine effects of disturbances, and understand mechanisms of declines. To employ condition indices in this manner, we need first to understand their baseline variability and sources of variation. Here, we used crimson finches (Neochmia phaeton), a tropical passerine, to describe the variation in seven commonly used condition indices by sex, age, breeding stage, time of day, and year. We found that packed cell volume, haemoglobin, total plasma protein, and scaled mass were all significantly affected by an interaction between sex and breeding stage. Furcular fat varied by sex and breeding stage and also trended by year, scaled mass showed a positive trend with age and varied by time of day, and haemoglobin additionally varied by year. Pectoral muscle scores varied and heterophil to lymphocyte ratio trended only by year. Year effects might reflect a response to annual variation in environmental conditions; therefore, those indices showing year effects may be especially worthy of further investigation of their potential for conservation applications. Pectoral muscle scores and heterophil to lymphocyte ratio may be particularly useful due to the lack of influence of other variables on them. For the other indices, the large variation that can be attributed to individual covariates, such as sex and breeding stage, suggests that one should not interpret the physiological condition of an individual as measured by these indices from their absolute value. Instead, the condition of an individual should be interpreted relative to conspecifics by sex, breeding stage, and possibly age. PMID:27293604

  15. Variation in body condition indices of crimson finches by sex, breeding stage, age, time of day, and year.

    PubMed

    Milenkaya, Olga; Weinstein, Nicole; Legge, Sarah; Walters, Jeffrey R

    2013-01-01

    Body condition indices are increasingly applied in conservation to assess habitat quality, identify stressed populations before they decline, determine effects of disturbances, and understand mechanisms of declines. To employ condition indices in this manner, we need first to understand their baseline variability and sources of variation. Here, we used crimson finches (Neochmia phaeton), a tropical passerine, to describe the variation in seven commonly used condition indices by sex, age, breeding stage, time of day, and year. We found that packed cell volume, haemoglobin, total plasma protein, and scaled mass were all significantly affected by an interaction between sex and breeding stage. Furcular fat varied by sex and breeding stage and also trended by year, scaled mass showed a positive trend with age and varied by time of day, and haemoglobin additionally varied by year. Pectoral muscle scores varied and heterophil to lymphocyte ratio trended only by year. Year effects might reflect a response to annual variation in environmental conditions; therefore, those indices showing year effects may be especially worthy of further investigation of their potential for conservation applications. Pectoral muscle scores and heterophil to lymphocyte ratio may be particularly useful due to the lack of influence of other variables on them. For the other indices, the large variation that can be attributed to individual covariates, such as sex and breeding stage, suggests that one should not interpret the physiological condition of an individual as measured by these indices from their absolute value. Instead, the condition of an individual should be interpreted relative to conspecifics by sex, breeding stage, and possibly age.

  16. Solar exposure(s) and facial clinical signs of aging in Chinese women: impacts upon age perception.

    PubMed

    Flament, Frederic; Bazin, Roland; Qiu, Huixia; Ye, Chengda; Laquieze, Sabine; Rubert, Virginie; Decroux, Aurelie; Simonpietri, Elisa; Piot, Bertrand

    2015-01-01

    A new reference clinical atlas of facial signs dedicated to photoaging was applied to 301 Chinese women of various ages through standardized photographs. Such approach aimed at better describing the facial changes induced by both real/chronological age and sun exposure and their respective impact on two subcohorts of different behavior with regard to sun exposure. A total of 28 various facial signs were individually graded according to their severity by a panel of experts, and a perceived apparent age of each subject was assessed. Results showed that the severity of major signs significantly increased rather linearly with age, with a higher rate in sun-exposed subjects as compared with subjects who regularly avoid sun exposure. The severity of facial signs, all impacted by sun exposure, better correlated with perceived apparent age than real/chronological age. The protocol used in the present work, similar to that previously applied to two cohorts of French women, assigned a greater impact of sun exposure in the facial aging signs of Asian women - all clinical signs are influenced by extrinsic factors - as compared with Caucasian women of comparable ages, likely related to much more intense ultraviolet (UV) radiation. PMID:25709490

  17. Solar exposure(s) and facial clinical signs of aging in Chinese women: impacts upon age perception.

    PubMed

    Flament, Frederic; Bazin, Roland; Qiu, Huixia; Ye, Chengda; Laquieze, Sabine; Rubert, Virginie; Decroux, Aurelie; Simonpietri, Elisa; Piot, Bertrand

    2015-01-01

    A new reference clinical atlas of facial signs dedicated to photoaging was applied to 301 Chinese women of various ages through standardized photographs. Such approach aimed at better describing the facial changes induced by both real/chronological age and sun exposure and their respective impact on two subcohorts of different behavior with regard to sun exposure. A total of 28 various facial signs were individually graded according to their severity by a panel of experts, and a perceived apparent age of each subject was assessed. Results showed that the severity of major signs significantly increased rather linearly with age, with a higher rate in sun-exposed subjects as compared with subjects who regularly avoid sun exposure. The severity of facial signs, all impacted by sun exposure, better correlated with perceived apparent age than real/chronological age. The protocol used in the present work, similar to that previously applied to two cohorts of French women, assigned a greater impact of sun exposure in the facial aging signs of Asian women - all clinical signs are influenced by extrinsic factors - as compared with Caucasian women of comparable ages, likely related to much more intense ultraviolet (UV) radiation.

  18. White Matter Integrity and Reaction Time Intraindividual Variability in Healthy Aging and Early-Stage Alzheimer Disease

    PubMed Central

    Jackson, Jonathan D.; Balota, David A.; Duchek, Janet M.; Head, Denise

    2011-01-01

    Aging and early-stage Alzheimer disease (AD) have been shown to be associated with increased RT intraindividual variability (IIV, as reflected by the coefficient of variation) and an exaggeration of the slow tail of the RT distribution in attentional control tasks, based on ex-Gaussian analyses. The current study examined associations between white matter volume, IIV, and ex-Gaussian RT distribution parameters in cognitively normal aging and early-stage AD. Three RT attention tasks (Stroop, Simon, and a consonant-vowel odd-even switching task) in conjunction with MRI-based measures of cerebral and regional white matter volume were obtained in 133 cognitively normal and 33 early-stage AD individuals. Larger volumes were associated with less IIV and less slowing in the tail of the RT distribution, and larger cerebral and inferior parietal white matter volumes were associated with faster modal reaction time. Collectively, these results support a role of white matter integrity in IIV and distributional skewing, and are consistent with the hypothesis that IIV and RT distributional skewing are sensitive to breakdowns in executive control processes in normal and pathological aging. PMID:22172547

  19. Clinically different stages of Alzheimer's disease associated by amyloid deposition with [11C]-PIB PET imaging.

    PubMed

    Hatashita, Shizuo; Yamasaki, Hidetomo

    2010-01-01

    We investigated whether [11C]-PIB PET detects underlying amyloid deposition at clinically different stages of Alzheimer's disease (AD) and preclinical dementia. The Japanese cohort of 214 subjects underwent cognitive testing and 60-min dynamic [11C]-PIB PET. [11C]-PIB data were acquired from 35-60 min after injection. Regions of interest were defined on co-registered MRI. Distribution volume ratios (DVR) of PIB retention were determined using Logan graphical analysis. All 56 patients with AD showed a robust increase in PIB retention in cortical areas (typical PIB AD-pattern). A mean DVR value in 11 patients with moderate AD (CDR: 2.1 ± 0.4) showed significantly higher PIB retention (2.38 ± 0.42, p < 0.01) than amyloid-negative healthy control (HC) subjects. The DVR values in 23 patients with very mild AD (CDR: 0.5) and 22 patients with mild AD (CDR: 1.0) were 2.32 ± 0.45 and 2.34 ± 0.42, respectively, similar to moderate AD. In contrast, 28 (48%) of the 58 mild cognitive impairment (MCI) patients (MMSE: 27.3 ± 1.7) showed a typical AD-like pattern with a DVR value of 2.07 ± 0.34. Further, 17 (18%) of 91 HC subjects had a typical AD-like pattern with a DVR value of 2.06 ± 0.28. They did not significantly differ from very mild AD. The prevalence of AD among the 53 amyloid positive patients aged 75 years or older increased greatly to 74% whereas that of amyloid positive HC decreased by only 9% and amyloid positive MCI by 17%. Prodromal AD and AD dementia is identified, based on cognitive function and amyloid deposition by PIB PET imaging. Further, the cortical amyloid deposition could be detected at preclinical stage of AD.

  20. The influence of number of high risk factors on clinical outcomes in patients with early-stage cervical cancer after radical hysterectomy and adjuvant chemoradiation

    PubMed Central

    Lim, Soyi; Lee, Seok-Ho; Park, Chan-Yong

    2016-01-01

    Objective The purpose of this study was to evaluate the prognosis according to the number of high risk factors in patients with high risk factors after radical hysterectomy and adjuvant chemoradiation therapy for early stage cervical cancer. Methods Clinicopathological variables and clinical outcomes of patients with FIGO (International Federation of Gynecology and Obstetrics) stage IB1 to IIA cervical cancer who had one or more high risk factors after radical hysterectomy and adjuvant chemoradiation therapy were retrospectively analyzed. Patients were divided into two groups according to the number of high risk factors (group 1, single high risk factor; group 2, two or more high risk factors). Results A total of 93 patients were enrolled in the present study. Forty nine out of 93 (52.7%) patients had a single high risk factor, and 44 (47.3%) had two or more high risk factors. Statistically significant differences in stage and stromal invasion were observed between group 1 and group 2. However, age, histology, tumor size, and lymphovascular space invasion did not differ significantly between the groups. Distant recurrence occurred more frequently in group 2, and the probability of recurrence and death was higher in group 2. Conclusion Patients with two or more high risk factors had worse prognosis in early stage cervical cancer. For these patients, consideration of new strategies to improve survival may be worthwhile. Conduct of further clinical trials is warranted for development of adjuvant treatment strategies individualized to each risk group. PMID:27200308

  1. APPLYING TEP MEASUREMENTS TO ASSESS THE AGING STAGE OF MARAGING 250 STEEL

    SciTech Connect

    Snir, Y.; Gelbstein, Y.; Pinkas, M.; Yeheskel, O.; Landau, A.

    2008-02-28

    Thermoelectric power (TEP) measurements had been proved as an effective method for evaluating the metallurgical state of various alloys. The current work was conducted in order to evaluate the influence of the aging state of Maraging 250 steel on TEP values. Commercial Maraging 250 steel was aged at 500 deg. C for 0.5-6 hours (hrs). TEP, hardness (Rc) and ultrasonic (US) measurements, were preformed on the as received and aged specimens. XRD measurements were used to identify the formation of precipitates (mainly Ni{sub 3}(Ti,Mo)), reverted austenite and to evaluate changes in the microstrain caused by the precipitation process. A correlation was found between the TEP and the various measurements as a function of the aging time.

  2. Applying Tep Measurements to Assess the Aging Stage of Maraging 250 Steel

    NASA Astrophysics Data System (ADS)

    Snir, Y.; Pinkas, M.; Gelbstein, Y.; Yeheskel, O.; Landau, A.

    2008-02-01

    Thermoelectric power (TEP) measurements had been proved as an effective method for evaluating the metallurgical state of various alloys. The current work was conducted in order to evaluate the influence of the aging state of Maraging 250 steel on TEP values. Commercial Maraging 250 steel was aged at 500 °C for 0.5-6 hours (hrs). TEP, hardness (Rc) and ultrasonic (US) measurements, were preformed on the as received and aged specimens. XRD measurements were used to identify the formation of precipitates (mainly Ni3(Ti,Mo)), reverted austenite and to evaluate changes in the microstrain caused by the precipitation process. A correlation was found between the TEP and the various measurements as a function of the aging time.

  3. Dental and Chronological Ages as Determinants of Peak Growth Period and Its Relationship with Dental Calcification Stages

    PubMed Central

    Litsas, George; Lucchese, Alessandra

    2016-01-01

    Purpose: To investigate the relationship between dental, chronological, and cervical vertebral maturation growth in the peak growth period, as well as to study the association between the dental calcification phases and the skeletal maturity stages during the same growth period. Methods: Subjects were selected from orthodontic pre-treatment cohorts consisting of 420 subjects where 255 were identified and enrolled into the study, comprising 145 girls and 110 boys. The lateral cephalometric and panoramic radiographs were examined from the archives of the Department of Orthodontics, Aristotle University of Thessaloniki, Greece. Dental age was assessed according to the method of Demirjian, and skeletal maturation according to the Cervical Vertebral Maturation Method. Statistical elaboration included Spearman Brown formula, descriptive statistics, Pearson’s correlation coefficient and regression analysis, paired samples t-test, and Spearman’s rho correlation coefficient. Results: Chronological and dental age showed a high correlation for both gender(r =0.741 for boys, r = 0.770 for girls, p<0.001). The strongest correlation was for the CVM Stage IV for both males (r=0.554) and females (r=0.68). The lowest correlation was for the CVM Stage III in males (r=0.433, p<0.001) and for the CVM Stage II in females (r=0.393, p>0.001). The t-test revealed statistically significant differences between these variables (p<0.001) during the peak period. A statistically significant correlation (p<0.001) between tooth calcification and CVM stages was determined. The second molars showed the highest correlation with CVM stages (CVMS) (r= 0.65 for boys, r = 0.72 for girls). Conclusion: Dental age was more advanced than chronological for both boys and girls for all CVMS. During the peak period these differences were more pronounced. Moreover, all correlations between skeletal and dental stages were statistically significant. The second molars showed the highest correlation whereas the

  4. The role of rumination in illness trajectories in youth: linking trans-diagnostic processes with clinical staging models.

    PubMed

    Grierson, A B; Hickie, I B; Naismith, S L; Scott, J

    2016-09-01

    Research in developmental psychopathology and clinical staging models has increasingly sought to identify trans-diagnostic biomarkers or neurocognitive deficits that may play a role in the onset and trajectory of mental disorders and could represent modifiable treatment targets. Less attention has been directed at the potential role of cognitive-emotional regulation processes such as ruminative response style. Maladaptive rumination (toxic brooding) is a known mediator of the association between gender and internalizing disorders in adolescents and is increased in individuals with a history of early adversity. Furthermore, rumination shows moderate levels of genetic heritability and is linked to abnormalities in neural networks associated with emotional regulation and executive functioning. This review explores the potential role of rumination in exacerbating the symptoms of alcohol and substance misuse, and bipolar and psychotic disorders during the peak age range for illness onset. Evidence shows that rumination not only amplifies levels of distress and suicidal ideation, but also extends physiological responses to stress, which may partly explain the high prevalence of physical and mental co-morbidity in youth presenting to mental health services. In summary, the normative developmental trajectory of rumination and its role in the evolution of mental disorders and physical illness demonstrates that rumination presents a detectable, modifiable trans-diagnostic risk factor in youth. PMID:27352637

  5. A study of the age attribute in a query tool for a clinical data warehouse.

    PubMed

    Scheufele, Elisabeth L; Scheufele, Elisabeth Lee; Dubey, Anil; Dubey, Anil Kumar; Murphy, Shawn N

    2008-11-06

    The RPDR, a clinical data warehouse with a user-friendly Querytool, allows researchers to perform studies on patient data. Currently, the RPDR represents age as the patient's age at the present time, which is problematic in situations where age at the time of the event is more appropriate. We will modify the Querytool to consider this by assessing the perception of age via survey, testing backend query solutions, and developing modifications based on these results.

  6. Treatment of early-stage human epidermal growth factor 2-positive cancers among medicare enrollees: age and race strongly associated with non-use of trastuzumab.

    PubMed

    Vaz-Luis, Ines; Lin, Nancy U; Keating, Nancy L; Barry, William T; Lii, Joyce; Burstein, Harold J; Winer, Eric P; Freedman, Rachel A

    2016-08-01

    Adjuvant trastuzumab for human epidermal growth factor receptor-2 (HER2)-positive breast cancer is highly efficacious regardless of age. Recent data suggested that many older patients with HER2-positive disease do not receive adjuvant trastuzumab. Nevertheless, some of this 'under-treatment' may be clinically appropriate. We used Surveillance, Epidemiology and End Results (SEER)-Medicare data to identify patients aged ≥ 66 with stage ≥ Ib-III, HER2-positive breast cancer diagnosed during 2010-2011 (HER2 status available) who did not have a history of congestive heart failure. We described all systemic treatments received and sociodemographic and clinical characteristics associated with treatment patterns. Among 770 women 44.4 % did not receive trastuzumab, including 21.8 % who received endocrine therapy only, 6.3 % who received chemotherapy (±endocrine therapy) and 16.2 % who did not receive any systemic therapy. In addition to age and grade, race was strongly associated with non-use of trastuzumab (64.4 % of Non-Hispanic blacks vs. 43.6 % of whites did not receive trastuzumab, adjusted ORNon-Hispanic black vs. white = 3.14, 95 %CI = 1.38-7.17), and many patients with stage III disease did not receive trastuzumab. Further, 16.2 % of patients did not receive any systemic treatment and this occurred more frequently for black patients. Over 40 % of older patients with indication to receive adjuvant trastuzumab did not receive it and nearly 20 % of these patients did not receive any other treatment. Although treatment omission may be appropriate in some cases, we observed concerning differences in trastuzumab receipt, particularly for black women. Strategies to optimize care for older patients and to eliminate treatment disparities are urgently needed. PMID:27484879

  7. Cases of acute gastroenteritis due to calicivirus in outbreaks: clinical differences by age and aetiological agent.

    PubMed

    Sala, M R; Broner, S; Moreno, A; Arias, C; Godoy, P; Minguell, S; Martínez, A; Torner, N; Bartolomé, R; de Simón, M; Guix, S; Domínguez, A

    2014-08-01

    The Caliciviridae family includes norovirus and sapovirus, which both cause acute gastroenteritis (AGE). Currently, norovirus is the most common cause of AGE in all age groups in many countries. We analysed clinical differences in reported cases of acute gastroenteritis caused by caliciviruses (AGC) by age group and agent involved. We conducted a descriptive study of AGE outbreaks reported to the Public Health Agency of Catalonia (Spain) in 2010 and 2011. The odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated to estimate the association between clinical symptoms and age. Clinical differences between the <15 years and ≥15 years age groups were statistically significant: children more frequently presented with vomiting (OR, 3.25; 95% CI, 2.56-4.13), abdominal pain (OR, 3.27; 95% CI, 2.60-4.12), fever (OR, 1.51; 95% CI, 1.17-1.96) and nausea (OR, 1.49; 95% CI, 1.19-1.85). Comparing clinical manifestations of sapovirus and norovirus infection in children aged <15 years, cases caused by norovirus more frequently presented with vomiting and fever (p <0.001), and cases caused by sapovirus more frequently presented with diarrhoea (p 0.013). Determination of the clinical differences associated with cases in outbreaks according to the age of the majority of cases and the symptoms most frequently detected may aid decision making and guide aetiological investigations and the adoption of prevention and control measures.

  8. Statistical Issues for Design and Analysis of Single-Arm Multi-Stage Phase II Cancer Clinical Trials

    PubMed Central

    Jung, Sin-Ho

    2015-01-01

    Summary Phase II trials have been very widely conducted and published every year for cancer clinical research. In spite of the fast progress in design and analysis methods, single-arm two-stage design is still the most popular for phase II cancer clinical trials. Because of their small sample sizes, statistical methods based on large sample approximation are not appropriate for design and analysis of phase II trials. As a prospective clinical research, the analysis method of a phase II trial is predetermined at the design stage and it is analyzed during and at the end of the trial as planned by the design. The analysis method of a trial should be matched with the design method. For two-stage single arm phase II trials, Simon's method has been the standards for choosing an optimal design, but the resulting data have been analyzed and published ignoring the two-stage design aspect with small sample sizes. In this article, we review analysis methods that exactly get along with the exact two-stage design method. We also discuss some statistical methods to improve the existing design and analysis methods for single-arm two-stage phase II trials. PMID:25749311

  9. Translating Advances from the Basic Biology of Aging into Clinical Application

    PubMed Central

    Kirkland, James L.

    2013-01-01

    Recently, lifespan and healthspan have been extended in experimental animals using interventions that are potentially translatable into humans. A great deal of thought and work are needed beyond the usual steps in drug development to advance these findings into clinical application. Realistic pre-clinical and clinical trials paradigms need to be devised. Focusing on subjects with symptoms of age-related diseases or frailty or who are at imminent risk of developing these problems, measuring effects on short-term, clinically relevant outcomes, as opposed to long-term outcomes such as healthspan or lifespan, and developing biomarkers and outcome measures acceptable to regulatory agencies will be important. Research funding is a major roadblock, as is lack of investigators with combined expertise in the basic biology of aging, clinical geriatrics, and conducting investigational new drug clinical trials. Options are reviewed for developing a path from the bench to the bedside for interventions that target fundamental aging processes. PMID:23237984

  10. Increased age of transformed mouse neural progenitor/stem cells recapitulates age-dependent clinical features of human glioma malignancy

    PubMed Central

    Mikheev, Andrei M.; Ramakrishna, Rohan; Stoll, Elizabeth A.; Mikheeva, Svetlana A.; Beyer, Richard P.; Plotnik, David A.; Schwartz, Jeffrey L.; Rockhill, Jason K.; Silber, John R.; Born, Donald E.; Kosai, Yoshito; Horner, Philip J.; Rostomily, Robert C.

    2012-01-01

    Increasing age is the most robust predictor of greater malignancy and treatment resistance in human gliomas. However, the adverse association of clinical course with aging is rarely considered in animal glioma models, impeding delineation of the relative importance of organismal versus progenitor cell aging in the genesis of glioma malignancy. To address this limitation, we implanted transformed neural stem/progenitor cells (NSPCs), the presumed cells of glioma origin, from 3 and 18month old mice into 3 and 20-month host animals. Transplantation with progenitors from older animals resulted in significantly shorter (p ≤ 0.0001) median survival in both 3month (37.5 vs 83 days) and 20-month (38 vs 67 days) hosts, indicating that age-dependent changes intrinsic to NSPCs rather than host animal age accounted for greater malignancy. Subsequent analyses revealed that increased invasiveness, genomic instability, resistance to therapeutic agents and tolerance to hypoxic stress accompanied aging in transformed NSPCs. Greater tolerance to hypoxia in older progenitor cells, as evidenced by elevated HIF-1 promoter reporter activity and hypoxia response gene (HRG) expression, mirror the upregulation of HRGs in cohorts of older vs younger glioma patients revealed by analysis of gene expression databases, suggesting that differential response to hypoxic stress may underlie age-dependent differences in invasion, genomic instability and treatment resistance. Our study provides strong evidence that progenitor cell aging is responsible for promoting the hallmarks of age-dependent glioma malignancy and that consideration of progenitor aging will facilitate development of physiologically and clinically relevant animal models of human gliomas. PMID:22958206

  11. Experimental ovine toxoplasmosis: influence of the gestational stage on the clinical course, lesion development and parasite distribution.

    PubMed

    Castaño, Pablo; Fuertes, Miguel; Regidor-Cerrillo, Javier; Ferre, Ignacio; Fernández, Miguel; Ferreras, M Carmen; Moreno-Gonzalo, Javier; González-Lanza, Camino; Pereira-Bueno, Juana; Katzer, Frank; Ortega-Mora, Luis Miguel; Pérez, Valentín; Benavides, Julio

    2016-03-16

    The relation between gestational age and foetal death risk in ovine toxoplasmosis is already known, but the mechanisms involved are not yet clear. In order to study how the stage of gestation influences these mechanisms, pregnant sheep of the same age and genetic background were orally dosed with 50 oocysts of Toxoplasma gondii (M4 isolate) at days 40 (G1), 90 (G2) and 120 (G3) of gestation. In each group, four animals were culled on the second, third and fourth week post infection (pi) in order to evaluate parasite load and distribution, and lesions in target organs. Ewes from G1 showed a longer period of hyperthermia than the other groups. Abortions occurred in all groups. While in G2 they were more frequent during the acute phase of the disease, in G3 they mainly occurred after day 20 pi. After challenge, parasite and lesions in the placentas and foetuses were detected from day 19 pi in G3 while in G2 or G1 they were only detected at day 26 pi. However, after initial detection at day 19 pi, parasite burden, measured through RT-PCR, in placenta or foetus of G3 did not increase significantly and, at in the third week pi it was lower than that measured in foetal liver or placenta from G1 to G3 respectively. These results show that the period of gestation clearly influences the parasite multiplication and development of lesions in the placenta and foetus and, as a consequence, the clinical course in ovine toxoplasmosis.

  12. "Electro-clinical syndromes" with onset in paediatric age: the highlights of the clinical-EEG, genetic and therapeutic advances

    PubMed Central

    2011-01-01

    The genetic causes underlying epilepsy remain largely unknown, and the impact of available genetic data on the nosology of epilepsy is still limited. Thus, at present, classification of epileptic disorders should be mainly based on electroclinical features. Electro-clinical syndrome is a term used to identify a group of clinical entities showing a cluster of electro-clinical characteristics, with signs and symptoms that together define a distinctive, recognizable, clinical disorder. These often become the focus of treatment trials as well as of genetic, neuropsychological, and neuroimaging investigations. They are distinctive disorders identifiable on the basis of a typical age onset, specific EEG characteristics, seizure types, and often other features which, when taken together, permit a specific diagnosis which, in turn, often has implications for treatment, management, and prognosis. Each electro-clinical syndrome can be classified according to age at onset, cognitive and developmental antecedents and consequences, motor and sensory examinations, EEG features, provoking or triggering factors, and patterns of seizure occurrence with respect to sleep. Therefore, according to the age at onset, here we review the more frequently observed paediatric electro-clinical syndrome from their clinical-EEG, genetic and therapeutic point of views. PMID:22182677

  13. Clinical Correlates of Insulin Sensitivity and Its Association with Mortality among Men with CKD Stages 3 and 4

    PubMed Central

    Xu, Hong; Huang, Xiaoyan; Ärnlöv, Johan; Cederholm, Tommy; Stenvinkel, Peter; Lindholm, Bengt; Risérus, Ulf

    2014-01-01

    Background and objectives Insulin resistance participates in the pathogenesis of multiple metabolic and cardiovascular diseases. CKD patients have impaired insulin sensitivity, but the clinical correlates and outcome associations of impaired insulin sensitivity in this vulnerable population are not well defined. Design, setting, participants, & measurements The prospective cohort study was from the third examination cycle of the Uppsala Longitudinal Study of Adult Men, a population-based survey of elderly men ages 70–71 years; insulin sensitivity was assessed by glucose disposal rate as measured with euglycemic clamps. Inclusion criterion was eGFR<60 ml/min per 1.73 m2 (n=543). Exclusion criteria were incomplete data on euglycemic clamp and diabetes (n=97), leaving 446 men with CKD stages 3 and 4 (eGFR median=51.9 ml/min per 1.73 m2; range=20.2–59.5 ml/min per 1.73 m2). Results The mean of glucose disposal rate was 5.4±1.9 mg/kg per minute. In multivariable analysis, the independent clinical correlates of glucose disposal rate were eGFR (slope, 0.02; 95% confidence interval, 0.01 to 0.04), hypertension (−0.48; 95% confidence interval, −0.86 to −0.11), hyperlipidemia (−0.51; 95% confidence interval, −0.84 to −0.18), and body mass index (−0.32; 95% confidence interval, −0.37 to −0.27). During follow-up (median=10.0 years; interquartile range=8.7–11.0 years), 149 participants died. In Cox regression models, glucose disposal rate was not associated with all-cause or cardiovascular mortality. Multiplicative interactions (P<0.05) were observed between glucose disposal rate and physical activity or smoking in total mortality association. After subsequent stratification, glucose disposal rate was an independent correlate of all-cause mortality in smokers (adjusted hazard ratio, 0.72; 95% confidence interval, 0.54 to 0.96 per 1 mg/kg per minute glucose disposal rate increase) and physically inactive individuals (hazard ratio, 0.77; 95% confidence

  14. Multiparametric magnetic resonance imaging for pre-treatment local staging of prostate cancer: A Cancer Care Ontario clinical practice guideline

    PubMed Central

    Salerno, Jennifer; Finelli, Antonio; Morash, Chris; Morgan, Scott C.; Power, Nicholas; Schieda, Nichola; Haider, Masoom A.

    2016-01-01

    Introduction: The utility of T2-weighted magnetic resonance imaging (MRI) in the local staging of prostate cancer is controversial. Due to the success of multiparametric MRI in cancer localization, there is renewed interested in MRI (± functional sequences) for local staging. Guidance on pre-treatment local staging of prostate cancer by MRI was developed using systematic review methodology and expert consultation. Methods: MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, and other databases were searched to identify studies comparing: (1) MRI staging vs. radical prostatectomy staging on diagnostic accuracy outcomes; and (2) MRI staging vs. routine clinical staging on clinical and patient outcomes. Studies meeting inclusion criteria were synthesized by outcome and sensitivity/specificity analysis by tumour location was performed. Evidence quality of included studies was assessed and considered in recommendation formulation. Results: The literature search identified 2510 citations; 62 studies were included. Analysis of MRI ≥1.5 T plus endorectal coil (ER) (± functional sequences) in the detection of extraprostatic extension or seminal vesicle invasion showed modest sensitivities (≥50%) and excellent specificities (>85%) among patients scheduled for radical prostatectomy. MRI upstaging was shown in 20/21 studies, with large variation in correctness (11–85%). Scarcity of clinical and patient outcomes among studies limited synthesis and evaluation. Quality assessment found non-trivial biases. Conclusions: Modest imaging performance was shown for MRI (1.5 T + ER and 3 T ± ER) ± functional sequences in regards to sensitivity. Limitations in study design, reporting of clinical and patient outcomes, and the heterogeneous use of MRI tempered the strength of the recommendations. PMID:27800062

  15. Effect of Habits and Nutritional Status on Clinical Grading and Histopathological Staging in Patients with Oral Sub Mucous Fibrosis

    PubMed Central

    Lanke, Rama Brahmam; Shetty, Rakhith; Akifuddin, Syed; Sahu, Manish; Singh, Navneet; Kaur, Gagandeep; Goyal, Garish

    2015-01-01

    Background Oral submucous fibrosis (OSMF) is a chronic progressive debilitating disease affecting the oral, oropharyngeal and sometimes the oesophageal mucosa resulting in inability to eat due to burning, ulcers and stiffness. Aim The study was undertaken, to evaluate the correlation of clinical staging, histological grading and nutritional status using body mass index (BMI) with gutkha (habit) index in OSMF patients. Materials and Methods The study group comprised of 50 patients clinically diagnosed and histopathologically confirmed cases of OSMF. Habit (gutkha) index was calculated by multiplying duration and frequency. Body mass index was calculated by dividing weight in kilograms and height in centimetres of the patient. Results Male to female ratio was 2.8:1. Clinical grading increased with increase in gutkha index, patients with gutkha index 1-50, maximum were in mild stage; with gutkha index 51-100, maximum in moderate and patients with gutkha index 101-150, all were in severe stage. Histological staging showed direct correlation with gutkha index, it increased with increase in gutkha index with p <0.05. Site analysis showed that buccal mucosa and retromolar area were involved in all the patient and floor of mouth in 46% of patients Body mass index analysis revealed that out of 27 patients with moderate clinical staging 3 was underweight; out of 3 with severe clinical staging, 2 was underweight. Conclusion The duration and frequency of areca nut product use effects on the incidence and severity of OSMF and the patient becomes unable to eat due to burning, ulcers and inability to open mouth which affect the health of the individual. Thus it is important to access the nutritional status to improve the survival rate of patients. PMID:26557616

  16. [GENDER AND AGE DIFFERENCES IN THE TREATMENT OF CHRONIC HEART FAILURE AT HOSPITAL OBSERVATIONS STAGE].

    PubMed

    Dadashova, G M

    2016-01-01

    Analysis of literature shows that very little data are available on gender differences and age-specific drug use in the treatment of chronic heart failure (CHF). In this work, the character of drug therapy was studied as dependent on the age and sex of patients with CHF under in-hospital observation conditions. Among hospitalized patients with CHF, an important role is played by modern drug therapy. Gender differences were found in respect of therapy with ACE inhibitors, which was used in men more frequently than in women (89 and 78%, respectively, p <0.001). Aldosterone antagonists were used in the treatment of women much less frequently than in men (32.9 and 42%, respectively, p < 0.001). Loop diuretics are more frequently prescribed to men (48 and 40%, respectively, p < 0.001) and thiazide diuretics, to women (38.9 and 27%, respectively, p < 0.001). In older age groups, CHF treatment both in men (p < 0.05) and in women (p < 0.001) is characterized by decreased use of beta-adrenoblockers and increased use of aldosterone antagonists (p < 0.05). In women, older age groups meet increased prescription frequency of ACE inhibitors/ARBs (from 79.1 to 95.3%p < 0.01) and aldosterone antagonists (from 29.3 to 38.2% p < 0.001). PMID:27416677

  17. Development: Ages & Stages--How Children Develop a Sense of Time

    ERIC Educational Resources Information Center

    Poole, Carla; Miller, Susan A.; Church, Ellen Booth

    2006-01-01

    This article presents suggestions on how to increase awareness of a sense of time for infants up to age 6. It recommends using children's personal experiences to help them understand time concepts. Individual components of this article include: (1) "I Go Now!"--Birth to 2 (Carla Poole); (2) "Today's My Birthday!"--3 to 4 (Susan A. Miller); and (3)…

  18. A new adaptive design based on Simon's two-stage optimal design for phase II clinical trials.

    PubMed

    Jin, Hua; Wei, Zhen

    2012-11-01

    Phase II clinical trials are conducted to determine whether a new agent or drug regimen has sufficient promise in treating cancer to merit further testing in larger groups of patients. Both ethical and practical considerations often require early termination of phase II trials if early results clearly indicate that the new regimen is not active or worthy of further investigation. Simon's two-stage designs (1989) are common methods for conducting phase II studies investigating new cancer therapies. Banerjee and Tsiatis (2006) proposed an adaptive two-stage design which allows the sample size at the second stage to depend on the results at the first stage. Their design is more flexible than Simon's, but it is somewhat counter-intuitive: as the response in the first stage increases, the second-stage sample size increases till a certain point and then abruptly becomes zero. In this paper, based on Simon's two-stage optimal design, we propose a new adaptive one which depends on the first stage results using the restrict conditions the conditional type I error and the conditional power. Comparisons are made between Banerjee and Tsiatis' results and our new adaptive designs. PMID:22772088

  19. [Change of clinical stomatological parameters in ageing (author's transl)].

    PubMed

    Fassauer, H; Schottke, C

    1978-01-01

    Morphological-functional changes occur in the oral cavity also in depended from the age. The morphological changes of the enamel, dentin, dental pulp, periodont, oral mucosa, salivary glands, tongue, maxillary bone and temporo-mandibular-joint change not only the functional cooperation of all parts in the orofacial system. They show effects for the whole body also. A complete gerostomatological standard does not exist for the whole gnathological system. But single indices for some partial components are known. For the judgement of the caries involvement it is possible to use the DMF-index, for which a special gerostomatological type exist. The periodontal diseases are classified adequately to the ARPA-nomenclature. For the judgement of odontolithiasis and oral hygienic conditions you can use the so called odontolith-Index (CI), the OH (oral hygienic debris) and the so called calculus-index (OHI-S). It is refered to different possibilities for classification of dentition with gaps.

  20. Prognostic Importance of Serum Alkaline Phosphatase in CKD Stages 3–4 in a Clinical Population

    PubMed Central

    Taliercio, Jonathan J.; Schold, Jesse D.; Simon, James F.; Arrigain, Susana; Tang, Anne; Saab, Georges; Nally, Joseph V.; Navaneethan, Sankar D.

    2013-01-01

    Background Elevated total serum alkaline phosphatase (ALP) levels have been associated with mortality in the general population and in dialysis patients. Study Design Retrospective cohort study. Setting & Participants 28,678 patients with chronic kidney disease (CKD) stages 3 and 4 (estimated glomerular filtration rate [eGFR], 15–59 ml/min/1.73 m2) were identified using the Cleveland Clinic Chronic Kidney Disease Registry. CKD was defined as two eGFR values <60 ml/min/1.73 m2 drawn >90 days apart using the Chronic Kidney Disease Epidemiology Collaboration creatinine equation. Predictor ALP levels measured using the calorimetric assay was examined as quartiles (quartile 1, <66 U/L; Q2, 66–81 U/L; Q3, 82–101 U/L; and Q4, ≥102 U/L) and as a continuous measure. Outcomes & Measurements All-cause mortality and ESRD were ascertained using the Social Security Death Index and US Renal Data System. Results After a median follow up of 2.2 years, 588 patients progressed to ESRD and 4,755 died. There was a graded increase in the risk for mortality with higher ALP quartiles (Q2, Q3, Q4) when compared to the reference quartile (Q1) after adjusting for demographics, comorbid conditions, use of relevant medications and liver function tests. The highest quartile of ALP was associated with a hazard ratio for ESRD of 1.38 (95% CI, 1.09–1.76). Each 1-standard deviation (42.7 U/L) higher ALP level was associated with 15% (95% CI, 1.09–1.22) and 16% (95% CI, 1.14–1.18) increased risk of ESRD and mortality respectively. Limitations Single center observational study, lack complete data including PTH for all study participants and attrition bias. Conclusions Higher serum ALP levels in CKD stages 3–4 were independently associated with all-cause mortality and ESRD. PMID:23769134

  1. Effectiveness of a thoracic multidisciplinary clinic in the treatment of stage III non-small-cell lung cancer

    PubMed Central

    Friedman, Eliot L; Kruklitis, Robert J; Patson, Brian J; Sopka, Dennis M; Weiss, Michael J

    2016-01-01

    Introduction The Institute of Medicine, the American Society of Clinical Oncology, and the European Society of Medical Oncology promote a multidisciplinary approach for the treatment of cancer. Stage III non-small-cell lung cancer (NSCLC) represents a heterogeneous group of diseases necessitating coordination of care among medical, radiation, and surgical oncology. The optimal care of stage III NSCLC underscores the need for a multidisciplinary approach. Methods From tumor registry data, we identified all cases of stage III NSCLC seen at Lehigh Valley Health Network between March 2010 and March 2013. The care received by patients when seen in the thoracic multidisciplinary clinic (MDC) was compared with the care received when not seen in the thoracic MDC. Results All patients seen in the MDC, compared to <50% of patients seen outside the MDC, were evaluated by more than one physician prior to beginning the treatment. Time to initiate treatment was shorter in MDC patients than in non-MDC patients. Patients seen in the MDC had a greater concordance with clinical pathways. A greater percentage of patients seen in the thoracic MDC had pathologic staging of their mediastinum. Patients seen in the MDC were more likely to receive all of their care at Lehigh Valley Health Network. Conclusion Multidisciplinary care is essential in the treatment of patients with stage III NSCLC. Greater utilization of MDCs for this complex group of patients will result in more efficient coordination of care, pretreatment evaluation, and therapy, which in turn should translate to improve patients’ outcomes. PMID:27358568

  2. Plasma 24-metabolite Panel Predicts Preclinical Transition to Clinical Stages of Alzheimer’s Disease

    PubMed Central

    Fiandaca, Massimo S.; Zhong, Xiaogang; Cheema, Amrita K.; Orquiza, Michael H.; Chidambaram, Swathi; Tan, Ming T.; Gresenz, Carole Roan; FitzGerald, Kevin T.; Nalls, Mike A.; Singleton, Andrew B.; Mapstone, Mark; Federoff, Howard J.

    2015-01-01

    We recently documented plasma lipid dysregulation in preclinical late-onset Alzheimer’s disease (LOAD). A 10 plasma lipid panel, predicted phenoconversion and provided 90% sensitivity and 85% specificity in differentiating an at-risk group from those that would remain cognitively intact. Despite these encouraging results, low positive predictive values limit the clinical usefulness of this panel as a screening tool in subjects aged 70–80 years or younger. In this report, we re-examine our metabolomic data, analyzing baseline plasma specimens from our group of phenoconverters (n = 28) and a matched set of cognitively normal subjects (n = 73), and discover and internally validate a panel of 24 plasma metabolites. The new panel provides a classifier with receiver operating characteristic area under the curve for the discovery and internal validation cohort of 1.0 and 0.995 (95% confidence intervals of 1.0–1.0, and 0.981–1.0), respectively. Twenty-two of the 24 metabolites were significantly dysregulated lipids. While positive and negative predictive values were improved compared to our 10-lipid panel, low positive predictive values provide a reality check on the utility of such biomarkers in this age group (or younger). Through inclusion of additional significantly dysregulated analyte species, our new biomarker panel provides greater accuracy in our cohort but remains limited by predictive power. Unfortunately, the novel metabolite panel alone may not provide improvement in counseling and management of at-risk individuals but may further improve selection of subjects for LOAD secondary prevention trials. We expect that external validation will remain challenging due to our stringent study design, especially compared with more diverse subject cohorts. We do anticipate, however, external validation of reduced plasma lipid species as a predictor of phenoconversion to either prodromal or manifest LOAD. PMID:26617567

  3. Improving Medical Residents' Attitudes toward HIV-Infected Persons through Training in an HIV Staging and Triage Clinic.

    ERIC Educational Resources Information Center

    Orlander, Jay D.; And Others

    1994-01-01

    A study assessed the effectiveness of a weekly outpatient clinic for staging and triage of newly identified human-immunodeficiency-virus (HIV)-infected patients on 21 medical residents' attitudes and knowledge regarding HIV patient care, as compared with 20 control students. Results indicated that the experience positively affected student…

  4. 326 Lung Age/Chronological Age Index as Indicator of Clinical Improvement or Severity in Asthma Patients

    PubMed Central

    Castrejon-Vázquez, Isabel; Vargas, Maria Eugenia; Sabido, Raúl Cicero; Tapía, Jorge Galicia

    2012-01-01

    Background Spirometry is a very useful clinical test to evaluate pulmonary function in asthma. However pulmonary function could be affected by the sex, time of clinical evolution, lung age (LA) and chronological age (CA). The aim of this study was to evaluate LA/CA as index of clinical improvement or severity in asthma patients. Methods The tenets of the Declaration of Helsinki were followed, and all patients gave their informed consent to participate in this study. Asthma severity was evaluated according with GINA classification. Spirometry was performed at the beginning of this study, at 46 days, 96 days, 192 days and after 8 months. Statistical analysis was performed using t test, 2-way ANOVA test, correlation and multiple regression models as well as ROC curves were also performed, a P < 0.05 was considered as significant. Results 70 asthma patients were included (22 male and 48 female), mean CA was 35-years old; mean LA was 48-years with a LA/CA index = 1.4, time of clinical evolution was 13 years. A LA/CA index = 1 (range 0.5 to 0.9) was observed in asymptomatic patients. LA/CA index over 1 were related with airway inflammation, and a LA/CA index more than 2 correlated with GINA step 3. Interestingly when we analyzed CA and LA, we observed that in female group more than 10 years of difference between CA and LA, (GINA Step2 and 3); while in male we observed (GINA Step1, Step2 and Step3). LA/CA index ≤ 1 was considered as normal. Conclusions LA/CA index is a good as clinical indicator of clinical improvement or severity in asthma patients in with excellent correlation of pulmonary function and age.

  5. The Prognostic Impact of Molecular Subtypes and Very Young Age on Breast Conserving Surgery in Early Stage Breast Cancer

    PubMed Central

    McGuire, Kandace; Alco, Gul; Nur Pilanci, Kezban; Koksal, Ulkuhan I; Elbüken, Filiz; Erdogan, Zeynep; Agacayak, Filiz; Ilgun, Serkan; Sarsenov, Dauren; Öztürk, Alper; İğdem, Şefik; Okkan, Sait; Eralp, Yeşim; Dincer, Maktav; Ozmen, Vahit

    2016-01-01

    Background Premenopausal breast cancer with a triple-negative phenotype (TNBC) has been associated with inferior locoregional recurrence free survival (LRFS) and overall survival (OS) after breast conserving surgery (BCS). The aim of this study is to analyze the association between age, subtype, and surgical treatment on survival in young women (≤40 years) with early breast cancer in a population with a high rate of breast cancer in young women. Methods Three hundred thirty-two patients ≤40 years old with stage I-II invasive breast cancer who underwent surgery at a single institution between 1998 and 2012 were identified retrospectively. Uni- and multivariate analysis evaluated predictors of LRFS, OS, and disease free survival (DFS). Results Most patients (64.2%) underwent BCS. Mean age and follow-up time were 35 (25 ± 3.61) years, and 72 months (range, 24–252), respectively. In multivariate analysis, multicentricity/multifocality and young age (<35 years) independently predicted for poorer DFS and OS. Those aged 35–40 years had higher LRFS and DFS than those <35 in the mastectomy group (p=0.007 and p=0.039, respectively). Patients with TNBC had lower OS compared with patients with luminal A subtype (p=0.042), and those who underwent BCS had higher OS than patients after mastectomy (p=0.015). Conclusion Young age (< 35 years) is an independent predictor of poorer OS and DFS as compared with ages 35–40, even in countries with a lower average age of breast cancer presentation. In addition, TNBC in the young predicts for poorer OS. BCS can be performed in young patients with TNBC, despite their poorer overall survival. PMID:27433412

  6. Age-Related Decline and Diagnostic Performance of More and Less Prevalent Clinical Cases

    ERIC Educational Resources Information Center

    St-Onge, Christina; Landry, Marjolaine; Xhignesse, Marianne; Voyer, Gilles; Tremblay-Lavoie, Stéphanie; Mamede, Sílvia; Schmidt, Henk; Rikers, Remy

    2016-01-01

    Since cognitive abilities have been shown to decrease with age, it is expected that older physicians would not perform as well as their younger counterparts on clinical cases unless their expertise can counteract the cognitive effects of aging. However, studies on the topic have shown contradictory results. This study aimed to further investigate…

  7. In vitro assays and clinical trials in red blood cell aging: Lost in translation.

    PubMed

    Prudent, Michel; Tissot, Jean-Daniel; Lion, Niels

    2015-06-01

    The age of erythrocyte concentrates (EC) in transfusion medicine and the adverse outcomes when transfusing long-term-stored EC are highly controversial issues. Whereas the definition of a short-term-stored EC or a long-term-stored EC is unclear in clinical trials, data based on in vitro storage assays can help defining a limit in addition of the expiration date. The present review merges together these data in order to highlight an EC age cut-off and points out potential misleading consideration. The analysis of in vitro data highlights the presence of reversible and irreversible storage lesions and demonstrates that red blood cells (RBC) exhibit two limits during storage: one around 2 weeks and another one around 4 weeks of storage. Of particular importance, the first lesions to appear, i.e. the reversible ones, are per se reversible once transfused, whereas the irreversible lesions are not. In clinical trials, the EC age cut-off for short-term storage is in general fewer than 14 days (11 ± 4 days) and more disperse for long-term-stored EC (17 ± 13 days), regardless the clinical outcomes. Taking together, EC age cut-off in clinical trials does not totally fall into line of in vitro aging data, whereas it is the key criteria in clinical studies. Long-term-stored EC considered in clinical trials are not probably old enough to answer the question: "Does transfusion of long-term-stored EC (older than 4 weeks) result in worse clinical outcomes?" Depending on ethical concerns and clinical practices, older EC than currently assayed in clinical trials should have to be considered. These two worlds trying to understand the aging of erythrocytes and the impact on patients do not seem to speak the same language.

  8. Age-related clinical and microbiological characteristics of enteric fever in India.

    PubMed

    Walia, Mandeep; Gaind, Rajni; Paul, Premila; Mehta, Rajesh; Aggarwal, Pushpa; Kalaivani, Mani

    2006-10-01

    A retrospective, hospital-based study at Safdarjang Hospital, India, was undertaken between January 1999 and December 2003 to estimate age-related epidemiological, clinical and microbiological characteristics in enteric fever cases. A total of 750 blood-culture-proven cases of enteric fever were studied. The majority of cases occurred in children aged 5-12 years and 24.8% of cases were in children up to 5 years of age. Salmonella serotypes showed an age-related predilection, with paratyphoid fever more common in adults. Classically-described clinical features of the disease were comparable among patients under and above 5 years of age. Hepatomegaly, anaemia and complications in general were more frequent in children up to 5 years of age. The antimicrobial resistance pattern, irrespective of Salmonella serotype, did not reveal a statistically significant difference across age groups for the different antibiotics tested. Multidrug resistance was seen only in Salmonella enterica serotype Typhi but not in S. Paratyphi A isolates. However, resistance to nalidixic acid was comparable in both serotypes. Age-related differences of serotype isolation rates, clinical presentation and associated complications are noteworthy for better case management and policy planning. More epidemiological studies regarding reasons for age-related differential serotype patterns would enable and guide public health strategies to contain enteric fever in endemic locations. PMID:16766005

  9. [Clinical reasoning learning (CRL) sessions. An example of a contextualized teaching activity adapted to clinical stages in medicine].

    PubMed

    Chamberland, M

    1998-12-01

    Clinical reasoning learning (CRL) sessions stem from an educational reform brought about since 1987 at the Faculty of Medicine of the Université de Sherbrooke. This reform is student-centered and based on situated learning and teaching. The objective of the CRL sessions, designed and implemented at the clerkship level, is to help students develop problem solving competencies through the use of effective general clinical reasoning strategies and the development of a highly organized network of specific knowledge. These sessions also strive to offset the difficulties of random clinical exposure and often highly complex cases encountered by trainees during clinical rotations in teaching hospitals. Formed of small groups, sessions recreate a clinical consultation setting focused on a specific priority problem and clinical condition identified among the mandatory objectives of the rotation. Emphasis is placed on early generation and subsequent testing of diagnostic hypothesis, and the active search and gradual disclosure of clinical data using hypothesis-driven inquiry strategy. Students are asked to verbalize their reasoning process under the close supervision of a clinical expert in the field under discussion. Implemented in 5 different clinical disciplines since 1990 in Sherbrooke, assessment data are now available and support the relevance and usefulness of CRL sessions.

  10. Clinical outcomes of video‐assisted thoracic surgery and stereotactic body radiation therapy for early‐stage non‐small cell lung cancer: A meta‐analysis

    PubMed Central

    Ma, Longfei

    2016-01-01

    Background We compared video‐assisted thoracoscopic surgery (VATS) lobectomy and stereotactic body radiation therapy (SABR) to explore clinical outcomes in the treatment of patients with early stage NSCLC. Methods Major medical databases were systematically searched to identify studies on VATS and SBRT published between January 2010 and October 2015. English publications of stage I and II NSCLC with adequate patients and SBRT doses were included. A multivariate random effects model was used to perform meta‐analysis to compare overall survival (OS) and disease‐free survival (DFS) between VATS and SBRT, adjusting for median age and operable patient numbers. Results Thirteen VATS (3436 patients) and 24 SBRT (4433) studies were eligible. The median age and follow‐up duration was 68 years and 42 months for VATS and 74 years and 29.4 months for SBRT patients. After adjusting for the proportion of operable patients and median age, the estimated OS rates at one, two, three, and five years with VATS were 94%, 89%, 84%, and 69% compared with 96%, 94%, 89%, and 82% for SBRT. The estimated DFS rates at one, two, three, and five years with VATS were 97%, 93%, 87%, and 77% compared with 86%, 80%, 73%, and 58% for SBRT. Conclusion Before adjustment, patients treated with SBRT had poorer clinical outcomes compared to those treated with VATS. A substantial difference between median age and operability exists between patients treated with SBRT and VATS. After adjusting for these differences, OS and DFS did not differ significantly between the two techniques. PMID:27385987

  11. Apolipoprotein D takes center stage in the stress response of the aging and degenerative brain☆

    PubMed Central

    Dassati, Sarah; Waldner, Andreas; Schweigreiter, Rüdiger

    2014-01-01

    Apolipoprotein D (ApoD) is an ancient member of the lipocalin family with a high degree of sequence conservation from insects to mammals. It is not structurally related to other major apolipoproteins and has been known as a small, soluble carrier protein of lipophilic molecules that is mostly expressed in neurons and glial cells within the central and peripheral nervous system. Recent data indicate that ApoD not only supplies cells with lipophilic molecules, but also controls the fate of these ligands by modulating their stability and oxidation status. Of particular interest is the binding of ApoD to arachidonic acid and its derivatives, which play a central role in healthy brain function. ApoD has been shown to act as a catalyst in the reduction of peroxidized eicosanoids and to attenuate lipid peroxidation in the brain. Manipulating its expression level in fruit flies and mice has demonstrated that ApoD has a favorable effect on both stress resistance and life span. The APOD gene is the gene that is upregulated the most in the aging human brain. Furthermore, ApoD levels in the nervous system are elevated in a large number of neurologic disorders including Alzheimer's disease, schizophrenia, and stroke. There is increasing evidence for a prominent neuroprotective role of ApoD because of its antioxidant and anti-inflammatory activity. ApoD emerges as an evolutionarily conserved anti-stress protein that is induced by oxidative stress and inflammation and may prove to be an effective therapeutic agent against a variety of neuropathologies, and even against aging. PMID:24612673

  12. Efficacy of one-stage surgical treatment and clinical features in patients with multiple pressure ulcers.

    PubMed

    Han, Hyun Ho; Choi, Eun Jeong; Choi, Jong Yun; Rhie, Jong Won

    2016-03-01

    Treating patients with multiple pressure ulcers is a very challenging task for physicians. However, there are very few reports on treatment protocols for multiple pressure ulcers and treatment outcomes. The authors have consistently treated multiple pressure ulcers in a one-stage operation rather than a staged operation. We evaluated multiple pressure ulcers patients who underwent a one-stage operation from 2007 to 2014. A comparison was made between 20 patients who underwent a one-stage operation on 44 foci and 68 patients with a single focus. Though the results, we could conclude that one-stage operation of multiple pressure ulcers was found to have a shorter recovery period and shorter hospitalization without a significant increase in complications.

  13. Age-stage, two-sex life table of Brontispa longissima (Gestro) (Coleoptera: Hispidae) feeding on four palm plant varieties.

    PubMed

    Jin, Tao; Lin, Yu-Ying; Jin, Qi-An; Wen, Hai-Bo; Peng, Zheng-Qiang

    2012-10-01

    The life history of Brontispa longissima (Gestro) (Coleoptera: Hispidae), reared under laboratory conditions on leaves of coconut (Cocos nucifera L.), royal palm [Roystonea regia (Kunth) O.F.Cook], bottle palm [Hyophorbe lagenicaulis (L. Bailey) H.E.Moore], and fishtail palm (Caryota ochlandra Hance) was analyzed using age-stage, two-sex life table. Means and standard errors of population growth parameters were calculated using the jackknife method. Moreover, survival rate and fecundity data were applied to project the population for revealing the different stage structure. The mean intrinsic rates of population growth when reared on each respective leaf type were 0.032, 0.031, 0.019, and 0.044. Individuals reared on C. nucifera achieved the highest net reproduction rate at 114.5 offspring per female. The mean generation times of B. longissima ranged from 93.2 d (reared on C. ochlandrai) to 161.5 d (reared on H. lagenicaulis). Projections from survival rate and fecundity data indicated that B. longissima populations can row considerably faster on C. ochlandra than on the other three host plants. The results validate the two-stage life history approach taken, providing an essential tool for developing and testing future control strategies. PMID:23068179

  14. Prognosis of Pregnancy-Associated Gastric Cancer: An Age-, Sex-, and Stage-Matched Case-Control Study

    PubMed Central

    Song, Min Jeong; Park, Young Soo; Song, Ho June; Park, Se Jeong; Ahn, Ji Yong; Choi, Kee Don; Lee, Gin Hyug; Jung, Hwoon-Yong; Yook, Jeong Hwan; Kim, Byung Sik

    2016-01-01

    Background/Aims Pregnancy-associated gastric cancer is a rare condition. This case-control study was performed to identify the clinicopathological features and prognostic factors of pregnancy-associated gastric cancer. Methods All consecutive patients who presented to our tertiary referral hospital with pregnancy-associated gastric cancer from 1991 to 2012 were identified. Two age-, sex-, and stage-matched controls for each case were also identified from the records. Clinicopathological, gynecological, and oncological outcomes were recorded. Immunohistochemical staining was performed for estrogen receptor, progesterone receptor, epidermal growth factor receptor, human epidermal growth factor receptor, and E-cadherin. Fluorescence in situ hybridization was performed for fibroblast growth factor receptor 2. Results The median overall survival rates of the pregnancy-associated gastric cancer and control groups were 7.0 months and 15.0 months, respectively (p=0.189). Poor prognostic factors included advanced stage and tumor location in the corpus or the entire stomach but not pregnancy status or loss of E-cadherin. Pregnancy-associated gastric cancer was associated with a longer time from diagnosis to treatment (21 days vs 7 days, p=0.021). The two groups did not differ in the expression of the receptors or E-cadherin. Conclusions The dismal prognosis of pregnancy-associated gastric cancer may related to the tumor stage and location rather than to pregnancy itself. PMID:27114414

  15. Age-Stage, Two-Sex Life Table Characteristics of Aedes albopictus and Aedes Aegypti in Penang Island, Malaysia.

    PubMed

    Maimusa, Hamisu A; Ahmad, Abu Hassan; Kassim, Nur Faeza A; Rahim, Junaid

    2016-03-01

    The life table developmental attributes of laboratory colonies of wild strains of Aedes albopictus and Aedes aegypti were analyzed and compared based on the age-stage, two-sex life table. Findings inclusive in this study are: adult preoviposition periods, total preoviposition period, mean intrinsic rate of increase (r), mean finite rate of increase (λ), net reproductive rates (R0), and mean generation time (T). The total preadult development time was 9.47 days for Ae. albopictus and 8.76 days for Ae. aegypti. The life expectancy was 19.01 days for Ae. albopictus and 19.94 days for Ae. aegypti. Mortality occurred mostly during the adult stage. The mean development time for each stage insignificantly correlated with temperature for Ae. albopictus (r  =  -0.208, P > 0.05) and (r  =  -0.312, P > 0.05) for Ae. aegypti. The population parameters suggest that Ae. albopictus and Ae. aegypti populations are r-strategists characterized by a high r, a large R0, and short T. This present study provides the first report to compare the life parameters of Ae. albopictus and Ae. aegypti strains from Penang island, Malaysia.

  16. Sclerosis in bisphosphonate-related osteonecrosis of the jaws and its correlation with the clinical stages: study of 43 cases.

    PubMed

    Bagan, J V; Cibrian, R M; Lopez, J; Leopoldo-Rodado, M; Carbonell, E; Bagán, L; Utrilla, J; Scully, C

    2015-03-01

    We analysed the degree of sclerosis in the different stages of bisphosphonate-related osteonecrosis of the jaws (BRONJ) and studied the relation between the grade of sclerosis, the clinical symptoms, and the depth of lucency. We compared 43 patients with mandibular BRONJ with a control group of 40 cases with no bony lesions. The presence of sclerotic bone, cortical irregularities, radiolucency, fragmentation or sequestration, periostitis, and narrowing of the mandibular canal were studied from computed tomographic (CT) scans using the program ImageJ 1.47v (National Institute of Health, Bethesda, USA) to measure the radiolucency, width of the cortices, and degree of sclerosis. Patients with BRONJ had more severe sclerosis than controls (p<0.01). There was also a significant difference among the different stages of BRONJ, with the highest values found in stage III (p=0.02). The degree of sclerosis differed according to sex, type of bisphosphonate, and the clinical characteristics such as pain, or suppuration, but not significantly so (p>0.05). We conclude that the degree of sclerosis increases with the clinical stage of BRONJ, and is correlated with the depth of lucency.

  17. Age-related infertility and unexplained infertility: an intricate clinical dilemma.

    PubMed

    Somigliana, Edgardo; Paffoni, Alessio; Busnelli, Andrea; Filippi, Francesca; Pagliardini, Luca; Vigano, Paola; Vercellini, Paolo

    2016-07-01

    A diagnosis of unexplained infertility is commonly made when clinical investigations fail to identify any obvious barriers to conception. As a consequence, unexplained infertility includes several heterogeneous conditions, one being women with age-related infertility. However, the latter represent a peculiar and different situation. Women with age-related infertility may have a different prognosis and may benefit from different treatments. Unfortunately, since fecundity declines with age, discerning between unexplained infertility and age-related infertility becomes more and more difficult as the woman's age increases. In this opinion, with the use of a mathematical model we show that the rate of false positive diagnoses of unexplained infertility increases rapidly after 35 years of age. Using a threshold of 2 years of unfruitful, regular unprotected intercourse, this rate exceeds 50% in women starting pregnancy seeking after 37 years. The scenario is much worse using a threshold of 1 year. From a clinical perspective, extrapolating results obtained in a population of young women with unexplained infertility to those with age-related infertility is not justified. It is noteworthy that, if Assisted Reproductive Technologies are unable to overcome age-related infertility, the older women erroneously labeled with unexplained infertility may receive inappropriate therapies. These may expose women to unjustified risks and waste financial resources. Unfortunately, the available literature about older women is scanty and does not provide valid evidence. Randomized controlled trials aimed at identifying the most suitable clinical management of older women with a normal infertility work-up are pressingly needed. PMID:27060173

  18. Chemotherapy-radiotherapy association in Hodgkin's disease, clinical stages IA, II/sub 2/A: results of a prospective clinical trial with 166 patients. [/sup 60/Co

    SciTech Connect

    Andrieu, J.M.; Montagnon, B.; Asselain, B.; Bayle-Weisgerber, C.; Chastang, C.; Teillet, F.; Bernard, J.

    1980-11-15

    One hundred sixty-six patients with clinical stages IA, II/sub 2/A Hodgkin's disease were treated between April 1972 and December 1976 with three courses of multiagent chemotherapy (methylchlorethamine, vincristine, procarbazine, prednisone) followed by mantle irradiation - excluding mediastinum for those with initial upper cervical presentation and absence of mediastinal involvement - or inverted Y radiotherapy. With a follow-up of 12 to 84 months, the overall survival is 93.5% and the overall relapse-free survival 89.9%. With chemotherapy-radiotherapy sequence, staging laparotomy is not indicated. Results and side effects of this treatment strategy are compared with those of other treatment policies.

  19. Analysis of the Clinical and Histopathological Patterns of 100 Consecutive Cases of Primary Cutaneous Melanoma and Correlation with Staging

    PubMed Central

    Nam, Kyung Wook; Bae, Seong Hwan; Song, Kyung Ho; Kim, Hoon Soo; Choi, Young Jin

    2015-01-01

    Background This study analyzed 100 consecutive patients with primary cutaneous melanoma over the course of 13 years to determine whether epidemiological differences correspond to different stages of the disease. We also investigated whether epidemiological characteristics affected the survival rate. Our results were compared with those of selected descriptive studies of melanoma in other East Asian populations, in order to determine whether cutaneous melanoma patterns are similar in East Asian populations. Methods The patients' medical records were reviewed retrospectively, and we analyzed the relationship of epidemiological characteristics to staging and survival rate. Additionally, papers from Hong Kong and Japan describing these phenomena in East Asian populations were subjected to a statistical comparison. Results The ratio of males to females was 1:1.8, and the foot was the most frequent tumor site (49%). Acral lentiginous melanoma occurred most frequently (55%). Nodular melanoma was associated with a higher stage. Stage III-IV tumors with Clark levels of IV-V were significantly associated with a low survival rate. A statistical analysis of comparable papers reported in Hong Kong and Japan showed similar results with regard to age, tumor location, and histopathological subtypes. Conclusions This study provides the first full epidemiological description of 100 consecutive cases of primary cutaneous melanoma in Korea, with results similar to those observed in other East Asian populations. Corresponding to previous findings, nodular melanoma tended to occur at a higher stage than other types, and tumors with high Clark levels and high stages showed a lower survival rate. PMID:26618123

  20. Serum protein profiling using an aptamer array predicts clinical outcomes of stage IIA colon cancer: A leave-one-out crossvalidation

    PubMed Central

    Huh, Jung Wook; Kim, Sung Chun; Sohn, Insuk; Jung, Sin-Ho; Kim, Hee Cheol

    2016-01-01

    Background In this study, we established and validated a model for predicting prognosis of stage IIA colon cancer patients based on expression profiles of aptamers in serum. Methods Bloods samples were collected from 227 consecutive patients with pathologic T3N0M0 (stage IIA) colon cancer. We incubated 1,149 serum molecule-binding aptamer pools of clinical significance with serum from patients to obtain aptamers bound to serum molecules, which were then amplified and marked. Oligonucleotide arrays were constructed with the base sequences of the 1,149 aptamers, and the marked products identified above were reacted with one another to produce profiles of the aptamers bound to serum molecules. These profiles were organized into low- and high-risk groups of colon cancer patients based on clinical information for the serum samples. Cox proportional hazards model and leave-one-out cross-validation (LOOCV) were used to evaluate predictive performance. Results During a median follow-up period of 5 years, 29 of the 227 patients (11.9%) experienced recurrence. There were 212 patients (93.4%) in the low-risk group and 15 patients (6.6%) in the high-risk group in our aptamer prognosis model. Postoperative recurrence significantly correlated with age and aptamer risk stratification (p = 0.046 and p = 0.001, respectively). In multivariate analysis, aptamer risk stratification (p < 0.001) was an independent predictor of recurrence. Disease-free survival curves calculated according to aptamer risk level predicted through a LOOCV procedure and age showed significant differences (p < 0.001 from permutations). Conclusion Aptamer risk stratification can be a valuable prognostic factor in stage II colon cancer patients. PMID:26908450

  1. Does age at onset have clinical significance in older adults with bipolar disorder?

    PubMed Central

    Chu, David; Gildengers, Ariel G.; Houck, Patricia R.; Anderson, Stewart J.; Mulsant, Benoit H.; Reynolds, Charles F.; Kupfer, David J.

    2011-01-01

    Objective While age at onset may be useful in explaining some of the heterogeneity of bipolar disorder (BD) in large, mixed age groups, investigations to date have found few meaningful clinical differences between early versus late age at onset in older adults with BD. Methods Data were collected from sixty-one subjects aged 60 years and older, mean (SD) age 67.6 (7.0), with BD I (75%) and II (25%). Subjects were grouped by early (<40 years; n=43) versus late (≥40 years; n=18) age at onset. Early versus late onset groups were compared on psychiatric comorbidity, medical burden, and percentage of days well during study participation. Results Except for family history of major psychiatric illnesses, there were no differences between the groups on demographic or clinical variables. Patients with early and late onset experienced similar percentages of days well; however, those with early onset had slightly more percentage of days depressed than those with late onset (22% versus 13%) Conclusion Distinguishing older adults with BD by early or late age at onset has limited clinical usefulness. PMID:20082348

  2. Clinical trials and late-stage drug development for Alzheimer's disease: an appraisal from 1984 to 2014.

    PubMed

    Schneider, L S; Mangialasche, F; Andreasen, N; Feldman, H; Giacobini, E; Jones, R; Mantua, V; Mecocci, P; Pani, L; Winblad, B; Kivipelto, M

    2014-03-01

    The modern era of drug development for Alzheimer's disease began with the proposal of the cholinergic hypothesis of memory impairment and the 1984 research criteria for Alzheimer's disease. Since then, despite the evaluation of numerous potential treatments in clinical trials, only four cholinesterase inhibitors and memantine have shown sufficient safety and efficacy to allow marketing approval at an international level. Although this is probably because the other drugs tested were ineffective, inadequate clinical development methods have also been blamed for the failures. Here, we review the development of treatments for Alzheimer's disease during the past 30 years, considering the drugs, potential targets, late-stage clinical trials, development methods, emerging use of biomarkers and evolution of regulatory considerations in order to summarize advances and anticipate future developments. We have considered late-stage Alzheimer's disease drug development from 1984 to 2013, including individual clinical trials, systematic and qualitative reviews, meta-analyses, methods, commentaries, position papers and guidelines. We then review the evolution of drugs in late clinical development, methods, biomarkers and regulatory issues. Although a range of small molecules and biological products against many targets have been investigated in clinical trials, the predominant drug targets have been the cholinergic system and the amyloid cascade. Trial methods have evolved incrementally: inclusion criteria have largely remained focused on mild-to-moderate Alzheimer's disease criteria, recently extending to early or prodromal Alzheimer disease or 'mild cognitive impairment due to Alzheimer's disease', for drugs considered to be disease modifying. The duration of trials has remained at 6-12 months for drugs intended to improve symptoms; 18- to 24-month trials have been established for drugs expected to attenuate clinical course. Cognitive performance, activities of daily living

  3. Clinical trials and late-stage drug development for Alzheimer’s disease: an appraisal from 1984 to 2014

    PubMed Central

    Schneider, Lon S.; Mangialasche, Francesca; Andreasen, Niels; Feldman, Howard; Giacobini, Ezio; Jones, Roy; Mantua, Valentina; Mecocci, Patrizia; Pani, Luca; Winblad, Bengt; Kivipelto, Miia

    2014-01-01

    The modern era of drug development for Alzheimer’s disease began with the proposal of the cholinergic hypothesis of memory impairment and the 1984 research criteria for Alzheimer’s disease. Since then, despite the evaluation of numerous potential treatments in clinical trials, only four cholinesterase inhibitors and memantine have shown sufficient safety and efficacy to allow marketing approval at an international level. Although this is probably because the other drugs tested were ineffective, inadequate clinical development methods have also been blamed for the failures. Here we review the development of treatments for Alzheimer’s disease during the past 30 years, considering the drugs, potential targets, late-stage clinical trials, development methods, emerging use of biomarkers and evolution of regulatory considerations in order to summarize advances and anticipate future developments. We have considered late-stage Alzheimer’s disease drug development from 1984 to 2013, including individual clinical trials, systematic and qualitative reviews, meta-analyses, methods, commentaries, position papers and guidelines. We then review the evolution of drugs in late clinical development, methods, biomarkers and regulatory issues. Although a range of small molecules and biological products against many targets have been investigated in clinical trials, the predominant drug targets have been the cholinergic system and the amyloid cascade. Trial methods have evolved incrementally: inclusion criteria have largely remained focused on mild to moderate Alzheimer’s disease criteria, recently extending to early or prodromal Alzheimer disease or ‘mild cognitive impairment due to Alzheimer’s disease’, for drugs considered to be disease modifying. The duration of trials has remained at 6 to 12 months for drugs intended to improve symptoms; 18- to 24-month trials have been established for drugs expected to attenuate clinical course. Cognitive performance, activities

  4. Parenting clinically anxious versus healthy control children aged 4-12 years.

    PubMed

    van der Sluis, C M; van Steensel, F J A; Bögels, S M

    2015-05-01

    This study investigated whether parenting behaviors differed between parents of 68 clinically anxious children and 106 healthy control children aged 4-12 years. The effects of parent gender, child gender and child age on parenting were explored. Mothers and fathers completed a questionnaire to assess parenting behaviors in for children hypothetically anxious situations. Results showed that parents of clinically anxious children reported more anxiety-enhancing parenting (reinforcement of dependency and punishment) as well as more positive parenting (positive reinforcement). For the clinical sample, fathers reported using more modeling/reassurance than mothers, and parents reported using more force with their 4-7-year-olds than with their 8-12-year-olds. No interaction effects were found for child gender with child anxiety status on parenting. Results indicate that for intervention, it is important to measure parenting behaviors, and to take into account father and mother differences and the age of the child. PMID:25819172

  5. Parenting clinically anxious versus healthy control children aged 4-12 years.

    PubMed

    van der Sluis, C M; van Steensel, F J A; Bögels, S M

    2015-05-01

    This study investigated whether parenting behaviors differed between parents of 68 clinically anxious children and 106 healthy control children aged 4-12 years. The effects of parent gender, child gender and child age on parenting were explored. Mothers and fathers completed a questionnaire to assess parenting behaviors in for children hypothetically anxious situations. Results showed that parents of clinically anxious children reported more anxiety-enhancing parenting (reinforcement of dependency and punishment) as well as more positive parenting (positive reinforcement). For the clinical sample, fathers reported using more modeling/reassurance than mothers, and parents reported using more force with their 4-7-year-olds than with their 8-12-year-olds. No interaction effects were found for child gender with child anxiety status on parenting. Results indicate that for intervention, it is important to measure parenting behaviors, and to take into account father and mother differences and the age of the child.

  6. Echinococcus granulosus-specific T-cell lines derived from patients at various clinical stages of cystic echinococcosis.

    PubMed

    Riganò, R; Buttari, B; De Falco, E; Profumo, E; Ortona, E; Margutti, P; Scottà, C; Teggi, A; Siracusano, A

    2004-01-01

    To investigate the role of T lymphocytes in the immune response to Echinococcus granulosus, using sheep hydatid fluid (SHF) and antigen B (AgB), we generated T-cell lines from patients with active, transitional and inactive hydatid cysts. We established 16 T-cell lines, eight specific to SHF and eight specific to AgB. At surface phenotyping 88-98% of cells displayed the helper/inducer CD4 antigen. In all patients, at all clinical stages of hydatid cyst disease, T-cell stimulation with SHF and AgB invariably amplified a large number of almost identical Vbeta subfamily fragments. Irrespective of antigen-specificity, the two cell lines from the patient with an inactive cyst had a Th1 profile, because they exclusively expressed and produced IFN-gamma. Conversely, the T-cell lines derived from the seven patients with active and transitional hydatid cysts had mixed Th1/Th2 and Th0 clones. The functional characteristics of the 16 T-cell lines differed markedly in the various clinical stages of cystic echinococcosis, thus providing new in vitro evidence that Th1 lymphocytes contribute decisively to the inactive stage of hydatid disease, Th2 lymphocytes in the active and transitional stages. The parasite-specific T-cell lines, especially the two Th1 lines from the patient with an inactive cyst, may help identify Th1 protective epitopes on SHF and AgB.

  7. The Effects of Comorbidity and Age on RTOG Study Enrollment in Stage III Non-Small Cell Lung Cancer Patients Who Are Eligible for RTOG Studies

    SciTech Connect

    Firat, Selim; Byhardt, Roger W.; Gore, Elizabeth

    2010-12-01

    Purpose: To determine the influence of measured comorbidity in Radiation Therapy Oncology Group (RTOG) combined modality therapy (CMT) study enrollment in Stage III non-small cell lung cancer (NSCLC). Methods and Materials: One hundred and seventy-one patients with a Karnofsky Performance Score {>=}70 and clinical Stage III NSCLC were analyzed retrospectively for comorbidity, RTOG study eligibility, and enrollment at initial consultation. Effect of comorbidity scores (Cumulative Illness Rating Scale) were tested on patient selection for CMT, RTOG enrollment, and overall survival. Results: Comorbidity (Grade 4; p < 0.005) and use of radiation only (p {<=} 0.001) were associated with inferior survival independent of other factors. Patient selection for CMT was affected by age ({>=}70, p < 0.001), comorbidity (severity index [SI]> 2, p = 0.001), and weight loss (>5%, p = 0.001). Thirty-three patients (19%) were enrolled in a CMT RTOG study (Group 1). Forty-nine patients (29%) were eligible but not enrolled (Group 2), and 57 (33%) were ineligible (Group 3). The most common ineligibility reasons were weight loss (67%) and comorbidity in the exclusion criteria of the RTOG studies (63%). Group 1 patients were the youngest (p = 0.02), with the lowest comorbidity scores (p < 0.001) and SI (p < 0.001) compared with Groups 2 and 3. Group 3 patients were the oldest with the most unfavorable comorbidity profile. Comorbidity scores (SI >2; p = 0.006) and age ({>=}70; p = 0.05) were independent factors influencing RTOG study enrollment in patients meeting study eligibility requirements (Groups 1 and 2). Conclusions: Comorbidity scales could be useful in stratification of patients in advanced lung cancer trials and interpretation of results particularly regarding the elderly population.

  8. Work-family conflict among members of full-time dual-earner couples: an examination of family life stage, gender, and age.

    PubMed

    Allen, Tammy D; Finkelstein, Lisa M

    2014-07-01

    Based on cross-sectional data from the 2008 National Study of the Changing Workforce, this study investigates relationships between gender, age, and work-family conflict across 6 family life stages. Participants were 690 married/partnered employees who worked 35 or more hours a week. Results indicated a small but negative relationship between age and work-family conflict. Work-family conflict was also associated with family stage, with the least amount of conflict occurring during the empty nest stage and the most occurring when the youngest child in the home was 5 years of age or younger. Gender differences were also observed. Specifically, men reported more work interference with family than did women when the youngest child in the home was a teen. Women overall reported more family interference with work than did men. Results concerning age and gender revealed a different pattern demonstrating that family stage is not simply a proxy for age. Age had a main effect on work-to-family conflict that was monotonic in nature and on family to-work conflict that was linear in nature. In conclusion, the results indicate gender, age, and family stage each uniquely relate to work-family conflict.

  9. [The MRT of scaphoid pseudarthrosis with Gd-DTPA. Its staging and clinical correlation].

    PubMed

    Vogl, T J; Beutel, F; Wilhelm, K; Tempka, A; Schedel, H; Haas, R; Felix, R

    1994-11-01

    During a period of two years, 134 patients with pseudo-arthrosis of the scaphoid were examined by conventional radiography and by MRI in the course of a prospective study. The aim of the study was to define radiological staging using contrast enhanced MRI in order to improve the prognostic criteria. All MRI examinations were carried out with a 1.5 tesla scanner (SP63) using a surface coil and T1 weighted spin echo sequences in sagittal and frontal projection and frontal FLASH T2 sequences and axial spin echo T2 sequences. The T1 weighted SE sequences in frontal projection were carried out before and after iv contrast (0.1 mmol Gd-DTPA/kg KG). All sequences were compared with conventional radiographs and the operative findings. Eight patients in stage 0 showed high signal intensity of both fragments in T1 weighted SE sequences and at surgery there was good vascularisation. In 22 cases there was reduced signal intensity in at least one fragment (stage I). 45 patients with scaphoid pseudo-arthrosis showed complete signal loss but marked contrast uptake with still vital nuclei at surgery (stage II). In 22 patients, there was no increase in signal intensity after contrast and complete loss of vitality of the fragments at surgery. Staging was not possible in 37 patients because of previous operative intervention. The use of contrast enhanced MRI provides additional information compared with conventional radiography or plain MRI. PMID:7948999

  10. Age-dependent role for Ras-GRF1 in the late stages of adult neurogenesis in the dentate gyrus.

    PubMed

    Darcy, Michael J; Trouche, Stéphanie; Jin, Shan-Xue; Feig, Larry A

    2014-03-01

    The dentate gyrus of the hippocampus plays a pivotal role in pattern separation, a process required for the behavioral task of contextual discrimination. One unique feature of the dentate gyrus that contributes to pattern separation is adult neurogenesis, where newly born neurons play a distinct role in neuronal circuitry. Moreover,the function of neurogenesis in this brain region differs in adolescent and adult mice. The signaling mechanisms that differentially regulate the distinct steps of adult neurogenesis in adolescence and adulthood remain poorly understood. We used mice lacking RASGRF1(GRF1), a calcium-dependent exchange factor that regulates synaptic plasticity and participates in contextual discrimination performed by mice, to test whether GRF1 plays a role in adult neurogenesis.We show Grf1 knockout mice begin to display a defect in neurogenesis at the onset of adulthood (~2 months of age), when wild-type mice first acquire the ability to distinguish between closely related contexts. At this age, young hippocampal neurons in Grf1 knockout mice display severely reduced dendritic arborization. By 3 months of age, new neuron survival is also impaired. BrdU labeling of new neurons in 2-month-old Grf1 knockout mice shows they begin to display reduced survival between 2 and 3 weeks after birth, just as new neurons begin to develop complex dendritic morphology and transition into using glutamatergic excitatory input. Interestingly, GRF1 expression appears in new neurons at the developmental stage when GRF1 loss begins to effect neuronal function. In addition, we induced a similar loss of new hippocampal neurons by knocking down expression of GRF1 solely in new neurons by injecting retrovirus that express shRNA against GRF1 into the dentate gyrus. Together, these findings show that GRF1 expressed in new neurons promotes late stages of adult neurogenesis. Overall our findings show GRF1 to be an age-dependent regulator of adult hippocampal neurogenesis, which

  11. Dental age assessment of adolescents and emerging adults in United Kingdom Caucasians using censored data for stage H of third molar roots.

    PubMed

    Boonpitaksathit, Teelana; Hunt, Nigel; Roberts, Graham J; Petrie, Aviva; Lucas, Victoria S

    2011-10-01

    The root of the third permanent molar is the only dental structure that continues development after completion of growth of the second permanent molar. It is claimed that the lack of a clearly defined end point for completion of growth of the third permanent molar means that this tooth cannot be used for dental age assessment. The aim of this study was to estimate the mean age of attainment of the four stages (E, F, G, and H) of root development of the third molar. The way in which the end point of completion of stage H can be identified is described. A total of 1223 dental panoramic tomographs (DPTs) available in the archives of the Eastman Dental Hospital, London, were used for this study. The ages of the subjects ranged from 12.6 to 24.9 years with 63 per cent of the sample being female. Demirjan's tooth development stages (TDSs), for the first and second molars, were applied to the third molars by a single examiner. For each of stages E, F, and G and for stage H censored data, the mean ages of the males and females were compared, separately within each tooth morphology type using the two sample t-test (P < 0.01). The same test was used to compare the mean ages of the upper and lower third molars on each side, separately for each gender. The mean age of attainment and the 99 per cent confidence interval (CI) for each TDS were calculated for each third molar. The final stage H data were appropriately censored to exclude data above the age of completion of root growth. The results showed that, for each gender, the age in years at which individuals attained each of the four TDSs was approximately normally distributed. The mean age for appropriately censored data was always lower than the corresponding mean age of the inappropriately censored data for stage H (male UR8 19.57, UL8 19.53, LL8 19.91, and LR8 20.02 and female UR8 20.08, UL8 20.13, LL8 20.78, and LR8 20.70). This inappropriately censored data overestimated the mean age for stage H. The appropriately

  12. Visible aging signs as risk markers for ischemic heart disease: Epidemiology, pathogenesis and clinical implications.

    PubMed

    Christoffersen, Mette; Tybjærg-Hansen, Anne

    2016-01-01

    Association of common aging signs (i.e., male pattern baldness, hair graying, and facial wrinkles) as well as other age-related appearance factors (i.e., arcus corneae, xanthelasmata, and earlobe crease) with increased risk of ischemic heart disease was initially described in anecdotal reports from clinicians observing trends in the physical appearance of patients with ischemic heart disease. Following these early observations numerous epidemiological studies have reported these associations. Since the prevalences of both visible aging signs and ischemic heart disease have a strong correlation with increasing age, it has been extensively debated whether the observed associations could be entirely explained by a common association with age. Furthermore, the etiologies of the visible aging signs are rarely fully understood, and pathophysiological explanations for these associations remain controversial, and are mostly speculative. As a consequence of inconsistent findings and lack of mechanistic explanations for the observed associations with ischemic heart disease, consensus on the clinical importance of these visible aging signs has been lacking. The aim of this review is for each of the visible aging signs to (i) review the etiology, (ii) to discuss the current epidemiological evidence for an association with risk of ischemic heart disease, and (iii) to present possible pathophysiological explanations for these associations. Finally this review discusses the potential clinical implications of these findings.

  13. Critical action research applied in clinical placement development in aged care facilities.

    PubMed

    Xiao, Lily D; Kelton, Moira; Paterson, Jan

    2012-12-01

    The aim of this study was to develop quality clinical placements in residential aged care facilities for undergraduate nursing students undertaking their nursing practicum topics. The proportion of people aged over 65 years is expected to increase steadily from 13% in 2006 to 26% of the total population in Australia in 2051. However, when demand is increasing for a nursing workforce competent in the care of older people, studies have shown that nursing students generally lack interest in working with older people. The lack of exposure of nursing students to quality clinical placements is one of the key factors contributing to this situation. Critical action research built on a partnership between an Australian university and five aged care organisations was utilised. A theoretical framework informed by Habermas' communicative action theory was utilised to guide the action research. Multiple research activities were used to support collaborative critical reflection and inform actions throughout the action research. Clinical placements in eight residential aged care facilities were developed to support 179 nursing students across three year-levels to complete their practicum topics. Findings were presented in three categories described as structures developed to govern clinical placement, learning and teaching in residential aged care facilities. PMID:23134277

  14. Regular physical activity is associated with improved small artery distensibility in young to middle-age stage 1 hypertensives.

    PubMed

    Saladini, Francesca; Benetti, Elisabetta; Mos, Lucio; Mazzer, Adriano; Casiglia, Edoardo; Palatini, Paolo

    2014-12-01

    The aim of the present study was to investigate the association of physical activity with small artery elasticity in the early stage of hypertension. We examined 366 young-to-middle-age stage 1 hypertensives (mean blood pressure 145.6±10.3/92.5±5.8 mmHg), divided into two categories of physical activity, sedentary (n=264) and non-sedentary (n=102) subjects. The augmentation index was measured using the Specaway DAT System. Small artery compliance (C2) was measured by applanation tonometry, at the radial artery, with an HDI CR2000 device. After 6 years of follow-up, arterial distensibility assessment was repeated in 151 subjects. Heart rate was lower in active than in sedentary subjects (71.2±8.9 vs 76.6±9.7 bpm, p<0.001). After adjusting for age, sex, heart rate, smoking, and blood pressure, C2 was higher (8.0±2.6 vs 6.4±3.0 ml/mmHg × 100, p=0.008) in non-sedentary than in sedentary patients. The augmentation index was smaller in the former (8.8±20.1 vs 16.8±26.5%, p=0.044) but the difference lost statistical significance after further adjustment for blood pressure. After 6 years, C2 was still higher in the non-sedentary than sedentary subjects. In addition, an improvement in the augmentation index accompanied by a decline in total peripheral resistance was found in the former. These data show that regular physical activity is associated with improved small artery elasticity in the early phase of hypertension. This association persists over time and is independent of blood pressure and heart rate.

  15. CD4+ T-lymphocyte telomere length is related to fibrosis stage, clinical outcome and treatment response in chronic hepatitis C virus infection

    PubMed Central

    Hoare, Matthew; Gelson, William T.H.; Das, Abhi; Fletcher, Jean M.; Davies, Susan E.; Curran, Martin D.; Vowler, Sarah L.; Maini, Mala K.; Akbar, Arne N.; Alexander, Graeme J.M.

    2010-01-01

    Background & Aims Increasing age is associated with impaired immune function and in chronic HCV infection specifically, with progressive fibrosis, liver failure, HCC and impaired responses to antiviral therapy. T-lymphocyte telomere length declines with age. We hypothesised that shorter T-lymphocyte telomere length would be associated with poor clinical outcome in HCV infection. Methods Circulating T-lymphocyte telomere length, an objective measure of immune senescence, was measured by flow-FISH in 135 HCV-RNA-positive, treatment-naïve patients and 41 healthy controls in relation to clinical outcome. Results Shorter CD4+CD45RO+ T-lymphocyte telomeres were associated with severe fibrosis (p = 0.003), independent of male sex (p = 0.04), CMV positivity (p = 0.003), previous HBV infection (p = 0.007), and age (p = ns) in viraemic patients compared to controls. There were inverse correlations between CD4+CD45RO+ telomere length and fibrosis stage (p <0.001), portal tract inflammatory grade (p = 0.035), prothrombin time (p <0.001) and bilirubin (p = 0.001). One hundred and twenty-four viraemic individuals were followed prospectively to a composite endpoint of death, hepatic decompensation or HCC. Independent of age, those with shorter CD4+CD45RO+ telomeres were less likely to be complication free after 2-years than those with longer telomeres (86% versus 96%, p = 0.009) with an age-adjusted hazard ratio of 0.93 (0.90–0.96). In addition, CD4+CD45RO+ telomere length predicted successful antiviral therapy (p = 0.001) independent of other factors. Conclusions CD4+ T-lymphocyte telomere length, independent of age, was related to inflammatory grade, fibrosis stage, laboratory indices of severity, subsequent hepatic decompensation and treatment outcome in patients with chronic HCV infection. PMID:20462651

  16. Frameworks for Proof-of-Concept Clinical Trials of Interventions That Target Fundamental Aging Processes

    PubMed Central

    Justice, Jamie; Miller, Jordan D.; Newman, John C.; Hashmi, Shahrukh K.; Halter, Jeffrey; Austad, Steve N.; Barzilai, Nir

    2016-01-01

    Therapies targeted at fundamental processes of aging may hold great promise for enhancing the health of a wide population by delaying or preventing a range of age-related diseases and conditions—a concept dubbed the “geroscience hypothesis.” Early, proof-of-concept clinical trials will be a key step in the translation of therapies emerging from model organism and preclinical studies into clinical practice. This article summarizes the outcomes of an international meeting partly funded through the NIH R24 Geroscience Network, whose purpose was to generate concepts and frameworks for early, proof-of-concept clinical trials for therapeutic interventions that target fundamental processes of aging. The goals of proof-of-concept trials include generating preliminary signals of efficacy in an aging-related disease or outcome that will reduce the risk of conducting larger trials, contributing data and biological samples to support larger-scale research by strategic networks, and furthering a dialogue with regulatory agencies on appropriate registration indications. We describe three frameworks for proof-of-concept trials that target age-related chronic diseases, geriatric syndromes, or resilience to stressors. We propose strategic infrastructure and shared resources that could accelerate development of therapies that target fundamental aging processes. PMID:27535966

  17. Correlative 99mTc-Labeled Tropane Derivative Single Photon Emission Computer Tomography and Clinical Assessment in the Staging of Parkinson Disease

    PubMed Central

    Shinto, Ajit S.; Antony, Joppy; Kamaleshwaran, Koramadai; Vijayan, Krishnan; Selvan, Arul; Korde, Aruna; Kameshwaran, Mythili; Samuel, Grace

    2014-01-01

    Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by a selective loss of dopamine in the striatum. Problems remain in the accurate diagnosis of PD. The diagnosis of idiopathic PD is based on the interpretation of clinical signs and symptoms could be incorrect at the time of initial presentation. In vivo imaging of the dopaminergic system has the potential to improve the diagnosis of PD in its early stages. The imaging of dopamine transporter (DAT) with 99mTc-labeled tropane derivative (TRODAT-1) single photon emission computer tomography/computer tomography (SPECT/CT) has been proposed to be a valuable and feasible means of assessment of the integrity of dopamine neurons. The purpose of this study was to investigate the potential usefulness of 99mTc-TRODAT-1 imaging in the evaluation of patients with PD and classify into different stages of the disease. SPECT imaging with 99mTc-TRODAT-1 was conducted in 16 consecutive PD patients (9 men; 7 women) and in 6 age matched healthy volunteers (4 men; 2 women). The images were obtained 3 h after the intra-venous injection of the tracer. Specific uptake in the striatum and its sub-regions, including the putamen and caudate nucleus was calculated and the ratios of specific striatal binding to nonspecific occipital binding were calculated. ANOVA with Dunnett C post-hoc analysis was conducted using SPSS 20. A stepwise reduction in specific striatal uptake of 99mTc-TRODAT-1 with increasing disease severity between healthy control versus Stage I versus Stage II versus Stage III was found in PD patients (i.e., 3.77 vs. 2.56 vs. 1.57 vs. 0.63, P < 0.05). The changes were magnified by measurement of specific putaminal uptake (1.43 vs. 0.79 vs. 0.54 vs. 0.19, P < 0.05) and specific caudate uptake (1.90 vs. 1.47 vs. 0.73 vs. 0.27, P < 0.05). No remarkable adverse reactions were found in either healthy volunteers or PD patients during or after imaging. 99mTc-TRODAT-1 is accurate and widely available

  18. Correlative (99m)tc-labeled tropane derivative single photon emission computer tomography and clinical assessment in the staging of Parkinson disease.

    PubMed

    Shinto, Ajit S; Antony, Joppy; Kamaleshwaran, Koramadai; Vijayan, Krishnan; Selvan, Arul; Korde, Aruna; Kameshwaran, Mythili; Samuel, Grace

    2014-09-01

    Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by a selective loss of dopamine in the striatum. Problems remain in the accurate diagnosis of PD. The diagnosis of idiopathic PD is based on the interpretation of clinical signs and symptoms could be incorrect at the time of initial presentation. In vivo imaging of the dopaminergic system has the potential to improve the diagnosis of PD in its early stages. The imaging of dopamine transporter (DAT) with (99m)Tc-labeled tropane derivative (TRODAT-1) single photon emission computer tomography/computer tomography (SPECT/CT) has been proposed to be a valuable and feasible means of assessment of the integrity of dopamine neurons. The purpose of this study was to investigate the potential usefulness of (99m)Tc-TRODAT-1 imaging in the evaluation of patients with PD and classify into different stages of the disease. SPECT imaging with (99m)Tc-TRODAT-1 was conducted in 16 consecutive PD patients (9 men; 7 women) and in 6 age matched healthy volunteers (4 men; 2 women). The images were obtained 3 h after the intra-venous injection of the tracer. Specific uptake in the striatum and its sub-regions, including the putamen and caudate nucleus was calculated and the ratios of specific striatal binding to nonspecific occipital binding were calculated. ANOVA with Dunnett C post-hoc analysis was conducted using SPSS 20. A stepwise reduction in specific striatal uptake of (99m)Tc-TRODAT-1 with increasing disease severity between healthy control versus Stage I versus Stage II versus Stage III was found in PD patients (i.e., 3.77 vs. 2.56 vs. 1.57 vs. 0.63, P < 0.05). The changes were magnified by measurement of specific putaminal uptake (1.43 vs. 0.79 vs. 0.54 vs. 0.19, P < 0.05) and specific caudate uptake (1.90 vs. 1.47 vs. 0.73 vs. 0.27, P < 0.05). No remarkable adverse reactions were found in either healthy volunteers or PD patients during or after imaging. (99m)Tc-TRODAT-1 is accurate and widely

  19. Ages and Stages: Teen

    MedlinePlus

    ... Featured Article Meningococcal Disease: Information for Teens and College Students Certain teens and young adults have a higher ... Managing Money Meningococcal Disease: Information for Teens and College Students Mental Health and Teens: Watch for Danger Signs ...

  20. Palynology, geochemistry and Re-Os age of the Lower-Middle Pennsylvanian stage boundary, central Appalachian basin, USA

    NASA Astrophysics Data System (ADS)

    Geboy, N.; Tripathy, G. R.; Ruppert, L. F.; Eble, C. F.; Blake, B. M.; Hannah, J. L.; Stein, H. J.

    2014-12-01

    Wales and Germany and therefore has implications across the Carboniferous Euramerican Belt. Further, the Betsie has been interpreted to represent the Lower-Middle Pennsylvanian stage boundary in North America, making this directly measured age an important marker not only within the CAB but also for refinement of the Carboniferous timescale.

  1. Relation between clinical findings and progression of cerebral cortical pathology in MM1-type sporadic Creutzfeldt-Jakob disease: proposed staging of cerebral cortical pathology.

    PubMed

    Iwasaki, Yasushi; Tatsumi, Shinsui; Mimuro, Maya; Kitamoto, Tetsuyuki; Hashizume, Yoshio; Yoshida, Mari

    2014-06-15

    In our pathologic observation of the cerebral cortex including the neocortex, hippocampus, and limbic cortex in 43 Japanese patients with MM1-type sporadic Creutzfeldt-Jakob disease, the earliest pathologic finding was spongiform change and next was gliosis. Subsequently, neuropil rarefaction appeared, followed by neuron loss. On the basis of these observations, we propose the following cortical pathologic staging: Stage I, spongiform change; Stage II, hypertrophic astrocytosis; Stage III, neuropil rarefaction; Stage IV, neuron loss; Stage V, status spongiosus; and Stage VI, large cavity formation. We also suggest a more simple staging classification: Stages I and II, mild; Stages III and IV, moderate; and Stages V and VI, severe involvement. Based on statistical analysis of the cases, strong correlation coefficients were obtained between the neocortical and limbic pathologic stage and both total disease duration and brain weight. We estimated that the first observation times of cortical hyperintensity on diffusion-weighted images of magnetic resonance imaging, myoclonus, and periodic sharp wave complexes on the electroencephalogram approximately correspond to the early phase of Stage II of the neocortex. The time to reach the akinetic mutism state approximately corresponds to the middle phase of Stage II of the neocortex. Therefore, we think that approximate clinical manifestations at death, total disease duration, and brain weight can be estimated according to the pathologic stage of the neocortex or limbic cortex. Panencephalopathic-type pathology appeared approximately 12 months after disease onset, and this time approximately corresponds to the middle phase of Stage III of the neocortex.

  2. Differential Profiles of Risk of Self-Harm among Clinically Referred Primary School Aged Children

    ERIC Educational Resources Information Center

    Angelkovska, Anne; Houghton, Stephen; Hopkins, Sarah

    2012-01-01

    Risk of self-harm among clinic referred children aged 6- to 12-years-old was investigated using the recently developed Self-Harm Risk Assessment for Children (SHRAC) instrument which comprises six factors: Affect traits; verbalizing of self-harm; socialization; dissociation; self-directing; and self-appraisal. The SHRAC was completed by the…

  3. Effects of Age Expectations on Oncology Social Workers' Clinical Judgment

    ERIC Educational Resources Information Center

    Conlon, Annemarie; Choi, Namkee G.

    2014-01-01

    Objective: This study examined the influence of oncology social workers' expectations regarding aging (ERA) and ERA with cancer (ERAC) on their clinical judgment. Methods: Oncology social workers (N = 322) were randomly assigned to one of four vignettes describing a patient with lung cancer. The vignettes were identical except for the…

  4. Evaluation of Nontraditional Age Learners' Experiences in Internet-Based Clinical Social Work Courses

    ERIC Educational Resources Information Center

    Swanke, Jayme; Zeman, Laura Dreuth

    2015-01-01

    This study involves an evaluation of online learners' experiences with two Internet-based clinical social work courses. The evaluation sought to discover whether there were differences in learning between traditional (under 25 years old) and nontraditional age learners (25 years and over) who completed the asynchronous online course. The study…

  5. The comparison between measurement of open apices of third molars and Demirjian stages to test chronological age of over 18 year olds in living subjects.

    PubMed

    Cameriere, R; Ferrante, L; De Angelis, D; Scarpino, F; Galli, F

    2008-11-01

    This paper concerns a method for assessing adult age based on the relationship between age and the third molar maturity index (I(3M)), which is related to the measurement of the open apices of the third molar. Furthermore, this method was compared to those based on Demirjian's stages G and H. The sample consisted of 906 Caucasian individuals aged between 14 and 23 years (53.6% females and 46.4% males). Orthopantomographs were analyzed by two observers and calibrated by means of the concordance correlation coefficient for the reproducibility of the third molar maturity index (I(3M)) and kappa statistics for reproducibility of the Demirjian stages. Probabilities for an individual to be older than 18 years of age (adult age) were derived using the measurements of the third molar maturity index (I(3M)). These results were exploited to set out a threshold value to assign an individual to juvenile or adult age. A cutoff value of I(3M) = 0.08 was taken. The sensitivity of this test was 70% and specificity was 98%. Furthermore, the proportion of individuals with a correct classification was 83%. The results of the test showed a better specificity when compared to the choice of stage G and a better sensitivity when compared to the choice of stage H for adult age.

  6. Evaluation of Rhubarb Supplementation in Stages 3 and 4 of Chronic Kidney Disease: A Randomized Clinical Trial

    PubMed Central

    Khan, Irfan A.; Nasiruddin, Mohammad; Haque, Shahzad F.; Khan, Rahat A.

    2014-01-01

    Objective. To evaluate the efficacy and safety of Rhubarb supplementation in patients of chronic kidney disease. Material and Methods. This study was a prospective comparative study conducted in patients of chronic kidney disease (stages 3 & 4) attending Renal Clinic of Department of Medicine, JN Medical College & Hospital, AMU, Aligarh. Patients were randomly divided into two interventional groups. Group I (Control) was given conservative management while Group II (Rhubarb) received conservative management along with Rhubarb capsule (350 mg, thrice daily) for 12 weeks. Haemogram and renal function tests were measured at 0, 4, 8, and 12 weeks of treatment. Results. There was progressive improvement in clinical features in both the groups after 12 weeks of treatment but Rhubarb group showed more marked improvement as compared to control group. Both groups showed gradual improvement in the biochemical parameters as compared to their pretreated values which was more marked in Rhubarb supplemented group. There was reduction in blood glucose, blood urea, serum creatinine, and 24 hour total urine protein (TUP). There was increase in haemoglobin, 24 hour total urine volume (TUV), and glomerular filtration rate (GFR). There was no statistical difference in two groups with respect to side effects (P > 0.05). Conclusion. Rhubarb supplementation improved the therapeutic effect of conservative management in stage 3 and stage 4 patients of chronic kidney disease. PMID:26464863

  7. The impact of adjuvant chemotherapy in older breast cancer patients on clinical and biological aging parameters

    PubMed Central

    Brouwers, Barbara; Hatse, Sigrid; Lago, Lissandra Dal; Neven, Patrick; Vuylsteke, Peter; Dalmasso, Bruna; Debrock, Guy; Van Den Bulck, Heidi; Smeets, Ann; Bechter, Oliver; Bailur, Jithendra Kini; Kenis, Cindy; Laenen, Annouschka; Schöffski, Patrick; Pawelec, Graham; Journe, Fabrice; Ghanem, Ghanem-Elias; Wildiers, Hans

    2016-01-01

    Purpose This prospective observational study aimed to evaluate the impact of adjuvant chemotherapy on biological and clinical markers of aging and frailty. Methods Women ≥ 70 years old with early breast cancer were enrolled after surgery and assigned to a chemotherapy (Docetaxel and Cyclophosphamide) group (CTG, n=57) or control group (CG, n=52) depending on their planned adjuvant treatment. Full geriatric assessment (GA) and Quality of Life (QoL) were evaluated at inclusion (T0), after 3 months (T1) and at 1 year (T2). Blood samples were collected to measure leukocyte telomere length (LTL), levels of interleukin-6 (IL-6) and other circulating markers potentially informative for aging and frailty: Interleukin-10 (IL-10), Tumor Necrosis Factor Alpha (TNF-α), Insulin-like Growth Factor 1 (IGF-1), Monocyte Chemotactic Protein 1 (MCP-1) and Regulated on Activation, Normal T cell Expressed and Secreted (RANTES). Results LTL decreased significantly but comparably in both groups, whereas IL-6 was unchanged at T2. However, IL-10, TNF-α, IGF-1 and MCP-1 suggested a minor biological aging effect of chemotherapy. Clinical frailty and QoL decreased at T1 in the CTG, but recovered at T2, while remaining stable in the CG. Conclusion Chemotherapy (TC) is unlikely to amplify clinical aging or induce frailty at 1 year. Accordingly, there is no impact on the most established aging biomarkers (LTL, IL-6). PMID:27102154

  8. A covariate adjusted two-stage allocation design for binary responses in randomized clinical trials.

    PubMed

    Bandyopadhyay, Uttam; Biswas, Atanu; Bhattacharya, Rahul

    2007-10-30

    In the present work, we develop a two-stage allocation rule for binary response using the log-odds ratio within the Bayesian framework allowing the current allocation to depend on the covariate value of the current subject. We study, both numerically and theoretically, several exact and limiting properties of this design. The applicability of the proposed methodology is illustrated by using some data set. We compare this rule with some of the existing rules by computing various performance measures.

  9. Funding opportunities for clinical investigators in the early stages of career development in cardiovascular research.

    PubMed

    Mentz, Robert J; Becker, Richard C

    2013-11-01

    Contemporary cardiovascular research offers junior investigators the opportunity to explore the gamut of biomedical questions. Despite the recent reduction in the availability of funding mechanisms that have historically served as the primary pathways for investigators in the early stages of career development, there remain numerous traditional and non-traditional funding opportunities. This article highlights these opportunities in order to assist early career investigators in the development of a personalized research trajectory, which optimizes the potential for career success.

  10. The geriatric clinic: dry and limp: aging queers, zombies, and sexual reanimation.

    PubMed

    McGlotten, Shaka; Moore, Lisa Jean

    2013-06-01

    This essay looks to the omission of aging queer bodies from new medical technologies of sex. We extend the Foucauldian space of the clinic to the mediascape, a space not only of representations but where the imagination is conditioned and different worlds dreamed into being. We specifically examine the relationship between aging queers and the marketing of technologies of sexual function. We highlight the ways queers are excluded from the spaces of the clinic, specifically the heternormative sexual scripts that organize biomedical care. Finally, using recent zombie theory, we gesture toward both the constraints and possibilities of queer inclusion within the discourses and practices that aim to reanimate sexual function. We suggest that zombies usefully frame extant articulations of aging queers with sex and the dangerous lure of medical treatments that promise revitalized, but normative, sexual function at the cost of other, perhaps queerer intimacies.

  11. The geriatric clinic: dry and limp: aging queers, zombies, and sexual reanimation.

    PubMed

    McGlotten, Shaka; Moore, Lisa Jean

    2013-06-01

    This essay looks to the omission of aging queer bodies from new medical technologies of sex. We extend the Foucauldian space of the clinic to the mediascape, a space not only of representations but where the imagination is conditioned and different worlds dreamed into being. We specifically examine the relationship between aging queers and the marketing of technologies of sexual function. We highlight the ways queers are excluded from the spaces of the clinic, specifically the heternormative sexual scripts that organize biomedical care. Finally, using recent zombie theory, we gesture toward both the constraints and possibilities of queer inclusion within the discourses and practices that aim to reanimate sexual function. We suggest that zombies usefully frame extant articulations of aging queers with sex and the dangerous lure of medical treatments that promise revitalized, but normative, sexual function at the cost of other, perhaps queerer intimacies. PMID:23468397

  12. Treatment with oral paricalcitol in daily clinical practice for patients with chronic kidney disease stage 3–4: a preliminary study

    PubMed Central

    Hadjiyannakos, Dimitrios; Filiopoulos, Vassilis; Trompouki, Sofia; Sonikian, Makroui; Karatzas, Ioannis; Panagiotopoulos, Konstantinos; Vlassopoulos, Dimosthenis

    2013-01-01

    Background Active vitamin D is an effective treatment for secondary hyperparathyroidism (SHPT) in chronic kidney disease (CKD) patients often complicated by hypercalcaemia and hyperphosphataemia. Treatment with paricalcitol, a selective vitamin D receptor activator, has shown benefits by adequately reducing parathyroid hormone (PTH) levels with minimal changes in serum calcium (Ca) and phosphorus (P). The purpose of this study is to present data on the use of oral paricalcitol in real-life clinical practice in patients with CKD stage 3–4 and SHPT. Methods We studied 43 patients, M/F: 25/18, median age: 74 years (47–87), CKD stage 3/4: 16/27, with SHPT, who were prescribed oral paricalcitol at recommended doses for 6 months. Monthly measurements of serum intact PTH (iPTH), Ca, P, alkaline phosphatase (ALP), haemoglobin, albumin (ALB), lipid profile, proteinuria and 24-h urine creatinine clearance were performed 3 months before and 6 months after treatment initiation. Results Paricalcitol induced a significant, early and sustained, through the end of follow-up period, decrease in iPTH and ALP levels and an increase in serum ALB. No significant increase in Ca and P levels as well as in Ca × P product was observed during the study period. No significant changes were found in protein excretion, kidney function and the other measured parameters between baseline and last evaluation. Paricalcitol final median dose was 5 μg/week ranging between 3 and 7 μg/week. Conclusions In the context of real-life clinical practice, oral paricalcitol for 6 months is an effective, well-tolerated treatment of SHPT in CKD stage 3–4 with minimal effects on calcium and phosphorus metabolism. PMID:26019845

  13. Clinical value and impact on prognosis of peri-operative CA 19-9 serum levels in stage I and II adenocarcinoma of the pancreas.

    PubMed

    Piagnerelli, Riccardo; Marrelli, Daniele; Roviello, Giandomenico; Ferrara, Francesco; Di Mare, Giulio; Voglino, Costantino; Petrioli, Roberto; Marini, Mario; Macchiarelli, Raffaele; Roviello, Franco

    2016-02-01

    CA 19-9 is a marker correlated to the clinical evolution of pancreatic adenocarcinoma. To analyze the clinical value of pre- and postoperative CA 19-9 serum levels in stage I and II pancreatic cancer. We analyzed 61 patients resected for pancreatic cancer. Patients were evaluated about the pre-operative CA 19-9 values and then divided into 3 groups: high, high-low and low, on the basis of pre- and postoperative CA 19-9 levels. The correlations between these groups and age, sex, pT, pN, tumor stage, jaundice, surgical radicality, tumor size, number of harvested and positive lymph nodes, grading, overall and major morbidities and post-operative mortality together with survival rates were analyzed. Higher values of pre-operative CA 19-9 were significantly correlated to the presence of jaundice, high pT, pN, stage and higher number of metastatic lymph nodes. In 49 patients (80.3 %) an R0 resection was performed. Five-year overall survival (OS) and disease free survival (DFS) were significantly better in patients with high levels of pre-operative CA 19-9, even in R0 cases. After stratification, 30 patients were included in the high group, 13 in the high-low group and 18 in the low group. A statistically significant correlation was found between the CA 19-9 groups and the lymph nodal positivity, not between CA 19-9 and pT. OS and DFS were significantly better in low group patients. We confirm the prognostic value of preoperative CA 19-9 serum levels. We do not support early postoperative modifications of CA19-9 as an adjunctive prognostic variable.

  14. Clinical and experimental use of probiotic formulations for management of end-stage renal disease: an update.

    PubMed

    Di Cerbo, Alessandro; Pezzuto, Federica; Palmieri, Lucia; Rottigni, Valentina; Iannitti, Tommaso; Palmieri, Beniamino

    2013-12-01

    Nowadays kidney transplantation and dialysis are the only available therapies for end-stage renal disease management. They imply a considerable increase in plasma concentration of uremic wastes including creatinine, urea and uric acid. These invasive procedures impose high social costs that prevent many low-income countries from adequately treating the patients affected by renal insufficiency. For years, many studies on uremic waste removal through the gut lumen have been published with conflicting results. More recently, microencapsulation of probiotic bacteria has been performed by different research groups. This evidence has opened a new perspective on therapeutic modification of gut bacterial flora in the context of renal disease. This review gives an overview of the experimental and clinical use of probiotic formulations in the context of end-stage renal disease. PMID:23584675

  15. The effect of mass screening by physical examination combined with regular breast self-examination on clinical stage and course of Japanese women with breast cancer.

    PubMed

    Koibuchi, Y; Iino, Y; Takei, H; Maemura, M; Horiguchi, J; Yokoe, T; Morishita, Y

    1998-01-01

    A mass screening program for breast cancer in Japan consists of physical examination (PE) and education on regular breast self-examination (BSE). The effect of PE with BSE on clinical stages and courses of breast cancer patients were retrospectively analyzed. Clinical stages and courses were compared between; i) patients who were examined in outpatient clinics (OPC, n=587), ii) patients who were detected by mass screening with regular BSE [BSE(+), n=68], and iii) without BSE [BSE(-), n=178]. Clinical stage in BSE(+) was significantly earlier than that in BSE(-) or OPC. As early stage cancer was most common in BSE(+), conservative surgery was mostly selected. Survival curve in BSE(+) was significantly better than those in BSE(-) or OPC. BSE complements the role of mass screening by PE for early detection and a more favorable clinical course.

  16. Art Therapy for an Individual with Late Stage Dementia: A Clinical Case Description

    ERIC Educational Resources Information Center

    Tucknott-Cohen, Tisah; Ehresman, Crystal

    2016-01-01

    This article describes the healing benefits of art therapy for an individual with dementia of the Alzheimer's type. In this clinical case description, a woman diagnosed with Alzheimer's disease received individual art therapy for 17 weeks. The treatment concerns that arose, altered view of reality, agitation, and retrogenesis provide insight on…

  17. Endosalpingiosis of Axillary Lymph Nodes: A Rare Histopathologic Pitfall with Clinical Relevance for Breast Cancer Staging

    PubMed Central

    Nomani, Laila; Calhoun, Benjamin C.; Biscotti, Charles V.; Grobmyer, Stephen R.; Sturgis, Charles D.

    2016-01-01

    Establishment of accurate axillary lymph node status is of essential importance in determining both prognosis and the potential need for adjuvant therapy in patients with invasive breast cancer. Axillary lymph node heterotopias can in some cases result in overdiagnosis of metastatic disease. Nodal endosalpingiosis is perhaps the least commonly reported type of axially lymph node heterotopia. We herein illustrate a case in which second opinion pathologic interpretation combined with ancillary immunohistochemical studies allowed for a specific diagnosis of axillary nodal müllerian-type inclusions, confirming ypN0 staging and resulting in appropriate disease management and prognostication. PMID:27088025

  18. Natural History of Clinically Staged Low- and Intermediate-Risk Prostate Cancer Treated With Monotherapeutic Permanent Interstitial Brachytherapy

    SciTech Connect

    Taira, Al V.; Merrick, Gregory S.; Galbreath, Robert W.; Wallner, Kent E.; Butler, Wayne M.

    2010-02-01

    Purpose: To evaluate the natural history of clinically staged low- and intermediate-risk prostate cancer treated with permanent interstitial seed implants as monotherapy. Methods and Materials: Between April 1995 and May 2005, 463 patients with clinically localized prostate cancer underwent brachytherapy as the sole definitive treatment. Men who received supplemental external beam radiotherapy or androgen deprivation therapy were excluded. Dosimetric implant quality was determined based on the minimum dose that covered 90% of the target volume and the volume of the prostate gland receiving 100% of the prescribed dose. Multiple parameters were evaluated as predictors of treatment outcomes. Results: The 12-year biochemical progression-free survival (bPFS), cause-specific survival, and overall survival rates for the entire cohort were 97.1%, 99.7%, and 75.4%, respectively. Only pretreatment prostate-specific antigen level, percent positive biopsy cores, and minimum dose that covered 90% of the target volume were significant predictors of biochemical recurrence. The bPFS, cause-specific survival, and overall survival rates were 97.4%, 99.6%, and 76.2%, respectively, for low-risk patients and 96.4%, 100%, and 74.0%, respectively, for intermediate-risk patients. The bPFS rate was 98.8% for low-risk patients with high-quality implants versus 92.1% for those with less adequate implants (p < 0.01), and it was 98.3% for intermediate-risk patients with high-quality implants versus 86.4% for those with less adequate implants (p < 0.01). Conclusions: High-quality brachytherapy implants as monotherapy can provide excellent outcomes for men with clinically staged low- and intermediate-risk prostate cancer. For these men, a high-quality implant can achieve results comparable to high-quality surgery in the most favorable pathologically staged patient subgroups.

  19. The experiences of close persons caring for people with chronic kidney disease stage 5 on conservative kidney management: Contested discourses of ageing

    PubMed Central

    Myers, Jason; Smith, Glenn; Higgs, Paul; Burns, Aine; Hopkins, Katherine; Jones, Louise

    2014-01-01

    Chronic kidney disease stage 5 is a global health challenge in the context of population ageing across the world. The range of treatment options available to patients at all ages has increased and includes transplantation and dialysis. However, these options are often seen as inappropriate for older frailer patients who are now offered the option of conservative kidney management, which is presented as a non-invasive alternative to dialysis, involving symptom management and addressing psychosocial needs. In this study, we conducted qualitative interviews with 26 close persons caring for someone with chronic kidney disease stage 5 in the United Kingdom to investigate how conservative kidney management interacted with implicit ideas of ageing, in both the experience of conservative kidney management and the understanding of the prognosis and future care of the kidney disease. Our findings highlighted participant confusion about the nature of conservative kidney management, which stems from an initial lack of clarity about how conservative kidney management differed from conventional treatments for chronic kidney disease stage 5. In particular, some respondents were not aware of the implicit palliative nature of the intervention or indeed the inevitable end-of-life issues. Although these findings can be situated within the context of communication failure, we would further argue that they also bring to the surface tensions in the discourses surrounding ageing and old age, drawing on the use of a ‘natural’ and a ‘normal’ paradigm of ageing. In the context of chronic kidney disease stage 5, more patients are being dialysed at older ages, but conservative kidney management is being advanced as a better option than dialysis in terms of quality of life and experience. However, in doing so, conservative kidney management implicitly draws on a notion of older age that echoes natural ageing rather than advocate a more interventionist approach. The role of discourses

  20. The experiences of close persons caring for people with chronic kidney disease stage 5 on conservative kidney management: contested discourses of ageing.

    PubMed

    Low, Joe; Myers, Jason; Smith, Glenn; Higgs, Paul; Burns, Aine; Hopkins, Katherine; Jones, Louise

    2014-11-01

    Chronic kidney disease stage 5 is a global health challenge in the context of population ageing across the world. The range of treatment options available to patients at all ages has increased and includes transplantation and dialysis. However, these options are often seen as inappropriate for older frailer patients who are now offered the option of conservative kidney management, which is presented as a non-invasive alternative to dialysis, involving symptom management and addressing psychosocial needs. In this study, we conducted qualitative interviews with 26 close persons caring for someone with chronic kidney disease stage 5 in the United Kingdom to investigate how conservative kidney management interacted with implicit ideas of ageing, in both the experience of conservative kidney management and the understanding of the prognosis and future care of the kidney disease. Our findings highlighted participant confusion about the nature of conservative kidney management, which stems from an initial lack of clarity about how conservative kidney management differed from conventional treatments for chronic kidney disease stage 5. In particular, some respondents were not aware of the implicit palliative nature of the intervention or indeed the inevitable end-of-life issues. Although these findings can be situated within the context of communication failure, we would further argue that they also bring to the surface tensions in the discourses surrounding ageing and old age, drawing on the use of a 'natural' and a 'normal' paradigm of ageing. In the context of chronic kidney disease stage 5, more patients are being dialysed at older ages, but conservative kidney management is being advanced as a better option than dialysis in terms of quality of life and experience. However, in doing so, conservative kidney management implicitly draws on a notion of older age that echoes natural ageing rather than advocate a more interventionist approach. The role of discourses of ageing

  1. The experiences of close persons caring for people with chronic kidney disease stage 5 on conservative kidney management: contested discourses of ageing.

    PubMed

    Low, Joe; Myers, Jason; Smith, Glenn; Higgs, Paul; Burns, Aine; Hopkins, Katherine; Jones, Louise

    2014-11-01

    Chronic kidney disease stage 5 is a global health challenge in the context of population ageing across the world. The range of treatment options available to patients at all ages has increased and includes transplantation and dialysis. However, these options are often seen as inappropriate for older frailer patients who are now offered the option of conservative kidney management, which is presented as a non-invasive alternative to dialysis, involving symptom management and addressing psychosocial needs. In this study, we conducted qualitative interviews with 26 close persons caring for someone with chronic kidney disease stage 5 in the United Kingdom to investigate how conservative kidney management interacted with implicit ideas of ageing, in both the experience of conservative kidney management and the understanding of the prognosis and future care of the kidney disease. Our findings highlighted participant confusion about the nature of conservative kidney management, which stems from an initial lack of clarity about how conservative kidney management differed from conventional treatments for chronic kidney disease stage 5. In particular, some respondents were not aware of the implicit palliative nature of the intervention or indeed the inevitable end-of-life issues. Although these findings can be situated within the context of communication failure, we would further argue that they also bring to the surface tensions in the discourses surrounding ageing and old age, drawing on the use of a 'natural' and a 'normal' paradigm of ageing. In the context of chronic kidney disease stage 5, more patients are being dialysed at older ages, but conservative kidney management is being advanced as a better option than dialysis in terms of quality of life and experience. However, in doing so, conservative kidney management implicitly draws on a notion of older age that echoes natural ageing rather than advocate a more interventionist approach. The role of discourses of ageing

  2. Distinctive Patterns of Initially Presenting Metastases and Clinical Outcomes According to the Histological Subtypes in Stage IV Non-Small Cell Lung Cancer

    PubMed Central

    Lee, Dong Soo; Kim, Yeon S.; Kay, Chul S.; Kim, Sung H.; Yeo, Chang D.; Kim, Jin W.; Kim, Seung Joon; Kim, Young K.; Ko, Yoon H.; Kang, Jin H.; Lee, Kyo Y.

    2016-01-01

    Abstract This study was designed to compare the primary patterns of metastases and clinical outcomes between adenocarcinoma (Adenoca) and squamous cell carcinoma (SQ) in initially diagnosed stage IV non-small cell lung cancer (NSCLC). Between June 2007 and June 2013, a total of 427 eligible patients were analyzed. These patients were histologically confirmed as Adenoca or SQ and underwent systemic imaging studies, including 18F-fluorodeoxyglucose positron emission tomography/computed tomography and brain imaging. Synchronous metastatic sites were categorized into 7 areas, and whole-body metastatic scores were calculated from 1 to 7 by summation of each involved region. We compared the patient, tumor, and metastatic characteristics according to the histological subtypes, and examined clinical outcomes. The enrolled study cohort comprised 81% (n = 346) Adenoca patients and 19% (n = 81) SQ patients. The median age of the study population was 65 years (range, 30–94 years), and 263 (61.6%) patients were male. The most common metastatic sites were thoracic lymph nodes (LNs) (84.3%), followed by lung to lung/lymphangitic spread (59%) and bone (54.8%). The distribution of patient characteristics revealed that age ≥65 years (69.1% vs 50.6%; P = 0.003) and male sex (84% vs 56.4%; P < 0.001) were more frequently found in SQ patients. Regarding metastatic features, bone metastasis (60.4% vs 30.9%; P < 0.001), lung to lung/lymphangitic metastasis (63% vs 42%; P = 0.001), and brain metastasis (35% vs 16%; P = 0.001) were significantly and more frequently found in Adenoca patients. Patients with high metastatic scores (score 3–6) were more frequently found to have Adenoca (91.6% vs 73.4%; P < 0.001). In multivariate prognostic evaluation, sex (P = 0.001), age (P < 0.001), histology (P < 0.001), LN status (P = 0.032), pleural/pericardial metastasis (P = 0.003), abdomen/pelvis metastasis (P < 0.001), axilla

  3. Chemical immobilization of adult female Weddell seals with tiletamine and zolazepam: effects of age, condition and stage of lactation

    PubMed Central

    Wheatley, Kathryn E; Bradshaw, Corey JA; Harcourt, Robert G; Davis, Lloyd S; Hindell, Mark A

    2006-01-01

    Background Chemical immobilization of Weddell seals (Leptonychotes weddellii) has previously been, for the most part, problematic and this has been mainly attributed to the type of immobilizing agent used. In addition to individual sensitivity, physiological status may play an important role. We investigated the use of the intravenous administration of a 1:1 mixture of tiletamine and zolazepam (Telazol®) to immobilize adult females at different points during a physiologically demanding 5–6 week lactation period. We also compared performance between IV and IM injection of the same mixture. Results The tiletamine:zolazepam mixture administered intravenously was an effective method for immobilization with no fatalities or pronounced apnoeas in 106 procedures; however, there was a 25 % (one animal in four) mortality rate with intramuscular administration. Induction time was slightly longer for females at the end of lactation (54.9 ± 2.3 seconds) than at post-parturition (48.2 ± 2.9 seconds). In addition, the number of previous captures had a positive effect on induction time. There was no evidence for effects due to age, condition (total body lipid), stage of lactation or number of captures on recovery time. Conclusion We suggest that intravenous administration of tiletamine and zolazepam is an effective and safe immobilizing agent for female Weddell seals. Although individual traits could not explain variation in recovery time, we suggest careful monitoring of recovery times during longitudinal studies (> 2 captures). We show that physiological pressures do not substantially affect response to chemical immobilization with this mixture; however, consideration must be taken for differences that may exist for immobilization of adult males and juveniles. Nevertheless, we recommend a mass-specific dose of 0.50 – 0.65 mg/kg for future procedures with adult female Weddell seals and a starting dose of 0.50 mg/kg for other age classes and other phocid seals. PMID

  4. Developmental screening in a Canadian First Nation (Mohawk): psychometric properties and adaptations of ages & stages questionnaires (2nd edition)

    PubMed Central

    2014-01-01

    Background The need for early intervention tools adapted to the First Nation culture is well documented. However, standards derived from First Nation communities are absent from the literature. This study examines the psychometric properties of an adaptation of a caregiver-completed screening tool, the Ages & Stages Questionnaires (ASQ), for the Mohawk population. Methods Participants who completed the questionnaires include 17 teachers, along with the parents of 282 children (130 girls and 152 boys) between the ages of 9 and 66 months who attend the Child and Family Center Mohawk Territory, Quebec. Results For the internal consistency of the four questionnaires (36-, 42-, 48- and 54-month intervals), Cronbach’s alphas varied between .61 and .84. Five results were below 0.60: “gross motor” (Q36 and Q42), “problem solving” (Q36) and “personal-social” (Q36 and Q42). A comparison of the results shows that parents and teachers agreed in 85% of the cases concerning the referral of the child for further evaluation. Moreover, the group discussion with the parents revealed that the use of the questionnaire was appreciated and was deemed appropriate for use within the community. Conclusion The results show that the ASQ is a screening test that may be appropriate for use with children from communities that are seemingly very different in terms of geographic, climatic and cultural backgrounds. This preliminary study with the Child and Family Center appears to support further study and the use of the ASQ with the Mohawk population. PMID:24467769

  5. Multiple stage MS in analysis of plasma, serum, urine and in vitro samples relevant to clinical and forensic toxicology.

    PubMed

    Meyer, Golo M; Maurer, Hans H; Meyer, Markus R

    2016-01-01

    This paper reviews MS approaches applied to metabolism studies, structure elucidation and qualitative or quantitative screening of drugs (of abuse) and/or their metabolites. Applications in clinical and forensic toxicology were included using blood plasma or serum, urine, in vitro samples, liquids, solids or plant material. Techniques covered are liquid chromatography coupled to low-resolution and high-resolution multiple stage mass analyzers. Only PubMed listed studies published in English between January 2008 and January 2015 were considered. Approaches are discussed focusing on sample preparation and mass spectral settings. Comments on advantages and limitations of these techniques complete the review.

  6. Age-Matched, Case-Controlled Comparison of Clinical Indicators for Development of Entropion and Ectropion

    PubMed Central

    Michels, Kevin S.; Czyz, Craig N.; Cahill, Kenneth V.; Foster, Jill A.; Burns, John A.; Everman, Kelly R.

    2014-01-01

    Purpose. To analyze the clinical findings associated with involutional entropion and ectropion and compare them to each other and to age-matched controls. Methods. Prospective, age-matched cohort study involving 30 lids with involutional entropion, 30 lids with involutional ectropion, and 52 age-matched control lids. Results. The statistically significant differences associated with both the entropion and ectropion groups compared to the control group were presence of a retractor dehiscence, presence of a “white line,” occurrence of orbital fat prolapse in the cul-de-sac, decreased lower lid excursion, increased lid laxity by the snapback test, and an increased lower lid distraction. Entropion also differed from the control group with an increased lid crease height and decreased lateral canthal excursion. Statistically significant differences associated with entropion compared to ectropion were presence of a retractor dehiscence, decreased lateral canthal excursion, and less laxity in the snapback test. Conclusion. Entropic and ectropic lids demonstrate clinically and statistically significant anatomical and functional differences from normal, age-matched lids. Many clinical findings associated with entropion are also present in ectropion. Entropion is more likely to develop with a pronounced retractor deficiency. Ectropion is more likely to develop with diminished elasticity as measured by the snapback test. PMID:24734167

  7. Clinical value of real-time elastography quantitative parameters in evaluating the stage of liver fibrosis and cirrhosis

    PubMed Central

    GE, LAN; SHI, BAOMIN; SONG, YE; LI, YUAN; WANG, SHUO; WANG, XIUYAN

    2015-01-01

    The aim of the present study was to assess the value of real-time elastography (RTE) quantitative parameters, namely the liver fibrosis (LF) index and the ratio of blue area (%AREA), in evaluating the stage of liver fibrosis. RTE quantitative analysis software was used to examine 120 patients with chronic hepatitis in order to obtain the values for 12 quantitative parameters from the elastic images. The diagnostic performance of two such parameters, the LF index and %AREA, were assessed with a receiver operating characteristic (ROC) curve to determine the optimal diagnostic cut-off values for liver cirrhosis and fibrosis. A good correlation was observed between the LF index and %AREA with the fibrosis stage. The areas under the ROC curve for the LF index were 0.985 for the diagnosis of liver cirrhosis and 0.790 for liver fibrosis. With regard to %AREA, the areas under the ROC curve for the diagnosis of liver cirrhosis and fibrosis were 0.963 and 0.770, respectively. An LF index of >3.25 and a %AREA of >28.83 for the diagnosis of cirrhosis stage resulted in sensitivity values of 100 and 100%, specificity values of 88.9 and 85.9% and accuracy values of 90.8 and 88.3%, respectively. The LF index and %AREA parameters exhibited higher reliability in the diagnosis of liver cirrhosis compared with the diagnosis of the liver fibrosis stage. However, the two parameters possessed a similar efficacy in the diagnosis of liver cirrhosis and the stage of liver fibrosis. Therefore, the quantitative RTE parameters of the LF index and %AREA may be clinically applicable as reliable indices for the early diagnosis of liver cirrhosis, without the requirement of an invasive procedure. PMID:26622426

  8. Cementless total hip arthroplasty in developmental dysplasia of the hip with end stage osteoarthritis: 2-7 years' clinical results.

    PubMed

    Yildirim, Tugrul; Guclu, Berk; Karaguven, Dogac; Kaya, Alper; Akan, Burak; Cetin, Ilker

    2015-01-01

    Between 2006 and 2011, 102 hips of 78 patients with end-stage osteoarthritis secondary to developmental dysplasia of the hip (DDH) underwent cementless total hip arthroplasty (THA). According to the Crowe's classification, 22 hips (21%) were type 1, 19 hips (18%) were type 2, 22 hips (21%) were type 3 and 39 hips (38%) were type 4 respectively. Functional and clinical analyses were performed by Harris Hip Scores (HHS). There were 73 (71%) excellent or good results according to HHS. The postoperative HHS was significantly lower in patients who underwent femoral shortening (p<0.01). We observed 25 (24.5%) complications in total, 15 (14.7%) of which required revision surgery. The authors concluded that THA for DDH is a safe and a reliable procedure with good clinical outcomes. PMID:25907395

  9. Electrodeposition and isothermal aging of Co and Mn layers on stainless steel for interconnectors: Initial stages of spinel phase formation

    NASA Astrophysics Data System (ADS)

    Pinto, R.; Carmezim, M. J.; Montemor, M. F.

    2014-06-01

    Electrodeposited Co and Mn spinel phase oxides for application as coatings for metallic interconnectors in Solid Oxide Fuel Cells were prepared. The study aims at understanding the initial stages of transformation of the metallic layers into the spinel phase. Co and Mn metallic layers were sequentially deposited over AISI 430 stainless steel substrate from acidic sulfate solutions and annealed in oxidizing and inert atmospheres between 600 °C and 800 °C. The coatings obtained showed a thickness above 20 μm. After 1 h of isothermal aging the coatings were composed of layers of un-reacted metallic elements and Mn based oxides. The spinel phase was studied by XRD and revealed Mn based tetragonal structure Mn3O4 with Co in solid solution and a non-determined Co/Mn ratio. According to EDS measurements this ratio should vary with depth. Full conversion was not obtained at these time frames with the presence other Mn oxides (MnO and Mn2O3). In inert atmosphere, the allotropic Mn transformation from α to β phase was detected. No outward diffusion of Cr was detected, due to the short exposure times.

  10. Accuracy of MRI in Prediction of Tumour Thickness and Nodal Stage in Oral Tongue and Gingivobuccal Cancer With Clinical Correlation and Staging

    PubMed Central

    Parihar, Pratap Singh; Parihar, Akhilesh; Goel, Ashok Kumar; Waghwani, Kapil; Gupta, Richa; Bhutekar, Umesh

    2016-01-01

    Introduction Squamous cell carcinoma of lower gingivo-buccal complex and tongue are the most common cancer in the Indian sub-continent. The value of imaging in the staging of Oral Squamous Cell Carcinoma (OSCC) is in judging operability, assessment of the prognostic characteristics and dimensions of the primary tumour, depth of tumour invasion, the presence of cervical metastasis and detection of bone infiltration. Aim This study evaluated squamous cell carcinomas of the oral cavity (tongue and gingivo-buccal complex) on the basis of their appearance, soft tissue extent, depth of tumour invasion and staging. Further, this study assessed the accuracy of MRI in the detection of cervical lymph nodal metastasis on the basis of ADC values on diffusion weighted MR sequence. Materials and Methods T1- and T2-weighted MR, diffusion-weighted sequences and post contrast T1W sequences were performed in various planes on biopsy proven squamous cell carcinomas (61 cases) involving tongue and/or gingivo-buccal region. Depth of tumour invasion was calculated on axial images of post contrast T1W images. The Apparent Diffusion Coefficient (ADC) was measured by using two b factors (500 and 1000 s/mm2). MRI findings were compared clinically and histopathologically. Results Average depth of invasion calculated on MRI was 8.47mm and by histopathology was 6.85mm. Pearson’s correlation coefficient was 0.988. Shrinkage factor was 0.8. A 71% of patients with depth of invasion greater than 9mm showed evidence of cervical lymph nodal metastasis at one or another levels. Cut-off value to discriminate between malignant and benign lymph nodes was 1.038 x10-3 mm2/s in the present study. Conclusion Depth of tumour invasion in oral malignancies can be measured reliably on MRI which helps in predicting cervical lymph node metastasis. Benign or malignant cervical lymph nodes can be differentiated on diffusion-weighted imaging of MRI on the basis of their ADC values. PMID:27504375

  11. Effect of Interval to Definitive Breast Surgery on Clinical Presentation and Survival in Early-Stage Invasive Breast Cancer

    SciTech Connect

    Vujovic, Olga; Yu, Edward; Cherian, Anil; Perera, Francisco; Dar, A. Rashid; Stitt, Larry; Hammond, A.

    2009-11-01

    Purpose: To examine the effect of clinical presentation and interval to breast surgery on local recurrence and survival in early-stage breast cancer. Methods and Materials: The data from 397 patients with Stage T1-T2N0 breast carcinoma treated with conservative surgery and breast radiotherapy between 1985 and 1992 were reviewed at the London Regional Cancer Program. The clinical presentation consisted of a mammogram finding or a palpable lump. The intervals from clinical presentation to definitive breast surgery used for analysis were 0-4, >4-12, and >12 weeks. The Kaplan-Meier estimates of the time to local recurrence, disease-free survival, and cause-specific survival were determined for the three groups. Cox regression analysis was used to evaluate the effect of clinical presentation and interval to definitive surgery on survival. Results: The median follow-up was 11.2 years. No statistically significant difference was found in local recurrence as a function of the interval to definitive surgery (p = .424). A significant difference was noted in disease-free survival (p = .040) and cause-specific survival (p = .006) with an interval of >12 weeks to definitive breast surgery. However, the interval to definitive surgery was dependent on the presentation for cause-specific survival, with a substantial effect for patients with a mammographic presentation and a negligible effect for patients with a lump presentation (interaction p = .041). Conclusion: The results of this study suggest that an interval of >12 weeks to breast surgery might be associated with decreased survival for patients with a mammographic presentation, but it appeared to have no effect on survival for patients presenting with a palpable breast lump.

  12. Clinical and Biomechanical Evaluations of Staged Bilateral Total Knee Arthroplasty Patients with Two Different Implant Designs

    PubMed Central

    Renaud, Alexandre; Fuentes, Alexandre; Hagemeister, Nicola; Lavigne, Martin; Vendittoli, Pascal-André

    2016-01-01

    Background: Various implants of total knee arthroplasty (TKA) are used in clinical practice and each presents specific design characteristics. No implant managed this day to reproduce perfectly the biomechanics of the natural knee during gait. Objectives: We therefore asked whether (1) differences in tridimensional (3D) kinematic data during gait could be observed in two different designs of TKA on the same patients, (2) if those gait kinematic data are comparable with those of asymptomatic knees and (3) if difference in clinical subjective scores can be observed between the two TKA designs on the same patient. Methods: We performed knee kinematic analysis on 15 patients (30 TKAs) with two different TKA implant designs (Nexgen, Zimmer and Triathlon, Stryker) on each knee and on 25 asymptomatic subjects (35 knees). Clinical evaluation included range of motion, weight bearing radiographs, questionnaire of joint perception, KOOS, WOMAC and SF-12. Results: Comparison between TKAs and asymptomatic knees revealed that asymptomatic knees had significantly less knee flexion at initial contact (p < 0.04) and more flexion for most of the swing phase (p between 0.004 and 0.04). Asymptomatic knees also had less varus at loading response, during stance phase and during most of the swing phase (p between 0.001 - 0.05). Transverse plane analysis showed a tendency for asymptomatic knees to be more in internal rotation during stance phase (p 0.02 - 0.04). Comparing both TKA designs, NexgenTM implant had significantly more flexion at the end of swing phase (p = 0.04) compared to knees with the TriathlonTM implant. In frontal plane, from initial contact to maximum mid stance angle and between the mean mid stance angle and initial contact NexgenTM TKA had significantly more adduction (varus, p =0.02 – 0.03). Clinical scores of both TKAs did not have significant difference. Conclusions: TKA with the tested implants did not reproduce natural knee kinematics during gait. In our cohort

  13. [Uterine cervix cancer. Clinical stage III. Combined radiotherapy and chemotherapy treatment].

    PubMed

    Ayala Hernández, J R; de la Huerta Sánchez, R; Morales Canfield, F; Fernández Orozco, A

    1991-07-01

    55 patients with stage III carcinoma of the uterine cervix were entered into a prospective randomized study to evaluate the possible radiation-potentiating properties of bleomycin. Group A received classical radiation treatment with telecobalt-therapy 50 Gy/25 fractions plus 32 Gy/4 fractions (Cathetron). The other two groups received 15 mg of bleomycin by continue infusion two time of week during 5 week, groups B before, and group C after, irradiation. The morbidity was minimal. The initial response was complete in 49 cases and partial in 6 cases. At 2 years there were 26 recurrences, 22 (88.8%), locoregional recurrences and 4 distant metastasis, 3 in the group of bleomycin treatment. The probability of actuarial survival was 62.1%, 30.1% and 35.6% respectively to groups A, B and C. Addition of bleomycin to radiotherapy failed to increase the recurrence-free survival.

  14. The incidence of cervical spondylosis decreases with aging in the elderly, and increases with aging in the young and adult population: a hospital-based clinical analysis

    PubMed Central

    Wang, Chuanling; Tian, Fuming; Zhou, Yingjun; He, Wenbo; Cai, Zhiyou

    2016-01-01

    Background and purpose Cervical spondylosis is well accepted as a common degenerative change in the cervical spine. Compelling evidence has shown that the incidence of cervical spondylosis increases with age. However, the relationship between age and the incidence of cervical spondylosis remains obscure. It is essential to note the relationship between age and the incidence of cervical spondylosis through more and more clinical data. Methods In the case-controlled study reported here, retrospective clinical analysis of 1,276 cases of cervical spondylosis has been conducted. We analyzed the general clinical data, the relationship between age and the incidence of cervical spondylosis, and the relationship between age-related risk factors and the incidence of cervical spondylosis. A chi-square test was used to analyze the associations between different variables. Statistical significance was defined as a P-value of less than 0.05. Results The imaging examination demonstrated the most prominent characteristic features of cervical spondylosis: bulge or herniation at C3-C4, C4-C5, and C5-C6. The incidence of cervical spondylosis increased with aging before age 50 years and decreased with aging after age 50 years, especially in the elderly after 60 years old. The occurrence rate of bulge or herniation at C3-C4, C4-C5, C5-C6, and C6-C7 increased with aging before age 50 years and decreased with aging after age 50 years, especially after 60 years. Moreover, the incidence of hyperosteogeny and spinal stenosis increased with aging before age 60 years and decreased with aging after age 60 years, although there was no obvious change in calcification. The age-related risk factors, such as hypertension, hyperlipidemia, diabetes, cerebral infarct, cardiovascular diseases, smoking, and drinking, have no relationship with the incidence of cervical spondylosis. Conclusion A decreasing proportion of cervical spondylosis with aging occurs in the elderly, while the proportion of

  15. Percutaneous microwave ablation of stage I medically inoperable non-small cell lung cancer: clinical evaluation of 47 cases

    PubMed Central

    Yang, Xia; Ye, Xin; Zheng, Aimin; Huang, Guanghui; Ni, Xiang; Wang, Jiao; Han, Xiaoying; Li, Wenhong; Wei, Zhigang

    2014-01-01

    Purpose To retrospectively evaluate safety and effectiveness of CT-guided percutaneous microwave ablation (MWA) in 47 patients with medically inoperable stage I peripheral non-small cell lung cancer (NSCLC). Methods From February 2008 to October 2012, 47 patients with stage I medically inoperable NSCLC were treated in 47 MWA sessions. The clinical outcomes were evaluated. Complications after MWA were also summarized. Results At a median follow-up period of 30 months, the median time to the first recurrence was 45.5 months. The local control rates at 1, 3, 5 years after MWA were 96%, 64% and 48%, respectively. The median cancer-specific and median overall survivals were 47.4 months and 33.8 months. The overall survival rates at 1, 2, 3 and 5 years after MWA were 89%, 63%, 43%, and 16 %, respectively. Tumors ≤3.5 cm were associated with better survival than were tumors >3.5 cm. The complications after MWA included pneumothorax (63.8%), hemoptysis (31.9%), pleural effusion (34%), pulmonary infection (14.9%), and bronchopleural fistula (2.1%). Conclusions MWA is safe and effective for the treatment of medically inoperable stage I peripheral NSCLC. PMID:24965604

  16. Pretreatment Modified Glasgow Prognostic Score Predicts Clinical Outcomes After Stereotactic Body Radiation Therapy for Early-Stage Non-Small Cell Lung Cancer

    SciTech Connect

    Kishi, Takahiro; Matsuo, Yukinori Ueki, Nami; Iizuka, Yusuke; Nakamura, Akira; Sakanaka, Katsuyuki; Mizowaki, Takashi; Hiraoka, Masahiro

    2015-07-01

    Purpose: This study aimed to evaluate the prognostic significance of the modified Glasgow Prognostic Score (mGPS) in patients with non-small cell lung cancer (NSCLC) who received stereotactic body radiation therapy (SBRT). Methods and Materials: Data from 165 patients who underwent SBRT for stage I NSCLC with histologic confirmation from January 1999 to September 2010 were collected retrospectively. Factors, including age, performance status, histology, Charlson comorbidity index, mGPS, and recursive partitioning analysis (RPA) class based on sex and T stage, were evaluated with regard to overall survival (OS) using the Cox proportional hazards model. The impact of the mGPS on cause of death and failure patterns was also analyzed. Results: The 3-year OS was 57.9%, with a median follow-up time of 3.5 years. A higher mGPS correlated significantly with poor OS (P<.001). The 3-year OS of lower mGPS patients was 66.4%, whereas that of higher mGPS patients was 44.5%. On multivariate analysis, mGPS and RPA class were significant factors for OS. A higher mGPS correlated significantly with lung cancer death (P=.019) and distant metastasis (P=.013). Conclusions: The mGPS was a significant predictor of clinical outcomes for SBRT in NSCLC patients.

  17. Gallium-67 scanning to stage the alveolitis of sarcoidosis: correlation with clinical studies, pulmonary function studies, and bronchoalveolar lavage

    SciTech Connect

    Line, B.R.; Hunninghake, G.W.; Keogh, B.A.; Jones, A.E.; Johnston, G.S.; Crystal, R.G.

    1981-04-01

    Current concepts of the pathogenesis of sarcoidosis suggest that the alveolitis of this disorder is related to increased numbers of mononuclear phagocytes and activated T-lymphocytes within the lung. To determine if 67Ga scanning, a procedure commonly used in the evaluation of inflammation, would be useful in staging the alveolitis of sarcoidosis, we studied 41 patients with this disorder and correlated estimates of pulmonary 67Ga accumulation with clinical, roentgenographic, physiologic, and bronchoalveolar lavage studies in these patients. Although 65% of patients with sarcoidosis showed increased amounts of 67Ga accumulation in the lung compared with control subjects, only weak correlations (r less than +/- 0.42, all comparisons) were found between the degree of gallium uptake and the clinical, roentgenographic, or physiologic data. In contrast, there was a strong correlation of 67Ga uptake and the number of lymphocytes and T-lymphocytes recovered from the lungs of these patients by bronchoalveolar lavage (p less than 0.0001, r greater than or equal to 0.67, both comparisons). This data suggested that gallium uptake reflects the intensity of the T-lymphocytes mediated component of the alveolitis in sarcoidosis. Because 67Ga scans are noninvasive, simple to perform, and widely available, they should prove useful to stage the activity of sarcoidosis and to make decisions regarding therapy directed against the alveolitis of the disease.

  18. Gallium-67 scanning to stage the alveolitis of sarcoidosis: correlation with clinical studies, pulmonary function studies, and bronchoalveolar lavage

    SciTech Connect

    Line, B.R.; Hunninghake, G.W.; Keogh, B.A.; Jones, A.E.; Johnston, G.S.; Crystal, R.G.

    1981-04-01

    Current concepts of the pathogenesis of sarcoidosis suggest that the alveolitis of this disorder is related to increased numbers of mononuclear phagocytes and activated T-lymphocytes within the lung. To determine if 67Ga scanning, a procedure commonly used in the evaluation of inflammation, would be useful in staging the alveolitis of sarcoidosis, researchers studied 41 patients with this disorder and correlated estimates of pulmonary /sup 67/Ga accumulation with clinical, roentgenographic, physiologic, and bronchoalveolar lavage studies in these patients. Although 65% of patients with sarcoidosis showed increased amounts of /sup 67/Ga accumulation in the lung compared with control subjects, only weak correlations (r less than +/- 0.42, all comparisons) were found between the degree of gallium uptake and the clinical, roentgenographic, or physiologic data. In contrast, there was a strong correlation of /sup 67/Ga uptake and the number of lymphocytes and T-lymphocytes recovered from the lungs of these patients by bronchoalveolar lavage (p less than 0.0001, r greater than or equal to 0.67, both comparisons). This data suggested that gallium uptake reflects the intensity of the T-lymphocytes mediated component of the alveolitis in sarcoidosis. Because /sup 67/Ga scans are noninvasive, simple to perform, and widely available, they should prove useful to stage the activity of sarcoidosis and to make decisions regarding therapy directed against the alveolitis of the disease.

  19. lncRNA profiling in early-stage chronic lymphocytic leukemia identifies transcriptional fingerprints with relevance in clinical outcome.

    PubMed

    Ronchetti, D; Manzoni, M; Agnelli, L; Vinci, C; Fabris, S; Cutrona, G; Matis, S; Colombo, M; Galletti, S; Taiana, E; Recchia, A G; Bossio, S; Gentile, M; Musolino, C; Di Raimondo, F; Grilli, A; Bicciato, S; Cortelezzi, A; Tassone, P; Morabito, F; Ferrarini, M; Neri, A

    2016-01-01

    Long non-coding RNAs (lncRNAs) represent a novel class of functional RNA molecules with an important emerging role in cancer. To elucidate their potential pathogenetic role in chronic lymphocytic leukemia (CLL), a biologically and clinically heterogeneous neoplasia, we investigated lncRNAs expression in a prospective series of 217 early-stage Binet A CLL patients and 26 different subpopulations of normal B-cells, through a custom annotation pipeline of microarray data. Our study identified a 24-lncRNA-signature specifically deregulated in CLL compared with the normal B-cell counterpart. Importantly, this classifier was validated on an independent data set of CLL samples. Belonging to the lncRNA signature characterizing distinct molecular CLL subgroups, we identified lncRNAs recurrently associated with adverse prognostic markers, such as unmutated IGHV status, CD38 expression, 11q and 17p deletions, and NOTCH1 mutations. In addition, correlation analyses predicted a putative lncRNAs interplay with genes and miRNAs expression. Finally, we generated a 2-lncRNA independent risk model, based on lnc-IRF2-3 and lnc-KIAA1755-4 expression, able to distinguish three different prognostic groups in our series of early-stage patients. Overall, our study provides an important resource for future studies on the functions of lncRNAs in CLL, and contributes to the discovery of novel molecular markers with clinical relevance associated with the disease. PMID:27611921

  20. lncRNA profiling in early-stage chronic lymphocytic leukemia identifies transcriptional fingerprints with relevance in clinical outcome

    PubMed Central

    Ronchetti, D; Manzoni, M; Agnelli, L; Vinci, C; Fabris, S; Cutrona, G; Matis, S; Colombo, M; Galletti, S; Taiana, E; Recchia, A G; Bossio, S; Gentile, M; Musolino, C; Di Raimondo, F; Grilli, A; Bicciato, S; Cortelezzi, A; Tassone, P; Morabito, F; Ferrarini, M; Neri, A

    2016-01-01

    Long non-coding RNAs (lncRNAs) represent a novel class of functional RNA molecules with an important emerging role in cancer. To elucidate their potential pathogenetic role in chronic lymphocytic leukemia (CLL), a biologically and clinically heterogeneous neoplasia, we investigated lncRNAs expression in a prospective series of 217 early-stage Binet A CLL patients and 26 different subpopulations of normal B-cells, through a custom annotation pipeline of microarray data. Our study identified a 24-lncRNA-signature specifically deregulated in CLL compared with the normal B-cell counterpart. Importantly, this classifier was validated on an independent data set of CLL samples. Belonging to the lncRNA signature characterizing distinct molecular CLL subgroups, we identified lncRNAs recurrently associated with adverse prognostic markers, such as unmutated IGHV status, CD38 expression, 11q and 17p deletions, and NOTCH1 mutations. In addition, correlation analyses predicted a putative lncRNAs interplay with genes and miRNAs expression. Finally, we generated a 2-lncRNA independent risk model, based on lnc-IRF2-3 and lnc-KIAA1755-4 expression, able to distinguish three different prognostic groups in our series of early-stage patients. Overall, our study provides an important resource for future studies on the functions of lncRNAs in CLL, and contributes to the discovery of novel molecular markers with clinical relevance associated with the disease. PMID:27611921

  1. Challenges and new opportunities for clinical nutrition interventions in the aged.

    PubMed

    Johnson, Mary Ann; Dwyer, Johanna T; Jensen, Gordon L; Miller, Joshua W; Speakman, John R; Starke-Reed, Pamela; Volpi, Elena

    2011-03-01

    Nutritional status plays a critical role in the prevention and management of many chronic health conditions that are common in the elderly and are likely to become more prevalent as the population ages. This paper highlights several aspects of nutrition that require additional basic science and clinical application research to improve the health and well-being of older adults. Topics addressed are selected demographic and health indices, the uncertain benefits of energy restriction in aged humans compared with other species, the impact of food insecurity on health, the relationship between dietary protein and sarcopenia, the prevention and management of obesity while maintaining muscle mass and functional status, and controversy regarding high intakes of folic acid. Research needs regarding the safety, efficacy, and application of clinical interventions related to these topics also are discussed.

  2. Clinical Diagnoses before Age 75 and Men's Survival to Their 85th Birthday: The Manitoba Follow-Up Study

    ERIC Educational Resources Information Center

    Tate, Robert B.; Michaels, Leon; Cuddy, T. Edward; Bayomi, Dennis J.

    2013-01-01

    Purpose: Of all Canadian and American men who live to age 75 years, about half can expect to live to age 85. Our objective is to examine how clinical diagnoses made before age 75 relate to a man's survival to age 85 years. Design and Methods: Since 1948, a cohort of 3,983 young men (mean age of 31 years at entry) has been followed with routine…

  3. [Role of the age factor in forming the clinical picture of anorexia nervosa].

    PubMed

    Korkina, M V; Zeĭgarnik, B V; Kareva, M A; Marilov, V V

    1976-12-01

    The results of long-term clinical and experimental-psychological studies of patients with nervous anorexia were analyzed from the point of view of age psychology. Such approaches permitted to distinguish a peculiarity in the formation mechanism of this form of pathology. Dynamical studies of the moving forces in the personality development in morbid conditions allowed one to distinguish certain disorders in the process of periodization of the mental development. This in its turn exerts influence on the development of nervous anorexia.

  4. Factors influencing adherence to regular exercise in middle-aged women: a qualitative study to inform clinical practice

    PubMed Central

    2014-01-01

    Background About half of women decrease their regular exercise during middle age. Concurrently, they experience a reduction in basal metabolic rate and loss of lean muscle as they transition to menopause. The combined effects place these women at increased risk for body weight gain and associated co-morbidities. Further research is required to better assess their barriers to regular exercise and to develop more applied knowledge aimed to improve the applicability of clinical interventions aimed at this population. The main aim of this study was to identify enablers and barriers influencing adherence to regular exercise in middle-aged women who exercise. Methods An interpretive description qualitative study was conducted using individual interviews. The two key questions were focused on planning to engage in physical activity and succeeding or planning to engage in physical activity and not succeeding. Inductive content analysis was used. Results Fifty-three women interviewed were aged 40–62 years and experiencing mild to moderate menopausal symptoms. Six broad themes influencing adhering to regular exercise were: routine, intrinsic motivation, biophysical issues, psychosocial commitments, environmental factors, and resources. Common sub-themes were identified as enabling factors: daily structure that incorporated physical activity (broad theme routine), anticipated positive feelings associated with physical activity (intrinsic), and accountability to others (psychosocial). Other common sub-themes identified as barriers were disruptions in daily structure (routine), competing demands (routine) and self-sacrifice (psychosocial). Conclusions The most common barrier middle-aged women describe as interfering with adhering to regular exercise was attributable to the demands of this life stage at home and with others. Lack of time and menopausal symptoms were not identified as the common barriers. To support women to adhere to regular exercise, healthcare professionals

  5. Negative perceptions about condom use in a clinic population: comparisons by gender, race and age.

    PubMed

    Crosby, R; Shrier, L A; Charnigo, R; Sanders, S A; Graham, C A; Milhausen, R; Yarber, W L

    2013-02-01

    We sought to elucidate the associations of 13 items assessing negative perceptions about condom use with gender, age and race in a sample of clinic attendees. Patients from four clinics, in three US cities, were recruited (N = 928). Data were collected using audio-computer-assisted self-interviewing. The primary measure was a 13-item adapted version of the Condom Barriers Scale. Logistic regression and chi-square tests were employed to relate the 13 items to gender, age and race. Gender, race and age all had significant associations with negative perceptions of condoms and their use. A primary finding was a large number of significant differences between men and women, with negative perceptions more common among women than among men. For African Americans, especially women, negative perceptions were more common among older participants than among younger participants. In conclusion, important demographic differences regarding negative perceptions may inform the tailoring of intervention efforts that seek to rectify negative perceptions about condoms and thus promote condom use among individuals at risk for sexually transmitted infections (STIs) in the USA. On the other hand, our findings also suggest that the majority of STI clinic attendees may hold positive perceptions about condoms and their use; maintaining and building upon these positive perceptions via education, counselling, and access is also important. PMID:23467292

  6. Dopamine transporter availability in clinically normal aging is associated with individual differences in white matter integrity.

    PubMed

    Rieckmann, Anna; Hedden, Trey; Younger, Alayna P; Sperling, Reisa A; Johnson, Keith A; Buckner, Randy L

    2016-02-01

    Aging-related differences in white matter integrity, the presence of amyloid plaques, and density of biomarkers indicative of dopamine functions can be detected and quantified with in vivo human imaging. The primary aim of the present study was to investigate whether these imaging-based measures constitute independent imaging biomarkers in older adults, which would speak to the hypothesis that the aging brain is characterized by multiple independent neurobiological cascades. We assessed MRI-based markers of white matter integrity and PET-based marker of dopamine transporter density and amyloid deposition in the same set of 53 clinically normal individuals (age 65-87). A multiple regression analysis demonstrated that dopamine transporter availability is predicted by white matter integrity, which was detectable even after controlling for chronological age. Further post-hoc exploration revealed that dopamine transporter availability was further associated with systolic blood pressure, mirroring the established association between cardiovascular health and white matter integrity. Dopamine transporter availability was not associated with the presence of amyloid burden. Neurobiological correlates of dopamine transporter measures in aging are therefore likely unrelated to Alzheimer's disease but are aligned with white matter integrity and cardiovascular risk. More generally, these results suggest that two common imaging markers of the aging brain that are typically investigated separately do not reflect independent neurobiological processes. Hum Brain Mapp 37:621-631, 2016. © 2015 Wiley Periodicals, Inc.

  7. A dedicated clinic for HIV-positive individuals over 50 years of age: a multidisciplinary experience.

    PubMed

    Waters, L; Patterson, B; Scourfield, A; Hughes, A; de Silva, S; Gazzard, B; Barton, S; Asboe, D; Pozniak, A; Boffito, M

    2012-08-01

    The HIV-infected population is ageing. Issues including polypharmacy and co-morbidities led us to develop a dedicated clinic for HIV-infected individuals over 50. We describe our service evaluation after two years. The over 50 clinic commenced in January 2009. The team comprises a registrar, consultant, nurse practitioner and is supported by a pharmacist and mental health services. Patients undergo a full medication and drug interactions review, neurocognitive assessment, adherence self-assessment and investigations including therapeutic drug monitoring (TDM), coronary artery calcium scores (CACS) and bone mineral density. Over two years of activity, 150 patients attended the service. Median (range) age was 58 (50-88), all were on combined antiretroviral therapy and 38% (57/150) were on ≥3 non-HIV drugs. CACS was high (>90th centile) in 14%. Thirty-eight percent had osteopaenia and 18% had osteoporosis requiring treatment. Thirteen out of 125 men had an increased prostate specific antigen, four were diagnosed with prostate cancer. Drug interaction, TDM and neurocognitive assessments were useful for several patients. Asymptomatic patients over 50 in long-term follow-up had new pathologies detected through targeted screening. The clinic has improved general practitioner (GP) liaison and facilitated closer working relationships with other specialties. Patients have reacted positively to the clinic, particularly as many do not routinely access their GP. PMID:22930290

  8. Sustained expression of a neuron-specific isoform of the Taf1 gene in development stages and aging in mice

    SciTech Connect

    Jambaldorj, Jamiyansuren; Makino, Satoshi; Munkhbat, Batmunkh; Tamiya, Gen

    2012-08-24

    Highlights: Black-Right-Pointing-Pointer We identified the mouse homologue of neuron-specific TAF1 (N-Taf1). Black-Right-Pointing-Pointer Taf1 mRNA was expressed in most tissues and cell lines. Black-Right-Pointing-Pointer N-Taf1 mRNA was expressed in the brain and Neuroblastoma N2a cell lines. Black-Right-Pointing-Pointer Taf1 and N-Taf1 showed different expression profile in development stage and aging. -- Abstract: TATA-box binding protein associated factor 1 (TAF1) protein is the largest and the essential component of the TFIID complex in the pathway of RNA polymerase II-mediated gene transcription, and it regulates transcription of a large number of genes related to cell division. The neuron-specific isoform of the TAF1 gene (N-TAF1), which we reported previously, may have an essential role in neurons through transcriptional regulation of many neuron-specific genes. In the present study, we cloned the full-length cDNA that encodes the mouse homologue of N-TAF1 (N-Taf1) protein. By carrying out of real time RT-PCR, we investigated the expression analysis of the N-Taf1 mRNA in mouse tissues and cell lines. As well as the human N-TAF1, the N-Taf1 showed limited expression in the brain and neuroblastoma, whereas Taf1 expressed elsewhere. Furthermore, in mouse embryo head or mouse brain, mRNA expression of TAF1 changes dramatically during development but N-Taf1 showed sustained expression. Our result suggests that the N-Taf1 gene has an important role in non-dividing neuronal cell rather than in cell division and proliferation during neurogenesis.

  9. Lymphadenectomy in locally advanced cervical cancer study (LiLACS): Phase III clinical trial comparing surgical with radiologic staging in patients with stages IB2-IVA cervical cancer.

    PubMed

    Frumovitz, Michael; Querleu, Denis; Gil-Moreno, Antonio; Morice, Philippe; Jhingran, Anuja; Munsell, Mark F; Macapinlac, Homer A; Leblanc, Eric; Martinez, Alejandra; Ramirez, Pedro T

    2014-01-01

    Radiation treatment planning for women with locally advanced cervical cancer (stages IB2-IVA) is often based on positron emission tomography (PET). PET, however, has poor sensitivity in detecting metastases in aortocaval nodes. We have initiated a study with the objective of determining whether pre-therapeutic laparoscopic surgical staging followed by tailored chemoradiation improves survival as compared with PET/computed tomography (CT) radiologic staging alone followed by chemoradiation. This international, multicenter phase III trial will enroll 600 women with stages IB2-IVA cervical cancer and PET/CT findings showing fluorodeoxyglucose-avid pelvic nodes and fluorodeoxyglucose-negative para-aortic nodes. Eligible patients will be randomized to undergo either pelvic radiotherapy with chemotherapy (standard-of-care arm) or surgical staging via a minimally invasive extraperitoneal approach followed by tailored radiotherapy with chemotherapy (experimental arm). The primary end point is overall survival. Secondary end points are disease-free survival, short- and long-term morbidity with pre-therapeutic surgical staging, and determination of anatomic locations of metastatic para-aortic nodes in relationship to the inferior mesenteric artery. We believe this study will show that tailored chemoradiation after pre-therapeutic surgical staging improves survival as compared with chemoradiation based on PET/CT in women with stages IB2-IVA cervical cancer.

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-01-30

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

  12. Mastectomy With Immediate Expander-Implant Reconstruction, Adjuvant Chemotherapy, and Radiation for Stage II-III Breast Cancer: Treatment Intervals and Clinical Outcomes

    SciTech Connect

    Wright, Jean L.; Cordeiro, Peter G.; Ben-Porat, Leah; Van Zee, Kimberly J.; Hudis, Clifford; Beal, Kathryn; McCormick, Beryl

    2008-01-01

    Purpose: To determine intervals between surgery and adjuvant chemotherapy and radiation in patients treated with mastectomy with immediate expander-implant reconstruction, and to evaluate locoregional and distant control and overall survival in these patients. Methods and Materials: Between May 1996 and March 2004, 104 patients with Stage II-III breast cancer were routinely treated at our institution under the following algorithm: (1) definitive mastectomy with axillary lymph node dissection and immediate tissue expander placement, (2) tissue expansion during chemotherapy, (3) exchange of tissue expander for permanent implant, (4) radiation. Patient, disease, and treatment characteristics and clinical outcomes were retrospectively evaluated. Results: Median age was 45 years. Twenty-six percent of patients were Stage II and 74% Stage III. All received adjuvant chemotherapy. Estrogen receptor staining was positive in 77%, and 78% received hormone therapy. Radiation was delivered to the chest wall with daily 0.5-cm bolus and to the supraclavicular fossa. Median dose was 5040 cGy. Median interval from surgery to chemotherapy was 5 weeks, from completion of chemotherapy to exchange 4 weeks, and from exchange to radiation 4 weeks. Median interval from completion of chemotherapy to start of radiation was 8 weeks. Median follow-up was 64 months from date of mastectomy. The 5-year rate for locoregional disease control was 100%, for distant metastasis-free survival 90%, and for overall survival 96%. Conclusions: Mastectomy with immediate expander-implant reconstruction, adjuvant chemotherapy, and radiation results in a median interval of 8 weeks from completion of chemotherapy to initiation of radiation and seems to be associated with acceptable 5-year locoregional control, distant metastasis-free survival, and overall survival.

  13. Demographic and Clinical Characteristics of Middle-Aged versus Younger Adults Enrolled in a Clinical Trial of a Web-Delivered Psychosocial Treatment for Substance Use Disorders

    PubMed Central

    Kalapatapu, Raj K.; Campbell, Aimee; Aharonovich, Efrat; Hu, Mei-Chen; Levin, Frances R.; Nunes, Edward V.

    2012-01-01

    Objective Evidence suggests that substance abuse is becoming more prevalent in middle-aged adults. The objective of this secondary analysis was to add to the growing empirical literature on the unique features of middle-aged substance abuse populations. Methods We descriptively compared baseline demographic and clinical characteristics of middle-aged (age 45–62, n = 111) and younger (age 18–44, n = 395) substance abusers entering a web-based psychosocial treatment study as part of the National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN). Results A significantly greater percentage of middle-aged adults were non-Caucasian and had a marital status other than single/never married. There was a significant association between frequency of Internet use and the age group. Forty-six percent of middle-aged adults versus 21% of younger adults reported no Internet use in the prior 90 days. A significantly greater percentage of middle-aged adults used cocaine, and a significantly greater percentage of younger adults used marijuana and opioids. Clinically significant cognitive impairment (z less than −1.0) was found for the average participant in both groups on logical association of familiar concepts. Conclusions This secondary analysis of a NIDA CTN study provides additional information on the unique features of middle-aged substance abusers. Increasing knowledge of similarities and differences between younger and middle-aged substance abusers can help with potential age-specific substance abuse treatment planning. PMID:23340711

  14. Exploring the Effects of Genetic Variants on Clinical Profiles of Parkinson's Disease Assessed by the Unified Parkinson's Disease Rating Scale and the Hoehn-Yahr Stage.

    PubMed

    Shi, Chen; Zheng, Zheng; Wang, Qi; Wang, Chaodong; Zhang, Dabao; Zhang, Min; Chan, Piu; Wang, Xiaomin

    2016-01-01

    Many genetic variants have been linked to familial or sporadic Parkinson's disease (PD), among which those identified in PARK16, BST1, SNCA, LRRK2, GBA and MAPT genes have been demonstrated to be the most common risk factors worldwide. Moreover, complex gene-gene and gene-environment interactions have been highlighted in PD pathogenesis. Compared to studies focusing on the predisposing effects of genes, there is a relative lack of research investigating how these genes and their interactions influence the clinical profiles of PD. In a cohort consisting of 2,011 Chinese Han PD patients, we selected 9 representative variants from the 6 above-mentioned common PD genes to analyze their main and epistatic effects on the Unified Parkinson's Disease Rating Scale (UPDRS) and the Hoehn and Yahr (H-Y) stage of PD. With multiple linear regression models adjusting for medication status, disease duration, gender and age at onset, none of the variants displayed significant main effects on UPDRS or the H-Y scores. However, for gene-gene interaction analyses, 7 out of 37 pairs of variants showed significant or marginally significant associations with these scores. Among these, the GBA rs421016 (L444P)×LRRK2 rs33949390 (R1628P) interaction was consistently significant in relation to UPDRS III and UPDRS total (I+II+III), even after controlling for the family-wise error rate using False Discovery Rate (FDR-corrected p values are 0.0481 and 0.0070, respectively). Although the effects of the remaining pairs of variants did not survive the FDR correction, they showed marginally significant associations with either UPDRS or the H-Y stage (raw p<0.05). Our results highlight the importance of epistatic effects of multiple genes on the determination of PD clinical profiles and may have implications for molecular classification and personalized intervention of the disease.

  15. Exploring the Effects of Genetic Variants on Clinical Profiles of Parkinson's Disease Assessed by the Unified Parkinson's Disease Rating Scale and the Hoehn-Yahr Stage.

    PubMed

    Shi, Chen; Zheng, Zheng; Wang, Qi; Wang, Chaodong; Zhang, Dabao; Zhang, Min; Chan, Piu; Wang, Xiaomin

    2016-01-01

    Many genetic variants have been linked to familial or sporadic Parkinson's disease (PD), among which those identified in PARK16, BST1, SNCA, LRRK2, GBA and MAPT genes have been demonstrated to be the most common risk factors worldwide. Moreover, complex gene-gene and gene-environment interactions have been highlighted in PD pathogenesis. Compared to studies focusing on the predisposing effects of genes, there is a relative lack of research investigating how these genes and their interactions influence the clinical profiles of PD. In a cohort consisting of 2,011 Chinese Han PD patients, we selected 9 representative variants from the 6 above-mentioned common PD genes to analyze their main and epistatic effects on the Unified Parkinson's Disease Rating Scale (UPDRS) and the Hoehn and Yahr (H-Y) stage of PD. With multiple linear regression models adjusting for medication status, disease duration, gender and age at onset, none of the variants displayed significant main effects on UPDRS or the H-Y scores. However, for gene-gene interaction analyses, 7 out of 37 pairs of variants showed significant or marginally significant associations with these scores. Among these, the GBA rs421016 (L444P)×LRRK2 rs33949390 (R1628P) interaction was consistently significant in relation to UPDRS III and UPDRS total (I+II+III), even after controlling for the family-wise error rate using False Discovery Rate (FDR-corrected p values are 0.0481 and 0.0070, respectively). Although the effects of the remaining pairs of variants did not survive the FDR correction, they showed marginally significant associations with either UPDRS or the H-Y stage (raw p<0.05). Our results highlight the importance of epistatic effects of multiple genes on the determination of PD clinical profiles and may have implications for molecular classification and personalized intervention of the disease. PMID:27299523

  16. The rates of change of the stochastic trajectories of acceleration variability are a good predictor of normal aging and of the stage of Parkinson's disease

    PubMed Central

    Torres, Elizabeth B.

    2013-01-01

    The accelerometer data from mobile smart phones provide stochastic trajectories that change over time. This rate of change is unique to each person and can be well-characterized by the continuous two-parameter family of Gamma probability distributions. Accordingly, on the Gamma plane each participant can be uniquely localized by the shape and the scale parameters of the Gamma probability distribution. The scatter of such points contains information that can unambiguously separate the normal controls (NC) from those patients with Parkinson's disease (PD) that are at a later stage of the disease. In general normal aging seems conducive of more predictable patterns of variation in the accelerometer data. Yet this trend breaks down in PD where the statistical signatures seem to be a more relevant predictor of the stage of the disease. Those patients at a later stage of the disease have more random and noisier patterns than those in the earlier stages, whose statistics resemble those of the older NC. Overall the peak rates of change of the stochastic trajectories of the accelerometer are a good predictor of the stage of PD and of the age of a “normally” aging individual. PMID:23882193

  17. Global estimate of the incidence of clinical pneumonia among children under five years of age.

    PubMed Central

    Rudan, Igor; Tomaskovic, Lana; Boschi-Pinto, Cynthia; Campbell, Harry

    2004-01-01

    OBJECTIVE: Clinical pneumonia (defined as respiratory infections associated with clinical signs of pneumonia, principally pneumonia and bronchiolitis) in children under five years of age is still the leading cause of childhood mortality in the world. In this paper we aim to estimate the worldwide incidence of clinical pneumonia in young children. METHODS: Our estimate for the developing world is based on an analysis of published data on the incidence of clinical pneumonia from community based longitudinal studies. Among more than 2000 studies published since 1961, we identified 46 studies that reported the incidence of clinical pneumonia, and 28 of these met pre-defined quality criteria. FINDINGS: The estimate of the median incidence from those studies was 0.28 episodes per child-year (e/cy). The 25-75% interquartile range was 0.21-0.71. We assessed the plausibility of this estimate using estimates of global mortality from acute respiratory infections and reported case fatality rates for all episodes of clinical pneumonia reported in community-based studies or the case-fatality rate reported only for severe cases and estimates of the proportion of severe cases occurring in a defined population or community. CONCLUSION: The overlap between the ranges of the estimates implies that a plausible incidence estimate of clinical pneumonia for developing countries is 0.29 e/cy. This equates to an annual incidence of 150.7 million new cases, 11-20 million (7-13%) of which are severe enough to require hospital admission. In the developed world no comparable data are available. However, large population-based studies report that the incidence of community-acquired pneumonia among children less than five years old is approximately 0.026 e/cy, suggesting that more than 95% of all episodes of clinical pneumonia in young children worldwide occur in developing countries. PMID:15654403

  18. Assessment and classification of early-stage multiple sclerosis with inertial sensors: comparison against clinical measures of disease state.

    PubMed

    Greene, Barry R; Rutledge, Stephanie; McGurgan, Iain; McGuigan, Christopher; OConnell, Karen; Caulfield, Brian; Tubridy, Niall

    2015-07-01

    A cross-sectional study on patients with early-stage multiple sclerosis (MS) was conducted to examine the reliability of manual and automatic mobility measures derived from shank-mounted inertial sensors during the Timed Up and Go (TUG) test, compared to control subjects. Furthermore, we aimed to determine if disease status [as measured by the Multiple Sclerosis Impact Scale (MSIS-20) and the Expanded Disability Status Score (EDSS)] can be explained by measurements obtained using inertial sensors. We also aimed to determine if patients with early-stage MS could be automatically distinguished from healthy controls subjects, using inertial parameters recorded during the TUG test. The mobility of 38 patients (aged 25-65 years, 14 M, 24 F), diagnosed with relapsing-remitting MS and 33 healthy controls (14 M, 19 F, age 50-65), was assessed using the TUG test, while patients wore inertial sensors on each shank. Reliability analysis showed that 36 of 53 mobility parameters obtained during the TUG showed excellent intrasession reliability, while nine of 53 showed moderate reliability. This compared favorably with the reliability of the mobility parameters in healthy controls. Exploratory regression models of the EDSS and MSIS-20 scales were derived, using mobility parameters and an elastic net procedure in order to determine which mobility parameters influence disease state. A cross-validated elastic net regularized regression model for MSIS-20 yielded a mean square error (MSE) of 1.1 with 10 degrees of freedom (DoF). Similarly, an elastic net regularized regression model for EDSS yielded a cross-validated MSE of 1.3 with 10 DoF. Classification results show that the mobility parameters of participants with early-stage MS could be distinguished from controls with 96.90% accuracy. Results suggest that mobility parameters derived from MS patients while completing the TUG test are reliable, are associated with disease state in MS, and may have utility in screening for early-stage

  19. Effects of laser immunotherapy on late-stage, metastatic breast cancer patients in a Phase II clinical trial

    NASA Astrophysics Data System (ADS)

    Ferrel, Gabriela L.; Zhou, Feifan; Li, Xiaosong; Hode, Tomas; Nordquist, Robert E.; Alleruzzo, Luciano; Chen, Wei R.

    2014-03-01

    Laser immunotherapy (LIT), a novel technique with a local intervention to induce systemic antitumor effects, was developed to treat metastatic cancers. The pre-clinical studies of LIT have shown its unique characteristics in generating a specific antitumor immunity in treating metastatic tumors in rats and mice. For late-stage, metastatic breast cancer patients, who were considered to be out of other available treatment options, we conducted a small Phase II clinical trial using LIT starting in 2009 in Lima, Peru. This Phase II study was closed in December of 2012, as acknowldged by the Ministry of Health (MOH) of Peur letter 438-2014-OGITT/INS dated March 5th, 2014. Ten patients were enrolled and received LIT in one or multiple 4-week treatment cycles. At the study closing date, four patients were alive and two of them remained cancer free. Here, following the successful conclusion of our Phase II study, we report the clinical effects of LIT on metastatic breast cancer patients. Specifically, we present the overall status of all the patients three years after the treatment and also the outcomes of two long-term surviving patients.

  20. Generation Changes over the Period of 1986-2006 in the Physical Fitness of Boys Aged 7-19 from Eastern Poland at Particular Stages of Education

    ERIC Educational Resources Information Center

    Saczuk, Jerzy; Wasiluk, Agnieszka; Zalech, Miroslaw

    2012-01-01

    Study aim: To assess the size of secular trends in the physical fitness of boys from eastern Poland taking into consideration stages of education. Material and methods: The physical fitness results of boys aged 7-19 years living in eastern regions of Poland were analyzed: 3188 students were examined in 1986 while in 2006 the research included 10…

  1. Evaluation of the Turkish Version of the "Ages and Stages Questionnaires: Social-Emotional" in Identifying Children with Social-Emotional Problems

    ERIC Educational Resources Information Center

    Kucuker, Sevgi; Kapci, Emine Gul; Uslu, Runa Idil

    2011-01-01

    The applicability of the Age and Stages Questionnaires: Social Emotional (ASQ-SE; J. Squires, D. Bricker & E. Twombly, 2003) for Turkish children was examined. A total of 608 mothers completed the ASQ-SE's. Overall sensitivity and overall specificity were 83.7% and 89.9%, respectively. Test-retest reliability, assessed by classifying children as…

  2. Early-Stage Breast Cancer in the Elderly: Confronting an Old Clinical Problem

    PubMed Central

    Dimitrakopoulos, Fotinos-Ioannis D.; Kottorou, Anastasia; Antonacopoulou, Anna G.; Makatsoris, Thomas

    2015-01-01

    Breast cancer generally develops in older women and its incidence is continuing to increase with increasing age of the population. The pathology and biology of breast cancer seem to be different in the elderly, often resulting in the undertreatment of elderly patients and thus in higher rates of recurrence and mortal-ity. The aim of this review is to describe the differences in the biology and treatment of early breast cancer in the elderly as well as the use of geriatric assessment methods that aid decision-making. Provided there are no contraindications, the cornerstone of treatment should be surgery, as the safety and efficacy of surgical resection in elderly women have been well documented. Because most breast cancers in the elderly are hormone responsive, hormonal therapy remains the mainstay of systemic treatment in the adjuvant setting. The role of chemotherapy is limited to patients who test negative for hormone receptors and demonstrate an aggressive tumor profile. Although the prognosis of breast cancer patients has generally improved during the last few decades, there is still a demand for evidence-based optimization of therapeutic interventions in older patients. PMID:26472970

  3. A new staging system for nasopharyngeal carcinoma based on intensity-modulated radiation therapy: results of a prospective multicentric clinical study

    PubMed Central

    Kang, Min; Long, Jianxiong; Li, Guisheng; Yan, Haolin; Feng, Guosheng; Liu, Meilian; Zhu, Jinxian; Wang, Rensheng

    2016-01-01

    Purpose To establish a new clinical staging standard for nasopharyngeal carcinoma (NPC), based on intensity-modulated radiotherapy (IMRT), through a prospective multicenter clinical trial. Experiment Design 492 NPC patients were selected from six hospitals in the Guangxi Zhuang Autonomous Region, China from January 2006 to December 2009. Kaplan-Meier method was adopted to calculate survival rates. Log-rank test was used to compare survival differences. Results According to the seventh edition of the UICC/AJCC staging system, the differences between T1, T2 and T3 are not statistically significant, suggesting that T1, T2 and T3 could be combined as new T1. There were significant differences between all N stages except those of N3a and N3b, suggesting that N3a and N3b could be combined as new N3. Additionally, the overall survival (OS) curves of stages I, II, III and IVa were not significantly different. Therefore, we propose a new clinical NPC staging standard based on magnetic resonance imaging (MRI) and IMRT as T stage (including T1 and T2), N stage (including N0, N1, N2 and N3) and clinical staging includes I (T1N0M0), II (T1N1-2M0, T2N0M0), III (T2N1-2M0), IVa (TxN3M0) and IVb (TxNxM1). Recommended staging system performs better in risk difference and distribution balance. Furthermore, the differences in the 5-year curves of local relapse-free survival (LRFS), distant metastasis-free survival (DMFS), and OS were all statistically more significant than the seventh edition of the UICC/AJCC staging system. Conclusions Proposed staging system is more adaptable to IMRT and predicts the prognosis of NPC patients more accurately. PMID:26918446

  4. Amyloid PET Screening for Enrichment of Early-Stage Alzheimer Disease Clinical Trials: Experience in a Phase 1b Clinical Trial.

    PubMed

    Sevigny, Jeff; Suhy, Joyce; Chiao, Ping; Chen, Tianle; Klein, Gregory; Purcell, Derk; Oh, Joonmi; Verma, Ajay; Sampat, Mehul; Barakos, Jerome

    2016-01-01

    Amyloid positron emission tomography (PET) imaging is being investigated as a screening tool to identify amyloid-positive patients as an enrichment strategy for Alzheimer disease (AD) clinical trial enrollment. In a multicenter, phase 1b trial, patients meeting clinical criteria for prodromal or mild AD underwent florbetapir PET scanning at screening. PET, magnetic resonance imaging, and coregistered PET/magnetic resonance imaging scans were reviewed by 2 independent readers and binary visual readings tabulated. Semiquantitative values of cortical to whole cerebellar standard uptake value ratios were computed (threshold 1.10). Of 278 patients with an evaluable PET scan, 170 (61%) and 185 (67%) were amyloid-positive by visual reading and quantitative analysis, respectively; 39% were excluded from the study due to an amyloid-negative scan based on visual readings. More ApoE ε4 carriers than noncarriers were amyloid-positive (80% vs. 43%). Comparison of visual readings with quantitative results identified 21 discordant cases (92% agreement). Interreader and intrareader agreements from visual readings were 98% and 100%, respectively. Amyloid PET imaging is an effective and feasible screening tool for enrollment of amyloid-positive patients with early stages of AD into clinical trials.

  5. Multi-stage uplift of the Colorado Plateau and the age of Grand Canyon and precursor canyons

    NASA Astrophysics Data System (ADS)

    Karlstrom, K. E.; Lee, J. P.; Kelley, S. A.; Crow, R.

    2012-12-01

    Debates about the age of Grand Canyon link to debates about the timing of surface uplift(s) of the Colorado Plateau- Rocky Mountain (CP-RM) region. One "old Grand Canyon" model proposes that a paleocanyon of almost the same depth and location as today's Grand Canyon was carved by a NE-flowing "California" paleoriver 80-70 Ma, then was re-used at ~55 Ma by a SW-flowing "Arizona" paleoriver. This model postulates the CP-RM region was uplifted to near modern elevations during the Laramide orogeny. A second model postulates a 17 Ma Grand Canyon; this time corresponds to Basin and Range extension and postulated mantle-driven surface uplift. The "young Grand Canyon" model postulates that >2/3 of modern Grand Canyon was carved by W-flowing Colorado River that became integrated to the Gulf of California at 5-6 Ma during Neogene mantle-driven uplift of the CP/RM region. Thermochronologic data are poised to substantially resolve these debates. Our thermochronology dataset combines published and new apatite fission-track and helium analyses, and joint thermal history modeling using both systems. This dataset reveals three major cooling episodes: 1) a multi-stage Sevier-Laramide contraction episode from about 90 Ma to 50 Ma with structural relief on upwarps on the order 0.5-1 km, compatible with a similar magnitude of surface uplift; 2) 30-20 Ma cooling that was associated with denudation and northward cliff retreat of most of the Mesozoic section from Grand Canyon region; 3) <10 Ma cooling that is best documented in eastern Grand Canyon as part of a general pattern of decreasing age of cooling/denudation to the NE. Combined geologic and thermochronologic data define the age and 3-D geometry of Cenozoic paleotopography that led to Grand Canyon carving. Combined AHe and AFT data indicate 2-4 km of sedimentary rocks covered the Grand Canyon region until about 40 Ma, negating the California River model. These strata were not removed from the Marble Canyon area until after about

  6. Clinical profile of patients with advanced age and inflammatoric dilated cardiomyopathy on endomyocardial biopsy

    PubMed Central

    Ohlow, Marc-Alexander; Chen, Ting-Hui; Schmidt, Andreas; Saenger, Joerg; Lauer, Bernward

    2015-01-01

    Background Endomyocardial biopsy (EMB) is an important tool when patients with inflammatoric cardiomyopathy (DCMi) are evaluated. We aimed to assess the clinical profile of elderly patients with DCMi on EMB. Methods Retrospective study of all consecutive patients hospitalized from January 2007 to December 2011 with clinical suspicion of DCMi undergoing EMB. Patients with evidence of DCMi on EMB (Group 1 ≥ 70 years, n = 85; Group 3 < 70 years; n = 418) were compared to patients of the same age group without evidence of DCMi on EMB (Group 2 ≥ 70 years, n = 45; Group 4 < 70 years; n = 147). Results Among 24,275 patients treated at our institution during the study period, 695 had clinical suspicion of DCMi and underwent EMB; 503 (2.1%) patients had DCMi on EMB. There were more male patients in Group 1, mean age was 74 ± 2.8 years, mean ejection fraction was 38% ± 14%. On presentation, signs of hemodynamic compromise (NYHA functional class III/IV, low cardiac output/index, and low cardiac power index) were more frequent in Group 1. EMB revealed viral genome in 78% of the patients, parvovirus B19 (PVB) was frequently encountered in both age groups (Group 1: 69.4% vs. Group 2: 59.6%); detection of more than one viral genome was more frequent in Group 1 (21.2% vs. 11.2%; P = 0.02) whereas the extent of immune response was significantly lower in individuals with advanced age. Conclusions In patients ≥ 70 years with DCMi on EMB signs of hemodynamic compromise, detection of multiple viral genomes together with an overall lower extent of immune response were more frequently observed. PMID:26788036

  7. Clinical Characteristics and Low Vision Rehabilitation Methods for Partially Sighted School-Age Children

    PubMed Central

    Özen Tunay, Zuhal; Çalışkan, Deniz; İdil, Aysun; Öztuna, Derya

    2016-01-01

    Objectives: To determine the clinical features and the distribution of diagnosis in partially sighted school-age children, to report the chosen low vision rehabilitation methods and to emphasize the importance of low vision rehabilitation. Materials and Methods: The study included 150 partially sighted children between the ages of 6 and 18 years. The distribution of diagnosis, accompanying ocular findings, visual acuity of the children both for near and distance with and without low vision devices, and the methods of low vision rehabilitation (for distance and for near) were determined. The demographic characteristics of the children and the parental consanguinity were recorded. Results: The mean age of children was 10.6 years and the median age was 10 years; 88 (58.7%) of them were male and 62 (41.3%) of them were female. According to distribution of diagnoses among the children, the most frequent diagnosis was hereditary fundus dystrophies (36%) followed by cortical visual impairment (18%). The most frequently used rehabilitation methods were: telescopic lenses (91.3%) for distance vision; magnifiers (38.7%) and telemicroscopic systems (26.0%) for near vision. A significant improvement in visual acuity both for distance and near vision were determined with low vision aids. Conclusion: A significant improvement in visual acuity can be achieved both for distance and near vision with low vision rehabilitation in partially sighted school-age children. It is important for ophthalmologists and pediatricians to guide parents and children to low vision rehabilitation. PMID:27800263

  8. Informing school sex education using the stages of change construct: sexual behaviour and attitudes towards sexual activity and condom use of children aged 13-16 in England.

    PubMed

    Wallace, Louise M; Evers, Kerry E; Wareing, Hilary; Dunn, Orla M; Newby, Kate; Paiva, Andrea; Johnson, Janet L

    2007-01-01

    A survey of 3820 school children in England aged 13-16 years examined sexual activity using the Transtheoretical Model (TTM) Stages of Change. A quarter (26%) of teens were sexually experienced, 44.8 per cent did not use contraception and 48.9 per cent did not use condoms, every time. Past history of condom and contraceptive use, and partner willingness to use condoms were the best predictors of being in Action or Maintenance stage for condom use. Of virgins, 19.82 per cent were in Contemplation or Preparation stages for intercourse, and 85.4 per cent would use condoms every time. Sex education should be tailored to Stage, and signposting to sexual health and contraception services.

  9. Age-dependent vitreous separation from the macula in a clinic population

    PubMed Central

    Syed, Zahid; Stewart, Michael W

    2016-01-01

    Background Vitreous degeneration begins soon after birth and accelerates throughout life. Vitreous liquefaction with a slowly progressive separation of the posterior hyaloid from the peripheral macula usually leads to complete posterior vitreous detachment. The purpose of this study is to measure the age-related prevalence of partial vitreous separation and the length of residual vitreous adhesion in an ophthalmology clinic population. Methods Patients examined by the senior author (MWS) during a 6-month period were included in a retrospective chart review. Demographic data and spectral domain optical coherence tomography scan results were gathered. Data analysis with descriptive statistics focused on the prevalence and extent of partial vitreous separation. Results The mean age of the study patients was 69.9 years, and 62% were phakic. The highest prevalence of partial posterior hyaloid separation from the internal limiting membrane (71.2%) was seen in the 50- to 54-year age group. This prevalence rate steadily decreased to 5.6% in the 95- to 99-year age group. The prevalence of complete vitreous detachment as determined by slit-lamp biomicroscopy increased from 1.7% in the <50-year age group to a maximum of 29.2% in the 75- to 79-year group. The length of vitreomacular adhesion averaged 4.6 mm in the 50- to 54-year age group and steadily decreased to 2.1 mm in the 90- to 95-year group. Conclusion Vitreomacular separation affects the majority of eyes in the sixth decade of life. The prevalence of partial vitreous separation decreases with advancing age, probably because an increasing number of these patients progress to complete posterior vitreous detachment. PMID:27462138

  10. Disparities in receipt of radiotherapy and survival by age, sex and ethnicity among patients with stage I diffuse large B-cell lymphoma.

    PubMed

    Shah, Binay Kumar; Bista, Amir; Shafii, Bahman

    2015-04-01

    Disparities in cancer care have been documented. However, less is known about the disparities in diffuse large B-cell lymphoma (DLBCL). We reviewed the Surveillance, Epidemiology and End Results database to evaluate disparities in receipt of radiotherapy (RT) and relative survival among patients diagnosed with stage I DLBCL between 1998 and 2008 on the basis of age, sex and ethnicity. African Americans and other races were significantly less likely to receive RT compared to Caucasians (adjusted odds ratio [OR] of 0.743 and 0.81, respectively). Similarly, patients aged 60 + years and males were less likely to receive RT compared to their counterparts (p < 0.001). Caucasian race, younger age and female sex were associated with better survival among patients receiving RT. This study showed that 38.2% of patients with stage I DLBCL received radiotherapy. Survival rates were significantly higher for patients who received RT.

  11. Phase I-II clinical trial of Californium-252. Treatment of stage IB carcinoma of the cervix.

    PubMed

    Maruyama, Y; VanNagell, J R; Yoneda, J; Donaldson, E; Gallion, H; Rowley, K; Kryscio, R; Beach, J L

    1987-04-15

    Intracavitary Californium-252 combined with whole-pelvis photon radiotherapy was tested as the sole form of treatment for 22 patients with Stage IB carcinoma of the cervix. Californium-252 (Cf) is a fast neutron-emitting radioisotope currently being tested in trials of neutron brachytherapy (NT). The outcomes of the treated group of patients were traced for local tumor control, survival, patterns of failure, and complications. The Cf intracavitary therapy combined with whole-pelvis photon radiotherapy resulted in 95% 2-year and 91% 5-year actuarial survival. There were 9% Grade II-III complications by the Stockholm scale and 4% local failures. These results were obtained in an early clinical trial with a group of largely poor-risk patients with tumors of mean diameter of 4.3 cm.

  12. Clinical Usefulness of Shoulder Stability Exercises for Middle-aged Women

    PubMed Central

    Choi, Seok-Hwa; Lee, Byoung-Hee

    2013-01-01

    [Purpose] This study examined the clinical usefulness of shoulder stability exercises and the effect of stability exercise on the shoulder pain of middle-aged women. [Subjects] Twenty-two middle-aged female subjects were randomly divided into two groups: a shoulder stability exercise group (Experimental group, n=11) and a control group (n=11). [Methods] Subjects in the experimental group performed a shoulder stability exercise, which was designed to correct abnormal location of the scapula, for 40 minutes per day, three times per week, over a period of four weeks. Range of motion, muscle strength, and grasping power were measured to determine the effect of the shoulder stability exercise. The measured parameters were evaluated before and after four weeks of exercise. [Results] Following intervention, range of motion, muscle strength, and grasping power showed greater improvements in the experimental group than in the control group. [Conclusion] The results of this study show that shoulder stability exercise can improve the shoulder function of middle-aged women, and prevent damage to the shoulder joint. We consider this exercise would be useful in clinical rehabilitation. PMID:24259767

  13. Clinical, functional and pathological correspondence in early stage idiopathic pulmonary fibrosis: evidence for small airway obstruction 1-2.

    PubMed

    Myre, M; Allard, S; Bernard, C; Martin, R R

    1988-01-01

    We describe the clinical, physiological and pathological features of 23 subjects with early stage idiopathic pulmonary fibrosis. Thirteen subjects who had no symptoms had been fortuitously recruited by a routine chest radiograph, whereas the 10 other subjects complained of dyspnea. Twenty-one subjects showed only light to moderate extent of abnormalities on the chest radiograph. Fourteen subjects had a reduced vital capacity whereas 16 and 17 showed a reduced pulmonary compliance and an increase in lung elastic recoil, respectively. Transfer factor was significantly reduced in 18 subjects. Evidence for significant airway obstruction, mainly located at the peripheral level, was demonstrated by a reduced specific lung conductance and upstream conductance in 13 subjects. Airway obstruction was not associated with smoking habits. Bronchial hyperresponsiveness was noted in 50% of the 18 subjects studied. Although fibrosis was mild to moderate in 15 instances, it was only focal, i.e. at least one zone of normal parenchyma in the lung specimen in 17 subjects. Peribronchial fibrosis was established in 8/11 satisfactory biopsy specimens. Significant correlations were observed between rales, the radiological score, some functional indices and the characteristics of fibrosis. We conclude that small airway obstruction documented by physiological and pathological means is frequent in early stage idiopathic pulmonary fibrosis. PMID:3420306

  14. Outcomes of Lobectomy in ‘Active’ Octogenarians with Clinical Stage I Non-Small-Cell Lung Cancer

    PubMed Central

    Nakayama, Haruhiko; Yamada, Kouzo; Yokose, Tomoyuki; Masuda, Munetaka

    2014-01-01

    Introduction: In octogenarians with early stage of lung cancer, sublobar resection has been shown to be no inferior survival to lobectomy. However, some octogenarians remain physically and mentally active. Methods: We retrospectively studied 65 octogenarians who underwent curative resection for clinical stage I NSCLC (excluding adenocarcinoma in situ). All patients were assessed by cardiologists and underwent stair-climbing tests (five flights, 18 m) and cognitive function tests. Lobectomy was performed in patients who could climb 5 flights of stairs without stopping or oxygen desaturation of >4%. Results: The actuarial survival rate was 68.6% at 5 years, and the median survival time was 109.2 months. Forty-three patients met the criteria for lobectomy. As compared with sublobar resection, lobectomy was associated with significantly higher rates of overall survival (78.4% vs. 48.5%; p = 0.02) and disease-specific survival (88.4% vs. 61.7%; p = 0.02) at 5 years. On multivariate analysis, male sex (hazard ratio, 3.827; 1.382–10.596) and sublobar resection (2.261; 1.054–5.360) were independent risk factors for survival. Mental disorders occurred in 6 patients (9.2%), and their score on preoperative cognitive function tests was significantly lower than that of patients without mental disorders (22.7 vs. 26.0, p <0.01). Conclusion: Outcomes of lobectomy are good in physically and mentally competent octogenarians. PMID:24747546

  15. Update on Clinical Trials in Dry Age-related Macular Degeneration

    PubMed Central

    Taskintuna, Ibrahim; Elsayed, M. E. A. Abdalla; Schatz, Patrik

    2016-01-01

    This review article summarizes the most recent clinical trials for dry age-related macular degeneration (AMD), the most common cause of vision loss in the elderly in developed countries. A literature search through websites https://www.pubmed.org and https://www.clinicaltrials.gov/, both accessed no later than November 04, 2015, was performed. We identified three Phase III clinical trials that were completed over the recent 5 years Age-Related Eye Disease Study 2 (AREDS2), implantable miniature telescope and tandospirone, and several other trials targeting a variety of mechanisms including, oxidative stress, complement inhibition, visual cycle inhibition, retinal and choroidal blood flow, stem cells, gene therapy, and visual rehabilitation. To date, none of the biologically oriented therapies have resulted in improved vision. Vision improvement was reported with an implantable mini telescope. Stem cells therapy holds a potential for vision improvement. The AREDS2 formulas did not add any further reduced risk of progression to advanced AMD, compared to the original AREDS formula. Several recently discovered pathogenetic mechanisms in dry AMD have enabled development of new treatment strategies, and several of these have been tested in recent clinical trials and are currently being tested in ongoing trials. The rapid development and understanding of pathogenesis holds promise for the future. PMID:26957835

  16. Update on Clinical Trials in Dry Age-related Macular Degeneration.

    PubMed

    Taskintuna, Ibrahim; Elsayed, M E A Abdalla; Schatz, Patrik

    2016-01-01

    This review article summarizes the most recent clinical trials for dry age-related macular degeneration (AMD), the most common cause of vision loss in the elderly in developed countries. A literature search through websites https://www.pubmed.org and https://www.clinicaltrials.gov/, both accessed no later than November 04, 2015, was performed. We identified three Phase III clinical trials that were completed over the recent 5 years Age-Related Eye Disease Study 2 (AREDS2), implantable miniature telescope and tandospirone, and several other trials targeting a variety of mechanisms including, oxidative stress, complement inhibition, visual cycle inhibition, retinal and choroidal blood flow, stem cells, gene therapy, and visual rehabilitation. To date, none of the biologically oriented therapies have resulted in improved vision. Vision improvement was reported with an implantable mini telescope. Stem cells therapy holds a potential for vision improvement. The AREDS2 formulas did not add any further reduced risk of progression to advanced AMD, compared to the original AREDS formula. Several recently discovered pathogenetic mechanisms in dry AMD have enabled development of new treatment strategies, and several of these have been tested in recent clinical trials and are currently being tested in ongoing trials. The rapid development and understanding of pathogenesis holds promise for the future. PMID:26957835

  17. Update on Clinical Trials in Dry Age-related Macular Degeneration.

    PubMed

    Taskintuna, Ibrahim; Elsayed, M E A Abdalla; Schatz, Patrik

    2016-01-01

    This review article summarizes the most recent clinical trials for dry age-related macular degeneration (AMD), the most common cause of vision loss in the elderly in developed countries. A literature search through websites https://www.pubmed.org and https://www.clinicaltrials.gov/, both accessed no later than November 04, 2015, was performed. We identified three Phase III clinical trials that were completed over the recent 5 years Age-Related Eye Disease Study 2 (AREDS2), implantable miniature telescope and tandospirone, and several other trials targeting a variety of mechanisms including, oxidative stress, complement inhibition, visual cycle inhibition, retinal and choroidal blood flow, stem cells, gene therapy, and visual rehabilitation. To date, none of the biologically oriented therapies have resulted in improved vision. Vision improvement was reported with an implantable mini telescope. Stem cells therapy holds a potential for vision improvement. The AREDS2 formulas did not add any further reduced risk of progression to advanced AMD, compared to the original AREDS formula. Several recently discovered pathogenetic mechanisms in dry AMD have enabled development of new treatment strategies, and several of these have been tested in recent clinical trials and are currently being tested in ongoing trials. The rapid development and understanding of pathogenesis holds promise for the future.

  18. Rhesus Rotavirus candidate vaccine. Clinical trial in children vaccinated between 2 and 5 months of age.

    PubMed

    Vesikari, T; Rautanen, T; Varis, T; Beards, G M; Kapikian, A Z

    1990-03-01

    Live attenuated oral rhesus Rotavirus candidate vaccine (strain MMU 18006 [lot RRV-1]) was evaluated for immunogenicity, safety, and clinical protection in a double-blind, placebo-controlled trial involving 200 infants aged 2 to 5 months when vaccinated. Vaccine-induced fourfold or greater rise of Rotavirus antibodies was seen in 62% of the infants. Febrile reactions of short duration on days 3 and/or 4 after vaccination occurred in 26% of the vaccine recipients. The clinical follow-up covered two Rotavirus seasons, in which serotypes 1 and 4 were prevalent. There were 16 cases of confirmed Rotavirus diarrhea in the placebo-treated group and 10 in the vaccine-treated group; from this a vaccine protection rate of 38% was derived. Clinical severity of Rotavirus diarrhea was assessed by a score; 13 cases in the placebo-treated group and 5 in the vaccine-treated group were regarded as severe or moderately severe, giving a vaccine protection rate of 67%. The rhesus Rotavirus vaccine induces partial protection against heterotypic Rotavirus disease, but the level of protection achieved with the present vaccine dose in this age group appears to be insufficient for a general Rotavirus vaccination.

  19. A low-vision clinic at a home for the aged.

    PubMed

    Kornzweig, A L

    1976-12-01

    The objective of a low-vision clinic developed at the Jewish Home and Hospital for Aged was to improve the visual capabilities of the residents who were not helped by the regular eye clinics. Eighty-three patients (72 women, 11 men) were examined the first year. Ages ranged from 71 to 101 years. The causes of poor vision were mainly senile macular degeneration, cataract formation, chronic glaucoma, severe myopia, aphakia, and combinations of these diseases. Vision ranged from 10/50 at 10 feet (20/100 at 20 feet) in the better eye, to only the ability to distinguish hand movements or to perceive light. With the use of visual aids such as distance or reading glasses and various forms of magnifying glasses, some improvement occurred in 61 of the 83 patients. The follow-up examination was within one year in most cases. It was concluded that in order to examine and treat such patients properly, much more time and patience were required than is usually possible in a regular eye clinic. This involved the help of more social workers and volunteer assistants. Nevertheless, the results were worthwhile for this type of patient.

  20. COGNITIVE-HD study: protocol of an observational study of neurocognitive functioning and association with clinical outcomes in adults with end-stage kidney disease treated with haemodialysis

    PubMed Central

    Palmer, Suetonia C; Ruospo, Marinella; Barulli, Maria Rosaria; Iurillo, Annalisa; Saglimbene, Valeria; Natale, Patrizia; Gargano, Letizia; Murgo, Angelo M; Loy, Clement; van Zwieten, Anita; Wong, Germaine; Tortelli, Rosanna; Craig, Jonathan C; Johnson, David W; Tonelli, Marcello; Hegbrant, Jörgen; Wollheim, Charlotta; Logroscino, Giancarlo; Strippoli, G F M

    2015-01-01

    Introduction The prevalence of cognitive impairment may be increased in adults with end-stage kidney disease compared with the general population. However, the specific patterns of cognitive impairment and association of cognitive dysfunction with activities of daily living and clinical outcomes (including withdrawal from treatment) among haemodialysis patients remain incompletely understood. The COGNITIVE impairment in adults with end-stage kidney disease treated with HemoDialysis (COGNITIVE-HD) study aims to characterise the age-adjusted and education-adjusted patterns of cognitive impairment (using comprehensive testing for executive function, perceptual-motor function, language, learning and memory, and complex attention) in patients on haemodialysis and association with clinical outcomes. Methods and analysis A prospective, longitudinal, cohort study of 750 adults with end-stage kidney disease treated with long-term haemodialysis has been recruited within haemodialysis centres in Italy (July 2013 to April 2014). Testing for neurocognitive function was carried out by a trained psychologist at baseline to assess cognitive functioning. The primary study factor is cognitive impairment and secondary study factors will be specific domains of cognitive function. The primary outcome will be total mortality. Secondary outcomes will be cause-specific mortality, major cardiovascular events, fatal and non-fatal myocardial infarction and stroke, institutionalisation, and withdrawal from treatment at 12 months. Ethics and dissemination This protocol was approved before study conduct by the following responsible ethics committees: Catania (approval reference 186/BE; 26/09/2013), Agrigento (protocol numbers 61–62; 28/6/2013), USL Roma C (CE 39217; 24/6/2013), USL Roma F (protocol number 0041708; 23/7/2013), USL Latina (protocol number 20090/A001/2011; 12/7/2013), Trapani (protocol number 3413; 16/7/2013) and Brindisi (protocol number 40259; 6/6/2013). All participants

  1. The National Anesthesia Clinical Outcomes Registry: A Sustainable Model for the Information Age?

    PubMed Central

    Dutton, Richard P.

    2014-01-01

    Anesthesiologists care for patients of all ages, with all conceivable comorbidities, in every kind of health care facility. This leads to a significant challenge in the collection of data to describe the specialty, and in the development of evidence-based performance measures for anesthesiologists. Whereas narrowly defined medical specialties have developed registries based on manual abstraction of clinical data from the medical record (e.g., cardiac surgery), this approach would be prohibitively expensive for anesthesiology, and is unlikely to generate statistically useful data when major adverse outcomes occur a handful of times in tens of thousands of cases. The American Society of Anesthesiologists (ASA) addressed this challenge in 2008 by funding a related organization, the Anesthesia Quality Institute (AQI), to develop the National Anesthesia Clinical Outcomes Registry (NACOR). The technical development of this registry and the approach taken to define the specialty of anesthesiology and the performance of anesthesiologists may serve as a model for other specialty society efforts. PMID:25848607

  2. Axis II comorbidity in borderline personality disorder is influenced by sex, age, and clinical severity.

    PubMed

    Barrachina, Judith; Pascual, Juan C; Ferrer, Marc; Soler, Joaquim; Rufat, M Jesús; Andión, Oscar; Tiana, Thais; Martín-Blanco, Ana; Casas, Miquel; Pérez, Víctor

    2011-01-01

    Borderline personality disorder (BPD) is a severe psychiatric disorder that has a high clinical heterogeneity and frequent co-occurrence with other personality disorders (PDs). Although several studies have been performed to assess axis II comorbidity in BPD, more research is needed to clarify associated factors. The aim of this study was to determine the prevalence of co-occurrent axis II disorders in a large sample of patients with BPD and to investigate the influence of sex, age, and severity on this comorbidity. Data were collected from 484 patients with BPD through 2 semistructured interviews. We analyzed the frequency of axis II comorbidity and assessed differences regarding sex, age, and severity of BPD. About 74% of patients with BPD had at least 1 co-occurrent axis II disorder. The most common were paranoid, passive-aggressive, avoidant, and dependent PDs. Significant sex differences were found. Women presented more comorbidity with dependent PD, whereas men showed higher rates of comorbidity with antisocial PD. We also observed a significant positive correlation between age and the number of co-occurrent axis II disorders in women with BPD. Another finding was the positive correlation between BPD severity and the number of co-occurrent axis II disorders. These findings suggest that comorbidity with other axis II disorders and sex, age, and severity should be taken into account when developing treatment strategies and determining the prognosis of BPD.

  3. Clinical assessment of balance: normative data, and gender and age effects.

    PubMed

    Vereeck, Luc; Wuyts, Floris; Truijen, Steven; Van de Heyning, Paul

    2008-02-01

    The purpose of this study was to provide age specific normative data of clinical gait and balance tests and to determine to what extent gender contributes to differences in postural control. Standing balance and walking performance was tested in 318 asymptomatic adults. The logistic regression, using both 10- and 30-second time limits as a dichotomization point, revealed a significant age effect for standing on foam with eyes closed, tandem Romberg with eyes closed (TR-EC), and one leg stance (eyes open and closed). The actual effect of decline was different for each test. Both tandem gait and dynamic gait index showed a ceiling effect up to 60 years of age, with a rapid decline of performance for subjects in their seventies. Linear regression equations indicated that for both men and women, timed up and go test (TUG) times increased with age, but even older subjects should perform the TUG in 10 seconds or less. Women performed significantly poorer on the TUG and TR-EC (30-second time limit). PMID:18236239

  4. Stages of Adolescence

    MedlinePlus

    ... Español Text Size Email Print Share Stages of Adolescence Page Content Article Body Adolescence, these years from puberty to adulthood, may be roughly divided into three stages: early adolescence, generally ages eleven to fourteen; middle adolescence, ages ...

  5. A Method for Utilizing Bivariate Efficacy Outcome Measures to Screen Regimens for Activity in 2-Stage Phase II Clinical Trials

    PubMed Central

    Rubinstein, Larry; Litwin, Samuel; Yothers, Greg

    2012-01-01

    Background Most phase II clinical trials utilize a single primary endpoint to determine the promise of a regimen for future study. However, many disorders manifest themselves in complex ways. For example, migraine headaches can cause pain, auras, photophobia, and emesis. Investigators may believe a drug is effective at reducing migraine pain and the severity of emesis during an attack. Nevertheless, they could still be interested in proceeding with development of the drug if it is effective against only one of these symptoms. Such a study would be a candidate for a clinical trial with co-primary endpoints. Purpose The purpose of the article is to provide a method for designing a 2-stage clinical trial with dichotomous co-primary endpoints of efficacy that has the ability to detect activity on either response measure with high probability when the drug is active on one or both measures, while at the same time rejecting the drug with high probability when there is little activity on both dimensions. The design enables early closure for futility and is flexible with regard to attained accrual. Methods The design is proposed in the context of cancer clinical trials where tumor response is used to assess a drug's ability to kill tumor cells and progression-free survival (PFS) status after a certain period is used to evaluate the drug's ability to stabilize tumor growth. Both endpoints are assumed to be distributed as binomial random variables, and uninteresting probabilities of success are determined from historical controls. Given the necessity of accrual flexibility, exhaustive searching algorithms to find optimum designs do not seem feasible at this time. Instead, critical values are determined for realized sample sizes using specific procedures. Then accrual windows are found to achieve a design's desired level of significance, probability of early termination (PET), and power. Results The design is illustrated with a clinical trial that examined bevacizumab in

  6. Additional value of F-18 FDG PET/CT for initial staging in breast cancer with clinically negative axillary nodes.

    PubMed

    Jeong, Young Jin; Kang, Do-Young; Yoon, Hyun Jin; Son, Hye Joo

    2014-05-01

    The aim of this study was to evaluate the clinical impact of the preoperative ¹⁸F-FDG PET/CT in the initial workup of breast cancer with clinically negative axillary nodes. Whether the status of the clinical axillary nodal involvement can be considered a parameter for making a decision to omit the preoperative ¹⁸F-FDG PET/CT in the situation reported herein was also determined. A total of 178 patients who had newly diagnosed breast cancer and for whom the conventional diagnostic modalities showed no sign of axillary node metastasis were retrospectively enrolled in this study. All the patients underwent preoperative ¹⁸F-FDG PET/CT. The images and histologic results that were obtained were analyzed. ¹⁸F-FDG PET/CT detected primary lesions in 156 of the 178 patients, with an overall sensitivity of 87.6 %, and false negative results were obtained for 22 patients (12.4 %). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of ¹⁸F-FDG PET/CT in the detection of axillary nodes were 20.8, 86.9, 37.0, 74.8, and 69.1 %, respectively. Extra-axillary node metastasis was identified in two patients (1.1 %) who had internal mammary nodes. There was no distant metastasis, but coexisting primary tumor was detected in five patients (2.8 %). In total, the therapeutic plan was changed based on ¹⁸F-FDG PET/CT in seven (3.9 %) of the 178 patients, but considering only the cases confined to breast cancer, the change occurred in only two patients (1.1 %). ¹⁸F-FDG PET/CT almost did not affect the initial staging and treatment plan in breast cancer with clinically negative axillary node. If the axillary node is clinically negative in the preoperative workup of breast cancer, then ¹⁸F-FDG PET/CT can be omitted.

  7. Bioinformatics Analysis Reveals Distinct Molecular Characteristics of Hepatitis B-Related Hepatocellular Carcinomas from Very Early to Advanced Barcelona Clinic Liver Cancer Stages.

    PubMed

    Kong, Fan-Yun; Wei, Xiao; Zhou, Kai; Hu, Wei; Kou, Yan-Bo; You, Hong-Juan; Liu, Xiao-Mei; Zheng, Kui-Yang; Tang, Ren-Xian

    2016-01-01

    Hepatocellular carcinoma (HCC)is the fifth most common malignancy associated with high mortality. One of the risk factors for HCC is chronic hepatitis B virus (HBV) infection. The treatment strategy for the disease is dependent on the stage of HCC, and the Barcelona clinic liver cancer (BCLC) staging system is used in most HCC cases. However, the molecular characteristics of HBV-related HCC in different BCLC stages are still unknown. Using GSE14520 microarray data from HBV-related HCC cases with BCLC stages from 0 (very early stage) to C (advanced stage) in the gene expression omnibus (GEO) database, differentially expressed genes (DEGs), including common DEGs and unique DEGs in different BCLC stages, were identified. These DEGs were located on different chromosomes. The molecular functions and biology pathways of DEGs were identified by gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and the interactome networks of DEGs were constructed using the NetVenn online tool. The results revealed that both common DEGs and stage-specific DEGs were associated with various molecular functions and were involved in special biological pathways. In addition, several hub genes were found in the interactome networks of DEGs. The identified DEGs and hub genes promote our understanding of the molecular mechanisms underlying the development of HBV-related HCC through the different BCLC stages, and might be used as staging biomarkers or molecular targets for the treatment of HCC with HBV infection. PMID:27454179

  8. Bioinformatics Analysis Reveals Distinct Molecular Characteristics of Hepatitis B-Related Hepatocellular Carcinomas from Very Early to Advanced Barcelona Clinic Liver Cancer Stages

    PubMed Central

    Hu, Wei; Kou, Yan-Bo; You, Hong-Juan; Liu, Xiao-Mei; Zheng, Kui-Yang; Tang, Ren-Xian

    2016-01-01

    Hepatocellular carcinoma (HCC)is the fifth most common malignancy associated with high mortality. One of the risk factors for HCC is chronic hepatitis B virus (HBV) infection. The treatment strategy for the disease is dependent on the stage of HCC, and the Barcelona clinic liver cancer (BCLC) staging system is used in most HCC cases. However, the molecular characteristics of HBV-related HCC in different BCLC stages are still unknown. Using GSE14520 microarray data from HBV-related HCC cases with BCLC stages from 0 (very early stage) to C (advanced stage) in the gene expression omnibus (GEO) database, differentially expressed genes (DEGs), including common DEGs and unique DEGs in different BCLC stages, were identified. These DEGs were located on different chromosomes. The molecular functions and biology pathways of DEGs were identified by gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and the interactome networks of DEGs were constructed using the NetVenn online tool. The results revealed that both common DEGs and stage-specific DEGs were associated with various molecular functions and were involved in special biological pathways. In addition, several hub genes were found in the interactome networks of DEGs. The identified DEGs and hub genes promote our understanding of the molecular mechanisms underlying the development of HBV-related HCC through the different BCLC stages, and might be used as staging biomarkers or molecular targets for the treatment of HCC with HBV infection. PMID:27454179

  9. Evaluation of the Reliability of Clinical Staging of T2N0 Esophageal Cancer: A Review of the Society of Thoracic Surgeons Database

    PubMed Central

    Crabtree, Traves D.; Kosinski, Andrzej S.; Puri, Varun; Burfeind, William; Bharat, Ankit; Patterson, G Alexander; Hofstetter, Wayne; Meyers, Bryan F.

    2014-01-01

    Background Clinical staging of esophageal cancer has improved with PET/CT and endoscopic ultrasound. Despite such progress, small single center studies have questioned the reliability of clinical staging of T2N0 esophageal cancer. This study broadly examines the adequacy of clinical staging of T2N0 disease using the Society of Thoracic Surgeons database. Methods We retrospectively studied 810 clinical stage T2N0 patients from 2002-2011. There were 58 excluded because of incomplete pathologic staging data. Clinical stage, pathologic stage, and preoperative characteristics were recorded. Logistic regression analysis was utilized to identify factors associated with upstaging at the time of surgery. Results Among 752 clinical stage T2N0 patients, 35.9 %(270) received induction therapy prior to surgery. Of 482 patients that went directly to surgery, 27.4%(132) were confirmed as pathologic T2N0, 25.9%(125) were downstaged(i.e. T0-1N0), while 46.7%(225) were upstaged at surgery (T3-4N0 or TanyN1-3). Exclusive tumor upstaging(i.e. pathological T3-4N0) accounted for 18.2%(41), while exclusive nodal upstaging(i.e. pathological T1-2N1-3) accounted for 44.5%(100). Combined tumor and nodal upstaging(i.e. pathological T3-4N1-3) accounted for 37.3%(84). Among patients who received induction therapy, 38.1%(103) were upstaged vs. 46.7%(225) without induction therapy(p=0.026). Comparing the induction therapy group and the primary surgical group, postoperative 30-day mortality(3.7% vs. 3.7%, p=1.0) and morbidity(46.3% vs. 45%, p=0.76) were similar. Conclusion Despite advances in staging techniques clinical staging of T2N0 esophageal cancer remains unreliable. Recognizing T2N0 as a threshold for induction therapy in esophageal cancer, many surgeons have opted to treat T2N0 disease with induction therapy, despite the fact that one quarter of these patients will be pathological T1N0. While this study demonstrated similar perioperative morbidity and mortality with and without induction

  10. Clinical predictors of cognitive decline in patients with mild cognitive impairment: the Chongqing aging study.

    PubMed

    Li, Ling; Wang, Yanjiang; Yan, Jiachuan; Chen, Yang; Zhou, Rui; Yi, Xu; Shi, Qianqian; Zhou, Huadong

    2012-07-01

    Mild cognitive impairment (MCI) is considered as the early stage of dementia which currently has no effective treatments. Reducing progression of cognitive decline at the MCI stage could be an important strategy for preventing conversion to dementia. The goal of this work was to screen for clinical predictors indicating the prognosis of MCI comprehensively; therefore, we assumed vascular risk factors (VRFs), carotid stenosis, and white matter changes (WMC) to be independent predictors. A total of 257 patients with MCI underwent collection of VRF information, neuropsychological evaluation, computed tomography angiography (CTA) to investigate carotid stenosis, and magnetic resonance imaging (MRI) to identify severity of WMC. After a 3-year follow-up period, the neuropsychological evaluation, CTA, and MRI were repeated to assess the progression of cognitive decline, carotid stenosis, and WMC. The conversion rate from MCI to dementia was 11.65% per year, and the conversion rate from MCI to Alzheimer's disease was 7.05% per year in our cohort. Cognitive decline (in terms of changes in Mini Mental State Examination scores) was associated with diabetes mellitus (p = 0.004), baseline WMC severity (p < 0.001), baseline carotid stenosis (p < 0.001), and WMC severity change (p < 0.001). Besides, diabetes, baseline WMC severity, baseline moderate-to-severe carotid stenosis, and carotid stenosis change during follow-up were predictors of conversion from MCI to dementia. Given the potential clinical predictors, our findings could imply that controlling blood glucose, removing carotid stenosis, and improving cerebral perfusion could be effective measures to delay cognitive decline in patients with MCI and prevent conversion from MCI to dementia. PMID:22186849

  11. Serum inhibin B in healthy pubertal and adolescent boys: relation to age, stage of puberty, and follicle-stimulating hormone, luteinizing hormone, testosterone, and estradiol levels.

    PubMed

    Andersson, A M; Juul, A; Petersen, J H; Müller, J; Groome, N P; Skakkebaek, N E

    1997-12-01

    Inhibin B levels were measured in serum from 400 healthy Danish prepubertal, pubertal, and adolescent males, aged 6-20 yr, in a cross-sectional study using a recently developed immunoassay that is specific for inhibin B, the physiologically important inhibin form in men. In addition, serum levels of FSH, LH, testosterone, and estradiol levels were measured. Serum levels of inhibin B, FSH, LH, testosterone, and estradiol all increased significantly between stages I and II of puberty. From stage II of puberty the inhibin B level was relatively constant, whereas the FSH level continued to increase between stages II and III. From stage III of puberty the FSH level was also relatively constant, although there was a nonsignificant trend of slightly decreased FSH levels at pubertal stage V compared to stage IV. The levels of serum LH, testosterone, and estradiol increased progressively throughout puberty. In prepubertal boys younger than 9 yr, there were no correlation between inhibin B and the other three hormones. In prepubertal boys older than 9 yr, a significant positive correlation was observed between inhibin B and FSH, LH, and testosterone. However, at this pubertal stage, each hormone correlated strongly with age, and when the effect of age was taken into account, only the partial correlation between inhibin B and LH/testosterone remained statistically significant. At stage II of puberty, the positive partial correlation between inhibin B and LH/testosterone was still present. At stage III of puberty, an negative partial correlation between inhibin B and FSH, LH, and estradiol was present, whereas no correlation between inhibin B and testosterone could be observed from stage III onward. The negative correlation between inhibin B and FSH persisted from stage III of puberty onward, whereas the correlation between inhibin B and LH and between inhibin B and estradiol was nonsignificant at stages IV and V of puberty. In conclusion, in boys, serum inhibin B levels

  12. Clinical prediction of Parkinson's disease: planning for the age of neuroprotection.

    PubMed

    Postuma, R B; Gagnon, J F; Montplaisir, J

    2010-09-01

    As a chronic progressive disease, Parkinson's disease (PD) has a presymptomatic interval; that is, a period during which the pathological process has begun, but motor signs required for the clinical diagnosis are absent. The ability to identify this preclinical stage may be critical in the development and eventual use of neuroprotective therapy. Recently proposed staging systems of PD have suggested that degeneration may occur initially in areas outside the substantia nigra, suggesting that non-motor manifestations may be markers of presymptomatic PD. Decreased olfaction has recently been demonstrated to predict PD in prospective pathological studies, although the lead time may be relatively short, and the positive predictive value is low. Idiopathic RBD has a very high predictive value, with approximately 50% of affected individuals developing PD or dementia within 10 years. This implies that idiopathic RBD patients are ideal candidates to test potential preclinical markers. However, the specificity of symptom screens for RBD is not established, not all persons with PD develop RBD, and there are only limited ways to predict which RBD patients will develop PD. Other simple screens based upon autonomic symptoms, depression and personality changes, quantitative motor testing and other sleep disorders may also be useful markers, but have not been extensively tested. Other more expensive measures such as detailed autonomic testing, cardiac MIBG-scintigraphy, dopaminergic imaging and transcranial ultrasound may be especially useful in defining disease risk in those identified through primary screening.

  13. Sex, age, race and intervention type in clinical studies of HIV cure: a systematic review.

    PubMed

    Johnston, Rowena E; Heitzeg, Mary M

    2015-01-01

    This systematic review was undertaken to determine the extent to which adult subjects representing sex (female), race (nonwhite), and age (>50 years) categories are included in clinical studies of HIV curative interventions and thus, by extension, the potential for data to be analyzed that may shed light on the influence of such demographic variables on safety and/or efficacy. English-language publications retrieved from PubMed and from references of retrieved papers describing clinical studies of curative interventions were read and demographic, recruitment year, and intervention-type details were noted. Variables of interest included participation by sex, age, and race; changes in participation rates by recruitment year; and differences in participation by intervention type. Of 151 publications, 23% reported full demographic data of study enrollees, and only 6% reported conducting efficacy analyses by demographic variables. Included studies recruited participants from 1991 to 2011. No study conducted safety analyses by demographic variables. The representation of women, older people, and nonwhites did not reflect national or international burdens of HIV infection. Participation of demographic subgroups differed by intervention type and study location. Rates of participation of demographic groups of interest did not vary with time. Limited data suggest efficacy, particularly of early therapy initiation followed by treatment interruption, may vary by demographic variables, in this case sex. More data are needed to determine associations between demographic characteristics and safety/efficacy of curative interventions. Studies should be powered to conduct such analyses and cure-relevant measures should be standardized.

  14. Reliability of Schmeling's stages of ossification of medial clavicular epiphyses and its validity to assess 18 years of age in living subjects.

    PubMed

    Cameriere, R; De Luca, S; De Angelis, D; Merelli, V; Giuliodori, A; Cingolani, M; Cattaneo, C; Ferrante, L

    2012-11-01

    Nowadays, due to the global increase in migration movements, forensic age estimation of living young adults has become an important focus of interest. Minors often have no identification documents providing their correct birth dates. Establishing the age of majority is therefore fundamental in order to determine whether juvenile penal systems or penal systems in force for adults are to be applied. Radiological examination of the clavicles is one of the methods recommended by the Study Group on Forensic Age Diagnostics. In this retrospective study, a sample of chest radiographs of 274 subjects, aged between 12 and 25 years, was studied according to Schmeling's method in order to examine the ossification of both medial clavicular epiphyses. All stage classifications were evaluated by five examiners. Intra- and inter-examiner reliability was analysed by Cohen's K statistic. Intra-examiner agreement was insufficient for two of the experts. Inter-examiner agreement, among the other three operators, was moderate (K = 0.509). Study of reliability highlighted difficulties in interpretation, the need to select qualified personnel and choice of the best radiographic image in order to reduce any anatomic overlaps. Although ossification of the medial clavicular epiphyses is recommended to assess whether an individual has already reached the age of majority or not, these results suggested that it is very difficult to clearly identify the five stages of ossification by using conventional chest radiography.

  15. Effects of leaf age within growth stages of pepper and sorghum plants on leaf thickness, water, chlorophyll, and light reflectance. [in spectral vegetation discrimination

    NASA Technical Reports Server (NTRS)

    Gausman, H. W.; Cardenas, R.; Berumen, A.

    1974-01-01

    Pepper and sorghum plants (characterized by porous and compact leaf mesophylls, respectively) were used to study the influence of leaf age on light reflectance. Measurements were limited to the upper five nodal positions within each growth stage, since upper leaves make up most of the reflectance surfaces remotely sensed. The increase in leaf thickness and water content with increasing leaf age was taken into consideration, since each of these factors affects the reflectance as well as the selection of spectral wavelength intervals for optimum discrimination of vegetation.

  16. AGING AND LIFE-STAGE SUSCEPTIBILITY: TOLUENE EFFECTS ON BRAIN OXIDATIVE STRESS PARAMETERS IN BROWN NORWAY RATS.

    EPA Science Inventory

    The influence of aging on susceptibility to environmental contaminants is poorly understood. The objectives of this study were to test whether oxidative stress (OS) is a potential toxicity pathway following toluene exposure and to determine if these effects are age-dependent. We ...

  17. Severe hypoxaemia can predict unfavourable clinical outcomes in individuals with pulmonary embolism aged over 40 years

    PubMed Central

    Souza, Caio Simoes; Resende, Fernanda Simoes Seabra; Rodrigues, Marcelo Palmeira

    2014-01-01

    INTRODUCTION Acute pulmonary embolism (APE) is an urgent clinical condition that can progress in a wide variety of ways. Therefore, we sought to develop an easy-to-apply algorithm, to be based on readily available clinical indicators, effective in predicting unfavourable outcomes. METHODS This was a retrospective cohort study based on systematically collected data in a database. The study included 102 patients with APE who were admitted to a tertiary care hospital. The following outcomes were defined as unfavourable shock, the need for mechanical ventilation, the use of thrombolytics, and death. Logistic regression analysis was used to explore variables significantly associated with outcome and to calculate post-test probabilities. RESULTS The prevalence of unfavourable outcomes was 25.5% (26 of the 102 patients with APE). The risk of an unfavourable outcome was reduced to 7.0% for patients with APE who were aged ≤ 40 years. In patients with APE who were aged > 40 years, the presence of hypoxaemia (i.e. peripheral oxygen saturation < 90%) alone increased the risk of an unfavourable outcome to 57.0%. A recent history of trauma and the presence of pre-existing lung or heart disease were significantly associated with unfavourable outcomes. The inclusion of those variables in the logistic regression model increased the post-test risk of an unfavourable outcome to 65.0%–86.0%. CONCLUSION Advanced age (i.e. > 40 years), the presence of hypoxaemia, a recent history of trauma and the presence of pre-existing lung or heart disease are risk factors for unfavourable outcome in patients with APE. PMID:25273933

  18. The impact of sleep on age-related sarcopenia: Possible connections and clinical implications.

    PubMed

    Piovezan, Ronaldo D; Abucham, Julio; Dos Santos, Ronaldo Vagner Thomatieli; Mello, Marco Tulio; Tufik, Sergio; Poyares, Dalva

    2015-09-01

    Sarcopenia is a geriatric condition that comprises declined skeletal muscle mass, strength and function, leading to the risk of multiple adverse outcomes, including death. Its pathophysiology involves neuroendocrine and inflammatory factors, unfavorable nutritional habits and low physical activity. Sleep may play a role in muscle protein metabolism, although this hypothesis has not been studied extensively. Reductions in duration and quality of sleep and increases in prevalence of circadian rhythm and sleep disorders with age favor proteolysis, modify body composition and increase the risk of insulin resistance, all of which have been associated with sarcopenia. Data on the effects of age-related slow-wave sleep decline, circadian rhythm disruptions and obstructive sleep apnea (OSA) on hypothalamic-pituitary-adrenal (HPA), hypothalamic-pituitary-gonadal (HPG), somatotropic axes, and glucose metabolism indicate that sleep disorder interventions may affect muscle loss. Recent research associating OSA with the risk of conditions closely related to the sarcopenia process, such as frailty and sleep quality impairment, indirectly suggest that sleep can influence skeletal muscle decline in the elderly. Several protein synthesis and degradation pathways are mediated by growth hormone (GH), insulin-like growth factor-1 (IGF-1), testosterone, cortisol and insulin, which act on the cellular and molecular levels to increase or reestablish muscle fiber, strength and function. Age-related sleep problems potentially interfere intracellularly by inhibiting anabolic hormone cascades and enhancing catabolic pathways in the skeletal muscle. Specific physical exercises combined or not with nutritional recommendations are the current treatment options for sarcopenia. Clinical studies testing exogenous administration of anabolic hormones have not yielded adequate safety profiles. Therapeutic approaches targeting sleep disturbances to normalize circadian rhythms and sleep homeostasis may

  19. The impact of sleep on age-related sarcopenia: Possible connections and clinical implications.

    PubMed

    Piovezan, Ronaldo D; Abucham, Julio; Dos Santos, Ronaldo Vagner Thomatieli; Mello, Marco Tulio; Tufik, Sergio; Poyares, Dalva

    2015-09-01

    Sarcopenia is a geriatric condition that comprises declined skeletal muscle mass, strength and function, leading to the risk of multiple adverse outcomes, including death. Its pathophysiology involves neuroendocrine and inflammatory factors, unfavorable nutritional habits and low physical activity. Sleep may play a role in muscle protein metabolism, although this hypothesis has not been studied extensively. Reductions in duration and quality of sleep and increases in prevalence of circadian rhythm and sleep disorders with age favor proteolysis, modify body composition and increase the risk of insulin resistance, all of which have been associated with sarcopenia. Data on the effects of age-related slow-wave sleep decline, circadian rhythm disruptions and obstructive sleep apnea (OSA) on hypothalamic-pituitary-adrenal (HPA), hypothalamic-pituitary-gonadal (HPG), somatotropic axes, and glucose metabolism indicate that sleep disorder interventions may affect muscle loss. Recent research associating OSA with the risk of conditions closely related to the sarcopenia process, such as frailty and sleep quality impairment, indirectly suggest that sleep can influence skeletal muscle decline in the elderly. Several protein synthesis and degradation pathways are mediated by growth hormone (GH), insulin-like growth factor-1 (IGF-1), testosterone, cortisol and insulin, which act on the cellular and molecular levels to increase or reestablish muscle fiber, strength and function. Age-related sleep problems potentially interfere intracellularly by inhibiting anabolic hormone cascades and enhancing catabolic pathways in the skeletal muscle. Specific physical exercises combined or not with nutritional recommendations are the current treatment options for sarcopenia. Clinical studies testing exogenous administration of anabolic hormones have not yielded adequate safety profiles. Therapeutic approaches targeting sleep disturbances to normalize circadian rhythms and sleep homeostasis may

  20. Radiofrequency ablation versus resection for Barcelona clinic liver cancer very early/early stage hepatocellular carcinoma: a systematic review

    PubMed Central

    He, Zhen-Xin; Xiang, Pu; Gong, Jian-Ping; Cheng, Nan-Sheng; Zhang, Wei

    2016-01-01

    Aim To compare the long-term survival outcomes of radiofrequency ablation and liver resection for single very early/early stage hepatocellular carcinoma (HCC). Methods The Cochrane Library (Issue 3, 2015), Embase (1974 to March 15, 2015), PubMed (1950 to March 15, 2015), Web of Science (1900 to March 15, 2015), and Chinese Biomedical Literature Database (1978 to March 15, 2015) were searched to identify relevant trials. Only trials that compared radiofrequency ablation and liver resection for single very early stage (≤2 cm) or early stage (≤3 cm) HCC according to the Barcelona clinic liver cancer (BCLC) staging system were considered for inclusion in this review. The primary outcomes that we analyzed were the 3-year and 5-year overall survival (OS) rates, and the secondary outcomes that we analyzed were the 3-year and 5-year disease-free survival (DFS) rates. Review Manager 5.3 was used to perform a cumulative meta-analysis. Possible publication bias was examined using a funnel plot. A random-effects model was applied to summarize the various outcomes. Results Six studies involving 947 patients were identified that compared radiofrequency ablation (n=528) to liver resection (n=419) for single BCLC very early HCC. In these six studies, the rates of 3-year OS, 5-year OS, 3-year DFS, and 5-year DFS were significantly lower in the radiofrequency ablation group than in the liver resection group (risk ratio [RR] =0.90, 95% confidence interval [CI]: 0.83–0.98, P=0.01; RR =0.84, 95% CI: 0.75–0.95, P=0.004; RR =0.77, 95% CI: 0.60–0.98, P=0.04; and RR =0.70, 95% CI: 0.52–0.94, P=0.02, respectively). Ten studies involving 2,501 patients were identified that compared radiofrequency ablation (n=1,476) to liver resection (n=1,025) for single BCLC early HCC. In these ten studies, the rates of 3-year OS, 5-year OS, 3-year DFS, and 5-year DFS were also significantly lower in the radiofrequency ablation group than in the liver resection group (RR =0.93, 95% CI: 0.88–0

  1. Recruitment strategies for an acupuncture randomized clinical trial of reproductive age women

    PubMed Central

    Pastore, Lisa M.; Dalal, Parchayi

    2009-01-01

    Summary Objectives To assess the most effective recruitment strategies for an acupuncture clinical trial of reproductive age women. Design The underlying study is an acupuncture randomized clinical trial for an ovulatory disorder that affects approximately 6.5% of reproductive age women (Polycystic Ovary Syndrome). Study participation involved 2 months of intervention and 3 months of follow-up with US$170 compensation. Success of each recruitment method used during the first 37 study months was analyzed. Setting Clinical trial in the Dept. of OB/GYN at the University of Virginia, US. The original geographic residency target was an 80 mile radius around a college town in Virginia (population 155,000), and was expanded to the state capital (population 850,000) in recruitment year 2. Main outcome measures Number of study inquiries (phone calls or emails) over time and by recruitment source. Results In the first 37 months of recruitment (Jan 2006 – Jan 2009), there were 800 study inquiries (582 by phone, 218 by email), of which 749 were screened via telephone questionnaire. The most successful recruitment methods were flyers (28% of inquiries and 26 % of participants) and direct mailing to targeted zip codes (26% and 27%, respectively). The direct mailing cost US$110/inquiry, while the flyers cost less than US$300 in total. Study inquiries were least likely in May and November. Almost all prospective participants (94%) were acupuncture-naïve. Conclusions Posters/flyers and direct mailings proved to be the most successful recruitment methods for this CAM study. Active recruitment with multiple methods was needed for continual enrollment. PMID:19632551

  2. [Comorbidity of opioid addiction and alcoholism in patients of young age: clinical variants of the double diagnosis].

    PubMed

    Bokhan, N A; Blagov, L N; Kurgak, D I

    2012-01-01

    A study included 115 male patients with opioid addiction, aged from 17 to 27 years. Comorbidity of opioid addiction and alcoholism in patients of young age was represented by two main variants distinguishing between primary dependence on opioid or alcohol. In the first variant, additional variants of vicarious alcoholization and replacement of addiction form were singled out. In the second case, alcoholism preceded opioid addiction that developed as a form of polyaddiction and the formation of preliminary (primary) alcoholism was considered as a protracted stage of searching narcotism with the transition from alcoholism to opioid addiction. Stages and differential criteria of the variants of double disorders are described.

  3. Clinical and neuroimaging differences between posterior cortical atrophy and typical amnestic Alzheimer’s disease patients at an early disease stage

    PubMed Central

    Peng, Guoping; Wang, Jianqin; Feng, Zhan; Liu, Ping; Zhang, Yafei; He, Fangping; Chen, Zhongqin; Zhao, Kui; Luo, Benyan

    2016-01-01

    To identify clinical and neuroimaging characteristics between posterior cortical atrophy (PCA) and typical amnestic Alzheimer’s disease (tAD) patients at an early disease stage, 16 PCA and 13 age-matched tAD patients were enrolled. Compared with tAD patients, PCA patients showed higher mean recognition and recall test scores, and lower mean calculation, spatial attention, shape discrimination, and writing test scores. Mean right hippocampal volume was larger in PCA patients compared with tAD patients, while cortical gray matter (GM) volume of bilateral parietal and occipital lobes was smaller in PCA patients. Further, when compared with tAD patients, significant hypometabolism was observed in bilateral parietal and occipital lobes, particularly the right occipitotemporal junction in PCA patients. Additionally, there were significant positive correlations in recognition and recall scores with hippocampal volumes. In PCA patients, calculation and visuospatial ability scores are positively associated with GM volume of parietal and occipital lobes. And only spatial attention and shape discrimination scores are positively associated with regional glucose metabolism of parietal and occipital lobes. Therefore, PCA patients display better recognition and recall scores, which are associated with larger hippocampal volumes and poorer performance in visual spatial tasks because of marked GM atrophy and hypometabolism of parietal and occipital lobes. PMID:27377199

  4. Aetiology and clinical features of dysentery in children aged <5 years in rural Bangladesh.

    PubMed

    Ferdous, F; Ahmed, S; DAS, S K; Farzana, F D; Latham, J R; Chisti, M J; Faruque, A S G

    2014-01-01

    The study identified the common aetiological agents and prominent clinical features of dysentery cases in children aged <5 years and compared this to non-dysentery diarrhoeal cases from the same population. From January 2010 to December 2011, 2324 children aged <5 years received treatment at Kumudini Hospital, of which 682 (29%) presented with dysentery. Of the dysenteric children, aetiology could not be determined for over half (61%). Shigella spp. accounted for 32% of dysentery cases. Significant associations were found between presence of blood in stool and: child age (24-59 months) [odds ratio (OR) 2.21, 95% confidence interval (CI) 1.49-3.27], no treatment of drinking water at home (OR 2.00, 95% CI 1.09-3.67), vomiting (OR 0.19, 95% CI 0.14-0.25), abdominal pain (OR 4.68, 95% CI 3.24-6.77), straining (OR 16.45, 95% CI 11.92-22.69), wasting (OR 1.66, 95% CI 1.15-2.41), and presence of Shigella in stool (OR 6.25, 95% CI 4.20-9.29) after controlling for confounders. This study makes it clear that appropriate public health strategies are needed to reduce the burden of dysentery in Bangladesh.

  5. Multiplex assays for biomarker research and clinical application: translational science coming of age.

    PubMed

    Fu, Qin; Schoenhoff, Florian S; Savage, William J; Zhang, Pingbo; Van Eyk, Jennifer E

    2010-03-01

    Over the last decade, translational science has come into the focus of academic medicine, and significant intellectual and financial efforts have been made to initiate a multitude of bench-to-bedside projects. The quest for suitable biomarkers that will significantly change clinical practice has become one of the biggest challenges in translational medicine. Quantitative measurement of proteins is a critical step in biomarker discovery. Assessing a large number of potential protein biomarkers in a statistically significant number of samples and controls still constitutes a major technical hurdle. Multiplexed analysis offers significant advantages regarding time, reagent cost, sample requirements and the amount of data that can be generated. The two contemporary approaches in multiplexed and quantitative biomarker validation, antibody-based immunoassays and MS-based multiple (or selected) reaction monitoring, are based on different assay principles and instrument requirements. Both approaches have their own advantages and disadvantages and therefore have complementary roles in the multi-staged biomarker verification and validation process. In this review, we discuss quantitative immunoassay and multiple reaction monitoring/selected reaction monitoring assay principles and development. We also discuss choosing an appropriate platform, judging the performance of assays, obtaining reliable, quantitative results for translational research and clinical applications in the biomarker field. PMID:21137048

  6. DNA damage response (DDR) and senescence: shuttled inflamma-miRNAs on the stage of inflamm-aging.

    PubMed

    Olivieri, Fabiola; Albertini, Maria Cristina; Orciani, Monia; Ceka, Artan; Cricca, Monica; Procopio, Antonio Domenico; Bonafè, Massimiliano

    2015-11-01

    A major issue in aging research is how cellular phenomena affect aging at the systemic level. Emerging evidence suggests that DNA damage response (DDR) signaling is a key mechanism linking DNA damage accumulation, cell senescence, and organism aging. DDR activation in senescent cells promotes acquisition of a proinflammatory secretory phenotype (SASP), which in turn elicits DDR and SASP activation in neighboring cells, thereby creating a proinflammatory environment extending at the local and eventually the systemic level. DDR activation is triggered by genomic lesions as well as emerging bacterial and viral metagenomes. Therefore, the buildup of cells with an activated DDR probably fuels inflamm-aging and predisposes to the development of the major age-related diseases (ARDs). Micro (mi)-RNAs - non-coding RNAs involved in gene expression modulation - are released locally and systemically by a variety of shuttles (exosomes, lipoproteins, proteins) that likely affect the efficiency of their biological effects. Here we suggest that some miRNAs, previously found to be associated with inflammation and senescence - miR-146, miR-155, and miR-21 - play a central role in the interplay among DDR, cell senescence and inflamm-aging. The identification of the functions of shuttled senescence-associated miRNAs is expected to shed light on the aging process and on how to delay ARD development. PMID:26431329

  7. DNA damage response (DDR) and senescence: shuttled inflamma-miRNAs on the stage of inflamm-aging.

    PubMed

    Olivieri, Fabiola; Albertini, Maria Cristina; Orciani, Monia; Ceka, Artan; Cricca, Monica; Procopio, Antonio Domenico; Bonafè, Massimiliano

    2015-11-01

    A major issue in aging research is how cellular phenomena affect aging at the systemic level. Emerging evidence suggests that DNA damage response (DDR) signaling is a key mechanism linking DNA damage accumulation, cell senescence, and organism aging. DDR activation in senescent cells promotes acquisition of a proinflammatory secretory phenotype (SASP), which in turn elicits DDR and SASP activation in neighboring cells, thereby creating a proinflammatory environment extending at the local and eventually the systemic level. DDR activation is triggered by genomic lesions as well as emerging bacterial and viral metagenomes. Therefore, the buildup of cells with an activated DDR probably fuels inflamm-aging and predisposes to the development of the major age-related diseases (ARDs). Micro (mi)-RNAs - non-coding RNAs involved in gene expression modulation - are released locally and systemically by a variety of shuttles (exosomes, lipoproteins, proteins) that likely affect the efficiency of their biological effects. Here we suggest that some miRNAs, previously found to be associated with inflammation and senescence - miR-146, miR-155, and miR-21 - play a central role in the interplay among DDR, cell senescence and inflamm-aging. The identification of the functions of shuttled senescence-associated miRNAs is expected to shed light on the aging process and on how to delay ARD development.

  8. Thymidine phosphorylase and hypoxia-inducible factor 1-α expression in clinical stage II/III rectal cancer: association with response to neoadjuvant chemoradiation therapy and prognosis.

    PubMed

    Lin, Shuhan; Lai, Hao; Qin, Yuzhou; Chen, Jiansi; Lin, Yuan

    2015-01-01

    The aim of this study was to determine whether pretreatment status of thymidine phosphorylase (TP), and hypoxia-inducible factor alpha (HIF-1α) could predict pathologic response to neoadjuvant chemoradiation therapy with oxaliplatin and capecitabine (XELOXART) and outcomes for clinical stage II/III rectal cancer patients. A total of 180 patients diagnosed with clinical stage II/III rectal cancer received XELOXART. The status of TP, and HIF-1α were determined in pretreatment biopsies by immunohistochemistry (IHC). Tumor response was assessed in resected regimens using the tumor regression grade system and TNM staging system. 5-year disease free survival (DFS) and 5-year overall survival (OS) were evaluated with the Kaplan-Meier method and were compared by the log-rank test. Over expression of TP and low expression of HIF-1α were associated with pathologic response to XELOXART and better outcomes (DFS and OS) in clinical stage II/III rectal cancer patients (P < 0.05). Our result suggested that pretreatment status of TP and HIF-1α were found to predict pathologic response and outcomes in clinical stage II/III rectal cancer received XELOXART. Additional well-designed, large sample, multicenter, prospective studies are needed to confirm the result of this study.

  9. Long-term (60-month) results for the implantable miniature telescope: efficacy and safety outcomes stratified by age in patients with end-stage age-related macular degeneration

    PubMed Central

    Boyer, David; Freund, K Bailey; Regillo, Carl; Levy, Marc H; Garg, Sumit

    2015-01-01

    Background The purpose of this study was to evaluate the long-term results of an implantable miniature telescope (IMT) in patients with bilateral, end-stage, age-related macular degeneration (AMD). Methods A prospective, open-label, multicenter clinical trial with fellow eye controls enrolled 217 patients (mean age 76 years) with AMD and moderate-to-profound bilateral central visual acuity loss (20/80–20/800) resulting from untreatable geographic atrophy, disciform scars, or both. A subgroup analysis was performed with stratification for age (patient age 65 to <75 years [group 1; n=70] and patient age ≥75 years [group 2; n=127]), with a comparative evaluation of change in best-corrected distance visual acuity (BCDVA), quality of life, ocular complications from surgery, adverse events, and endothelial cell density (ECD). Follow-up in an extension study was 60 months. Results Data were available for 22, 38, and 31 patients in group 1 and 42, 46, and 32 patients in group 2 at 36, 48, and 60 months, respectively. Mean BCDVA improvement from baseline to 60 months was 2.41±2.69 lines in all patients (n=76), with 2.64±2.55 lines in group 1 and 2.09±2.88 lines in group 2. Quality of life scores were significantly higher in group 1. The most common significant surgery-related ocular complications in group 1 were iritis >30 days after surgery (7/70; 10%) and persistent corneal edema (3/70; 4.3%); and in group 2 were a decrease in BCDVA in the implanted eye or IMT removal (10/127 each; 7.9%), corneal edema >30 days after surgery (9/127; 7.1%), and persistent corneal edema (6/127; 4.7%). Significant adverse events included four corneal transplants, comprising two (2.9%) in group 1 and two (1.6%) in group 2. At 60 months, one patient in group 1 (3.2%) and three patients in group 2 (9.4%) had lost ≥2 lines of vision. The IMT was removed in one (1.4%) and ten (7.9%) patients in group 1 and group 2, respectively. Mean ECD loss was 20% at 3 months. Chronic loss was 3% per

  10. The association between institution at orchiectomy and outcomes on active surveillance for clinical stage I germ cell tumours

    PubMed Central

    Nayan, Madhur; Jewett, Michael A.S.; Anson-Cartwright, Lynn; Bedard, Philippe L.; Moore, Malcolm; Chung, Peter; Warde, Padraig; Sweet, Joan; O’Malley, Martin; Hamilton, Robert J.

    2016-01-01

    Introduction: Institutional experience has been associated with improved outcomes for various malignancies, including testicular cancer. The present study evaluated whether institution at orchiectomy was associated with outcomes on active surveillance (AS) for clinical stage (CS) I germ cell tumours (GCT). Methods: 815 patients with CSI GCT managed with AS at the Princess Margaret Cancer Centre were identified. Princess Margaret is a tertiary academic institution with a multidisciplinary testicular cancer clinic involving radiation oncologists, medical oncologists, and urologists, and has research experience in testicular cancer care. The association between institution of orchiectomy (Princess Margaret vs. Other) and time to progression on AS was analyzed using multivariable Cox proportional hazards models. Academic vs. non-academic institutions were compared in a sensitivity analysis. Results: Patients undergoing orchiectomy at Princess Margaret for non-seminoma GCT were significantly less likely to have pure embryonal carcinoma (EC) in orchiectomy pathology (odds ratio [OR] 0.33; p=0.008) and CSIB disease (OR 0.47; p=0.014). Seminoma characteristics did not differ significantly between institution groups. In non-seminoma GCT, median followup was 5.4 years, 27% progressed on AS, and institution of orchiectomy was not associated with time to progression in either univariate (hazard ratio [HR] 0.79; p=0.33) or multivariable analyses (HR 1.01; p=0.97). In seminoma, median followup was 4.7 years, 12% progressed on AS, and institution of orchiectomy was not associated with progression (univariate: HR 0.87; p=0.73; multivariable: HR 0.98; p=0.96). Sensitivity analyses demonstrated similar results. Conclusions: Among CSI GCT patients managed on AS at a specialized cancer centre, there appears to be no difference in oncologic outcomes based upon the institution where orchiectomy was performed.

  11. Clinical results of high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation in children with advanced stage rhabdomyosarcoma.

    PubMed

    Kim, Nam Kyun; Kim, Hyo Sun; Suh, Chang-Ok; Kim, Hyun Ok; Lyu, Chuhl Joo

    2012-09-01

    Regardless of improvement in cure of Rhabdomyosarcoma (RMS), the results in treatment of advanced stage of RMS in children are still dismal. Recently, high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (HDC/APBSCT) has been tried to manage the advanced high-risk RMS patients. We investigated the effectiveness of HDC/APBSCT by reviewing the clinical records of high-risk pediatric RMS patients in single institute database. Over twenty years, 37 patients were diagnosed as RMS with high-risk at the time of first diagnosis. These patients were classified as two groups according to treatment method. The first group was HDC/APBSCT and the other was conventional multi-agent chemotherapy group. Differences of clinical results between the two groups were analyzed. The median age of patients was 5 yr, ranging from 6 months to 15 yr. The 5-yr event free survival rate (EFS) of all patients was 24.8% ± 4.8%. HDC/APBSCT group and conventional multi-agent chemotherapy group were 41.3% ± 17.8% and 16.7% ± 7.6% for 5-yr EFS, respectively (P = 0.023). There was a significant difference in the result of HDC/APBSCT between complete remission or very good partial response group and poor response group (50% ± 20.4% vs 37.5% ± 28.6%, P = 0.018). HDC/APBSCT can be a promising treatment modality in high-risk RMS patients. PMID:22969254

  12. The Role of Postmastectomy Radiation Therapy After Neoadjuvant Chemotherapy in Clinical Stage II-III Breast Cancer Patients With pN0: A Multicenter, Retrospective Study (KROG 12-05)

    SciTech Connect

    Shim, Su Jung; Park, Won; Huh, Seung Jae; Choi, Doo Ho; Shin, Kyung Hwan; Lee, Nam Kwon; Suh, Chang-Ok; Keum, Ki Chang; Kim, Yong Bae; Ahn, Seung Do; Kim, Su Ssan; Ha, Sung W.; Chie, Eui Kyu; Kim, Kyubo; Shin, Hyun Soo; Kim, Jin Hee; Lee, Hyung-Sik

    2014-01-01

    Purpose: The purpose of this study was to investigate the role of postmastectomy radiation therapy (PMRT) after neoadjuvant chemotherapy (NAC) in clinical stage II-III breast cancer patients with pN0. Methods and Materials: We retrospectively identified 417 clinical stage II-III breast cancer patients who achieved an ypN0 at surgery after receiving NAC between 1998 and 2009. Of these, 151 patients underwent mastectomy after NAC. The effect of PMRT on disease-free survival (DFS), locoregional recurrence-free survival (LRRFS), and overall survival (OS) was evaluated by multivariate analysis including known prognostic factors using the Kaplan-Meier method and compared using the log–rank test and Cox proportional regression analysis. Results: Of the 151 patients who underwent mastectomy, 105 (69.5%) received PMRT and 46 patients (30.5%) did not. At a median follow-up of 59 months, 5 patients (3.3%) developed LRR (8 sites of recurrence) and 14 patients (9.3%) developed distant metastasis. The 5-year DFS, LRRFS, and OS rates were 91.2, 98.1, and 93.3% with PMRT and 83.0%, 92.3%, and 89.9% without PMRT, respectively (all P values not significant). By univariate analysis, only age (≤40 vs >40 years) was significantly associated with decreased DFS (P=.027). By multivariate analysis, age (≤40 vs >40 years) and pathologic T stage (0-is vs 1 vs 2-4) were significant prognostic factors affecting DFS (hazard ratio [HR] 0.353, 95% confidence interval [CI] 0.135-0.928, P=.035; HR 2.223, 95% CI 1.074-4.604, P=.031, respectively). PMRT showed no correlation with a difference in DFS, LRRFS, or OS by multivariate analysis. Conclusions: PMRT might not be necessary for pN0 patients after NAC, regardless of clinical stage. Prospective randomized clinical trial data are needed to assess whether PMRT can be safely omitted in pN0 patients after NAC and mastectomy for clinical stage II-III breast cancer.

  13. Predicting the risk of mild cognitive impairment in the Mayo Clinic Study of Aging

    PubMed Central

    Pankratz, V. Shane; Roberts, Rosebud O.; Mielke, Michelle M.; Knopman, David S.; Jack, Clifford R.; Geda, Yonas E.; Rocca, Walter A.

    2015-01-01

    Objective: We sought to develop risk scores for the progression from cognitively normal (CN) to mild cognitive impairment (MCI). Methods: We recruited into a longitudinal cohort study a randomly selected, population-based sample of Olmsted County, MN, residents, aged 70 to 89 years on October 1, 2004. At baseline and subsequent visits, participants were evaluated for demographic, clinical, and neuropsychological measures, and were classified as CN, MCI, or dementia. Using baseline demographic and clinical variables in proportional hazards models, we derived scores that predicted the risk of progressing from CN to MCI. We evaluated the ability of these risk scores to classify participants for MCI risk. Results: Of 1,449 CN participants, 401 (27.7%) developed MCI. A basic model had a C statistic of 0.60 (0.58 for women, 0.62 for men); an augmented model resulted in a C statistic of 0.70 (0.69 for women, 0.71 for men). Both men and women in the highest vs lowest sex-specific quartiles of the augmented model's risk scores had an approximately 7-fold higher risk of developing MCI. Adding APOE ε4 carrier status improved the model (p = 0.002). Conclusions: We have developed MCI risk scores using variables easily assessable in the clinical setting and that may be useful in routine patient care. Because of variability among populations, validation in independent samples is required. These models may be useful in identifying patients who might benefit from more expensive or invasive diagnostic testing, and can inform clinical trial design. Inclusion of biomarkers or other risk factors may further enhance the models. PMID:25788555

  14. Clinical correlates of obsessive-compulsive symptom dimensions in at-risk mental states and psychotic disorders at early stages.

    PubMed

    Mariné, Rosa; Creus, Marta; Solé, Montse; Cabezas, Ángel; Algora, Maria José; Moreno, Irene; Izquierdo, Eduard; Stojanovic-Pérez, Alexander; Labad, Javier

    2015-08-30

    We studied the clinical correlates of obsessive-compulsive symptom dimensions in 109 individuals with early psychosis (31 At-Risk Mental States [ARMS], 78 psychotic disorders with <3 years of illness) and 59 healthy subjects. Obsessive-compulsive symptoms were assessed by the Obsessive-Compulsive Inventory - Revised. We also assessed the severity of psychotic symptoms, depressive symptoms and functioning. ARMS and psychotic disorder patients reported more obsessive-compulsive symptoms than did healthy subjects. The ARMS individuals also reported more overall and checking obsessive-compulsive symptoms compared with the PD patients. Different types of obsessive-compulsive symptoms were related with depressive symptoms in both diagnostic groups. However, a different pattern was observed in the relationship between obsessive-compulsive dimensions and functioning by diagnosis (better functioning in ARMS; poorer functioning in psychotic disorders). Our study suggests that obsessive-compulsive symptoms are present in the early stages of psychotic illness, as well as in individuals at risk for psychosis. Future prospective studies are needed to elucidate how obsessive-compulsive symptoms in ARMS may influence the prognosis in terms of global functioning and the risk of psychosis transition.

  15. An Alternative to Farmer Age as an Indicator of Life-Cycle Stage: The Case for a Farm Family Age Index

    ERIC Educational Resources Information Center

    Burton, Rob J. F.

    2006-01-01

    In studies of farming, the age of the principal decision-maker (PDM) has been associated with numerous farm structural and managerial features and has been widely accepted as a good indicator of the influence of life-cycle factors on decision-making. As such, it has become an important aspect of many quantitative studies of agricultural change.…

  16. Phase II clinical trials with time-to-event endpoints: Optimal two-stage designs with one-sample log-rank test

    PubMed Central

    Kwak, Minjung; Jung, Sin-Ho

    2014-01-01

    Summary Phase II clinical trials are often conducted to determine whether a new treatment is sufficiently promising to warrant a major controlled clinical evaluation against a standard therapy. We consider single-arm phase II clinical trials with right censored survival time responses where the ordinary one-sample logrank test is commonly used for testing the treatment efficacy. For planning such clinical trials this paper presents two-stage designs that are optimal in the sense that the expected sample size is minimized if the new regimen has low efficacy subject to constraints of the type I and type II errors. Two-stage designs which minimize the maximal sample size are also determined. Optimal and minimax designs for a range of design parameters are tabulated along with examples. PMID:24338995

  17. Outcomes of Positron Emission Tomography-Staged Clinical N3 Breast Cancer Treated With Neoadjuvant Chemotherapy, Surgery, and Radiotherapy

    SciTech Connect

    Park, Hae Jin; Shin, Kyung Hwan; Cho, Kwan Ho; Park, In Hae; Lee, Keun Seok; Ro, Jungsil; Jung, So-Youn; Lee, Seeyoun; Kim, Seok Won; Kang, Han-Sung; Chie, Eui Kyu; Ha, Sung Whan

    2011-12-01

    Purpose: To evaluate the treatment outcome and efficacy of regional lymph node irradiation after neoadjuvant chemotherapy (NCT) and surgery in positron emission tomography (PET)-positive clinical N3 (cN3) breast cancer patients. Methods and Materials: A total of 55 patients with ipsilateral infraclavicular (ICL), internal mammary (IMN), or supraclavicular (SCL) lymph node involvement in the absence of distant metastases, as revealed by an initial PET scan, were retrospectively analyzed. The clinical nodal stage at diagnosis (2002 AJCC) was cN3a in 14 patients (26%), cN3b in 12 patients (22%), and cN3c in 29 patients (53%). All patients were treated with NCT, followed by mastectomy or breast-conserving surgery and subsequent radiotherapy (RT) with curative intent. Results: At the median follow-up of 38 months (range, 9-80 months), 20 patients (36%) had developed treatment failures, including distant metastases either alone or combined with locoregional recurrences that included one ipsilateral breast recurrence (IBR), six regional failures (RF), and one case of combined IBR and RF. Only 3 patients (5.5%) exhibited treatment failure at the initial PET-positive clinical N3 lymph node. The 5-year locoregional relapse-free survival, disease-free survival (DFS), and overall survival rates were 80%, 60%, and 79%, respectively. RT delivered to PET-positive IMN regions in cN3b patients and at higher doses ({>=}55 Gy) to SCL regions in cN3c patients was not associated with improved 5-year IMN/SCL relapse-free survival or DFS. Conclusion: NCT followed by surgery and RT, including the regional lymph nodes, resulted in excellent locoregional control for patients with PET-positive cN3 breast cancer. The primary treatment failure in this group was due to distant metastasis rather than RF. Neither higher-dose RT directed at PET-positive SCL nodes nor coverage of PET-positive IMN nodes was associated with additional gains in locoregional control or DFS.

  18. A two-stage clinical decision support system for early recognition and stratification of patients with sepsis: an observational cohort study

    PubMed Central

    Lyons, Jason J; Greene, Tracy L; Haley, James M

    2015-01-01

    Objective To examine the diagnostic accuracy of a two-stage clinical decision support system for early recognition and stratification of patients with sepsis. Design Observational cohort study employing a two-stage sepsis clinical decision support to recognise and stratify patients with sepsis. The stage one component was comprised of a cloud-based clinical decision support with 24/7 surveillance to detect patients at risk of sepsis. The cloud-based clinical decision support delivered notifications to the patients’ designated nurse, who then electronically contacted a provider. The second stage component comprised a sepsis screening and stratification form integrated into the patient electronic health record, essentially an evidence-based decision aid, used by providers to assess patients at bedside. Setting Urban, 284 acute bed community hospital in the USA; 16,000 hospitalisations annually. Participants Data on 2620 adult patients were collected retrospectively in 2014 after the clinical decision support was implemented. Main outcome measure ‘Suspected infection’ was the established gold standard to assess clinical decision support clinimetric performance. Results A sepsis alert activated on 417 (16%) of 2620 adult patients hospitalised. Applying ‘suspected infection’ as standard, the patient population characteristics showed 72% sensitivity and 73% positive predictive value. A postalert screening conducted by providers at bedside of 417 patients achieved 81% sensitivity and 94% positive predictive value. Providers documented against 89% patients with an alert activated by clinical decision support and completed 75% of bedside screening and stratification of patients with sepsis within one hour from notification. Conclusion A clinical decision support binary alarm system with cross-checking functionality improves early recognition and facilitates stratification of patients with sepsis. PMID:26688744

  19. Incidence of WHO Stage 3 and 4 Events, Tuberculosis, and Mortality in Untreated, HIV-Infected Children Enrolling in Care Before 1 Year of Age: An Iedea (International Epidemiologic Databases To Evaluate AIDS) East Africa Regional Analysis

    PubMed Central

    Ciaranello, Andrea; Lu, Zhigang; Ayaya, Samuel; Losina, Elena; Musick, Beverly; Vreeman, Rachel; Freedberg, Kenneth A.; Abrams, Elaine J.; Dillabaugh, Lisa; Doherty, Katie; Ssali, John; Yiannoutsos, Constantin T.; Wools-Kaloustian, Kara

    2014-01-01

    Background Few studies have reported CD4%- and age-stratified rates of WHO Stage 3 (WHO3) events, WHO Stage 4 (WHO4) events, tuberculosis (TB), and mortality in HIV-infected infants before initiation of antiretroviral therapy (ART). Methods HIV-infected children enrolled before 1 year of age in the International Epidemiologic Databases to Evaluate AIDS (IeDEA) East Africa region (10/01/2002-11/30/2008) were included. We estimated incidence rates of earliest clinical event (WHO3, WHO4, and TB), prior to ART initiation per local guidelines, stratified by current age (< or ≥6 months) and current CD4% (<15%, 15–24%, ≥25%). CD4%-stratified mortality rates were estimated separately for children who did not experience a clinical event (“background” mortality) and for children who experienced an event, including “acute” mortality (≤30 days post-event) and “later” mortality (>30 days post-event). Results Among 847 children (median enrollment age: 4.8 months; median pre-ART follow-up: 10.8 months; 603 (71%) with ≥1 CD4% recorded), event rates were comparable for those aged <6 and ≥6 months. Current CD4% was associated with risk of WHO4 events for children <6 months old, and with all evaluated events for children ≥6 months old (p<0.05). “Background” mortality was 3.7–8.4/100py. “Acute” mortality (≤30 days post-event) was 33.8/100py (after TB) and 41.1/100py (after WHO3 or WHO4). “Later” mortality (>30 days post-event) ranged by CD4% from 4.7–29.1/100py. Conclusions In treatment-naïve, HIV-infected infants, WHO3, WHO4, and TB events were common before and after 6 months of age and led to substantial increases in mortality. Early infant HIV diagnosis and treatment are critically important, regardless of CD4%. PMID:24378935

  20. Clinical Trial Participation and Time to Treatment Among Adolescents and Young Adults With Cancer: Does Age at Diagnosis or Insurance Make a Difference?

    PubMed Central

    Parsons, Helen M.; Harlan, Linda C.; Seibel, Nita L.; Stevens, Jennifer L.; Keegan, Theresa H.M.

    2011-01-01

    Purpose Because adolescent and young adult (AYA) patients with cancer have experienced variable improvement in survival over the past two decades, enhancing the quality and timeliness of cancer care in this population has emerged as a priority area. To identify current trends in AYA care, we examined patterns of clinical trial participation, time to treatment, and provider characteristics in a population-based sample of AYA patients with cancer. Methods Using the National Cancer Institute Patterns of Care Study, we used multivariate logistic regression to evaluate demographic and provider characteristics associated with clinical trial enrollment and time to treatment among 1,358 AYA patients with cancer (age 15 to 39 years) identified through the Surveillance, Epidemiology, and End Results Program. Results In our study, 14% of patients age 15 to 39 years had enrolled onto a clinical trial; participation varied by type of cancer, with the highest participation in those diagnosed with acute lymphoblastic leukemia (37%) and sarcoma (32%). Multivariate analyses demonstrated that uninsured, older patients and those treated by nonpediatric oncologists were less likely to enroll onto clinical trials. Median time from pathologic confirmation to first treatment was 3 days, but this varied by race/ethnicity and cancer site. In multivariate analyses, advanced cancer stage and outpatient treatment alone were associated with longer time from pathologic confirmation to treatment. Conclusion Our study identified factors associated with low clinical trial participation in AYA patients with cancer. These findings support the continued need to improve access to clinical trials and innovative treatments for this population, which may ultimately translate into improved survival. PMID:21931022

  1. Serum Biomarkers Associated with Clinical Outcomes Fail to Predict Brain Metastases in Patients with Stage IV Non-Small Cell Lung Cancers

    PubMed Central

    Li, Bob T.; Lou, Emil; Hsu, Meier; Yu, Helena A.; Naidoo, Jarushka; Zauderer, Marjorie G.; Sima, Camelia; Johnson, Melissa L.; Daras, Mariza; DeAngelis, Lisa M.; Fleisher, Martin; Kris, Mark G.; Azzoli, Christopher G.

    2016-01-01

    Background Lung cancers account for the majority of brain metastases which pose major therapeutic challenges. Biomarkers prognosticating for the development of brain metastases in patients with non-small cell lung cancers (NSCLC) may improve personalized care. Six serum proteomic biomarkers were previously investigated at Memorial Sloan Kettering but their associations with brain metastases were unknown. Methods Serum NSE, CYFRA 21–1, ProGRP, SCC-Ag, TIMP1, and HE4 by ELISA-based proteomic assays were prospectively collected from consecutive patients with stage IV NSCLC. Pre-treatment serum biomarker levels as well as age, histology, and epidermal growth factor receptor (EGFR) mutation status were evaluated for association with the baseline presence of brain metastases using logistic regression and multivariable analysis. For patients without brain metastases at baseline, the cumulative incidence of subsequent brain metastases were compared according to baseline biomarkers and clinical factors using Gray’s test. Results A total of 118 patients were enrolled, 31 (26%; 95% CI 0.19–0.35) had brain metastases at baseline and a further 26 (22%; 95% CI 0.15–0.30) developed brain metastases subsequently. Pre-treatment serum biomarker levels were available in 104 patients. There was no significant association between the six serum biomarkers and the baseline presence or subsequent development of brain metastases. Age younger than 65 years was the only clinical factor significantly associated with brain metastasis at baseline (OR 3.00; 95% CI 1.22–7.34, P = 0.02) by multivariable analysis. A trend toward increased cumulative incidence of subsequent brain metastases was observed in patients with EGFR mutation (p = 0.2), but this was not statistically significant possibly due to small sample size. Conclusions Serum NSE, CYFRA 21–1, Pro-GRP, SCC-Ag, TIMP1, and HE4 are not significantly associated with brain metastases. Our methods taking into account follow-up time

  2. Age modifies the immunologic response and clinical presentation of American tegumentary leishmaniasis.

    PubMed

    Carvalho, Augusto M; Amorim, Camila F; Barbosa, Juliana L S; Lago, Alexsandro S; Carvalho, Edgar M

    2015-06-01

    Leishmania (Viannia) braziliensis is the main causal agent of American tegumentary leishmaniasis (ATL) that may present as cutaneous, mucosal, or disseminated cutaneous leishmaniasis. The disease is highly prevalent in young males and there is a lack of studies of ATL in the elderly. Herein, we compared clinical manifestations, immunologic response, and response to antimony therapy between patients > 60 years of age (N = 58) and patients who were 21-30 years of age (N = 187). The study was performed in Corte de Pedra, Bahia, Brazil, a well-known area of L. braziliensis transmission. Cytokine production by cultured peripheral blood mononuclear cells stimulated with soluble Leishmania antigen was performed. Elderly subjects more frequently had a previous history of cutaneous leishmaniasis, large lesions, or mucosal leishmaniasis, and they were less likely to have lymphadenopathy. There was no difference regarding gender and response to therapy. Peripheral blood mononuclear cells from elderly subjects produced a similar amount of tumor necrosis factor than young patients but they produced less interferon-gamma and more interleukin-10 than young subjects. We concluded that elderly patients with cutaneous leishmaniasis should be searched for mucosal or disseminated leishmaniasis. The decreased interferon-gamma production and increase in interleukin-10 observed in elderly patients may contribute to parasite persistence and L. braziliensis infection dissemination.

  3. 5-azacitidine efficacy and safety in patients aged >65 years with myelodysplastic syndromes outside clinical trials.

    PubMed

    Breccia, Massimo; Loglisci, Giuseppina; Salaroli, Adriano; Serrao, Alessandra; Petrucci, Luigi; Mancini, Marco; Alimena, Giuliana

    2012-08-01

    The efficacy and safety of azacitidine in elderly patients (aged >65 years) with myelodysplastic syndromes (MDS) treated outside clinical trials are reported. Thirty-eight patients with MDS received azacitidine (75 mg/m(2), schedule 5+2 +2): seven patients were classified as having refractory cytopenia with multilineage dysplasia (RCMD), nine patients with refractory anemia with excess of blasts (RAEB) type 1, 18 patients with RAEB type 2 and four patients with chronic myelomonocytic leukemia type 2 (CMML-2). According to International Working Group (IWG) 2006 criteria, after the first four cycles we detected complete remission in seven patients (CR, 18%), improvement of bone marrow dysplasia and reduction of blast percentage in seven patients (partial response, 18%), stable disease in 20 patients (53%) and progression to acute leukemia in four patients (10%). Median overall survival for all patients treated was 16.4 months. Only mild non-hematologic toxicity was detected (grade 1-2 nausea and pruritus), whereas 55% of patients experienced hematologic side effects (25% grade 3-4 thrombocytopenia and 30% grade 3-4 neutropenia). Our results suggest that advanced age should not preclude effective treatment with azacitidine in non-selected elderly patients wih MDS.

  4. A clinical practice model for treatment of college-aged incest survivors.

    PubMed

    Barney, E E

    1990-05-01

    Adult incest survivors frequently exhibit signs and symptoms of posttraumatic stress disorder. Many clinicians have geared their group treatment of incest survivors to address these manifestations. Given the nature of the sexual abuse, the early developmental periods in which some trauma occurs, the past and current relationship between the victim and the perpetrator, and the dynamics inherent in this violation and betrayal of trust, love, and power within the family unit, additional clinical concerns and safeguards must be considered. In addition, the struggles of college-aged incest survivors to come to terms with their history of sexual abuse often mirror the developmental tasks faced by their peers--autonomy, intimacy, sexuality, and formation of personal values and ethics. To focus solely on the incest without also considering these developmental issues may solidify a gridlock between inadequate resolution of the developmental issues and the continued victimization of the student incest survivor. The author discusses a time-limited group treatment for college-aged incest survivors that uses a modified posttraumatic stress disorder model as a conceptual framework and addresses both sets of concerns.

  5. Age Modifies the Immunologic Response and Clinical Presentation of American Tegumentary Leishmaniasis

    PubMed Central

    Carvalho, Augusto M.; Amorim, Camila F.; Barbosa, Juliana L. S.; Lago, Alexsandro S.; Carvalho, Edgar M.

    2015-01-01

    Leishmania (Viannia) braziliensis is the main causal agent of American tegumentary leishmaniasis (ATL) that may present as cutaneous, mucosal, or disseminated cutaneous leishmaniasis. The disease is highly prevalent in young males and there is a lack of studies of ATL in the elderly. Herein, we compared clinical manifestations, immunologic response, and response to antimony therapy between patients > 60 years of age (N = 58) and patients who were 21–30 years of age (N = 187). The study was performed in Corte de Pedra, Bahia, Brazil, a well-known area of L. braziliensis transmission. Cytokine production by cultured peripheral blood mononuclear cells stimulated with soluble Leishmania antigen was performed. Elderly subjects more frequently had a previous history of cutaneous leishmaniasis, large lesions, or mucosal leishmaniasis, and they were less likely to have lymphadenopathy. There was no difference regarding gender and response to therapy. Peripheral blood mononuclear cells from elderly subjects produced a similar amount of tumor necrosis factor than young patients but they produced less interferon-gamma and more interleukin-10 than young subjects. We concluded that elderly patients with cutaneous leishmaniasis should be searched for mucosal or disseminated leishmaniasis. The decreased interferon-gamma production and increase in interleukin-10 observed in elderly patients may contribute to parasite persistence and L. braziliensis infection dissemination. PMID:25918209

  6. Acute right lower abdominal pain in women of reproductive age: Clinical clues

    PubMed Central

    Hatipoglu, Sinan; Hatipoglu, Filiz; Abdullayev, Ruslan

    2014-01-01

    AIM: To study possible gynecological organ pathologies in the differential diagnosis of acute right lower abdominal pain in patients of reproductive age. METHODS: Following Clinical Trials Ethical Committee approval, the retrospective data consisting of physical examination and laboratory findings in 290 patients with sudden onset right lower abdominal pain who used the emergency surgery service between April 2009 and September 2013, and underwent surgery and general anesthesia with a diagnosis of acute appendicitis were collated. RESULTS: Total data on 290 patients were obtained. Two hundred and twenty-four (77.2%) patients had acute appendicitis, whereas 29 (10%) had perforated appendicitis and 37 (12.8%) had gynecological organ pathologies. Of the latter, 21 (7.2%) had ovarian cyst rupture, 12 (4.2%) had corpus hemorrhagicum cyst rupture and 4 (1.4%) had adnexal torsion. Defense, Rovsing’s sign, increased body temperature and increased leukocyte count were found to be statistically significant in the differential diagnosis of acute appendicitis and gynecological organ pathologies. CONCLUSION: Gynecological pathologies in women of reproductive age are misleading in the diagnosis of acute appendicitis. PMID:24744594

  7. Improving function in age-related macular degeneration: design and methods of a randomized clinical trial.

    PubMed

    Rovner, Barry W; Casten, Robin J; Hegel, Mark T; Massof, Robert W; Leiby, Benjamin E; Tasman, William S

    2011-03-01

    Age-Related Macular Degeneration (AMD) is the leading cause of severe vision loss in older adults and impairs the ability to read, drive, and live independently and increases the risk for depression, falls, and earlier mortality. Although new medical treatments have improved AMD's prognosis, vision-related disability remains a major public health problem. Improving Function in AMD (IF-AMD) is a two-group randomized, parallel design, controlled clinical trial that compares the efficacy of Problem-Solving Therapy (PST) with Supportive Therapy (ST) (an attention control treatment) to improve vision function in 240 patients with AMD. PST and ST therapists deliver 6 one-hour respective treatment sessions to subjects in their homes over 2 months. Outcomes are assessed masked to treatment assignment at 3 months (main trial endpoint) and 6 months (maintenance effects). The primary outcome is targeted vision function (TVF), which refers to specific vision-dependent functional goals that subjects highly value but find difficult to achieve. TVF is an innovative outcome measure in that it is targeted and tailored to individual subjects yet is measured in a standardized way. This paper describes the research methods, theoretical and clinical aspects of the study treatments, and the measures used to evaluate functional and psychiatric outcomes in this population.

  8. A clinic-based study of refractive errors, strabismus, and amblyopia in pediatric age-group

    PubMed Central

    Al-Tamimi, Elham R.; Shakeel, Ayisha; Yassin, Sanaa A.; Ali, Syed I.; Khan, Umar A.

    2015-01-01

    Purpose: The purpose of this cross-sectional observational study was to determine the distribution and patterns of refractive errors, strabismus, and amblyopia in children seen at a pediatric eye care. Materials and Methods: The study was conducted in a Private Hospital in Dammam, Kingdom of Saudi Arabia, from March to July 2013. During this period, a total of 1350 children, aged 1–15 years were seen at this Center's Pediatric Ophthalmology Unit. All the children underwent complete ophthalmic examination with cycloplegic refraction. Results: Refractive errors accounted for 44.4% of the cases, the predominant refractive error being hypermetropia which represented 83%. Strabismus and amblyopia were present in 38% and 9.1% of children, respectively. Conclusions: In this clinic-based study, the focus was on the frequency of refractive errors, strabismus, and amblyopia which were considerably high. Hypermetropia was the predominant refractive error in contrast to other studies in which myopia was more common. This could be attributed to the criteria for sample selection since it was clinic-based rather than a population-based study. However, it is important to promote public education on the significance of early detection of refractive errors, and have periodic screening in schools. PMID:26392796

  9. Metering Self-Reported Adherence to Clinical Outcomes in Malaysian Patients with Hypertension: Applying the Stages of Change Model to Healthful Behaviors in the CORFIS Study

    ERIC Educational Resources Information Center

    Karupaiah, Tilakavati; Wong, Kimberly; Chinna, Karuthan; Arasu, Kanimolli; Chee, Winnie Siew Swee

    2015-01-01

    The CORFIS ("Community-Based Cardiovascular Risk Factors Intervention Strategies") program was piloted in community clinics in Malaysia to address the lack of health education in chronic disease management. The stages of change model was applied in a multicenter quasi-experimental design to evaluate adherence to advocated behaviors in…

  10. Ginkgo for elderly people with dementia and age-associated memory impairment: a randomized clinical trial.

    PubMed

    van Dongen, Martien; van Rossum, Erik; Kessels, Alphons; Sielhorst, Hilde; Knipschild, Paul

    2003-04-01

    Preparations based on special extracts of the Ginkgo biloba tree are popular in various European countries. Previous studies have suggested the clinical efficacy of Ginkgo in patients with dementia, cerebral insufficiency, or related cognitive decline. However, most of these studies did not fulfill the current methodologic requirements. We assessed the efficacy of the G. biloba special extract EGb 761 in patients with dementia and age-associated memory impairment in relation to dose and duration of treatment. Our study was a 24-week, randomized, double-blind, placebo-controlled, parallel-group, multicenter trial. Study participants were elderly patients with dementia (Alzheimer disease or vascular dementia) or age-associated memory impairment (AAMI). A total of 214 participants, recruited from 39 homes for the elderly in the Netherlands, were randomly allocated to Ginkgo (either 240 mg/d or 160 mg/d) or placebo (0 mg/d). After 12 weeks, the subjects in the two Ginkgo groups were randomized to continued Ginkgo treatment or placebo treatment. Primary outcome measures in this study were the Syndrome Kurz Test (SKT; psychometric functioning), the Clinical Global Impression of change (CGI-2; psychopathology, assessed by nursing staff), and the Nuremberg Gerontopsychological Rating Scale for Activities of Daily Living (NAI-NAA; behavioral functioning). One hundred twenty-three patients received Ginkgo (n=79, 240 and 160 mg/d combined) or placebo (n=44) during the 24-week intervention period. We found no statistically significant differences in mean change of scores between Ginkgo and placebo. The differences were SKT: +0.4 (90% confidence interval [CI] -0.9-1.7); CGI-2: +0.1 (90% CI -0.3-0.4), and NAI-NAA: -0.4 (90% CI -1.9-1.2). A positive difference is in favor of Ginkgo. Neither the dementia subgroup (n=36) nor the AAMI subgroup (n=87) experienced a significant effect of Ginkgo treatment. There was no dose-effect relationship and no effect of prolonged Ginkgo

  11. An analysis of meiotic stage of nondisjunction and clinical characteristics in 27 children with Down syndrome and leukemia

    SciTech Connect

    Shugar, A.; Soukup, S.

    1994-09-01

    The observation that children with Down syndrome experience a significantly increased risk for leukemia was made in the 1950`s. Recent research has revealed that two specific forms of leukemia, acute non-lymphoblastic leukemia (specifically the subtype M7) and transient leukemia (TL) are preferentially associated with trisomy 21. The specific association of these leukemias with trisomy 21 has suggested to others that there may be a gene on chromosome 21 which predisposes to TL and M7 leukemia. If a recessive gene for susceptibility existed, then trisomies arising as a duplication of one parental centromere through a mitotic or meiosis II error would be expected to have a higher frequency of TL and M7 leukemia. The purpose of this study was (i) To test the models which propose that disomic homozygosity is preponderant in cases of TL and M7 leukemia in a Down syndrome population (ii) To further characterize the clinical characteristics of leukemia in the Down syndrome population. We utilized a combination of cytogenetic and DNA polymorphism analyses to determine stage of non-disjunction and parental orgin of the extra chromosome in 18 children with Down syndrome and leukemia. The DNA analyses are reported elsewhere. Among 27 cases of Down Syndrome leukemics, meiosis II or mitotic errors were seen in 4 out of 5 informative TL and M7 cases and in only 1 out of 5 cases of other leukemias. Clinical analysis revealed that the frequency of M7 leukemia is significantly higher in DS-leukemics compared to non-Down syndrome-leukemics. A case of Down syndrome TL with subsequent development of M7 leukemia was anecdotal evidence that TL and M7 leukemia may be of common clonal origin. The fact that fewer than 100% of TL and M7 leukemia cases demonstrated meiosis II or mitotic errors indicates that disomic homozygosity is not necessary for the development of these leukemias, however it may be an important factor which predisposes to TL and M7 leukemia in Down syndrome.

  12. Perioperative outcomes and long-term survival in clinically early-stage thymic malignancies: video-assisted thoracoscopic thymectomy versus open approaches

    PubMed Central

    Wang, Hao; Gu, Zhitao; Tan, Lijie; Fu, Jianhua; Shen, Yi; Wei, Yucheng; Zhang, Peng; Han, Yongtao; Chen, Chun; Zhang, Renquan; Li, Yin; Chen, Keneng; Chen, Hezhong; Liu, Yongyu; Cui, Youbing; Wang, Yun; Pang, Liewen; Yu, Zhentao; Zhou, Xinming; Liu, Yangchun; Liu, Yuan

    2016-01-01

    Background Video-assisted thoracoscopic surgery (VATS) theoretically offers advantages over open thymectomy for clinically early-stage (Masaoka-Koga stage I and II) thymic malignancies. However, long-term outcomes have not been well studied. We compared the postoperative outcomes and survival from a cohort study based on the database of the Chinese Alliance for Research in Thymomas (ChART). Methods Between 1994 and 2012, data of 1,117 patients having surgery for clinically early-stage (Masaoka-Koga stage I and II) tumors were enrolled for the study. Among them, 241 cases underwent VATS thymectomy (VATS group), while 876 cases underwent open thymectomy (Open group). Univariate analyses were used to compare the clinical character and perioperative outcomes between the two groups. And multivariate analysis was performed to determine the independent predictive factors for long-term survival. Results Compared with the Open group, the VATS group had higher percentage of total thymectomy (80.5% vs. 73.9%, P=0.028), resection rate (98.8% vs. 88.7%, P=0.000) and less recurrence (2.9% vs. 16.0%, P=0.000). Five-year overall survival was 92% after VATS and 92% after open thymectomy, with no significant difference between the two groups (P=0.15). However, 5-year disease free survival were 92% in VATS group and 83% in Open group (P=0.011). Cox proportional hazards model revealed that WHO classification, Masaoka-Koga stage and adjuvant therapy were independent predictive factors for overall survival, while surgical approach had no significant impact on long-term outcome. Conclusions This study suggests that VATS thymectomy is an effective approach for clinically early-stage thymic malignancies. And it may offer better perioperative outcomes, as well as equal oncological survival. PMID:27114834

  13. Young and Middle-Aged Rats Exhibit Isometric Forelimb Force Control Deficits in a Model of Early-Stage Parkinson's disease

    PubMed Central

    Bethel-Brown, Crystal S.; Morris, Jill K.; Stanford, John A.

    2011-01-01

    Deficits in manual motor control often accompany the early stages of Parkinson’s disease (PD), and are often revealed through isometric force tasks. In order to determine whether similar deficits occur in a rat model of early-stage PD, young (8 months) and middle-aged (18 months) rats were trained to produce sustained press-hold-release isometric forelimb responses that allowed for analyses of force output and spectral analysis of forelimb stability and tremor. Rats then received a 6-hydroxydopamine (6-OHDA) infusion into the striatum contralateral to the trained forelimb and were tested for four weeks post-lesion. The resulting partial striatal dopamine depletions (which at 41 ± 12% and 43 ± 6% in young and middle-aged rats, respectively, did not differ between the two groups) resulted in isometric forelimb deficits. Specifically, rats exhibited significantly diminished force stability and increased high frequency (10–25 Hz) tremor, indicating potential postural disturbances and increased postural tremor respectively. Durations of press-hold-release bouts were also increased post-lesion, suggesting difficulty in task disengagement. Despite pre-lesion differences in some of the force measures, the effects of partial nigrostriatal DA depletion did not differ between the two age groups. These results support the use of the press-while-licking task in preclinical studies modeling isometric force control deficits in PD. PMID:21767573

  14. Advanced maternal age and the risk of Down syndrome characterized by the meiotic stage of the chromosomal error: A population-based study

    SciTech Connect

    Yoon, P.W.; Khoury, M.J.; Freeman, S.B.

    1996-03-01

    The identification of DNA polymorphisms makes it possible to classify trisomy 21 according to the parental origin and stage (meiosis I [MI], meiosis II [MII], or postzygotic mitotic) of the chromosomal error. Studying the effect of parental age on these subgroups could shed light on parental exposures and their timing. From 1989 through 1993, 170 infants with trisomy 21 and 267 randomly selected control infants were ascertained in a population-based, case-control study in metropolitan Atlanta. Blood samples for genetic studies were obtained from case infants and their parents. Using logistic regression, we independently examined the association between maternal and paternal age and subgroups of trisomy 21 defined by parental origin and meiotic stage. The distribution of trisomy 21 by origin was 86% maternal (75% MI and 25% MII), 9% paternal (50% MI and 50% MII), and 5% mitotic. Compared with women <25 years of age, women {>=}40 years old had an odds ratio of 5.2 (95% confidence interval, 1.0-27.4) for maternal MI (MMI) errors and 51.4 (95% confidence interval, 2.3-999.0) for maternal MII (MMII) errors. Birth-prevalence rates for women {>=}40 years old were 4.2/1,000 births for MMI errors and 1.9/1,000 births for MMII errors. These results support an association between advanced maternal age and both MMI and MMII errors. The association with MI does not pinpoint the timing of the error; however, the association with MII implies that there is at least one maternal age-related mechanism acting around the time of conception. 16 refs., 1 fig., 2 tabs.

  15. Phase I Clinical Trial of a Recombinant Blood Stage Vaccine Candidate for Plasmodium falciparum Malaria Based on MSP1 and EBA175

    PubMed Central

    Chitnis, Chetan E.; Mukherjee, Paushali; Mehta, Shantanu; Yazdani, Syed Shams; Dhawan, Shikha; Shakri, Ahmad Rushdi; Bharadwaj, Rukmini; Gupta, Puneet Kumar; Hans, Dhiraj; Mazumdar, Suman; Singh, Bijender; Kumar, Sanjeev; Pandey, Gaurav; Parulekar, Varsha; Imbault, Nathalie; Shivyogi, Preethi; Godbole, Girish; Mohan, Krishna; Leroy, Odile; Singh, Kavita; Chauhan, Virander S.

    2015-01-01

    Background A phase I randomised, controlled, single blind, dose escalation trial was conducted to evaluate safety and immunogenicity of JAIVAC-1, a recombinant blood stage vaccine candidate against Plasmodium falciparum malaria, composed of a physical mixture of two recombinant proteins, PfMSP-119, the 19 kD conserved, C-terminal region of PfMSP-1 and PfF2 the receptor-binding F2 domain of EBA175. Method Healthy malaria naïve Indian male subjects aged 18–45 years were recruited from the volunteer database of study site. Fifteen subjects in each cohort, randomised in a ratio of 2:1 and meeting the protocol specific eligibility criteria, were vaccinated either with three doses (10μg, 25μg and 50μg of each antigen) of JAIVAC-1 formulated with adjuvant Montanide ISA 720 or with standard dosage of Hepatitis B vaccine. Each subject received the assigned vaccine in the deltoid muscle of the upper arms on Day 0, Day 28 and Day 180. Results JAIVAC-1 was well tolerated and no serious adverse event was observed. All JAIVAC-1 subjects sero-converted for PfF2 but elicited poor immune response to PfMSP-119. Dose-response relationship was observed between vaccine dose of PfF2 and antibody response. The antibodies against PfF2 were predominantly of IgG1 and IgG3 isotype. Sera from JAIVAC-1 subjects reacted with late schizonts in a punctate pattern in immunofluorescence assays. Purified IgG from JAIVAC-1 sera displayed significant growth inhibitory activity against Plasmodium falciparum CAMP strain. Conclusion Antigen PfF2 should be retained as a component of a recombinant malaria vaccine but PfMSP-119 construct needs to be optimised to improve its immunogenicity. Trial Registration Clinical Trial Registry, India CTRI/2010/091/000301 PMID:25927360

  16. Interaction of age and foam types used in Clinical Test for Sensory Interaction and Balance (CTSIB).

    PubMed

    Chaikeeree, Nithinun; Saengsirisuwan, Vitoon; Chinsongkram, Butsara; Boonsinsukh, Rumpa

    2015-01-01

    Clinical Test for Sensory Interaction and Balance (CTSIB) is a simplified method for investigating the organization of multiple sensory inputs in postural control. The accuracy of the test is based partly on the foam types. Several types of foam are available, but the validity of these foams on CTSIB and the interaction of age and foam types have not been addressed. In this study, postural sway of young (21.6 ± 3.3 years) and older (53.2 ± 4.9 years) participants were assessed while standing on four types of foam: NeuroCom(®), sponge, Ethylene Vinyl Acetate (EVA), and memory foams. Postural sway during stance on solid floor and foams with eyes open and eyes closed were quantified by root-mean-square (RMS) of center of body mass acceleration in the mediolateral (ML) and anteroposterior (AP) directions using the acceleration-based OPAL system. Physical properties of foams including density, Young's modulus, and indentation force deflection (IFD) were determined. Results demonstrated that RMS-ML in older subjects was larger than younger subjects (p ≤ 0.001), especially when standing on the NeuroCom(®) foam with eyes closed (p = 0.001). There was an interaction of age and foam types as larger differences in RMS-ML were observed between young and older subjects on the NeuroCom(®) and EVA foams, but not the other foams. The sway characteristics were largest when standing on the NeuroCom(®) foam which demonstrated high density and high compliance. Our findings suggested the importance of foam selection in CTSIB on accurate postural sway analysis and balance assessment.

  17. Bevacizumab for neovascular age-related macular degeneration in Chinese patients in a clinical setting

    PubMed Central

    Ng, Danny Siu-Chun; Kwok, Alvin Kwan-Ho; Tong, Justin Man-Kit; Chan, Clement Wai-Nang; Li, Walton Wai-Tat

    2016-01-01

    AIM To determine the outcome of non-investigational treatment with intravitreal bevacizumab (IVB) in neovascular age-related macular degeneration (AMD) patients. METHODS Retrospective chart review of 81 eyes with neovascular AMD followed-up for at least 12mo and received 3-monthly loading IVB injections. Re-treat was based upon the individual clinician's judgment. Best-corrected visual acuity (BCVA) and optical coherence tomography measurements of central foveal thickness outcomes were evaluated at 12, 24mo. RESULTS Eighty-one eyes (of 75 patients) completed 12mo of follow-up and 44 eyes (of 41 patients) completed 24mo of follow-up. The mean baseline logMAR BCVA significantly improved from 0.94±0.69 to 0.85±0.68 at 12mo (P<0.001) and from 0.91±0.65 to 0.85±0.60 (P=0.004) at 24mo. The proportion of eyes that lost <15 logMAR letters at 12mo was 90.1% and at 24mo was 81.8%. IVB was effective in improving visual acuity in both treatment naïve and previous photodynamic therapy (PDT)-treated subgroups. Treatment naive patients required significantly fewer injections than patients with prior PDT. Multiple regression analysis identified that poorer baseline visual acuity was associated with greater improvement in visual acuity (P=0.015). CONCLUSION Fewer injections in clinical practice may result in suboptimal visual outcomes compared with clinical trials of IVB in neovascular AMD patients. Poor baseline visual acuity and prior PDT treatment may also improve vision after IVB. The safety and durability of effect was maintained at 24mo. PMID:27158614

  18. Aging with HIV: a cross-sectional study of comorbidity prevalence and clinical characteristics across decades of life.

    PubMed

    Vance, David E; Mugavero, Michael; Willig, James; Raper, James L; Saag, Michael S

    2011-01-01

    Nurses and nurse practitioners require information on the health problems faced by aging HIV-infected adults. In this descriptive, cross-sectional study, we reviewed the electronic medical records of 1,478 adult patients seen in an HIV clinic between May 2006 and August 2007 to examine patterns of comorbidities, and immunological and clinical characteristics across each decade of life. With increasing age, patients were found to have lower HIV viral loads, more prescribed medications, and a higher prevalence of comorbid conditions, including coronary artery disease, hypertension, hypercholesterolemia, hypogonadism, erectile dysfunction, diabetes, peripheral neuropathy, hepatitis C, esophageal gastric reflux disease, and renal disease. Fortunately, with increasing age, patients were also more likely to have public or private health insurance and tended to be more compliant to medical appointments. With growing interest in aging with HIV, this study highlights the vastly different comorbidity profiles across decades of life, calling into question what constitutes "older" with HIV. PMID:20471864

  19. Progression and survival in prostatic adenocarcinoma: a comparison of clinical stage, Gleason grade, S-phase fraction and DNA ploidy.

    PubMed

    Vesalainen, S; Nordling, S; Lipponen, P; Talja, M; Syrjänen, K

    1994-08-01

    Clinical data were reviewed in 325 patients with prostatic adenocarcinoma followed up for a mean of 13 years. Paraffin-embedded tumour biopsy specimens from the primary tumours were available for flow cytometry (FCM) in 273 cases. Intra-tumour heterogeneity in DNA index (DI) was found in 4% of the tumours (54 cases were analysed). S-phase fraction (SPF) and DNA ploidy were significantly interrelated. Aneuploidy and high SPF were significantly related to both a high T category and high Gleason score. The progression in T1-2M0 tumours was related to Gleason score (P = 0.009), DNA ploidy (P = 0.006) and SPF (P = 0.007), while the Gleason score (P = 0.0013), DNA ploidy (P = 0.002) and SPF (P < 0.001) had prognostic value in univariate survival analysis. In the entire cohort, the T category (P < 0.001), M category (P < 0.001), Gleason score (P < 0.001), DNA ploidy (P < 0.001) and SPF (P < 0.001) were significant prognostic factors. In Cox's analysis, the M category (P < 0.001), Gleason score (P < 0.001), T category (P = 0.003), age (P = 0.001) and SPF (P = 0.087) were independently related to prognosis. In the T1-2M0 tumours, Gleason score (P < 0.001), T category (P = 0.022) and SPF (P = 0.058) were independent predictors. A novel classification system in which the DNA ploidy or SPF and the Gleason score were combined was found to be of significant prognostic value in all M0 tumours (P < 0.001). The results suggest that FCM can be used as an adjunct to conventional histological assessments for determination of the correct prognostic category in prostatic adenocarcinoma.

  20. Immune-related Adverse Events of Dendritic Cell Vaccination Correlate With Immunologic and Clinical Outcome in Stage III and IV Melanoma Patients.

    PubMed

    Boudewijns, Steve; Westdorp, Harm; Koornstra, Rutger H T; Aarntzen, Erik H J G; Schreibelt, Gerty; Creemers, Jeroen H A; Punt, Cornelis J A; Figdor, Carl G; de Vries, I Jolanda M; Gerritsen, Winald R; Bol, Kalijn F

    2016-01-01

    The purpose of this study was to determine the toxicity profile of dendritic cell (DC) vaccination in stage III and IV melanoma patients, and to evaluate whether there is a correlation between side effects and immunologic and clinical outcome. This is a retrospective analysis of 82 stage III and 137 stage IV melanoma patients, vaccinated with monocyte-derived or naturally circulating autologous DCs loaded with tumor-associated antigens gp100 and tyrosinase. Median follow-up time was 54.3 months in stage III patients and 12.9 months in stage IV patients. Treatment-related adverse events occurred in 84% of patients; grade 3 toxicity was present in 3% of patients. Most common adverse events were flu-like symptoms (67%) and injection site reactions (50%), and both correlated with the presence of tetramer-positive CD8 T cells (both P<0.001). In stage III melanoma patients experiencing flu-like symptoms, median overall survival (OS) was not reached versus 32.3 months in patients without flu-like symptoms (P=0.009); median OS in patients with an injection site reaction was not reached versus 53.7 months in patients without an injection site reaction (P<0.05). In stage IV melanoma patients (primary uveal and mucosal melanomas excluded), median OS in patients with or without flu-like symptoms was 13.1 versus 8.9 months, respectively (P=0.03); median OS in patients with an injection site reaction was 15.7 months versus 9.8 months in patients without an injection site reaction (P=0.003). In conclusion, DC vaccination is safe and tolerable and the occurrence of the immune-related side effects, such as flu-like symptoms and injection site reactions, correlates with immunologic and clinical outcome. PMID:27227325

  1. Immune-related Adverse Events of Dendritic Cell Vaccination Correlate With Immunologic and Clinical Outcome in Stage III and IV Melanoma Patients

    PubMed Central

    Boudewijns, Steve; Westdorp, Harm; Koornstra, Rutger H.T.; Aarntzen, Erik H.J.G.; Schreibelt, Gerty; Creemers, Jeroen H.A.; Punt, Cornelis J.A.; Figdor, Carl G.; Gerritsen, Winald R.; Bol, Kalijn F.

    2016-01-01

    The purpose of this study was to determine the toxicity profile of dendritic cell (DC) vaccination in stage III and IV melanoma patients, and to evaluate whether there is a correlation between side effects and immunologic and clinical outcome. This is a retrospective analysis of 82 stage III and 137 stage IV melanoma patients, vaccinated with monocyte-derived or naturally circulating autologous DCs loaded with tumor-associated antigens gp100 and tyrosinase. Median follow-up time was 54.3 months in stage III patients and 12.9 months in stage IV patients. Treatment-related adverse events occurred in 84% of patients; grade 3 toxicity was present in 3% of patients. Most common adverse events were flu-like symptoms (67%) and injection site reactions (50%), and both correlated with the presence of tetramer-positive CD8+ T cells (both P<0.001). In stage III melanoma patients experiencing flu-like symptoms, median overall survival (OS) was not reached versus 32.3 months in patients without flu-like symptoms (P=0.009); median OS in patients with an injection site reaction was not reached versus 53.7 months in patients without an injection site reaction (P<0.05). In stage IV melanoma patients (primary uveal and mucosal melanomas excluded), median OS in patients with or without flu-like symptoms was 13.1 versus 8.9 months, respectively (P=0.03); median OS in patients with an injection site reaction was 15.7 months versus 9.8 months in patients without an injection site reaction (P=0.003). In conclusion, DC vaccination is safe and tolerable and the occurrence of the immune-related side effects, such as flu-like symptoms and injection site reactions, correlates with immunologic and clinical outcome. PMID:27227325

  2. Factors Associated with Blood Culture Contamination in the Emergency Department: Critical Illness, End-Stage Renal Disease, and Old Age

    PubMed Central

    Chang, Chih-Jan; Wu, Chi-Jung; Hsu, Hsiang-Chin; Wu, Chiu-Hui; Shih, Fang-Ying; Wang, Shou-Wen; Wu, Yi-Hui; Chang, Chia-Ming; Tu, Yi-Fang; Chi, Chih-Hsien; Shih, Hsin-I

    2015-01-01

    Background Blood culture contamination in emergency departments (ED) that experience a high volume of patients has negative impacts on optimal patient care. It is therefore important to identify risk factors associated with blood culture contamination in EDs. Methodology/Principal Findings A prospectively observational study in a university-affiliated hospital were conducted between August 2011 and December 2012. Positive monomicrobial and negative blood cultures drawn from adult patients in the ED were analyzed to evaluate the possible risk factors for contamination. A total of 1,148 positive monomicrobial cases, 391 contamination cases, and 13,689 cases of negative blood culture were identified. Compared to patients with negative blood cultures, patients in triage levels 1 and 2 (Incidence Rate Ratio, IRR = 2.24), patients with end-stage renal disease (ESRD) (IRR = 2.05), and older patients (IRR: 1.02 per year) were more likely to be associated with ED blood culture contamination. Conclusions/Significance Critical patients (triage levels 1 and 2), ESRD patients, and older patients were more commonly associated with blood culture contamination in the ED. Further studies to evaluate whether the characteristics of skin commensals contribute to blood culture contamination is warranted, especially in hospitals populated with high-risk patients. PMID:26448628

  3. Nature and Age of Neighbours Matter: Interspecific Associations among Tree Species Exist and Vary across Life Stages in Tropical Forests.

    PubMed

    Ledo, Alicia

    2015-01-01

    Detailed information about interspecific spatial associations among tropical tree species is scarce, and hence the ecological importance of those associations may have been underestimated. However, they can play a role in community assembly and species diversity maintenance. This study investigated the spatial dependence between pairs of species. First, the spatial associations (spatial attraction and spatial repulsion) that arose between species were examined. Second, different sizes of trees were considered in order to evaluate whether the spatial relationships between species are constant or vary during the lifetime of individuals. Third, the consistency of those spatial associations with the species-habitat associations found in previous studies was assessed. Two different tropical ecosystems were investigated: a montane cloud forest and a lowland moist forest. The results showed that spatial associations among species exist, and these vary among life stages and species. The rarity of negative spatial interactions suggested that exclusive competition was not common in the studied forests. On the other hand, positive interactions were common, and the results of this study strongly suggested that habitat associations were not the only cause of spatial attraction among species. If this is true, habitat associations and density dependence are not the only mechanisms that explain species distribution and diversity; other ecological interactions, such as facilitation among species, may also play a role. These spatial associations could be important in the assembly of tropical tree communities and forest succession, and should be taken into account in future studies. PMID:26581110

  4. Nature and Age of Neighbours Matter: Interspecific Associations among Tree Species Exist and Vary across Life Stages in Tropical Forests.

    PubMed

    Ledo, Alicia

    2015-01-01

    Detailed information about interspecific spatial associations among tropical tree species is scarce, and hence the ecological importance of those associations may have been underestimated. However, they can play a role in community assembly and species diversity maintenance. This study investigated the spatial dependence between pairs of species. First, the spatial associations (spatial attraction and spatial repulsion) that arose between species were examined. Second, different sizes of trees were considered in order to evaluate whether the spatial relationships between species are constant or vary during the lifetime of individuals. Third, the consistency of those spatial associations with the species-habitat associations found in previous studies was assessed. Two different tropical ecosystems were investigated: a montane cloud forest and a lowland moist forest. The results showed that spatial associations among species exist, and these vary among life stages and species. The rarity of negative spatial interactions suggested that exclusive competition was not common in the studied forests. On the other hand, positive interactions were common, and the results of this study strongly suggested that habitat associations were not the only cause of spatial attraction among species. If this is true, habitat associations and density dependence are not the only mechanisms that explain species distribution and diversity; other ecological interactions, such as facilitation among species, may also play a role. These spatial associations could be important in the assembly of tropical tree communities and forest succession, and should be taken into account in future studies.

  5. Nature and Age of Neighbours Matter: Interspecific Associations among Tree Species Exist and Vary across Life Stages in Tropical Forests

    PubMed Central

    Ledo, Alicia

    2015-01-01

    Detailed information about interspecific spatial associations among tropical tree species is scarce, and hence the ecological importance of those associations may have been underestimated. However, they can play a role in community assembly and species diversity maintenance. This study investigated the spatial dependence between pairs of species. First, the spatial associations (spatial attraction and spatial repulsion) that arose between species were examined. Second, different sizes of trees were considered in order to evaluate whether the spatial relationships between species are constant or vary during the lifetime of individuals. Third, the consistency of those spatial associations with the species-habitat associations found in previous studies was assessed. Two different tropical ecosystems were investigated: a montane cloud forest and a lowland moist forest. The results showed that spatial associations among species exist, and these vary among life stages and species. The rarity of negative spatial interactions suggested that exclusive competition was not common in the studied forests. On the other hand, positive interactions were common, and the results of this study strongly suggested that habitat associations were not the only cause of spatial attraction among species. If this is true, habitat associations and density dependence are not the only mechanisms that explain species distribution and diversity; other ecological interactions, such as facilitation among species, may also play a role. These spatial associations could be important in the assembly of tropical tree communities and forest succession, and should be taken into account in future studies. PMID:26581110

  6. Improving quality of life in patients with end-stage age-related macular degeneration: focus on miniature ocular implants.

    PubMed

    Singer, Michael A; Amir, Nancy; Herro, Angela; Porbandarwalla, Salman S; Pollard, Joseph

    2012-01-01

    Low vision devices in the past have been mainly extraocular. There are now four new devices in different stages of development and implementation that are currently available. Three of them, the Implantable Miniature Telescope (IMT, VisionCare Ophthalmic Technologies, Saratoga, CA), Intraocular Lens for Visually Impaired People (IOL-VIP, IOL-VIP System, Soleko, Pontecorvo, Italy), and Lipschitz Mirror Implant (LMI, Optolight Vision Technology, Herzlia, Israel) are implanted into the anterior segment while the Argus II (Second Sight Medical Products, Sylmar, CA) is implanted into the posterior segment. The goal of these devices is to increase the patient quality of life which has been measured by Visual Functioning Questionnaire (VFQ) scales. The IMT is the only device that has been shown to increase the VFQ score by seven points at 6 months compared to baseline. It is the only FDA-approved device in the US while the Argus has been approved in Europe. Each of these prosthetics has potential benefits for patients.

  7. Dante and cardiology: Physiopathology and clinical features of cardiovascular diseases in the Middle Ages.

    PubMed

    Riva, M A; Cambioli, L; Castagna, F; Cianci, N; Varrenti, M; Giannattasio, C; Cesana, G

    2015-02-15

    Ancient non-medical texts can unexpectedly provide useful information on the development of knowledge about the heart and its diseases throughout history. The 750th anniversary of the birth of the Italian poet Dante Alighieri (1265-1321) provides a timely opportunity to analyze medical references in his works, in particular, focusing on literary descriptions that may be attributed to cardiovascular disorders. Dante's high level of medical knowledge, probably derived from his academic studies, is testified by his affiliation to the Florentine Guild of physicians and pharmacists. In all his works, the poet shows a deep interest for the heart. However, his anatomical and physiological knowledge of the circulatory system appears to be poor, probably due to it being based on theories and concepts brought forth by Aristotle and Galen, which were taught in medieval universities. Despite this, accurate descriptions of some symptoms (emotional syncope, orthopnea, dyspnea on exertion) and signs (ascites, paleness), which may be attributed to cardiovascular disorders, can be easily found in Dante's works, particularly in his masterpiece, the Divine Comedy. The literary and historical analysis of cardiovascular signs and symptoms allows us to assume that clinical features due to alterations of heart function were probably known by medieval physicians, but their etiology and pathophysiological mechanisms were not completely understood in that period. Historians of cardiology and clinicians should consider analysis of non-medical texts (including poetry) as an opportunity to better investigate the evolution of their discipline throughout the ages.

  8. Dante and cardiology: Physiopathology and clinical features of cardiovascular diseases in the Middle Ages.

    PubMed

    Riva, M A; Cambioli, L; Castagna, F; Cianci, N; Varrenti, M; Giannattasio, C; Cesana, G

    2015-02-15

    Ancient non-medical texts can unexpectedly provide useful information on the development of knowledge about the heart and its diseases throughout history. The 750th anniversary of the birth of the Italian poet Dante Alighieri (1265-1321) provides a timely opportunity to analyze medical references in his works, in particular, focusing on literary descriptions that may be attributed to cardiovascular disorders. Dante's high level of medical knowledge, probably derived from his academic studies, is testified by his affiliation to the Florentine Guild of physicians and pharmacists. In all his works, the poet shows a deep interest for the heart. However, his anatomical and physiological knowledge of the circulatory system appears to be poor, probably due to it being based on theories and concepts brought forth by Aristotle and Galen, which were taught in medieval universities. Despite this, accurate descriptions of some symptoms (emotional syncope, orthopnea, dyspnea on exertion) and signs (ascites, paleness), which may be attributed to cardiovascular disorders, can be easily found in Dante's works, particularly in his masterpiece, the Divine Comedy. The literary and historical analysis of cardiovascular signs and symptoms allows us to assume that clinical features due to alterations of heart function were probably known by medieval physicians, but their etiology and pathophysiological mechanisms were not completely understood in that period. Historians of cardiology and clinicians should consider analysis of non-medical texts (including poetry) as an opportunity to better investigate the evolution of their discipline throughout the ages. PMID:25544198

  9. Tools for Improving Clinical Preventive Services Receipt Among Women with Disabilities of Childbearing Ages and Beyond

    PubMed Central

    Taft, Kate E.; Sloan, Michelle L.; Stevens, Alissa C.; Krahn, Gloria L.

    2015-01-01

    Efforts to improve clinical preventive services (CPS) receipt among women with disabilities are poorly understood and not widely disseminated. The reported results represent a 2-year, Centers for Disease Control and Prevention and Association of Maternal and Child Health Programs partnership to develop a central resource for existing tools that are of potential use to maternal and child health practitioners who work with women with disabilities. Steps included contacting experts in the fields of disability and women’s health, searching the Internet to locate examples of existing tools that may facilitate CPS receipt, convening key stakeholders from state and community-based programs to determine their potential use of the tools, and developing an online Toolbox. Nine examples of existing tools were located. The tools focused on facilitating use of the CPS guidelines, monitoring CPS receipt among women with disabilities, improving the accessibility of communities and local transportation, and training clinicians and women with disabilities. Stakeholders affirmed the relevance of these tools to their work and encouraged developing a Toolbox. The Toolbox, launched in May 2013, provides information and links to existing tools and accepts feedback and proposals for additional tools. This Toolbox offers central access to existing tools. Maternal and child health stakeholders and other service providers can better locate, adopt and implement existing tools to facilitate CPS receipt among adolescent girls with disabilities who are transitioning into adult care as well as women with disabilities of child-bearing ages and beyond. PMID:25359095

  10. Effect of Advancing Age and Multiple Chronic Conditions on Mortality in Patients with End-Stage Renal Disease after Implantable Cardioverter-Defibrillator Placement

    PubMed Central

    Krishnaswami, Ashok; Kiley, Mary-Lou; Anthony, Faith F; Chen, Yuexin; Chen, Jason; Rajagopal, Sumanth; Liu, Taylor I; Young, Charlie; Paxton, Elizabeth W

    2016-01-01

    Context: There is insufficient information on the effect that advancing age and multiple chronic conditions (MCC) have on mortality after placement of an implantable cardioverter-defibrillator in patients with end-stage renal disease (ESRD) vs non-ESRD. Objective: To assess whether a differential effect of age and MCC exists between ESRD and non-ESRD. Design: Population-based, retrospective cohort study using data from the national Kaiser Permanente Cardiac Device Registry of patients who underwent placement of an implantable cardioverter-defibrillator between January 1, 2007, and December 31, 2013. Main Outcome Measures: All-cause mortality. Results: Of 7825 patients with implantable cardioverter-defibrillator placement, ESRD-affected patients constituted 4.0% of the cohort (n = 311), were similar in age (p = 0.91), and presented with a larger comorbidity burden (3.3 ± 1.3 vs 2.4 ± 1.5, p < 0.001). The effect of advancing age (every 5 years) on mortality in the ESRD cohort (hazard ratio [HR] = 1.11, 95% confidence interval [CI] = 1.03–1.20) was less than in the non-ESRD cohort (HR = 1.28, 95% CI = 1.25–1.32). Similarly, the effect of each additional comorbidity in the ESRD cohort was less (HR = 1.04, 95% CI = 0.91–1.19) than in the non-ESRD group (HR = 1.20, 95% CI = 1.16–1.25). Lastly, ESRD was independently associated with a 3-fold greater hazard of mortality. Conclusions: Advancing age and increasing number of MCC have a differential effect on mortality risk in patients with ESRD compared with their non-ESRD counterparts. Future studies should focus on assessment of nonlinear relationships of age, MCC, and naturally occurring clusters of MCC on mortality. PMID:26562307

  11. [Neuromuscular status of children of different gestational age on the stage of transition from intrauterine immersion to the earth's gravity].

    PubMed

    2012-01-01

    The work was aimed at describing the neuromuscular status of premature baby in the context of the ontogenetic and zero gravity model using the results of superficial interference electromyography (IEMG). Throughout six postnatal weeks, IEMG of premature babies is similar to EMG of full-term child on the first days of extrauterine life; IEMG is characterized by a "simplified" temporal structure, low amplitude and frequency, IEMG dynamics of fullterm child is slow in contrast to premature baby; the reason seems to be maximum long intrauterine life during which the motor system gets better prepared and maturates. On the other hand, complexity and high amplitude of premature baby IEMG as compared with full-term child of the same postconceptual age are associated with the inevitable sensory stimulation after birth. Abilitation procedures provided to premature baby could be adapted to the purposes of post-flight rehabilitation of cosmonauts.

  12. Which Stage of ADPKD Is More Appropriate for Decortication? A Retrospective Study of 137 Patients from a Single Clinic

    PubMed Central

    Li, Ruipeng; Liu, Hailong; Kong, Xiangjie; Duan, Liujian; Qi, Jun

    2015-01-01

    Objective To study retrospectively the efficacy of decortication in patients with different stages of ADPKD and to determine which stage for decortication is more appropriate. Materials and Methods We analyzed 137 patients with ADPKD from 2001 to 2010. All patients were divided into three stages. A total of 70 patients underwent decortication, and we studied intraoperative indicators and postoperative indicators at 1 and 3 years follow-up. Results In 70 patients who underwent decortication, significant differences were observed in operative duration and bleeding volume between patients with stage I and II ADPKD (P<0.05), but no significant differences were observed in intestinal recovery time, pain medication dose, and the days of postoperative hospitalization (P > 0.05). The total complication occurrence rate was significantly different between them (P < 0.05). The serum creatinine (Scr) levels in patients with stage I ADPKD were within normal limits 1 and 3 years postoperatively and did not differ significantly (P > 0.05). Scr levels were significantly decreased in patients with stage II ADPKD in the 1st postoperative year (P < 0.05), but these were not significant differences in the 3rd postoperative year (P > 0.05). In the 1st postoperative year, VAS value, blood pressure and renal volume significantly differed (P < 0.05). However, no significant differences were observed 3 years later (P > 0.05). Conclusions Decortication in patients with stage I ADPKD can alleviate back pain symptoms and decrease blood pressure within 1 year, but the long-term efficacy is not ideal. Scr levels can be maintained within normal limits, suggesting that decortication does not lead to deterioration of renal function. For patients with stage II ADPKD, decortication can significantly improve renal function over the short term. However, after 3 years, renal function returns to the preoperative level, and surgical difficulties and complications also increase. PMID:25939015

  13. Highly retentive core domains in K-feldspar preserve argon ages from high temperature stages of granite exhumation

    NASA Astrophysics Data System (ADS)

    Forster, Marnie; Lister, Gordon

    2016-04-01

    Retentive core domains are characterized by diffusion parameters that imply K-feldspar should be able to retain argon even at temperatures near or above the granite solidus. In this case it should be possible to date granite emplacement using argon geochronology, and the same answer should be obtained as by using other methods. We present one case study where this is the case, from the elevated Capoas granite stock on Palawan, in the Philippines, and another where it is not, from the South Cyclades Shear Zone, on Ios, Greece. We attempt to determine the factors such as the role of fluid ingress in triggering the in situ recrystallization that can eliminate and/or modify the core domains, leading to relatively youthful ages. Thermochronology is still possible, because less retentive diffusion domains exist, but different methods need to be applied to interpret the data. The work also demonstrates that K-feldspar can be sufficiently retentive as to allow direct dating of processes that reduce the dimensions of diffusion domains, e.g., cataclased and/or recrystallized K-feldspar in fault rock and/or mylonite. These are important developments in the methodology of 40Ar/39Ar geochronology, but to further advance we need to clarify the nature of these highly retentive core domains. In particular, we need better understand how they are modified by microstructural processes during deformation and metamorphism. We need also to assess the role of any crystal structural changes during step-heating in vacuo.

  14. Regarding the real diversity of Glyptodontidae (Mammalia, Xenarthra) in the late Pliocene (Chapadmalalan Age/Stage) of Argentina.

    PubMed

    Zurita, Alfredo E; Taglioretti, Matías; DE Los Reyes, Martín; Cuadrelli, Francisco; Poire, Daniel

    2016-06-01

    A large diversity of Glyptodontidae has been proposed as characterizing the Chapadmalalan Age (Pliocene). Most of these taxa were recognized on the basis of partial dorsal carapaces and/or caudal tubes, whereas the main diagnostic characteristic is a particular morphology of the exposed surface of the osteoderms. From a biostratigraphic point of view some species are biostratigraphically important. The Upper Chapadmalalan is based on the Paraglyptodon chapadmalensis biozone. Both the re-evaluation of the type and referred materials and new significant findings from the Chapadmalal and El Polvorín Formations indicate that the diversity of Pliocene Glyptodontidae is more limited than previously supposed. The particular morphology of the exposed surface of the osteoderms that characterizes some of the species actually corresponds to a taphonomic alteration, which results in a non-real ornamentation pattern. Thus, the Glyptodontinae P. chapadmalensis must be replaced as a fossil guide because neither this species nor the species included in the genera Urotherium, Trachycalyptus and Lomaphorus are well characterized. Taking into account the diversity of Glyptodontidae for this lapse, the Glyptodontinae are very scarce (a situation that contrasts with its records in the Pleistocene), whereas Eosclerocalyptus, "Plohophorini" (Plohophorus) and Doedicurinae (cf. Eleutherocercus antiquus) are among the most recorded taxa. PMID:27276376

  15. Regarding the real diversity of Glyptodontidae (Mammalia, Xenarthra) in the late Pliocene (Chapadmalalan Age/Stage) of Argentina.

    PubMed

    Zurita, Alfredo E; Taglioretti, Matías; DE Los Reyes, Martín; Cuadrelli, Francisco; Poire, Daniel

    2016-06-01

    A large diversity of Glyptodontidae has been proposed as characterizing the Chapadmalalan Age (Pliocene). Most of these taxa were recognized on the basis of partial dorsal carapaces and/or caudal tubes, whereas the main diagnostic characteristic is a particular morphology of the exposed surface of the osteoderms. From a biostratigraphic point of view some species are biostratigraphically important. The Upper Chapadmalalan is based on the Paraglyptodon chapadmalensis biozone. Both the re-evaluation of the type and referred materials and new significant findings from the Chapadmalal and El Polvorín Formations indicate that the diversity of Pliocene Glyptodontidae is more limited than previously supposed. The particular morphology of the exposed surface of the osteoderms that characterizes some of the species actually corresponds to a taphonomic alteration, which results in a non-real ornamentation pattern. Thus, the Glyptodontinae P. chapadmalensis must be replaced as a fossil guide because neither this species nor the species included in the genera Urotherium, Trachycalyptus and Lomaphorus are well characterized. Taking into account the diversity of Glyptodontidae for this lapse, the Glyptodontinae are very scarce (a situation that contrasts with its records in the Pleistocene), whereas Eosclerocalyptus, "Plohophorini" (Plohophorus) and Doedicurinae (cf. Eleutherocercus antiquus) are among the most recorded taxa.

  16. Lazaroid compounds prevent early but not late stages of oxidant-induced cell injury: potential explanation for the lack of efficacy of lazaroids in clinical trials.

    PubMed

    Huang, H; Patel, P B; Salahudeen, A K

    2001-01-01

    Earlier in vitro studies demonstrated the remarkable potency of the lazaroid compounds to prevent oxidant-induced early cell injury. However, the ability of lazaroid compounds to limit oxidative injury in vivo(including renal ischemia-reperfusion) has been less certain, and the early clinical trials using lazaroids to limit CNS injury or organ injury in the setting of transplantation have not been promising. Lazaroid compounds are potent inhibitors of lipid peroxidation, and their inability to influence other key injury processes, particularly during the late stages of cell injury, might partly explain the limited clinical efficacy. To test this, renal tubular (LLC-PK1) cells were incubated with 250 micromH(2)O(2)for 135 min, in the presence or absence of 2-methyl aminochroman (2-MAC, U-83836E), a lazaroid with potent ability to inhibit lipid peroxidation, or desferrioxamine, (DFO) an iron chelator with broader antioxidant efficacy. Cell injury, lipid peroxidation, DNA damage and ATP depletion were measured in the early (immediately after H(2)O(2)incubation) and late (24 h after H(2)O(2)incubation) stages of cell injury. In the early stage, 2-MAC suppressed H(2)O(2)-induced lipid peroxidation and LDH release, but not the DNA damage, ATP depletion or loss of cell replication. In contrast, DFO suppressed all of the measurements. In the late stages, despite continued suppression of lipid peroxidation, only DFO maintained significant cytoprotection against H(2)O(2), and this was accompanied by reduced DNA damage, higher ATP levels and preservation of cell proliferation. Thus, the inability of the lazaroid compound 2-MAC to sustain cytoprotection in the later stages of cell injury might provide at least a partial explanation for the inefficiency of lazaroids to limit tissue injury in clinical and certain in vivo settings. PMID:11207066

  17. Validation of Transient Elastography and Comparison with Spleen Length Measurement for Staging of Fibrosis and Clinical Prognosis in Primary Sclerosing Cholangitis

    PubMed Central

    Ehlken, Hanno; Wroblewski, Raluca; Corpechot, Christophe; Arrivé, Lionel; Rieger, Tim; Hartl, Johannes; Lezius, Susanne; Hübener, Peter; Schulze, Kornelius; Zenouzi, Roman; Sebode, Marcial; Peiseler, Moritz; Denzer, Ulrike W.; Quaas, Alexander; Weiler-Normann, Christina; Lohse, Ansgar W.; Chazouilleres, Olivier; Schramm, Christoph

    2016-01-01

    Background Patients with primary sclerosing cholangitis (PSC) develop progressive liver fibrosis and end-stage liver disease. Non-invasive and widely available parameters are urgently needed to assess disease stage and the risk of clinical progression. Transient elastography (TE) has been reported to predict fibrosis stage and disease progression. However, these results have not been confirmed in an independent cohort and comparison of TE measurement to other non-invasive means is missing. Methods In a retrospective study we collected data from consecutive PSC patients receiving TE measurements from 2006 to 2014 (n = 139). Data from 62 patients who also underwent a liver biopsy were used to assess the performance of TE and spleen length (SL) measurement for the staging of liver fibrosis. Follow-up data from this cohort (n = 130, Hamburg) and another independent cohort (n = 80, Paris) was used to compare TE and SL as predictors of clinical outcome applying Harrel’s C calculations. Results TE measurement had a very good performance for the diagnosis and exclusion of higher fibrosis stages (≥F3: AUROC 0.95) and an excellent performance for the diagnosis and exclusion of cirrhosis (F4 vs. < F4: AUROC 0.98). Single-point TE measurement had very similar predictive power for patient outcome as previously published. In a combined cohort of PSC patients (n = 210), SL measurements had a similar performance as TE for the prediction of patient outcome (5 x cross-validated Harrel’s C 0.76 and 0.72 for SL and TE, respectively). Conclusions Baseline TE measurement has an excellent performance to diagnose higher fibrosis stages in PSC. Baseline measurements of SL and TE have similar usefulness as predictive markers for disease progression in patients with PSC. PMID:27723798

  18. Improving Function in Age-Related Macular Degeneration: A Randomized Clinical Trial

    PubMed Central

    Rovner, Barry W.; Casten, Robin J.; Hegel, Mark T.; Massof, Robert W.; Leiby, Benjamin E.; Ho, Allen C.; Tasman, William S.

    2013-01-01

    Purpose To compare the efficacy of Problem-Solving Therapy (PST) with Supportive Therapy (ST) to improve Targeted Vision Function in Age-Related Macular Degeneration (AMD). Design Single-masked, attention controlled randomized clinical trial with outcome assessments at 3 months (main trial endpoint) and 6 months (maintenance effects). Participants Patients with AMD (N = 241) attending retina practices. Interventions PST uses a structured problem-solving approach to reduce vision-related task difficulty. ST is a standardized attention control treatment. Main Outcome Measures Targeted Vision Function (TVF); National Eye Institute Vision Function Questionnaire - 25 plus Supplement (NEI VFQ); Activities Inventory (AI); and Vision-Related Quality of Life. Results There were no significant between-group differences in TVF scores at 3 months (p = 0.47) or 6 months (p = 0.62). For PST subjects, mean [standard deviation (SD)] TVF scores improved from 2.71 (0.52) at baseline to 2.18 (0.88) at 3 months (p = 0.001) and were 2.18 (0.95) at 6 months (change from 3 to 6 months, p = .74). For ST subjects, TVF scores improved from 2.73 (0.52) at baseline to 2.14 (0.96) at 3 months (p = 0.001) and were 2.15 (0.96) at 6 months (change from 3 to 6 months, p = .85). Similar proportions of PST and ST subjects had less difficulty performing a TVF goal at 3 months (77.4% vs. 78.6%, respectively; p = 0.83) and 6 months (76.2% vs. 79.1%, respectively; p = 0.61). There were no significant changes in the NEI VFQ or AI. Vision-related quality-of-life improved for PST relative to ST subjects at 3 months [F (4,192) = 2.46; p = 0.05] and 6 months [F (4,178) = 2.55; p = 0.05)]. PST subjects also developed more adaptive coping strategies than ST subjects. Conclusions We found that PST was not superior to ST at improving vision function in patients with AMD but PST improved their vision-related quality of life. Despite the benefits of anti-vascular endothelial growth factor (anti-VEGF) treatments

  19. Mutational Analysis in Pediatric Thyroid Cancer and Correlations with Age, Ethnicity, and Clinical Presentation

    PubMed Central

    Nikita, Maria Eleni; Jiang, Wen; Cheng, Shih-Min; Hantash, Feras M.; McPhaul, Michael J.; Newbury, Robert O.; Phillips, Susan A.; Reitz, Richard E.; Waldman, Frederic M.

    2016-01-01

    Background: Well-differentiated thyroid cancer (WDTC) incidence in pediatrics is rising, most being papillary thyroid carcinoma (PTC). The objective of the study was to assess the prevalence of different mutations in pediatric WDTC and correlate the genotype with the clinical phenotype. Methods: This is a single-center retrospective study. Thyroid tissue blocks from 42 consecutive pediatric WDTC patients who underwent thyroidectomy between 2001 and 2013 were analyzed at Quest Diagnostics for BRAFV600E, RAS mutations (N,K,H), and RET/PTC and PAX8/PPARγ rearrangements, using validated molecular methods. Thyroid carcinomas included PTC, follicular thyroid carcinoma (FTC), and follicular variant of PTC (FVPTC). Results: Thirty-nine samples (29 females) were genotyped. The mean age at diagnosis was 14.7 years (range 7.9–18.4 years), and most were Hispanic (56.4%) or Caucasian (35.9%). The mean follow-up period was 2.9 years. Mutations were noted in 21/39 (53.8%), with both BRAFV600E (n = 9), and RET/PTC (n = 6) detected only in PTC. Mutations were detected in 2/5 FTC (PAX8/PPARγ and NRAS) and 3/6 FVPTC cases (PAX8/PPARγ). Of 28 PTC patients, 57.1% had mutations: 32.1% with BRAFV600E, 21.4% with RET/PTC, and 3.6% with NRAS. Of patients with BRAFV600E, 77.8% were Hispanic and 88.9% were >15 years, while all RET/PTC-positive patients were ≤15 years (p = 0.003). Tumor size, lymph node involvement, and distant metastasis at diagnosis (or soon after 131I ablation) did not vary significantly based on the mutation. Conclusions: BRAFV600E was the most common mutation, especially in older and Hispanic adolescents. A larger, ethnically diverse pediatric cohort followed long term will enable the genotypic variability, clinical presentation, and response to therapy to be better assessed. PMID:26649796

  20. Prognostic Significance of Clinical/Pathological Stage IA Non-Small-Cell Lung Cancer Showing Partially Solid or Solid Tumours on Radiological Exam

    PubMed Central

    Matsuura, Yosuke; Nakao, Masayuki; Mun, Mingyon; Nakagawa, Ken; Ishikawa, Yuichi; Okumura, Sakae

    2015-01-01

    Purpose: Although curative resection is expected to be effective in patients with clinical (c-) stage IA/pathological (p-) stage IA non-small-cell lung cancers, recurrence is often observed. Hence, the aim of this study was to identify predictors of recurrence. Methods: Between 2005 and 2009, 138 patients with c-stage IA/p-stage IA non-small-cell lung cancers underwent resection. Recurrence and recurrence-free survival (RFS) were compared with clinical, radiographic and pathological findings. Results: The 5-year cancer-specific survival rate was 97% and the RFS rate was 89% at a median follow-up time of 91 months. Recurrence was observed in 10 patients (7.2%). Significant differences were observed in RFS according to tumour dimensions on the mediastinal window image (>1.5 cm), serum carcinoembryonic antigen levels (>5.0 ng/mL), maximum standardised uptake values (SUVmax >2.5) and angiolymphatic invasion. Patients were grouped according to the number of risk factors for poor RFS. Patients with 0–1 of the identified risk factors had an RFS of 97%, where those with 2–4 factors had an RFS of 68% (p <0.001). Conclusion: Prognosis of patients exhibiting more than two of these risk factors is considerably poor. Thus, close observation and individualised adjuvant therapy may be beneficial to these patients. PMID:25740451

  1. Lung Cancer Staging and Prognosis.

    PubMed

    Woodard, Gavitt A; Jones, Kirk D; Jablons, David M

    2016-01-01

    The seventh edition of the non-small cell lung cancer (NSCLC) TNM staging system was developed by the International Association for the Staging of Lung Cancer (IASLC) Lung Cancer Staging Project by a coordinated international effort to develop data-derived TNM classifications with significant survival differences. Based on these TNM groupings, current 5-year survival estimates in NSLCC range from 73 % in stage IA disease to 13 % in stage IV disease. TNM stage remains the most important prognostic factor in predicting recurrence rates and survival times, followed by tumor histologic grade, and patient sex, age, and performance status. Molecular prognostication in lung cancer is an exploding area of research where interest has moved beyond TNM stage and into individualized genetic tumor analysis with immunohistochemistry, microarray, and mutation profiles. However, despite intense research efforts and countless publications, no molecular prognostic marker has been adopted into clinical use since most fail in subsequent cross-validation with few exceptions. The recent interest in immunotherapy for NSCLC has identified new biomarkers with early evidence that suggests that PD-L1 is a predictive marker of a good response to new immunotherapy drugs but a poor prognostic indicator of overall survival. Future prognostication of outcomes in NSCLC will likely be based on a combination of TNM stage and molecular tumor profiling and yield more precise, individualized survival estimates and treatment algorithms. PMID:27535389

  2. Atlantic Ocean Circulation During the Last Ice Age: A 231Pa/230Th Record of Marine Isotope Stage 3

    NASA Astrophysics Data System (ADS)

    Major, C. O.; McManus, J. F.; Keigwin, L. D.; Francois, R.; Brown-Leger, S.

    2005-12-01

    Millennial-scale oscillations in climate-sensitive geochemical proxies are seen throughout Marine Isotope Stage 3 (MIS3, ~30 to 60 ka BP) in marine and ice-core records, with variability nearly as large as that seen on the last deglaciation. Nutrient proxies, such as δ13C, have been widely used to reconstruct water mass reorganizations associated with this so-called stadial-interstadial variability. While such passive tracers are invaluable in determining the configuration of water masses they cannot provide direct information about the rate of thermohaline circulation. The burial ratio of unsupported 231Pa:230Th in bulk North Atlantic sediments is a function of the residence time of water in this basin, and thus serves as a dynamical proxy sensitive to the vigor of thermohaline circulation and an important complement to passive proxies. We present a suite of data, including 231Pa/230Th, 230Th-normalized fluxes, and stable isotopes, from the Blake Outer Ridge (BOR) (core KNR140-8JPC, ~3400 m), a drift deposit underlying the deep western boundary current in the subtropical north Atlantic. 231Pa/230Th data indicate moderate-amplitude millennial-scale variations in circulation rate during MIS3. 231Pa/230Th ranges between maximum values less than the production rate ratio (0.093) and minimum values close to the core-top ratio (~0.058), with high and low ratios associated with stadials and interstadials, respectively. These data indicate continuous but on average less vigorous ventilation of the western basin compared to present, with substantially reduced circulation during stadials. Heinrich events during MIS3 do not appear to be associated with the particularly dramatic drop in circulation rate seen in the deglacial H1 interval on the Bermuda Rise (McManus et al., 2004). 230Th-normalized fluxes account for only 10 to 50 percent of the total mass accumulation, indicating significant sediment focusing at this site particularly during the stadials. Benthic δ18O from

  3. Natural growth and diet of known-age pallid sturgeon (Scaphirhynchus albus) early life stages in the upper Missouri River basin, Montana and North Dakota

    USGS Publications Warehouse

    Braaten, P.J.; Fuller, D.B.; Lott, R.D.; Haddix, T.M.; Holte, L.D.; Wilson, R.H.; Bartron, M.L.; Kalie, J.A.; DeHaan, P.W.; Ardren, W.R.; Holm, R.J.; Jaeger, M.E.

    2012-01-01

    Prior to anthropogenic modifications, the historic Missouri River provided ecological conditions suitable for reproduction, growth, and survival of pallid sturgeon Scaphirhynchus albus. However, little information is available to discern whether altered conditions in the contemporary Missouri River are suitable for feeding, growth and survival of endangered pallid sturgeon during the early life stages. In 2004 and 2007, nearly 600 000 pallid sturgeon free embryos and larvae were released in the upper Missouri River and survivors from these releases were collected during 2004–2010 to quantify natural growth rates and diet composition. Based on genetic analysis and known-age at release (1–17 days post-hatch, dph), age at capture (dph, years) could be determined for each survivor. Totals of 23 and 28 survivors from the 2004 and 2007 releases, respectively, were sampled. Growth of pallid sturgeon was rapid (1.91 mm day-1) during the initial 13–48 dph, then slowed as fish approached maximum length (120–140 mm) towards the end of the first growing season. The diet of young-of-year pallid sturgeon was comprised of Diptera larvae, Diptera pupae, and Ephemeroptera nymphs. Growth of pallid sturgeon from ages 1–6 years was about 48.0 mm year-1. This study provides the first assessment of natural growth and diet of young pallid sturgeon in the wild. Results depict pallid sturgeon growth trajectories that may be expected for naturally produced wild stocks under contemporary habitat conditions in the Missouri River and Yellowstone River.

  4. Late-Stage HIMU-Type Volcanism on the Walvis Ridge: Not just Part of an Age-Progressive Tristan-Gough Hotspot Track

    NASA Astrophysics Data System (ADS)

    Homrighausen, S.; Hoernle, K.; Hauff, F.; Portnyagin, M.; Werner, R.; Geldmacher, J.; Garbe-Schoenberg, C. D.

    2015-12-01

    The Walvis Ridge forms the NE portion of the Tristan-Gough hotspot track. It links the Etendeka large igneous province (LIP) in Africa, initially connected to the Parana LIP in South America, to the Guyot Province, that ends at the active volcanic islands of Tristan da Cunha and Gough. After the plume head stage, the hotspot changed from a ridge-centered plume tail, forming the Walvis Ridge and Rio Grande Rise (130-60 Ma), to an intraplate setting resulting in the geochemical distinct Tristan and Gough subtracks (Rohde et al. 2013; Geology 41). New major and trace element and radiogenic isotope data have been generated from 36 new dredge locations on the Walvis Ridge during R/V Sonne cruises SO233 and SO234. Based on the bathymetric data, we have identified tectonic structures and subsidence rates which indicate a complex geodynamic interplay of the Walvis Ridge formation and westward migration of the Mid Atlantic Ridge and the Rio Grande Rise. Our new results confirm that the age-progressive basement of the Walvis Ridge reflects only the enriched Gough component with no evidence of the Tristan component being present (Hoernle et al., 2015; Nat. Comm.). Superimposed large seamounts (including ridge- and guyot-like structures), especially in the SE portion of the Walvis Ridge, belong to a later-stage of alkalic volcanism with distinct HIMU incompatible element and Sr-Nd-Pb-Hf isotopic composition. The HIMU late-stage volcanism (206Pb/204Pb up to 20.8) is similar in composition to St. Helena and a late-stage (Eocene) sample from the Rio Grande Rise (Rohde et al., 2013; Tectonophysics 604). The new geochemical, bathymetric and existing age data indicate a magmatic reactivation c. 20-40 Ma after the formation of the Walvis Ridge basement, which may be related to passage of the Walvis Ridge over a batch of upwelling St. Helena type plume material. Our new results indicate a more complex formation of the Walvis Ridge than previously thought, which included two major

  5. Radiotherapy for Early-Stage Hodgkin's Lymphoma: A 21st Century Perspective and Review of Multiple Randomized Clinical Trials

    SciTech Connect

    Bar Ad, Voichita Paltiel, Ora; Glatstein, Eli

    2008-12-01

    The treatment of Hodgkin's lymphoma has improved dramatically over the past decades. Over the last half century, Hodgkin's lymphoma has become one of the most curable cancers of adulthood. More than 90% of the patients with localized stages of the disease can be cured with modern treatment strategies. Long-term toxicities are now the major concern for survivors of early-stage disease. Contemporary therapeutic approaches for Hodgkin's lymphoma attempt to preserve the high cure rate achieved, while reducing treatment-related acute and late toxicities. The aim of this review is to re-examine the historical and the current role of radiotherapy for early-stage Hodgkin's lymphoma, given the latest evidence of an increasing role of chemotherapy for the treatment of this malignancy. The literature search was performed in PubMed Plus. Studies on children were excluded.

  6. Stimulant Abuser Groups to Engage in 12-Step (STAGE-12): A Multisite Trial in the NIDA Clinical Trials Network

    PubMed Central

    Donovan, Dennis M.; Daley, Dennis C.; Brigham, Gregory S.; Hodgkins, Candace C.; Perl, Harold I.; Garrett, Sharon; Doyle, Suzanne; Floyd, Anthony S.; Knox, Patricia C.; Botero, Christopher; Kelly, Thomas; Killeen, Therese; Hayes, Carole; Baumhofer, Nicole Kau’i; Seamans, Cindy; Zammarelli, Lucy

    2012-01-01

    Aims The study evaluated the effectiveness of an 8-week combined group plus individual 12-step facilitative intervention on stimulant drug use and 12-step meeting attendance and service. Design Multisite randomized controlled trial, with assessments at baseline, mid-treatment, end of treatment, and 3- and 6-month post-randomization follow-ups (FU). Setting Intensive outpatient substance treatment programs. Participants Individuals with stimulant use disorders (n = 471) randomly assigned to treatment as usual (TAU) or TAU into which the STAGE-12 intervention was integrated. Measurements Urinalysis and self-reports of substance use and 12-step attendance and activities. Intervention Group sessions focused on increasing acceptance of 12-step principles; individual sessions incorporated an intensive referral procedure connecting participants to 12-step volunteers. Findings Compared to TAU, STAGE-12 participants had significantly greater odds of self-reported stimulant abstinence during the active 8-week treatment phase; however, among those who had not achieved abstinence during this period, STAGE-12 participants had more days of use. STAGE-12 participants had lower ASI Drug Composite scores at and a significant reduction from baseline to the 3-month FU, attended 12-step meetings on a greater number of days during the early phase of active treatment, engaged in more other types of 12-step activities throughout the active treatment phase and the entire FU period, and had more days of self-reported service at meetings from mid-treatment through the 6-month FU. Conclusions The present findings are mixed with respect to the impact of integrating the STAGE-12 intervention into intensive outpatient drug treatment compared to TAU on stimulant drug use. However, the results more clearly indicate that individuals in STAGE-12 had higher rates of 12-step meeting attendance and were engaged in more related activities throughout both the active treatment phase and the entire 6

  7. Effect of {sup 18}F-FDG PET/CT Imaging in Patients With Clinical Stage II and III Breast Cancer

    SciTech Connect

    Groheux, David Moretti, Jean-Luc; Baillet, Georges; Espie, Marc; Giacchetti, Sylvie; Hindie, Elif; Hennequin, Christophe; Vilcoq, Jacques-Robert; Cuvier, Caroline; Toubert, Marie-Elisabeth; Filmont, Jean-Emmanuel; Sarandi, Farid; Misset, Jean-Louis

    2008-07-01

    Purpose: To investigate the potential effect of using {sup 18}F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) in the initial assessment of patients with clinical Stage II or III breast cancer. Methods and Materials: During 14 consecutive months, 39 patients (40 tumors) who presented with Stage II or III breast cancer on the basis of a routine extension assessment were prospectively included in this study. PET/CT was performed in addition to the initial assessment. Results: In 3 cases, PET/CT showed extra-axillary lymph node involvement that had not been demonstrated with conventional techniques. Two of these patients had hypermetabolic lymph nodes in the subpectoral and infraclavicular regions, and the third had a hypermetabolic internal mammary node. PET/CT showed distant uptake in 4 women. Of these 4 women, 1 had pleural involvement and 3 had bone metastasis. Overall, of the 39 women, the PET/CT results modified the initial stage in 7 (18%). The modified staging altered the treatment plan for 5 patients (13%). It led to radiotherapy in 4 patients (bone metastasis, pleural lesion, subpectoral lymph nodes, and internal mammary nodes) and excision of, and radiotherapy to, the infraclavicular lymph nodes in 1 patient. Conclusions: PET/CT can provide information on extra-axillary lymph node involvement and can uncover occult distant metastases in a significant percentage of patients. Therefore, initial PET/CT could enable better treatment planning for patients with Stage II and III breast cancer.

  8. The clinical impact of staging bone marrow examination on treatment decisions and prognostic assessment of lymphoma patients.

    PubMed

    Painter, Dan; Smith, Alexandra; de Tute, Ruth; Crouch, Simon; Roman, Eve; Jack, Andrew

    2015-07-01

    This study investigates the value of performing a staging bone marrow in patients with diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and classical hodgkin lymphoma (CHL). The results of 3112 staging bone marrow examinations were assessed for impact on prognostic assessment and critical treatment decisions. The detection of marrow involvement altered the disease-specific prognostic index for 4·3% of DLBCL, 6·2% of FL and 0·6% of CHL but marrow involvement in DLBCL was an independent prognostic factor. Knowing the marrow status potentially changed treatment in 92 patients, detection of these patients would have required 854 examinations to be performed.

  9. Quality of care and health-related quality of life of climacteric stage women cared for in family medicine clinics in Mexico

    PubMed Central

    2010-01-01

    Objectives 1) To design and validate indicators to measure the quality of the process of care that climacteric stage women receive in family medicine clinics (FMC). 2) To assess the quality of care that climacteric stage women receive in FMC. 3) To determine the association between quality of care and health-related quality of life (HR-QoL) among climacteric stage women. Methods The study had two phases: I. Design and validation of indicators to measure the quality of care process by using the RAND/UCLA Appropriateness Method. II. Evaluation of the quality of care and its association with HR-QoL through a cross-sectional study conducted in two FMC located in Mexico City that included 410 climacteric stage women. The quality of care was measured by estimating the percentage of recommended care received (PRCR) by climacteric stage women in three process components: health promotion, screening, and treatment. The HR-QoL was measured using the Cervantes scale (0-155). The association between quality of care and HR-QoL was estimated through multiple linear regression analysis. Results The lowest mean of PRCR was for the health promotion component (24.1%) and the highest for the treatment component (86.6%). The mean of HR-QoL was 50.1 points. The regression analysis showed that in the treatment component, for every 10 additional points of the PRCR, the global HR-QoL improved 2.8 points on the Cervantes scale (coefficient -0.28, P < 0.0001). Conclusion The indicators to measure quality of care for climacteric stage women are applicable and feasible in family medicine settings. There is a positive association between the quality of the treatment component and HR-QoL; this would encourage interventions to improve quality of care for climacteric stage women. PMID:20144238

  10. Gamma-delta T cell responses in subclinical and clinical stages of Bovine Mycobacterium Avium Paratuberculosis infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The early immune response to Mycobacterium avium subsp. paratuberculosis (MAP) in cattle is characterized by a Th1-like immune response effective in controlling bacterial proliferation during the subclinical stage of infection. In young calves nearly 60% of circulating lymphocytes are gamma delta T ...

  11. Breast cancer screening outcomes in women ages 40-49: clinical experience with service screening using modern mammography.

    PubMed

    Sickles, E A

    1997-01-01

    The several randomized controlled trials (RCTs) of breast cancer screening among women of ages 40 to 49 now collectively show a statistically significant reduction in breast cancer mortality. However, there have been numerous recent advances in mammography, such that it now is demonstrably better than when the RCTs were conducted. The use of surrogate measures of screening efficacy (tumor size, lymph node status, cancer stage), readily derived from modern service screening programs, demonstrates how the improved mammography of the 1990s should produce a greater degree of mortality reduction among women ages 40-49 than that already demonstrated in the RCTs. Indeed, these surrogate measures of mortality reduction are as favorable for women of ages 40-49 and 65+ as they are for women of ages 50-64, strongly suggesting that, since modern service screening is accepted as effectively reducing mortality among women of ages 50-64, it should also effectively reduce mortality among women in the 40-49 and 65+ age groups.

  12. HIV-1 RNA levels in an African population-based cohort and their relation to CD4 lymphocyte counts and World Health Organization clinical staging.

    PubMed

    Morgan, D; Rutebemberwa, A; Malamba, S; Ross, A; Whitworth, J; Kaleebu, P; Gotch, F

    1999-10-01

    Apart from a small number of reports from people who are based in hospitals, data on viral load in HIV-infected people in sub-Saharan Africa, where most infections occur, are lacking. We report serum HIV-1 RNA levels in a population-based cohort in rural Uganda using the nucleic acid sequence-based amplification procedure (NASBA) test kit and describe their relation to CD4 counts and World Health Organization (WHO) clinical staging. The median (interquartile range [IQR]) viral loads were 87,000 copies/ml (37,500-295,000 copies/ml) in 40 prevalent cases infected for >6 years, and 31,000 copies/ml (7800-174,000 copies/ml) in 65 incident cases with seroconversion dates within the previous 6 years. Although we found a correlation between viral load and absolute CD4 count (p < .0001), there was no evidence for an association with CD4 decline (p = .1). Overall, there was a significant trend of increasing viral load with worsening clinical stage from a median viral load of 15,000 for those in WHO stage 1 (asymptomatic) to 150,600 copies/ml for those in stage 4 (AIDS; p < .001). However, the association was seen only in incident cases. Thus, we found that the NASBA test on serum was a useful indicator of disease stage especially in persons known to be infected for <6 years. Such baseline data are important for vaccine research, and if antiretroviral drugs become available to more than a few people in Africa, it will be important that accurate viral load estimations are available at least in a proportion of people to monitor the effectiveness of treatment, and measure the compliance and emerging resistance to these drugs. PMID:10843531

  13. Modeling the Effects of Constant and Variable Temperatures on the Vital Rates of an Age-, Stage-, and Sex-Structured Population by Means of the SANDY Approach.

    PubMed

    Nachman, G; Gotoh, T

    2015-06-01

    We present a general and flexible mathematical model (called SANDY) that can be used to describe many biological phenomena, including the phenology of arthropods. In this paper, we demonstrate how the model can be fitted to vital rates (i.e., rates associated with development, survival, hatching, and oviposition) of the two-spotted spider mite (Tetranychus urticae (Koch)) exposed to different constant temperatures ranging from 15°C to 37.5°C. SANDY was incorporated into an age-, stage- and sex-structured dynamic model, which was fitted to cohort life-tables of T. urticae conducted at five constant temperatures (15, 20, 25, 30, and 35°C). Age- and temperature-dependent vital rates for the three main stages (eggs, immatures, and adults) constituting the life-cycle of mites were adequately described by the SANDY model. The modeling approach allows for simulating the growth of a population in a variable environment. We compared the predicted net reproductive rate (R0) and intrinsic rate of natural increase (rm) at fluctuating temperatures with empirical values obtained from life-table experiments conducted at temperatures that changed with a daily amplitude (±0, ±3, ±6, ±9, and ±12°C) around an average of 22°C. Results show that R0 decreases with increasing amplitude, while rm is more robust to variable temperatures. An advantage of SANDY is that the same simple mathematical expression can be applied to describe all the vital rates. Besides, the approach is not confined to modeling the influence of a single factor on population growth but allows for incorporating the combined effect of several limiting factors, provided that the combined effect of the factors is multiplicative. PMID:26313989

  14. Factors influencing the outcome of intrauterine insemination (IUI): age, clinical variables and significant thresholds.

    PubMed

    Speyer, B E; Abramov, B; Saab, W; Doshi, A; Sarna, U; Harper, J C; Serhal, P

    2013-10-01

    The aim was to investigate the influence of various biological factors upon the outcome of intrauterine insemination (IUI). The total IUI history (856 cycles) of 352 couples was studied. Live-birth showed a strong negative correlation with female age but no correlation with male age. Antimüllerian hormone (AMH) and antral follicle count (AFC) correlated negatively with female age, and follicle stimulating hormone (FSH) correlated positively. Significant thresholds were found for all three variables, and also for total motile count (TMC) in the prepared sperm. Calculating pregnancy losses per positive pregnancy showed a strong correlation with increasing female age. This was highly significant for biochemical losses but not for fetal heart miscarriages. Male age had no effect on rate of pregnancy loss. In conclusion, female age, FSH, AMH and TMC are good predictive factors for live-birth and therefore relate to essential in vivo steps in the reproductive process. PMID:24127958

  15. How Practice and Science Are Balanced and Blended in the NIDA Clinical Trials Network: The Bidirectional Process in the Development of the STAGE-12 Protocol as an Example

    PubMed Central

    Donovan, Dennis M.; Daley, Dennis C.; Brigham, Gregory S.; Hodgkins, Candace C.; Perl, Harold I.; Floyd, Anthony S.

    2012-01-01

    Background Bidirectional, collaborative partnerships between academic researchers and practitioners have been a fundamental vehicle to achieve the National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN) goal of improving outcomes of community-based drug treatment. These partnerships blend clinical perspectives of practitioners and methodological expertise of researchers working together to address clinically meaningful issues through randomized clinical trials conducted in community treatment settings. Objectives Bidirectionality is a guiding principle of the CTN, but its operationlization at the practical level in protocol development and implementation has not been articulated. This descriptive article presents the development of one protocol as an example and model of this bidirectional, collaborative, iterative partnership between researchers and practitioners. Methods This article illuminates several specific issues encountered while developing STAGE-12, a behavioral intervention to facilitate 12-step mutual support group involvement, as well as the rationale for decisions taken to resolve each. Results The STAGE-12 protocol was successfully developed through a series of decisions taking into account both design factors and clinical practice needs and realities, thus maintaining a balance between methodological rigor and generalizability. Conclusion The review demonstrates the process by which research and practice have been blended in protocol development, exemplifying the underlying principle of bidirectionality, a key element in the success of the NIDA CTN. Scientific Significance Bidirectional partnerships as derived in the CTN, employing a hybrid model of efficacy-effectiveness research, are capable of designing and implementing protocols that are both methodologically rigorous and clinically meaningful, thus increasing likelihood of adoption and eventual improvement in public health. PMID:21854284

  16. Phase I clinical study with multiple peptide vaccines in combination with tetanus toxoid and GM-CSF in advanced-stage HLA-A*0201-positive melanoma patients.

    PubMed

    Bins, Adriaan; Mallo, Henk; Sein, Johan; van den Bogaard, Colette; Nooijen, Willem; Vyth-Dreese, Florry; Nuijen, Bastiaan; de Gast, Gijsbert C; Haanen, John B A G

    2007-01-01

    Successful induction of functional tumor-specific T cells by peptide vaccination in animal models has resulted in many clinical trials to test this approach in advanced-stage melanoma patients. In this phase I clinical trial, 11 end-stage melanoma patients were vaccinated intradermally with 3 peptides: MART-1(26-35) E27L (ELAGIGILTV), tyrosinase(368-376) N375Q (YMDGTMSQV), and gp100(209-217) T210M (IMQVPFSV), admixed with tetanus toxoid and granulocyte-monocyte colony stimulating factor. The peptide vaccine was well tolerated at all tested doses, and led to grade 1-2 toxicity only. Although all patients did show a rise in antitetanus IgG titers, in only 3 patients peptide-specific CD8 T-cells were induced. In 2 cases, the response was directed against MART-1(26-35) and consisted of 0.2% and 3.3% of the CD8 population; however, in both instances these cells did not produce interferon-gamma on stimulation with the unmodified peptide. The third patient mounted a small (0.1%) response against gp100. In a fourth patient, a nonfunctional tyrosinase-specific response (0.6%) was found that was present before vaccination, but was not affected in size nor in function by the vaccine. None of the 11 patients responded clinically according to response evaluation criteria in solid tumors criteria. Although this study is a small scale phase I clinical trial, the efficacy that was observed was disappointingly low. In accordance with previously published peptide vaccination studies, these results add to the increasing evidence that peptide vaccination in itself is not potent enough as an effective melanoma immunotherapy in advanced-stage patients.

  17. [Clinical curative efficacy of inducing remission for the newly diagnosed aged AML patients by chemotherapy with IA and DA regimens].

    PubMed

    Tian, Dong-Hua; Gan, Si-Lin; Xing, Hai-Zhou; Liu, Yan-Fang; Xie, Xin-Sheng; Sun, Hui

    2014-10-01

    This study was aimed to explore the clinical efficacy and toxicity of idarubicin (IA regimen) and daunoru-bicin combined with cytarabine (DA regimen) for treating aged patients with AML as induction chemotherapy. The clinical data of 60 newly diagnosed AML aged patients treated with IA or DA regimen were analyzed retrospectively. IA regimen group included 22 patients (8 male and 14 females with median age of 66 yrs), while the DA regimen group included 38 patients (20 males and 18 females with median age of 64 yrs). The complete remission rate, total effective rate and adverse effects after one chemotherapy course were compared. The results showed that the CR rate in IA regimen group was 63.63%, which was significantly higer than that in DA regimen group (31.58%) (P < 0.05). The total effective rate was 63.63% and 36.84% respectively in IA and DA regimen groups, there was significant difference between the two groups (P < 0.05). Both the hematological and non-hematological adverse effects were observed and no difference was found in the two regimen groups, neither in myelosupression (P > 0.05), the major hematological adverse effects, nor in non-hematological adverse effects (P > 0.05). It is concluded that for aged AML patients, IA regimen can achieve a higher CR rate and higher total effective rate than that in DA regimen without increase of adverse effects after one induction chemotherapy course.

  18. Impact of donor age in liver transplantation from donation after circulatory death donors: A decade of experience at Cleveland Clinic.

    PubMed

    Firl, Daniel J; Hashimoto, Koji; O'Rourke, Colin; Diago-Uso, Teresa; Fujiki, Masato; Aucejo, Federico N; Quintini, Cristiano; Kelly, Dympna M; Miller, Charles M; Fung, John J; Eghtesad, Bijan

    2015-12-01

    The use of liver grafts from donation after circulatory death (DCD) donors remains controversial, particularly with donors of advanced age. This retrospective study investigated the impact of donor age in DCD liver transplantation. We examined 92 recipients who received DCD grafts and 92 matched recipients who received donation after brain death (DBD) grafts at Cleveland Clinic from January 2005 to June 2014. DCD grafts met stringent criteria to minimize risk factors in both donors and recipients. The 1-, 3-, and 5-year graft survival in DCD recipients was significantly inferior to that in DBD recipients (82%, 71%, 66% versus 92%, 87%, 85%, respectively; P = 0.03). Six DCD recipients (7%), but no DBD recipients, experienced ischemic-type biliary stricture (P = 0.01). However, the incidence of biliary stricture was not associated with donor age (P = 0.57). Interestingly, recipients receiving DCD grafts from donors who were <45 years of age (n = 55) showed similar graft survival rates compared to those receiving DCD grafts from donors who were ≥45 years of age (n = 37; 80%, 69%, 66% versus 83%, 72%, 66%, respectively; P = 0.67). Cox proportional hazards modeling in all study populations (n = 184) revealed advanced donor age (P = 0.05) and the use of a DCD graft (P = 0.03) as unfavorable factors for graft survival. Logistic regression analysis showed that the risk of DBD graft failure increased with increasing age, but the risk of DCD graft failure did not increase with increasing age (P = 0.13). In conclusion, these data suggest that stringent donor and recipient selection may ameliorate the negative impact of donor age in DCD liver transplantation. DCD grafts should not be discarded because of donor age, per se, and could help expand the donor pool for liver transplantation.

  19. Hypofractionated High-Dose Proton Beam Therapy for Stage I Non-Small-Cell Lung Cancer: Preliminary Results of A Phase I/II Clinical Study

    SciTech Connect

    Hata, Masaharu . E-mail: mhata@syd.odn.ne.jp; Tokuuye, Koichi; Kagei, Kenji; Sugahara, Shinji; Nakayama, Hidetsugu; Fukumitsu, Nobuyoshi; Hashimoto, Takayuki; Mizumoto, Masashi; Ohara, Kiyoshi; Akine, Yasuyuki

    2007-07-01

    Purpose: To present treatment outcomes of hypofractionated high-dose proton beam therapy for Stage I non-small-cell lung cancer (NSCLC). Methods and Materials: Twenty-one patients with Stage I NSCLC (11 with Stage IA and 10 with Stage IB) underwent hypofractionated high-dose proton beam therapy. At the time of irradiation, patient age ranged from 51 to 85 years (median, 74 years). Nine patients were medically inoperable because of comorbidities, and 12 patients refused surgical resection. Histology was squamous cell carcinoma in 6 patients, adenocarcinoma in 14, and large cell carcinoma in 1. Tumor size ranged from 10 to 42 mm (median, 25 mm) in maximum diameter. Three and 18 patients received proton beam irradiation with total doses of 50 Gy and 60 Gy in 10 fractions, respectively, to primary tumor sites. Results: Of 21 patients, 2 died of cancer and 2 died of pneumonia at a median follow-up period of 25 months. The 2-year overall and cause-specific survival rates were 74% and 86%, respectively. All but one of the irradiated tumors were controlled during the follow-up period. Five patients showed recurrences 6-29 months after treatment, including local progression and new lung lesions outside of the irradiated volume in 1 and 4 patients, respectively. The local progression-free and disease-free rates were 95% and 79% at 2 years, respectively. No therapy-related toxicity of Grade {>=}3 was observed. Conclusions: Hypofractionated high-dose proton beam therapy seems feasible and effective for Stage I NSCLC. Proton beams may contribute to enhanced efficacy and lower toxicity in the treatment of patients with Stage I NSCLC.

  20. Staging of the baboon response to group A streptococci administered intramuscularly: a descriptive study of the clinical symptoms and clinical chemical response patterns.

    PubMed

    Taylor, F B; Bryant, A E; Blick, K E; Hack, E; Jansen, P M; Kosanke, S D; Stevens, D L

    1999-07-01

    Group A streptococcal infections, ranging from necrotizing fasciitis and myositis to toxic shock syndrome, have increased over the last 10 years. We developed the first primate model of necrotizing fasciitis and myositis. Thirteen baboons were inoculated intramuscularly with group A streptococci (GAS). Eleven animals survived for > or = 11 days before sacrifice, and two animals died within 2 days. The site of inoculation of the survivors exhibited an intense neutrophilic influx (stage I), followed by a lymphoplasmacytic influx (stages II and III). This was accompanied by the appearance of markers of an acute and then a chronic systemic inflammatory response. In contrast, the site of inoculation of the two nonsurvivors exhibited intravascular aggregates of neutrophils at its margin with no influx of neutrophils and with extensive bacterial colonization. We conclude that GAS inoculation induces a local and systemic acute neutrophilia followed by a chronic lymphoplasmacytic response; failure, initially, of neutrophilic influx into the site of inoculation predisposes to systemic GAS sepsis and death; and this three-stage primate model approximates the human disease.

  1. Impact of MammaPrint on Clinical Decision-Making in South African Patients with Early-Stage Breast Cancer.

    PubMed

    Pohl, Heinrich; Kotze, Maritha J; Grant, Kathleen A; van der Merwe, Lize; Pienaar, Fredrieka M; Apffelstaedt, Justus P; Myburgh, Ettienne J

    2016-07-01

    The aim of the study was to evaluate the impact of MammaPrint on treatment decision-making in patients with breast cancer. Clinicopathologic information of all breast cancer patients referred for MammaPrint testing in South Africa was collected from 2007 until 2014. A total of 107 patients (109 tumors) with estrogen receptor/progesterone receptor positive and human epidermal growth factor receptor-2 negative tumors were selected with tumors ≥10 mm, or when 1-3 nodes were involved without extra-nodal extension. None of the clinical indicators correlated significantly with the MammaPrint risk classification, which changed the decision for adjuvant chemotherapy in 52% of patients. Of 60 patients who were clinically high risk, 62% had a low-risk MammaPrint result and of the 47 clinically low -risk patients 40% had a high-risk MammaPrint result. This study indicates that MammaPrint could reduce the need for adjuvant chemotherapy by 17% using the selection criteria stipulated. The significant impact on treatment decisions confirmed the clinical utility of MammaPrint independent of standard clinicopathologic risk factors as supported by long-term clinical outcome studies.

  2. Impact of MammaPrint on Clinical Decision-Making in South African Patients with Early-Stage Breast Cancer.

    PubMed

    Pohl, Heinrich; Kotze, Maritha J; Grant, Kathleen A; van der Merwe, Lize; Pienaar, Fredrieka M; Apffelstaedt, Justus P; Myburgh, Ettienne J

    2016-07-01

    The aim of the study was to evaluate the impact of MammaPrint on treatment decision-making in patients with breast cancer. Clinicopathologic information of all breast cancer patients referred for MammaPrint testing in South Africa was collected from 2007 until 2014. A total of 107 patients (109 tumors) with estrogen receptor/progesterone receptor positive and human epidermal growth factor receptor-2 negative tumors were selected with tumors ≥10 mm, or when 1-3 nodes were involved without extra-nodal extension. None of the clinical indicators correlated significantly with the MammaPrint risk classification, which changed the decision for adjuvant chemotherapy in 52% of patients. Of 60 patients who were clinically high risk, 62% had a low-risk MammaPrint result and of the 47 clinically low -risk patients 40% had a high-risk MammaPrint result. This study indicates that MammaPrint could reduce the need for adjuvant chemotherapy by 17% using the selection criteria stipulated. The significant impact on treatment decisions confirmed the clinical utility of MammaPrint independent of standard clinicopathologic risk factors as supported by long-term clinical outcome studies. PMID:27079770

  3. Clinical Approach to the Heavy Cannabis User in the Age of Medical Marijuana.

    PubMed

    Cermak, Timmen L

    2016-01-01

    This article begins with a case vignette exemplifying the common clinical problem of heavy marijuana users. The epidemiology and basic science underlying cannabis dependence is outlined, followed by clinical strategies for basing a therapeutic alliance on known research findings and using motivational interviewing to deal with typical patterns of denial.

  4. Stimulating Healthy Aging with a Model Nurse-Managed Free Clinic in a Senior Center.

    ERIC Educational Resources Information Center

    Franklin, Ruth H.

    As part of a Geriatric Education and Health Management program, a model nurse-managed free clinic has been established at an urban senior center by faculty and students of the University of New Mexico College of Nursing. Funded by a 3-year grant from the Department of Health and Human Services, the weekly clinic is based on Orem's self-care theory…

  5. Radiotherapy With 8-MHz Radiofrequency-Capacitive Regional Hyperthermia for Stage III Non-Small-Cell Lung Cancer: The Radiofrequency-Output Power Correlates With the Intraesophageal Temperature and Clinical Outcomes

    SciTech Connect

    Ohguri, Takayuki Imada, Hajime; Yahara, Katsuya; Morioka, Tomoaki; Nakano, Keita; Terashima, Hiromi; Korogi, Yukunori

    2009-01-01

    Purpose: To assess the efficacy of radiotherapy (RT) combined with regional hyperthermia (HT) guided by radiofrequency (RF)-output power and intraesophageal temperature and evaluate the potential contribution of HT to clinical outcomes in patients with Stage III non-small-cell lung cancer (NSCLC). Methods and Materials: Thirty-five patients with Stage III NSCLC treated with RT plus regional HT were retrospectively analyzed. Twenty-two of the 35 patients underwent intraesophageal temperature measurements. Patients with subcutaneous fat of 2.5 cm or greater, older age, or other serious complications did not undergo this therapy. The 8-MHz RF-capacitive heating device was applied, and in all patients, both the upper and lower electrodes were 30 cm in diameter, placed on opposite sides of the whole thoracic region, and treatment posture was the prone position. The HT was applied within 15 minutes after RT once or twice a week. Results: All thermal parameters, minimum, maximum, and mean of the four intraesophageal temperature measurements at the end of each session and the proportion of the time during which at least one of the four intraesophageal measurements was 41{sup o}C or higher in the total period of each session of HT, of the intraesophageal temperature significantly correlated with median RF-output power. Median RF-output power ({>=}1,200 W) was a statistically significant prognostic factor for overall, local recurrence-free, and distant metastasis-free survival. Conclusions: The RT combined with regional HT using a higher RF-output power could contribute to better clinical outcomes in patients with Stage III NSCLC. The RF-output power thus may be used as a promising parameter to assess the treatment of deep regional HT if deep heating using this device is performed with the same size electrodes and in the same body posture.

  6. Elevated pentraxin 3 level at the early stage of exercise training is associated with reduction of arterial stiffness in middle-aged and older adults.

    PubMed

    Zempo-Miyaki, A; Fujie, S; Sato, K; Hasegawa, N; Sanada, K; Maeda, S; Hamaoka, T; Iemitsu, M

    2016-09-01

    Regular exercise improves aging-induced deterioration of arterial stiffness, and is associated with elevated production of pentraxin 3 (PTX3) and anti-inflammatory as well as anti-atherosclerotic effects. However, the time-dependent effect of exercise training on arterial stiffness and PTX3 production remains unclear. The purpose of this study was to investigate the time course of the association between the effects of training on the circulating PTX3 level and arterial stiffness in middle-aged and older adults. Thirty-two healthy Japanese subjects (66.2±1.3 year) were randomly divided into two groups: training (exercise intervention) and sedentary controls. Subjects in the training group completed 8 weeks of aerobic exercise training (60-70% peak oxygen uptake (VO2peak) for 45 min, 3 days per week); during the training period, we evaluated plasma PTX3 concentration and carotid-femoral pulse wave velocity (cfPWV) every 2 wk. cfPWV gradually declined over the 8-week training period, and was significantly reduced after 6 and 8 week of exercise intervention (P<0.05). Plasma PTX3 level was significantly increased after 4 weeks of the intervention (P<0.05). In addition, the exercise training-induced reduction in cfPWV was negatively correlated with the percent change in plasma PTX3 level after 6 week (r=-0.54, P<0.05) and 8 weeks (r=-0.51, P<0.05) of the intervention, but not correlated at 4 weeks. Plasma PTX3 level was elevated at the early stage of the exercise training intervention, and was subsequently associated with training-induced alteration of arterial stiffness in middle-aged and older adults.

  7. Management of multivessel coronary disease after primary angioplasty: staged reintervention versus optimized clinical treatment and two-year follow-up

    PubMed Central

    de Paula, José Guilherme Rodrigues; de Godoy, Moacir Fernandes; dos Santos, Márcio Antônio; Pivatelli, Flávio Corrêa; Osti, Alan Vinicius Gamero; Trindade, Luciano Folchine; Novelli, Diego; Nakazone, Marcelo Arruda

    2014-01-01

    Objective In the clinical scenario of ST-segment elevation acute myocardial infarction, several patients with multivessel coronary atherosclerotic disease are discharged without a defined strategy to monitor the residual atherosclerotic lesions. The clinical endpoints evaluated were cardiovascular death, symptoms of angina pectoris, rehospitalization for a new acute coronary syndrome, and the necessity of reintervention during the two-year follow-up. Methods This observational, prospective, and historical study included multivessel coronary atherosclerotic disease patients who were admitted to a tertiary care university hospital with ST-segment elevation acute myocardial infarction and underwent primary percutaneous coronary intervention with stent implantation only at the culprit lesion site; these patients were monitored in the outpatient clinic according to two treatments: the Clinical Group - CG (optimized pharmacological therapy associated with counseling for a healthy diet and cardiac rehabilitation) or the Intervention Group - IG (new staged percutaneous coronary intervention or surgical coronary artery bypass graft surgery combined with the previously prescribed treatment). Results Of 143 patients consecutively admitted with ST-segment elevation acute myocardial infarction, 57 were eligible for the study (CG=44 and IG=13). Regarding the clinical endpoints, the cardiovascular death rate did not differ between the CG and IG. The symptom of angina pectoris and the rehospitalization rate for a new episode of acute coronary syndrome were accentuated in the CG (P=0.020 and P=0.049, respectively) mainly in individuals with evidence of ischemia evidenced by myocardial scintigraphy (P<0.001 and P=0.001, respectively) which culminated in an even greater need for reintervention (P=0.001) in this subgroup of patients. Conclusion The staged intervention was demonstrated to be safe and able to reduce angina pectoris and rehospitalization for a new episode of acute

  8. Age, Predisposing Diseases, and Ultrasonographic Findings in Determining Clinical Outcome of Acute Acalculous Inflammatory Gallbladder Diseases in Children

    PubMed Central

    2016-01-01

    We evaluated clinical factors such as age, gender, predisposing diseases and ultrasonographic findings that determine clinical outcome of acute acalculous inflammatory gallbladder diseases in children. The patients were divided into the four age groups. From March 2004 through February 2014, clinical data from 131 children diagnosed as acute acalculous inflammatory gallbladder disease by ultrasonography were retrospectively reviewed. Systemic infectious diseases were the most common etiology of acute inflammatory gallbladder disease in children and were identified in 50 patients (38.2%). Kawasaki disease was the most common predisposing disease (28 patients, 21.4%). The incidence was highest in infancy and lowest in adolescence. The age groups were associated with different predisposing diseases; noninfectious systemic disease was the most common etiology in infancy and early childhood, whereas systemic infectious disease was the most common in middle childhood and adolescence (P = 0.001). Gallbladder wall thickening was more commonly found in malignancy (100%) and systemic infection (94.0%) (P = 0.002), whereas gallbladder distension was more frequent in noninfectious systemic diseases (60%) (P = 0.000). Ascites seen on ultrasonography was associated with a worse clinical course compared with no ascites (77.9% vs. 37.7%, P = 0.030), and the duration of hospitalization was longer in patients with ascites (11.6 ± 10.7 vs. 8.0 ± 6.6 days, P = 0.020). In conclusion, consideration of age and predisposing disease in addition to ultrasonographic gallbladder findings in children suspected of acute acalculous inflammatory gallbladder disease might result in better outcomes. PMID:27550491

  9. Age, Predisposing Diseases, and Ultrasonographic Findings in Determining Clinical Outcome of Acute Acalculous Inflammatory Gallbladder Diseases in Children.

    PubMed

    Yi, Dae Yong; Chang, Eun Jae; Kim, Ji Young; Lee, Eun Hye; Yang, Hye Ran

    2016-10-01

    We evaluated clinical factors such as age, gender, predisposing diseases and ultrasonographic findings that determine clinical outcome of acute acalculous inflammatory gallbladder diseases in children. The patients were divided into the four age groups. From March 2004 through February 2014, clinical data from 131 children diagnosed as acute acalculous inflammatory gallbladder disease by ultrasonography were retrospectively reviewed. Systemic infectious diseases were the most common etiology of acute inflammatory gallbladder disease in children and were identified in 50 patients (38.2%). Kawasaki disease was the most common predisposing disease (28 patients, 21.4%). The incidence was highest in infancy and lowest in adolescence. The age groups were associated with different predisposing diseases; noninfectious systemic disease was the most common etiology in infancy and early childhood, whereas systemic infectious disease was the most common in middle childhood and adolescence (P = 0.001). Gallbladder wall thickening was more commonly found in malignancy (100%) and systemic infection (94.0%) (P = 0.002), whereas gallbladder distension was more frequent in noninfectious systemic diseases (60%) (P = 0.000). Ascites seen on ultrasonography was associated with a worse clinical course compared with no ascites (77.9% vs. 37.7%, P = 0.030), and the duration of hospitalization was longer in patients with ascites (11.6 ± 10.7 vs. 8.0 ± 6.6 days, P = 0.020). In conclusion, consideration of age and predisposing disease in addition to ultrasonographic gallbladder findings in children suspected of acute acalculous inflammatory gallbladder disease might result in better outcomes. PMID:27550491

  10. Aging and Lung Disease. Clinical Impact and Cellular and Molecular Pathways.

    PubMed

    Rojas, Mauricio; Mora, Ana L; Kapetanaki, Maria; Weathington, Nathaniel; Gladwin, Mark; Eickelberg, Oliver

    2015-12-01

    With the expected rapid growth of the aging population worldwide, there is a clear need to understand the complex process of aging to develop interventions that might extend the health span in this group of patients. Aging is associated with increased susceptibility to a variety of chronic diseases, and lung pathologies are no exception. The prevalence of lung diseases such as idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease has been found to increase considerably with age. In October 2014, the Division of Pulmonary, Allergy, and Critical Care of the University of Pittsburgh cohosted the Pittsburgh-Munich Lung Conference focused in aging and lung disease with the Comprehensive Pneumology Center, Institute of Lung Biology and Disease, Ludwig-Maximilians University and Helmholtz Zentrum Munich Germany. The purpose of the conference was to disseminate novel concepts in aging mechanisms that have an impact in lung physiology and pathogenesis of pulmonary diseases that commonly occur in older populations. The conference included 28 presentations on diverse topics, which are summarized in this report. The participants identified priorities for future basic and translational investigations that will assist in the identification of molecular insights involved in the pathogenesis of age-related pulmonary diseases and the design of therapeutic interventions for these lung conditions. PMID:26653202

  11. [Postoperative Adjuvant Chemotherapy for Stage III Colon Cancer--Drug Selection, Tolerability, and Safety in Clinical Practice].

    PubMed

    Okada, Kazutake; Sadahiro, Sotaro; Saito, Gota; Tanaka, Akira; Suzuki, Toshiyuki

    2016-05-01

    In the National Comprehensive Cancer Network (NCCN) guidelines, oxaliplatin (L-OHP)-based chemotherapeutic regimens, including 5-fluorouracil, Leucovorin (LV), and L-OHP (FOLFOX); capecitabine and L-OHP (CapeOX); and 5-fluorouracil, folinic acid, and L-OHP (FLOX) are designated as category 1 recommendations for postoperative adjuvant chemotherapy in Stage III colon cancer, followed by capecitabine and 5-fluorouracil plus LV as category 2A recommendations. We studied the selection of drugs for adjuvant chemotherapy and assessed the tolerability and safety of CapeOX and tegafur-uracil (UFT) plus LV (UFT/LV) in patients with Stage III colon cancer. The study group included 104 consecutive patients with Stage III colon cancer who underwent curative surgery. One patient changed hospitals immediately after surgery. Among the remaining 103 patients, 82 (80%) received adjuvant chemotherapy and 21 (20%) did not. CapeOX was administered to 32 patients (31%), UFT/LV to 49 patients (48%), and capecitabine to 1 patient (1%). In 59 patients, the treatment choice was determined according to the patient's preference; 32 patients (54%) selected CapeOX, 26 (44%) selected UFT/LV, and 1 (2%) selected no chemotherapy. The treatment completion rate was 80% for CapeOX and 84% for UFT/LV. Among patients who completed chemotherapy, dose reduction and drug withdrawal were not required in 22% of patients who received CapeOX and 80% of those who received UFT/LV. Neither CapeOX nor UFT/LV was associated with any serious adverse events. The tolerability and safety of CapeOX and UFT/LV were acceptable. However, CapeOX dose had to be carefully adjusted according to each patient's condition.

  12. LMO2 expression reflects the different stages of blast maturation and genetic features in B-cell acute lymphoblastic leukemia and predicts clinical outcome

    PubMed Central

    Malumbres, Raquel; Fresquet, Vicente; Roman-Gomez, Jose; Bobadilla, Miriam; Robles, Eloy F.; Altobelli, Giovanna G.; Calasanz, M.ª José; Smeland, Erlend B.; Aznar, Maria Angela; Agirre, Xabier; Martin-Palanco, Vanesa; Prosper, Felipe; Lossos, Izidore S.; Martinez-Climent, Jose A.

    2011-01-01

    Background LMO2 is highly expressed at the most immature stages of lymphopoiesis. In T-lymphocytes, aberrant LMO2 expression beyond those stages leads to T-cell acute lymphoblastic leukemia, while in B cells LMO2 is also expressed in germinal center lymphocytes and diffuse large B-cell lymphomas, where it predicts better clinical outcome. The implication of LMO2 in B-cell acute lymphoblastic leukemia must still be explored. Design and Methods We measured LMO2 expression by real time RT-PCR in 247 acute lymphoblastic leukemia patient samples with cytogenetic data (144 of them also with survival and immunophenotypical data) and in normal hematopoietic and lymphoid cells. Results B-cell acute lymphoblastic leukemia cases expressed variable levels of LMO2 depending on immunophenotypical and cytogenetic features. Thus, the most immature subtype, pro-B cells, displayed three-fold higher LMO2 expression than pre-B cells, common-CD10+ or mature subtypes. Additionally, cases with TEL-AML1 or MLL rearrangements exhibited two-fold higher LMO2 expression compared to cases with BCR-ABL rearrangements or hyperdyploid karyotype. Clinically, high LMO2 expression correlated with better overall survival in adult patients (5-year survival rate 64.8% (42.5%–87.1%) vs. 25.8% (10.9%–40.7%), P= 0.001) and constituted a favorable independent prognostic factor in B-ALL with normal karyotype: 5-year survival rate 80.3% (66.4%–94.2%) vs. 63.0% (46.1%–79.9%) (P= 0.043). Conclusions Our data indicate that LMO2 expression depends on the molecular features and the differentiation stage of B-cell acute lymphoblastic leukemia cells. Furthermore, assessment of LMO2 expression in adult patients with a normal karyotype, a group which lacks molecular prognostic factors, could be of clinical relevance. PMID:21459790

  13. Stage IV and age over 45 years are the only prognostic factors of the International Prognostic Score for the outcome of advanced Hodgkin lymphoma in the Spanish Hodgkin Lymphoma Study Group series.

    PubMed

    Guisado-Vasco, Pablo; Arranz-Saez, Reyes; Canales, Miguel; Cánovas, Araceli; Garcia-Laraña, José; García-Sanz, Ramón; Lopez, Andrés; López, José Luis; Llanos, Marta; Moraleda, José Maria; Rodriguez, José; Rayón, Consuelo; Sabin, Pilar; Salar, Antonio; Marín-Niebla, Ana; Morente, Manuel; Sánchez-Godoy, Pedro; Tomás, José Francisco; Muriel, Alfonso; Abraira, Victor; Piris, Miguel A; Garcia, Juán F; Montalban, Carlos

    2012-05-01

    The International Prognostic Score (IPS) is the most widely used system to date for identifying risk groups for the outcome of patients with advanced Hodgkin lymphoma, although important limitations have been recognized. We analyzed the value of the IPS in a series of 311 patients with advanced classical Hodgkin lymphoma (cHL) (Ann Arbor stage III, IV or stage II with B symptoms and/or bulky masses) treated with first-line chemotherapy including adriamycin (adriamycin, bleomycin, vinblastine, dacarbazine [ABVD] or equivalent variants). In univariate and multivariate analyses, stage IV disease and age ≥ 45 years were the only factors with independent predictive significance for overall survival (OS) (p = 0.002 and p < 0.001, respectively). Stage IV was still significant for freedom from progression (FFP) (p = 0.001) and age ≥ 45 years was borderline significant (p = 0.058). IPS separates prognostic groups, as in the original publication, but this is mainly due to the high statistical significance of stage IV and age ≥ 45 years. Moreover, the combination of these two factors enables a simpler system to be constructed that separates groups with different FFP and OS. In conclusion, in our series, stage IV and age ≥ 45 years are the key prognostic factors for the outcome of advanced cHL.

  14. Assessment of cobalt 57 tagged bleomycin as a clinical aid in staging of head and neck carcinoma

    SciTech Connect

    Cummings, C.W.; Larson, S.M.; Dobie, R.A.; Weymuller, E.A. Jr.; Rudd, T.G.; Merello, A.

    1981-04-01

    Critical assessment of head and neck cancer with respect to staging has, on occasion, been disappointingly ineffective. The incidence of measurable uptake of cobalt 57 tagged bleomycin by primary squamous cell carcinoma and metastatic cervical lymph nodes has been correlated. Forty-six cases have been evaluated with respect to histopathological confirmation of the suspected metastatic disease. We have found that this diagnostic measure increases our acumen in staging of head and neck cancer. The relevance of the Co-Bleo scans as a diagnostic aid is reported in 46 cases. Malignant tumors greater than 2 cm in size appear to demonstrate active uptake of the imaging agent. Small tumor size and excess background radioactivity contribute to the false-negatives (17%). Inflammatory conditions or benign tumors of the salivary apparatus may result in minimal uptake, thus, a false-positive result (10%). An increase in the radioactivity of the Co-Bleo may enhance the benefits of this procedure in the search for an undiagnosed primary, as well as undiagnosed local or distant metastases.

  15. Assessment of cobalt 57 tagged bleomycin as a clinical aid in staging of head and neck carcinoma

    SciTech Connect

    Cummings, C.W.; Larson, S.M.; Dobie, R.A.; Weymuller, E.A. Jr.; Rudd, T.G.; Merello, A.

    1981-04-01

    Critical assessment of head and neck cancer with respect to staging has, on occasion, been disappointingly ineffective. We have attempted to correlate the incidence of measureable uptake of cobalt 57 tagged bleomycin by primary squamous cell carcinoma and metastatic cervical lymph nodes. Forty-six cases have been evaluated with respect to histopathological confirmation of the suspected metastatic disease. We have found that this diagnostic measure increases our acumen in staging of head and neck cancer. The relevance of the Co-Bleo scans as a diagnostic aid is reported in 46 cases. Malignant tumors greater than 2 cm in size appear to demonstrate active uptake of the imaging agent. Small tumor size and excess background radioactivity contribute to the false-negatives (17%). Inflammatory conditions or benign tumors of the salivary apparatus may result in minimal uptake, thus, a false-positive result (10%). An increase in the radioactivity of the Co-Bleo may enhance the benefits of this procedure in the search for an undiagnosed primary, as well as undiagnosed local or distant metastases.

  16. Assessment of cobalt 57 tagged bleomycin as a clinical aid in staging of head and neck carcinoma.

    PubMed

    Cummings, C W; Larson, S M; Dobie, R A; Weymuller, E A; Rudd, T G; Merello, A

    1981-04-01

    Critical assessment of head and neck cancer with respect to staging has, on occasion, been disappointingly ineffective. We have attempted to correlate the incidence of measureable uptake of cobalt 57 tagged bleomycin by primary squamous cell carcinoma and metastatic cervical lymph nodes. Forty-six cases have been evaluated with respect to histopathological confirmation of the suspected metastatic disease. We have found that this diagnostic measure increases our acumen in staging of head and neck cancer. The relevance of the Co-Bleo scans as a diagnostic aid is reported in 46 cases. Malignant tumors greater than 2 cm in size appear to demonstrate active uptake of the imaging agent. Small tumor size and excess background radioactivity contribute to the false-negatives (17%). Inflammatory conditions or benign tumors of the salivary apparatus may result in minimal uptake, thus, a false-positive result (10%). An increase in the radioactivity of the Co-Bleo may enhance the benefits of this procedure in the search for an undiagnosed primary, as well as undiagnosed local or distant metastases.

  17. Dosimetric and Clinical Outcomes of Involved-Field Intensity-Modulated Radiotherapy After Chemotherapy for Early-Stage Hodgkin's Lymphoma With Mediastinal Involvement

    SciTech Connect

    Lu Ningning; Li Yexiong; Wu Runye; Zhang Ximei; Wang Weihu; Jin Jing; Song Yongwen; Fang Hui; Ren Hua; Wang Shulian; Liu Yueping; Liu Xinfan; Chen Bo; Dai Jianrong; Yu Zihao

    2012-09-01

    Purpose: To evaluate the dosimetric and clinical outcomes of involved-field intensity-modulated radiotherapy (IF-IMRT) for patients with early-stage Hodgkin's lymphoma (HL) with mediastinal involvement. Methods and Materials: Fifty-two patients with early-stage HL that involved the mediastinum were reviewed. Eight patients had Stage I disease, and 44 patients had Stage II disease. Twenty-three patients (44%) presented with a bulky mediastinum, whereas 42 patients (81%) had involvement of both the mediastinum and either cervical or axillary nodes. All patients received combination chemotherapy followed by IF-IMRT. The prescribed radiation dose was 30-40 Gy. The dose-volume histograms of the target volume and critical normal structures were evaluated. Results: The median mean dose to the primary involved regions (planning target volume, PTV1) and boost area (PTV2) was 37.5 Gy and 42.1 Gy, respectively. Only 0.4% and 1.3% of the PTV1 and 0.1% and 0.5% of the PTV2 received less than 90% and 95% of the prescribed dose, indicating excellent PTV coverage. The median mean lung dose and V20 to the lungs were 13.8 Gy and 25.9%, respectively. The 3-year overall survival, local control, and progression-free survival rates were 100%, 97.9%, and 96%, respectively. No Grade 4 or 5 acute or late toxicities were reported. Conclusions: Despite the large target volume, IF-IMRT gave excellent dose coverage and a favorable prognosis, with mild toxicity in patients with early-stage mediastinal HL.

  18. Differential effects of propofol and isoflurane on the relationship between EEG Narcotrend index and clinical stages of anaesthetic depth in sheep undergoing experimental cardiac surgery.

    PubMed

    Otto, Klaus A

    2016-02-01

    The electroencephalogram (EEG) Narcotrend index (NI) has been shown to improve anaesthetic depth monitoring in isoflurane-anaesthetised sheep. Data obtained from 13 anaesthetised juvenile female sheep were analysed retrospectively in order to assess the relationship between clinical stages of anaesthesia (CS) and NI during both propofol and isoflurane anaesthesia. Polynomial regression analysis revealed no significant association between CS and NI for propofol (R = 0.374, R(2) = 0.140, P = 0.403) but for isoflurane anaesthesia (R = 0.548, R(2) = 0.301, P = 0.010) there was a significant relationship. Furthermore, a strong correlation existed between end-tidal isoflurane concentration (ISOET) and CS (r = -0.463, P = 0.008). A combination of assessment of clinical signs and analogous EEG patterns is recommended during propofol anaesthesia.

  19. Acid Mediated Ring Closing Metathesis: A Powerful Synthetic Tool Enabling the Synthesis of Clinical Stage Kinase Inhibitors.

    PubMed

    William, Anthony D; Lee, Angeline C-H

    2015-01-01

    The powerful olefin metathesis reaction was employed for the construction of late-phase clinical agents SB1317 and SB1518. In both cases RCM seems to proceed only in the presence of an acid and to predominantly furnish trans isomers. In case of SB1518 it proceeded in the presence of acid HCl, while for SB1317, it mainly proceeds in the presence of TFA (trifluroacetic acid).

  20. Acid Mediated Ring Closing Metathesis: A Powerful Synthetic Tool Enabling the Synthesis of Clinical Stage Kinase Inhibitors.

    PubMed

    William, Anthony D; Lee, Angeline C-H

    2015-01-01

    The powerful olefin metathesis reaction was employed for the construction of late-phase clinical agents SB1317 and SB1518. In both cases RCM seems to proceed only in the presence of an acid and to predominantly furnish trans isomers. In case of SB1518 it proceeded in the presence of acid HCl, while for SB1317, it mainly proceeds in the presence of TFA (trifluroacetic acid). PMID:26507218

  1. Transforming Clinical Education in Obstetrics and Gynecology: Gone Is the Day of the Sage on the Stage.

    PubMed

    Smith, Marshall L; Foley, Michael R

    2016-04-01

    Many traditional approaches to clinical education today are outdated and inefficient with disruptive changes on the horizon. Millennials are the new wave of learners in health care and do not learn the same way as their older faculty. Merging health care systems are moving to standardizations of care and reduction of errors, and health care providers are going to be increasingly held more accountable for their clinical outcomes. Computers, digitalization, and connectivity are revolutionizing learning environments, and simulation learning in the form of trainers, mannequins, and team training is already widespread. Newer technologies like virtual and augmented reality are beginning to be used for clinical education and will be a more efficient and standardized way of providing simulation learning. Emerging technologies like holograms and head-mounted displays will follow soon after and be even more disruptive. Faculty and mentors will always be crucial to learning in health care but will be empowered to teach in more focused and comprehensive ways. The educational model of the future will be a hybrid model of experienced faculty, interactive learning, and innovative and emerging technology. It is time we start to train health care providers for their future, not our past.

  2. Transforming Clinical Education in Obstetrics and Gynecology: Gone Is the Day of the Sage on the Stage.

    PubMed

    Smith, Marshall L; Foley, Michael R

    2016-04-01

    Many traditional approaches to clinical education today are outdated and inefficient with disruptive changes on the horizon. Millennials are the new wave of learners in health care and do not learn the same way as their older faculty. Merging health care systems are moving to standardizations of care and reduction of errors, and health care providers are going to be increasingly held more accountable for their clinical outcomes. Computers, digitalization, and connectivity are revolutionizing learning environments, and simulation learning in the form of trainers, mannequins, and team training is already widespread. Newer technologies like virtual and augmented reality are beginning to be used for clinical education and will be a more efficient and standardized way of providing simulation learning. Emerging technologies like holograms and head-mounted displays will follow soon after and be even more disruptive. Faculty and mentors will always be crucial to learning in health care but will be empowered to teach in more focused and comprehensive ways. The educational model of the future will be a hybrid model of experienced faculty, interactive learning, and innovative and emerging technology. It is time we start to train health care providers for their future, not our past. PMID:26959215

  3. Validity of the ages and stages questionnaires in Korean compared to Bayley Scales of infant development-II for screening preterm infants at corrected age of 18-24 months for neurodevelopmental delay.

    PubMed

    Kwun, Yoojin; Park, Hye Won; Kim, Min-Ju; Lee, Byong Sop; Kim, Ellen Ai-Rhan

    2015-04-01

    This study aimed to evaluate the validity of the ages and stages questionnaire in Korean (ASQ 1st edition, Korean Questionnaires, Seoul Community Rehabilitation Center, 2000) for premature infants. The study population consisted of 90 premature infants born between January 1, 2005, and December 31, 2011, who were tested using the ASQ (Korean) and Bayley Scales of Infant Development (BSID) (II) at a corrected age of 18-24 months. The validity of the ASQ (Korean) using cut-off values set at < -2 SD was examined by comparing it to the BSID (II) components, namely, the mental developmental index (MDI) or psychomotor developmental index (PDI), which were both set at < 85. The calculation of the sensitivities, specificities, positive predictive values, and negative predictive values of the ASQ (Korean) components revealed that they detected infants with neurodevelopmental delay with low sensitivity and positive predictive values, however, the communication domain showed moderate correlations with MDI. The failure in more than one domain of the ASQ (Korean) was significantly correlated with the failure in MDI. The ASQ (Korean) showed low validity for screening neurodevelopmentally delayed premature infants. PMID:25829813

  4. Validity of the ages and stages questionnaires in Korean compared to Bayley Scales of infant development-II for screening preterm infants at corrected age of 18-24 months for neurodevelopmental delay.

    PubMed

    Kwun, Yoojin; Park, Hye Won; Kim, Min-Ju; Lee, Byong Sop; Kim, Ellen Ai-Rhan

    2015-04-01

    This study aimed to evaluate the validity of the ages and stages questionnaire in Korean (ASQ 1st edition, Korean Questionnaires, Seoul Community Rehabilitation Center, 2000) for premature infants. The study population consisted of 90 premature infants born between January 1, 2005, and December 31, 2011, who were tested using the ASQ (Korean) and Bayley Scales of Infant Development (BSID) (II) at a corrected age of 18-24 months. The validity of the ASQ (Korean) using cut-off values set at < -2 SD was examined by comparing it to the BSID (II) components, namely, the mental developmental index (MDI) or psychomotor developmental index (PDI), which were both set at < 85. The calculation of the sensitivities, specificities, positive predictive values, and negative predictive values of the ASQ (Korean) components revealed that they detected infants with neurodevelopmental delay with low sensitivity and positive predictive values, however, the communication domain showed moderate correlations with MDI. The failure in more than one domain of the ASQ (Korean) was significantly correlated with the failure in MDI. The ASQ (Korean) showed low validity for screening neurodevelopmentally delayed premature infants.

  5. Non-Randomized Confirmatory Trial of Laparoscopy-Assisted Total Gastrectomy and Proximal Gastrectomy with Nodal Dissection for Clinical Stage I Gastric Cancer: Japan Clinical Oncology Group Study JCOG1401

    PubMed Central

    Kataoka, Kozo; Mizusawa, Junki; Katayama, Hiroshi; Nakamura, Kenichi; Morita, Shinji; Yoshikawa, Takaki; Ito, Seiji; Kinoshita, Takahiro; Fukagawa, Takeo; Sasako, Mitsuru

    2016-01-01

    Several prospective studies on laparoscopy-assisted distal gastrectomy for early gastric cancer have been initiated, but no prospective study evaluating laparoscopy-assisted total gastrectomy or laparoscopy-assisted proximal gastrectomy has been completed to date. A non-randomized confirmatory trial was commenced in April 2015 to evaluate the safety of laparoscopy-assisted total gastrectomy and laparoscopy-assisted proximal gastrectomy for clinical stage I gastric cancer. A total of 245 patients will be accrued from 42 Japanese institutions over 3 years. The primary endpoint is the proportion of patients with anastomotic leakage. The secondary endpoints are overall survival, relapse-free survival, proportion of patients with completed laparoscopy-assisted total gastrectomy or laparoscopy-assisted proximal gastrectomy, proportion of patients with conversion to open surgery, adverse events, and short-term clinical outcomes. The UMIN Clinical Trials Registry number is UMIN000017155. PMID:27433394

  6. Clinical pharmacokinetics of new-generation antiepileptic drugs at the extremes of age: an update.

    PubMed

    Italiano, Domenico; Perucca, Emilio

    2013-08-01

    Epilepsies occur across the entire age range, and their incidence peaks in the first years of life and in the elderly. Therefore, antiepileptic drugs (AEDs) are commonly used at the extremes of age. Rational prescribing in these age groups requires not only an understanding of the drugs' pharmacodynamic properties, but also careful consideration of potential age-related changes in their pharmacokinetic profile. The present article, which updates a review published in 2006 in this journal, focuses on recent findings on the pharmacokinetics of new-generation AEDs in neonates, infants, children, and the elderly. Significant new information on the pharmacokinetics of new AEDs in the perinatal period has been acquired, particularly for lamotrigine and levetiracetam. As a result of slow maturation of the enzymes involved in glucuronide conjugation, lamotrigine elimination occurs at a particularly slow rate in neonates, and becomes gradually more efficient during the first months of life. In the case of levetiracetam, elimination occurs primarily by renal excretion and is also slow at birth, but drug clearance increases rapidly thereafter and can even double within 1 week. In general, infants older than 2-3 months and children show higher drug clearance (normalized for body weight) than adults. This pattern was confirmed in recent studies that investigated the pediatric pharmacokinetics of several new AEDs, including levetiracetam, rufinamide, stiripentol, and eslicarbazepine acetate. At the other extreme of age, in the elderly, drug clearance is generally reduced compared with younger adults because of less efficient drug-metabolizing activity, decreased renal function, or both. This general pattern, described previously for several AEDs, was confirmed in recent studies on the effect of old age on the clearance of felbamate, levetiracetam, pregabalin, lacosamide, and retigabine. For those drugs which are predominantly eliminated by renal excretion, aging

  7. Role of Nutritional Factors at the Early Life Stages in the Pathogenesis and Clinical Course of Type 1 Diabetes

    PubMed Central

    Kagohashi, Yukiko

    2015-01-01

    Nutrition has been suggested as an important environmental factor other than viruses and chemicals in the pathogenesis of type 1 diabetes (T1D). Whereas various maternal dietary nutritional elements have been suggested and examined in T1D of both humans and experimental animals, the results largely remain controversial. In a series of studies using T1D model nonobese diabetic (NOD) mice, maternal dietary n-6/n-3 essential fatty acid ratio during pregnancy and lactation period, that is, early life stages of the offspring, has been shown to affect pathogenesis of insulitis and strongly prevent overt T1D of the offspring, which is consistent with its preventive effects on other allergic diseases. PMID:25883958

  8. Quantitative clinical pharmacology for size and age scaling in pediatric drug development: A systematic review.

    PubMed

    Samant, Tanay S; Mangal, Naveen; Lukacova, Viera; Schmidt, Stephan

    2015-11-01

    The establishment of drug dosing in children is often hindered by the lack of actual pediatric efficacy and safety data. To overcome this limitation, scaling approaches are frequently employed to leverage adult clinical information for informing pediatric dosing. The objective of this review is to provide a comprehensive overview of the different scaling approaches used in pediatric pharmacotherapy as well as their proper implementation in drug development and clinical use. We will start out with a brief overview of the current regulatory requirements in pediatric drug development, followed by a review of the most commonly employed scaling approaches in increasing order of complexity ranging from simple body weight-based dosing to physiologically-based pharmacokinetic (PBPK) modeling approaches. Each of the presented approaches has advantages and limitations, which will be highlighted throughout the course of the review by the use of clinically-relevant examples. The choice of the approach employed consequently depends on the clinical question at hand and the availability of sufficient clinical data. The main effort while establishing and qualifying these scaling approaches should be directed towards the development of safe and effective dosing regimens in children rather than identifying the best model, ie models should be fit for purpose.

  9. Inhibin B, follicle stimulating hormone, luteinizing hormone and testosterone during childhood and puberty in males: changes in serum concentrations in relation to age and stage of puberty.

    PubMed

    Chada, M; Průsa, R; Bronský, J; Kotaska, K; Sídlová, K; Pechová, M; Lisá, L

    2003-01-01

    Inhibin B is a gonadal dimeric polypeptide hormone that regulates synthesis and secretion of follicle stimulating hormone (FSH) in a negative feedback loop. The aim of the present study was to determine changes in serum inhibin B, gonadotropins and testosterone concentrations during childhood and puberty in males. We studied the relationship between circulating inhibin B, gonadotropins and testosterone in serum of healthy boys during the first two years of life and then in pubertal development. Using a recently developed two-side enzyme-linked immunosorbent assay (ELISA), inhibin B levels were measured in the serum of 78 healthy boys divided into eleven age groups from birth to the end of pubertal development. In addition, serum levels of gonadotropins and testosterone were measured. Serum inhibin B, gonadotropins and testosterone increased during the first months of postnatal life. A peak in serum inhibin B and gonadotropins concentrations was observed around 3-4 months of age. There was a significant positive correlation between serum inhibin B and gonadotropins and testosterone levels during the first 2 years of life. After this early increase, serum inhibin B, gonadotropins and testosterone levels decreased significantly and remained low until puberty followed by an increase beginning with the onset of puberty. Serum levels of inhibin B reached a peak at stage G3 of puberty. Around midpuberty, inhibin B lost its positive correlation with luteinizing hormone (LH) and testosterone from early puberty, and developed a strong negative correlation with FSH, which persisted into adulthood. We conclude that inhibin B plays a key role in the regulation of the hypothalamic-pituitary-gonadal hormonal axis during male childhood and pubertal development. Inhibin B is a direct marker of the presence and function of Sertoli cells and appears to reflect testicular function in boys.

  10. Flapless CAD/CAM-guided surgery for staged transition from failing dentition to complete arch implant rehabilitation: a 3-year clinical report.

    PubMed

    Papaspyridakos, Panos; White, George Shelby; Lal, Kunal

    2012-03-01

    The transition of patients from failing dentition to complete arch implant rehabilitation often requires that the patient be rendered edentulous and has to wear a complete removable dental prosthesis for varying periods of time. This is objectionable to many patients. A staged treatment approach allows a fixed interim restoration, patient comfort, and prosthodontic control throughout the rehabilitation process. CAD/CAM-guided flapless implant surgery has the advantage of prosthetically driven implant placement and minimal postoperative sequelae. A patient with a failing dentition was treated with this combined protocol and was followed up for 3 years after loading. Implant and prosthesis survival rates were 100%, with no technical complications encountered up to the last recall. The purpose of this clinical report is to describe a combination of CAD/CAM-guided flapless surgery and a staged treatment approach, thereby giving the patient a tooth-supported or implant-supported fixed interim prosthesis during the entire rehabilitation process. The various surgical, laboratory, and prosthetic stages are illustrated for the complete arch prosthetic rehabilitation, and the 3-year follow-up outcome is reported.

  11. Treatment response for acute depression is not associated with number of previous episodes: lack of evidence for a clinical staging model for major depressive disorder.

    PubMed

    Dodd, Seetal; Berk, Michael; Kelin, Katarina; Mancini, Michele; Schacht, Alexander

    2013-09-01

    Mental illness has been observed to follow a neuroprogressive course, commencing with prodrome, then onset, recurrence and finally chronic illness. In bipolar disorder and schizophrenia responsiveness to treatment mirrors these stages of illness progression, with greater response to treatment in the earlier stages of illness and greater treatment resistance in chronic late stage illness. Using data from 5627 participants in 15 controlled trials of duloxetine, comparator arm (paroxetine, venlafaxine, escitalopram) or placebo for the treatment of an acute depressive episode, the relationship between treatment response and number of previous depressive episodes was determined. Data was dichotomised for comparisons between participants who had >3 previous episodes (n=1697) or ≤3 previous episodes (n=3930), and additionally for no previous episodes (n=1381) or at least one previous episode (n=4246). Analyses were conducted by study arm for each clinical trial, and results were then pooled. There was no significant difference between treatment response and number of previous depressive episodes. This unexpected finding suggests that treatments to reduce symptoms of depression during acute illness do not lose efficacy for patients with a longer history of illness.

  12. Comparison of the clinical value of multi-band mucosectomy versus endoscopic mucosal resection for the treatment of patients with early-stage esophageal cancer

    PubMed Central

    CHEN, ZI-YANG; YANG, YUN-CHAO; LIU, LI-MEI; LIU, XIAO-GANG; LI, YI; LI, LIANG-PING; HU, XIAO; ZHANG, REN-YI; SONG, YAN; QIN, QIN

    2015-01-01

    The present study aimed to compare the clinical value of multi-band mucosectomy (MBM) versus endoscopic mucosal resection (EMR) for the treatment of patients with early-stage esophageal cancer. Between January 2011 and December 2012, 68 patients with early-stage esophageal cancer who underwent MBM and EMR were enrolled into the present study. The curative resection rate, duration of surgery, complications and follow-up records were retrospectively analyzed. Of the 68 patients included, 33 were treated with MBM and 35 with EMR. There was no significant difference in the rate of complete resection between the MBM and EMR groups (P>0.05). The mean duration of surgery in the MBM group was statistically lower than that in the EMR group (P<0.05). There was no statistically significant difference in the intraoperative and post-operative complications between the MBM and EMR groups (P>0.05). Esophageal cancer reoccurred in 2 patients treated with MBM and 1 patient treated with EMR during the follow-up period (range, 3–24 months). Overall, MBM can be considered a better surgical option for the management of patients with early-stage esophageal cancer, as it offers higher histological curative resection rates and improved safety. However, further studies and a larger follow-up period are required to confirm the long-term curative effect. PMID:26137134

  13. A prospective, randomized clinical trial to assess the cost-effectiveness of a modern foam dressing versus a traditional saline gauze dressing in the treatment of stage II pressure ulcers.

    PubMed

    Payne, Wyatt G; Posnett, John; Alvarez, Oscar; Brown-Etris, Marie; Jameson, Gayle; Wolcott, Randall; Dharma, Hussein; Hartwell, Samantha; Ochs, Diane

    2009-02-01

    Modern dressings such as hydrocolloids, gels, and foams are typically more expensive than traditional dressings such as gauze. However, if modern dressings require fewer changes, the overall cost of treatment may be lower despite the higher initial purchase price. If healing rates are comparable or better, modern dressings also may be cost-effective. A 4-week, prospective, randomized clinical trial to assess differences in treatment costs and cost-effectiveness between a modern foam dressing and saline-soaked gauze was conducted among 36 patients (22 men, 14 women, mean age 72.8 years) with a Stage II pressure ulcer (mean duration 35 weeks) at five centers in the United States. Participants were randomized to treatment with a self-adhesive polyurethane foam (n = 20) or saline-soaked gauze dressing (n = 16). No difference in time to wound closure was observed (P = 0.817). Patients in the foam group had less frequent dressing changes (P <0.001). Total cost over the study period was lower by $466 per patient (P = 0.055) and spending on dressings was lower by $92 per patient in the foam group (P = 0.025). Cost per ulcer healed was lower by $1,517 and cost per ulcer-free day was lower by $80 for patients in the foam group. On the evidence of this study, the foam dressing is a more cost-effective treatment than saline-soaked gauze for the treatment of Stage II pressure ulcers.

  14. Experience of an incontinence clinic for older women: no apparent age limit for potential physical and psychological benefits.

    PubMed

    Tannenbaum, C; Bachand, G; Dubeau, C E; Kuchel, G A

    2001-10-01

    Urinary incontinence (UI) is a common but undertreated condition in older women. Although a variety of noninvasive interventions is available, older women may be hesitant to seek care for UI because of misconceptions about normal aging and treatment futility. We sought to evaluate the effectiveness of a UI clinic specifically tailored to the needs of older women to promote a sense of empowerment and to enhance satisfaction with treatment and outcome. We describe a case series of 52 women between the ages of 65 and 98 who were evaluated at the Geriatric Incontinence Clinic at the McGill University Health Centre over a 1-year period. A standardized telephone questionnaire was administered by a nurse consultant 6 months after each subject's final visit to assess patient satisfaction and current incontinence status. Forty-five women (86%) were available for telephone follow-up and completed the questionnaire. Mean age was 80 years, with urge incontinence in 45%, mixed incontinence (stress and urge) in 33%, impaired bladder emptying with urge symptoms in 10%, and other diagnoses in 12%. Overall, a mean reduction of 1.4 incontinent episodes per day was reported. At follow-up, 30% of the subjects reported being cured of their incontinence, 30% had improved, 20% were the same, and 20% were worse. Over 85% of all women reported satisfaction with their new incontinence status. Women of all ages, independent of the type of UI, type of treatment, and cognitive status, were able to achieve reductions in incontinence symptoms. All patients who had worsened were noncompliant with treatment recommendations at follow-up. Older women can derive significant benefit from a UI assessment. Neither advanced age nor category of incontinence precludes improvements or enhanced satisfaction with treatment. Efforts to improve targeting and compliance may improve outcomes. PMID:11703887

  15. Age-related changes in protein metabolism of beech (Fagus sylvatica L.) seeds during alleviation of dormancy and in the early stage of germination.

    PubMed

    Ratajczak, Ewelina; Kalemba, Ewa M; Pukacka, Stanislawa

    2015-09-01

    The long-term storage of seeds generally reduces their viability and vigour. The aim of this work was to evaluate the effect of long-term storage on beech (Fagus sylvatica L.) seeds at optimal conditions, over 9 years, on the total and soluble protein levels and activity of proteolytic enzymes, including endopeptidases, carboxypeptidases and aminopeptidases, as well as free amino acid levels and protein synthesis, in dry seeds, after imbibition and during cold stratification leading to dormancy release and germination. The same analyses were conducted in parallel on seeds gathered from the same tree in the running growing season and stored under the same conditions for only 3 months. The results showed that germination capacity decreased from 100% in freshly harvested seeds to 75% in seeds stored for 9 years. The levels of total and soluble proteins were highest in freshly harvested seeds and decreased significantly during storage, these proportions were retained during cold stratification and germination of seeds. Significant differences between freshly harvested and stored seeds were observed in the activities of proteolytic enzymes, including endopeptidases, aminopeptidases and carboxypeptidases, and in the levels of free amino acids. The neosynthesis of proteins during dormancy release and in the early stage of seed germination was significantly weaker in stored seeds. These results confirm the importance of protein metabolism for seed viability and the consequences of its reduction during seed ageing.

  16. Tandem high-dose chemotherapy and autologous stem cell rescue in patients over 1 year of age with stage 4 neuroblastoma.

    PubMed

    Sung, K W; Lee, S H; Yoo, K H; Jung, H L; Cho, E J; Koo, H H; Lee, S K; Kim, J; Lim, D H; Suh, Y L; Kim, D W

    2007-07-01

    From June 1997 to August 2005, 52 consecutive newly diagnosed stage 4 neuroblastoma patients over 1 year of age were assigned to receive tandem high-dose chemotherapy and autologous stem cell rescue (HDCT/ASCR) as consolidation therapy. Fifty of the 52 patients underwent a first HDCT/ASCR and 44 patients underwent a second HDCT/ASCR. Eight patients (15.4%) died from treatment-related toxicity (seven during the second HDCT/ASCR). Total body irradiation (TBI) in the first HDCT/ASCR and a shorter interval (< 12 weeks) between the first and second HDCT/ASCR were associated with a higher rate of treatment-related death in the second HDCT/ASCR (P = 0.032 and 0.095, respectively). The tumor relapsed or progressed in 11 patients, and 33 patients remained event free with a median follow-up of 53 months (range 19-117) from diagnosis. The 5-year event-free survival (EFS) (+/- 95% confidence interval) for all 52 patients was 62.1+/-13.7%. The application of TBI and local radiotherapy, and a longer interval between the first and second HDCT/ASCR were independently associated with a better EFS (P = 0.026, 0.007 and 0.020, respectively). However, further studies will be needed to decrease the toxic death rate in the second HDCT/ASCR while reducing the relapse rate.